Rare Tumors

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rare
tumors
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Editor-in-Chief: Robert C. Miller, USA
Volume 1, 2009
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RARE TUMORS Sheva, Israel
Antoniades Konstantinos, School of Dentistry, Aristotle University of Thessaloniki,
ISSN 2036-3605 - eISSN 2036-3613 Thessaloniki, Greece
Masafumi Koshiyama, Department of Ob/Gy at Otsu Red Cross Hospital, Otsu, Japan
Editor-in-Chief Sunil Krishnan, Radiation Oncology, Gastrointestinal Translational Research, M.D.
Anderson Cancer Center, Houston, TX, USA
Robert C. Miller, Rochester, MN, USA
Calin Lazar, Department of Plastic and Reconstructive Surgery, Rouen University
Editorial Staff Hospital, Rouen, France
Nicole Pezzolo, Managing Editor Wei Li, Institute of Biomedical Engineering, School of Control Science and
Cristiana Poggi, Production Editor Engineering, Shandong University, Shandong, China
Anne Freckleton, Copy Editor Simon Lo, Department of Radiation Medicine, The Ohio State University Arthur G.
James Cancer Hospital, Columbus, OH, USA
Jeanette Mitchell, Copy Editor
Lorenzo Lo Muzio, Surgical Sciences Department, Faculty of Medicine, University of
Filippo Lossani, Technical Support Foggia, Foggia, Italy
Paulette M. Fauceglia, Roswell Park Cancer Institute, Buffalo, New York, USA
Sridhar Mani, Departments of Medicine and Molecular Genetics, Division of
Editorial Board Oncology, Albert Einstein School of Medicine, New York, USA
Prakash Adhikari, Department of ENT and Head and Neck Surgery, GMS Memorial Hiroyuki Matsubayashi, Shizuoka Cancer Center, Shizuoka-ken, Japan
Academy of ENT and Head and Neck Studies, TU Teaching Hospital, Kathmandu,
Nepal Toshihiro Matsuo, Department of Artificial Joints and Biomaterial, Hiroshima
University, Hiroshima, Japan
Rafael Álvarez-González, Graduate School of Biomedical Sciences, University of
North Texas, Healt Science Center at Forth Worth, Forth Worth, Texas, USA Axel Merseburger, Department of Urology, Eberhard-Karls-University, Tübingen,
Germany
Armando Bartolazzi, Cellular and Molecular Tumor Pathology Laboratory, Cancer
Center Karolinska, Karolinska Hospital, Stockholm, Sweden Oliver Micke, Department of Radiotherapy and Radiation Oncology, Franziskus
Hospital, Bielefeld, Germany
Archit Bhatt, Department of Neurology and Ophtalmology, Clinical Center East
Lansing, East Lansing, Michigan, USA Rene Mirimanoff, Service de Radio-Oncologie, Centre Hospitalier Universitaire
Vaudois, Lausanne, Switzerland
Kevin Camphausen, Radiation Oncology Branch, National Cancer Institute, Bethesda,
Maryland, USA Luca Morelli, Operative Unit of Patological Anatomy and Cytological Diagnostics, P.O.
S. Chiara, Hospital of Trento, Trento, Italy
Joseph R. Carver, Abramson Cancer Center, University of Pennsylvania, Pennsylvania,
USA Charbel D. Moussallem, Orthpedic Surgery, Faculty of Medical Sciences, Lebanese
William Cho, Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong University, Beirut, Lebanon
Domenico Coppola, Anatomic Pathology and Neuroendocrine Cancer Research Hidenari Nagai, Division of Gastroenterology and Hepatology, Toho University
Divisions, Moffit Cancer Center and Research Institute, Tampa, Florida, USA Medical Center, Omori Hospital, Tokyo, Japan
Undurti N. Fams Das, UND Life Sciences, Shaker Heights, Ohio, USA Tan Dat Ngyuen, Department of Radiation Oncology, Institut Jean-Godinot, Reims,
France
Ozsahin E. Mahmut, Department of Radiooncology, Centre Hospitalier Universitaire
Vaudois, Lausanne, Switzerland Athanasios Papatsoris, University of Athens, Athens, Greece
Jimmy Thomas Efird, Centre of Health Vulnerable Populations, University of Carolina, Nicholas A. Pavlidis, Department of Medical Oncology, School of Medicine, University
Greensboro, Carolina, USA of Ioannina, Ioannina, Greece
Amany Elwakkad, National Research Center, Cairo, Egypt Yi Chu Pei, Department of Surgical Pathology, Changhua Christian Hospital,
Changhua, Taiwan
Gulgun Engin, Department of Radiology, Faculty of Medicine, Istanbul University,
Istanbul, Turkey Shahid Pervez, Department of Pathology and Microbiology, Agakhan University
Hospital, Karachi, Pakistan
Guy Eslick, Harvard School of Public Health, MA, USA
Camillo Porta, IRCCS San Matteo University Hospital Foundation, Pavia, Italy
Patricia D. Evilliers, Department of Anatomic Pathology, University of Alabama at
Birmingham, Birmingham, USA Fernando Quevedo, Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA
Luis E. Fayad, Department of Lymphoma & Myeloma, University of Texas MD Malcolm Schinstine, Division of Pathology, Hilo Medical Center Laboratories, Hilo,
Anderson Cancer Center, Houston, Texas, USA Hawaii, USA
Faris Farassati, Department of Medicine, University of Kansas School of Medicine, Andrzej Semczuk, Lublin Medical University, Lublin, P oland
Kansas City, Kansas, USA Khan Shah Alam, Department of Orthopaedics, All India Institute of Medical Sciences
Ali Gholamrezanezhad, Research Institute for Nuclear Medicine, Shariati Hospital, Ansari Nagar, New Delhi, India
Tehran University of Medical Sciences, Tehran, Iran Mark G. Shrime, Department of Otolaryngology/Head and Neck Surgery, Boston
Samy Lewiz Habib, Department of Medicine, Division of Nephrology, University of University Medical Center, Boston, Massachusetts, USA
Texas Health Science Center, San Antonio, Texas, USA Vernon Keith Sondak, Department of Cutaneous Oncology, H. Lee Moffitt Cancer
Paul H. Hartel, Broaddus Hospital of Davis Health System, Elkins, West Virginia, USA Center and Research Institute, Tampa, Florida, USA
Ghulam Sarwar Hashmi, Department of Oral and Maxillofacial Surgery, Z.A. Dental Giuseppe Spriano, Department of Otolaryngology/Head and Neck Surgery, National
College, Medical Colony, A.M.U. Aligarh, India Cancer Institute Regina Elena, Rome, Italy
Joseph Herman, Department of Oncology, The Sol Goldman Pancreatic Cancer Keith Stubbs, University of Western Australia, Perth, Australia
Research Center, Johns Hopkins School of Medicine, Baltimore Maryland USA Fabio Tavora, Department of Genitourinary Pathology, Armed Forces Institute of
Kanya Honoki, Department of Orthopedic Surgery, Nara Medical University, Nara, Pathology, Washington, DC, USA
Japan Juliette Thariat, Department of Radiation Oncology, Anti Cancer Center Antoine-
Charles Hsu, Division of Plastic and Reconstructive Surgery, Stanford University Lacassagne, University Nice Sophia-Antipolis, Nice, France
Medical Center, Palo Alto, CA, USA Takeshi Tomonaga, Department of Molecular Diagnosis, Graduate School of
Sergio Huerta, Dallas VA Medical Center Surgical Services, Dallas, Texas, USA Medicine, Chiba University, Chiba Japan
Abdul Hussain, Minimal Access Unit, General Surgery Department, Princess Royal Mark Gerard Trombetta, Department of Radiation Oncology, West Penn Allegheny
University Hospital, London, UK Health System Allegheny General Hospital, PA, USA
Rafael Jimenez, Division of Anatomic Pathology, Department of Laboratory Medicine Lyuba Varticovski, Laboratory of Human Carcinogenesis, Center for Cancer Research,
and Pathology, Mayo Clinic, Rochester, Minnesota, USA National Cancer Institute, Bethesda, MD, USA
Bleddyn Jones, Gray Institute for Radiation Oncology and Biology, University of Salvador Villa I Freixa, Department of Radiation Oncology, Hospital Universitari
Oxford, Oxford, UK Germans Trías, Badalona, Catalunya, Spain
Honoki Kanya, Department of Orthopedic Surgery, Nara Medical University, Nara, Takuya Watanabe, Department of Internal Medicine and Gastroenterology, Medical
Japan Hospital, The Nippon Dental University of Life Dentistry at Nigata, Nigata, Japan
Babak Kateb, Intraoperative Surgical Planning Society, Los Angeles, CA, USA Shigeru Yamada, Research Center for Charged Particle Therapy, National Institute of
Sunali Khanna, Department of Oral Medicine & Radiology, Nair Hospital Dental Radiological Sciences, Chiba, Japan
College, Mumbai, India Leandra Náira Zambelli Ramalho, Department of Pathology, Faculty of Medicine of
Boris Kirshtein, Department of Surgery, Soroka University Medical Center, Beer Ribeirão Preto, University of São Paulo, Ribeirdo Preto, SP, Brazil
RARE TUMORS
2009; Volume 1
Metastatic pleomorphic sarcoma to left atrium

Ammar H. Hawasli, Rachael Cayce, Trung Luong, Evelyn Taiwo, Michael N. Feliciano, Sharon C. Reimold, John M. DiMaio,
Barbara B. Haley..........................................................................................................................................................................................................................................................1
Squamous cell carcinoma of the scrotum in a Nigerian: case report

Jerome E. Azike, N.O. Chukwujama, T.C. Oguike...................................................................................................................................................................................................4
Extraosseous osteosarcoma in Ibadan: case series over a 20-year period

Temitope O. Alonge, Henry A. Obamuyide, Gabriel Olabiyi Ogun......................................................................................................................................................................6
A multimodal approach to the treatment of bilateral choroidal metastases from thyroid carcinoma
Maria Grazia Fabrini, Federica Genovesi-Ebert, Franco Perrone, Mario De Liguoro, Clara Giovannetti, Fausto Bogazzi, Stanislao Rizzo,
Enio Martino, Luca Cionini.......................................................................................................................................................................................................................................9
Pleomorphic sarcoma metastatic to the duodenum?

Fabio R. Tavora, Allen P. Burke ...............................................................................................................................................................................................................................12
Complete small bowel obstruction caused by metastasis from primary nasopharyngeal carcinoma
Chi Pan Lau, Edwin Pun Hui, Anthony Tak-Cheung Chan .................................................................................................................................................................................16
Diagnosis of vulvar lesions by non-invasive optical analysis: a pilot study

Anne-Therese Vlastos, Igor Charvet, Ilaria Dellacasa, Federica Capanna, Marie-Françoise Pelte, Philippe Thueler,
Michel Saint-Ghislain, Christian Depeursinge, Paolo Meda.............................................................................................................................................................................18
Congenital giant melanocytic nevi

Ghulam S. Hashmi, Syed S. Ahmed, Shahla Khan ................................................................................................................................................................................................23
Intramedullary capillary hemangioma of the thoracic spine: case report and review of the literature
Rahul Kasukurthi, Wilson Z. Ray, Spiros L. Blackburn, Eriks A. Lusis, Paul Santiago..................................................................................................................................26
A case report of surgical debulking for a huge mass of elephantiasis neuromatosa

Manabu Hoshi, Makoto Ieguchi, Susumu Taguchi, Shinya Yamasaki.............................................................................................................................................................29
Value of centrifugated liquid-based cytology by Papanicolaou and May-Grünwald in oral epithelial cells
Hussain Gadelkarim Ahmed, Ali Mahmmoud Edris, Eneel Ahmed Mohmed, Mohammed Omer M. Hussein ..........................................................................................31
Retroperitoneal lipoma arising from the urinary bladder

Shingo Ukita, Masafumi Koshiyama, Megumi Ohnaka, Naoyuki Miyagawa, Yukio Yamanishi, Fumitomo Nishimura,
Michikazu Nagura, Tomoko Kim, Masaya Hirose, Tomoyuki Shirase, Hisato Kobayashi, Hiroshi Ozasa ..............................................................................................34
Primary breast lymphomas

Olivier Julen, Ilaria Dellacasa, Marie-Françoise Pelte, Bettina Borish, Christine Bouchardy, Federica Capanna, Georges Vlastos,
Jean-Bernard Dubuisson, Anne-Thérèse Vlastos..................................................................................................................................................................................................36
Neuroblastoma occurring in a 38-year old Nigerian man: a rare finding

Martin A. Nzegwu, Aloy Aghaji................................................................................................................................................................................................................................42
Primary lymphoepithelial carcinoma of the parotid gland in a North African woman

Soumaya Ben Abdelkrim, Amel Trabelsi, Faten Hammedi, Monia Omezzine, Soumaya Rammeh, Atef Ben Abdelkader,
Badreddine Sriha .......................................................................................................................................................................................................................................................44
A review of the history, epidemiology and treatment of squamous cell carcinoma of the scrotum
Jerome E. Azike ..........................................................................................................................................................................................................................................................47
Assessment of cytological atypia, AgNOR and nuclear area in epithelial cells of normal oral mucosa exposed
to toombak and smoking
Hussain Gadelkarim Ahmed, Abd-Elraheem Ali Babiker ...................................................................................................................................................................................50
Desmoplastic small round cell tumor: impact of 18F-FDG PET induced treatment strategy
in a patient with long-term outcome
Dorra Ben-Sellem, Kun-Lun Liu, Sébastien Cimarelli, André Constantinesco, Alessio Imperiale ..............................................................................................................53
[Rare Tumors 2009; volume 1]

Epithelioid hemangioendothelioma of the temporal artery presenting as temporal
arteritis: case report and literature review
Dina El Demellawy, Ahmed Nasr, Salem Alowami ..............................................................................................................................................................................................56
Retrorectal epidermoid cyst with unusually elevated serum SCC level, initially diagnosed as an ovarian tumor
Masaru Hayashi, Shigeki Tomita, Takahiro Fujimori, Hitoshi Nagata, Keiichi Kubota, Akiko Shoda, Kazumi Tada, Nobuaki Kosaka,
Ichio Fukasawa, Noriyuki Inaba ...........................................................................................................................................................................................................................59
Metastatic rectal cancer to the breast

Hsiao C. Li, Prapti Patel, Payal Kapur, Sergio Huerta .........................................................................................................................................................................................63
Plexiform neurofibroma in the hepatic hilum associated with neurofibromatosis type 1: a case report
Sojun Hoshimoto, Zenichi Morise, Chinatsu Takeura, Masahiro Ikeda, Tadashi Kagawa, Yoshinao Tanahashi, Yasuhiro Okabe,
Yoshikazu Mizoguchi, Atsushi Sugioka .................................................................................................................................................................................................................66
Cystadenofibroma of the rete ovarii: a case report with review of literature

Manisha Ram, Abdel Abdulla, Khalil Razvi, Ivilina Pandeva, Awatif Al-Nafussi..........................................................................................................................................69
Angiomyomatous hamartoma: a rare case report with review of the literature

Manisha Ram, Nazar Alsanjari, Naseem Ansari...................................................................................................................................................................................................75
Malignant neuroectodermal tumor with melanocytic and rhabdomyoblastic differentiation

Munir R. Tanas and Brian P. Rubin ........................................................................................................................................................................................................................79
Malignant Triton tumor in the retroperitoneal space associated with neurofibromatosis type 1: a case study
Sojun Hoshimoto, Zenichi Morise, Chinatsu Takeura, Masahiro Ikeda,Tadashi Kagawa, Yoshinao Tanahashi, Yasuhiro Okabe,
Yoshikazu Mizoguchi, Atsushi Sugioka ................................................................................................................................................................................................................82
A case of primary renal angiosarcoma
Kazuhiko Yoshida, Fumio Ito, Hayakazu Nakazawa, Yoshiko Maeda, Hikaru Tomoe, Motohiko Aiba..................................................................................................85
A legacy of tinnitus: multiple head and neck paragangliomas

Tricia M.M. Tan, Emma C.I. Hatfield, Rajesh V. Thakker, Eamonn R. Maher, Karim Meeran, Niamh M. Martin, Jeremy J. Turner......................................................88
Soft tissue mixed tumor of the hand

Hiroshi Shimosawa, Michiro Susa, Takayuki Honma, Eiichi Hiraishi, Hiroshi Sakihara .........................................................................................................................90
Primary sarcoma of the liver and transplantation: a case study and literature review
Benjamin Bismuth, Hélène Castel, Emmanuel Boleslawski, David Buob, Marc Lambert, Nicole Declerck,Valérie Canva,
Eli-Serge Zafrani, Philippe Mathurin, François-René Pruvot, Sébastien Dharancy ......................................................................................................................................93
Pitfalls in neuroendocrine tumor diagnosis

Emilio Bajetta, Marco Platania ..............................................................................................................................................................................................................................96
Hepatic angiosarcoma five years following spontaneous intraperitoneal bleed of a hepatic mass
Jessica L. Cioffi-Pretti, Alexandra N. Kalof, George Ebert, Laurence E. McCahill .........................................................................................................................................98
Colonic cancer in adolescents. A report of three cases

M.A.C. Odike, A.E. Dongo, E.F. Alufohai, A.I. Odike............................................................................................................................................................................................102
Tumors and tumor-like lesions of the heart valves

Shi-Min Yuan, Hua Jing, Jacob Lavee ..................................................................................................................................................................................................................105
Treatment outcome of maxillary sinus cancer

Hye Sung Won, Sang Hoon Chun, Bum-soo Kim, So Ryoung Chung, Ie Ryung Yoo, Chan-Kwon Jung, Yeon-Sil Kim,
Dong-il Sun, Min Sik Kim, Jin-Hyoung Kang ......................................................................................................................................................................................................110
Invasive neuroendocrine tumor of the kidney: a case report

Ephrem O. Olweny, Michael H. Hsieh, Jill C. Buckley, Jack W. McAninch.....................................................................................................................................................115
Bilateral angiosarcoma of the breast in a fourteen-year-old child

Albertus N. van Geel, Michael A. den Bakker......................................................................................................................................................................................................117
Primary extrauterine endometrial stromal sarcoma: response to hormone therapy

Gunjal Garg, Awoniyi O. Awonuga, Eugene P. Toy .............................................................................................................................................................................................119

The managament of rare nasal mass-nasal dermoid sinus cysts: open rhinoplasty
Emel Cadalli Tatar, Ömer Tarik Selçuk, Güleser Saylam, Ali Özdek, Hakan Korkmaz ..............................................................................................................................121
Lipid-rich histology in a basal-type immuno-profile breast carcinoma: a clinicopathological histochemical and

immunohistochemical analysis of a case
Serena Russo, Diana Coppola, Paola Vinaccia, Antonella Siciliano, Francesca Baldassarre, Giovanni Battista, Giuseppe Pisani.................................................124
Synchronous malignant B-cell lymphoma and gastric tubular adenocarcinoma associated with paraneoplastic cutaneous vasculitis:
hypereosinophilic syndrome with mixed cryoglobulinemia is an important sign of paraneoplastic syndrome
Kazuhisa Nozawa, Hiroshi Kaneko, Tomoyasu Itoh, Yoko Katsura, Masaaki Noguchi, Fujihiko Suzuki, Yoshinari Takasaki,
Hideoki Ogawa, Kenji Takamori, Iwao Sekigawa.............................................................................................................................................................................................128
Hemangiopericytomas of the spine: case report and review of the literature

Chad D. Cole Meic H. Schmidt...............................................................................................................................................................................................................................132
Cervical intramedullary schwannoma: a case report and review of the literature

Jardel Mendonça Nicácio, José Carlos Rodrigues Jr, Marcos Henrique Lima Galles, Igor Vilela Faquini,
Clemente Augusto de Brito Pereira, Mario Ganau.............................................................................................................................................................................................137
Primary mediastinal giant cell tumor

Judd Goldberg, Shameen Azizad, Jela Bandovic, Arfa Khan............................................................................................................................................................................141
Benign multicystic mesothelioma: a case report of three sisters

Eve M. Bernstein, Alison Tate, Dan Arin Silasi, Thomas Rutherford...............................................................................................................................................................143
Congenital infantile digital fibromatosis: a case report and review of the literature
Valérie Failla, Odile Wauters, Nazli Nikkels-Tassoudji, Alain Carlier, Josette André, Arjen F. Nikkels....................................................................................................146
Giant mesenteric cystic lymphangioma presenting with abdominal pain and masquerading as a gynecologic malignancy
John Maa, Christianne Wa, Adnan Jaigirdir, Soo-Jin Cho, Carlos U. Corvera ..............................................................................................................................................148
Malignant peritoneal mesothelioma. Is there a new treatment?

Kakil Ibrahim Rasul, David J. Kerr .......................................................................................................................................................................................................................150
Intracystic papillary carcinoma of the breast in a 21-year old premenopausal Nigerian woman: a case report
Ivy N. Umanah, Akpan S. Okpongette ..................................................................................................................................................................................................................155
Diagnostic confusion resulting from CD56 expression by cutaneous myeloid sarcoma

Thanh Ho, Franklin Sedarat, Nagesh Rao, Sheeja T. Pullarkat........................................................................................................................................................................156
The epidemiology of malignant giant cell tumors of bone: an analysis of data from the Surveillance, Epidemiology
and End Results Program (1975-2004)
Jennifer L. Beebe-Dimmer, Karynsa Cetin, Jon P. Fryzek, Scott M. Schuetze, Kendra Schwartz ...............................................................................................................159
Temsirolimus in the treatment of renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion proteins:
a case report and review of literature
Jigarkumar Parikh, Teresa Coleman....................................................................................................................................................................................................................164
Metastasizing pleomorphic adenoma presenting as an asymptomatic kidney tumor twenty-nine years after
parotidectomy – urological viewpoint and overview of the literature to date
Jan Ebbing, Carolin Blind, Harald Stein, Kurt Miller, Christoph Loddenkemper ........................................................................................................................................167
A case of primary mucosa-associated lymphoid tissue lymphoma of the prostate

Noriko Koga, Masanori Noguchi, Fukuko Moriya, Kouichi Ohshima, Nobuyuki Yoshitake, Kei Matsuoka, Jan Ebbing, Carolin Blind,
Harald Stein, Kurt Miller, Christoph Loddenkemper.........................................................................................................................................................................................169
Re: Koga et al. A case of primary mucosa-associated lymphoid tissue lymphoma of the prostate
Damien C. Weber......................................................................................................................................................................................................................................................171
A clinical and molecular project on gonadoblastoma needs international collaboration

Nicolas Kalfa, Olivier Maillet, Charles Sultan....................................................................................................................................................................................................172
Primary NK/T cell lymphoma nasal type of the stomach with skin involvement: a case report
Sebastian Kobold, Hartmut Merz, Markus Tiemann, Carolina Mahuad, Carsten Bokemeyer, Irmtraut Koop, Walter Fiedler............................................................173

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Rare Tumors 2009; volume 1:e1
Metastatic pleomorphic strength, focal tenderness over the sacrum,

pitting edema in the lower extremities and a Correspondence: Dr. Barbara B. Haley, The
sarcoma to left atrium murmur of mitral regurgitation with basilar Harold C. Simmons Comprehensive Cancer
crackles and dullness. Computed tomography Center, University of Texas Southwestern
Ammar H. Hawasli,1 Rachael Cayce,2 (CT) showed a wedge-shaped splenic infarct Medical Center at Dallas, Dallas, TX, USA
Trung Luong,2 Evelyn Taiwo,1 and magnetic resonance imaging (MRI) of the E-mail: barbara.haley@utsouthwestern.edu
Michael N. Feliciano3, spine demonstrated osseous metastatic dis-
Key words: sarcoma, cardiac metastases, tumor,
Sharon C. Reimold,2,4 John M. DiMaio,5 ease involving the vertebral bodies, with
cancer.
Barbara B. Haley1,2 epidural and neuroforaminal tumor extension
Departments of 1Hematology-Oncology, in the sacrum. A TTE was performed in antici- Received for publication: 1 May 2009.
2 pation of chemotherapy with adriamycin and Accepted for publication: 5 May 2009.
Internal Medicine, 3Pathology,
4
revealed a large vegetation attached to the
Cardiology, and 5Cardiothoracic Surgery, Acknowledgement: we would like to thank Dr.
anterior leaflet of the mitral valve with pro-
University of Texas Southwestern lapse into the left atrium and ventricle (Figure John Bagwell and Leah Gaither for their assis-
Medical Center, Dallas, TX, USA 1A, arrow) and hypoechoic regions within the tance.
cardiac tissue (Figure 1A, arrowhead). The
This work is licensed under a Creative Commons
patient was taken to the operating room to Attribution 3.0 License (by-nc 3.0)
remove the vegetation, biopsy the hypoechoic
Abstract mass and replace the mitral valve. A 9 cm veg- ©Copyright A.H. Hawasli et al., 2009
etation was excised from the anterior mitral Rare Tumors 2009; 1:e1
Although several thousand patients are valve leaflet (Figure 1B, left and middle). doi:10.4081/rt.2009.e1
diagnosed with sarcoma annually in the Intraoperatively, the patient was noted to have
United States, metastases to the heart are very diffuse disease throughout the atrial septum
uncommon. In this case report, an overall low and mitral valve (Figure 1B, right) and the pro- (Figure 1C; mass indicated with arrowheads).
frequency cancer presents masquerading with cedure was terminated. Post-operative cardiac Histology of the atrial mass revealed a high-
common cardiac symptomology. This case MRI showed a lobulated cardiac mass infiltrat- grade pleomorphic sarcoma, metastatic to
illustrates the importance for detailed diagnosing the atrial septum, the posterior aortic wall heart. Low power frozen sections of the atrial
tic cardiac evaluations and heightened suspi- and the posterior aspect of the anterior mitral wall showed hypercellularity (Figure 2A).
cion by physicians to consider metastatic dis- valve annulus. In the axial plane, the mass Medium and high power frozen (Figure 2B and
ease to the heart in cancer patients with car- measured at least 5.3 x 2.2 cm and extended to C) and permanent (Figure 2D) sections
diovascular complications. Also discussed is a the superior portion of the left atrium near the showed tumor giant cells (indicated with
review of surgical and chemotherapeutic entry of the right superior pulmonary vein arrowheads) among spindled and epithelioid
options for this problem.
Introduction
A 53-year-old Caucasian gentleman present-
ed with progressive lower back pain, urinary
and bowel incontinence, and lower extremity
swelling over a one month period. He had
been diagnosed six months prior at an outside
institution with a high-grade pleomorphic sar-
coma with focal myxoid and epithelioid ele-
ments of the duodenum. Small bowel resection
was performed because of bowel obstruction.
Perioperatively, the patient suffered a myocar-
dial infarction (MI) due to focal narrowing of
the left anterior descending artery and a drug-
eluting stent was placed during cardiac
catheterization. Post-operative transthoracic
echocardiogram (TTE) was interpreted as mild
mitral valve thickening, with flail chordae
tendineae and an estimated ejection fraction
of 35-40%. After discharge, the patient was lost
to follow-up.
Case report
On presentation to our facility, physical Figure 1. Echocardiography (A) performed before excision of vegitation (B) and post-
operative cardiac MRI (C).
examination revealed normal lower extremity
[Rare Tumors 2009; 1:e1] [page 1]

Case Report
tumor cells. The atrial mass was immunohisto-

chemically positive for vimentin, confirming
mesenchymal differentiation (Figure 2E).
Immunohistochemical stains for other mark-
ers, including CD117, AE1/AE3, desmin, myo-
genin, caldesmon, S100, HMB-34, calretinin,
CD31 and CD34 were negative (Figure 2F).
A diagnosis of metastatic cardiac sarcoma
was established and treatment with gemc-
itabine and docetaxel was initiated. Adria-
mycin-based therapy was not considered sec-
ondary to the patient’s reduced cardiac func-
tion (37% ejection fraction). Five weeks after
initiating chemotherapy, the patient was
admitted for worsening lower extremity edema
but denied shortness of breath, orthopnea,
paroxysmal nocturnal dyspnea, chest pains, Figure 2. Histology of atrial mass.
palpitations, weight gain, or symptoms of tran-
sient ischemic attacks. Electrocardiogram
revealed atrial flutter at 119 beats per minute
with 2:1 block and the old anterolateral infarct. sarcoma.3 In this patient, cardiac metastasis rubicin/mesna,13 and gemcitabine/docetaxel.14-16
The patient declined cardioconversion and was was only incidentally discovered during pre- However, the use of doxorubicin was felt to be
treated with amiodarone. At the time of prepa- chemotherapy cardiac evaluation. However, contraindicated due to the depressed cardiac
ration of this report, the patient was tolerating several aspects of this patient’s clinical course function in this patient. If a sarcoma expresses
palliative gemcitabine and docetaxel chemo- suggested the presence of this diagnosis. The CD117, imatinib would be a viable treatment
therapy. patient’s initial myocardial infarction prompt- option due to the drug’s oral administration,
ed cardiac catheterization, which showed favorable toxicity profile, and anti-tumor activ-
luminal narrowing assumed to be secondary to ity on some subsets of sarcoma, particularly
atherosclerotic disease. Yet, on repeat studies, gastrointestinal stromal tumors.17-19 Expression
Discussion the patient had no evidence of significant ath- of this marker is felt to be favorable due to this
erosclerotic disease. The patient’s infarct like- relationship. Thus far, reports do not associate
Soft-tissue sarcomas are a diverse mix of ly resulted from an embolic event originating imatinib with induction of cardiac failure.20
cancers with an incidence of 10,390 new cases from the large mitral valve vegetation or from Unfortunately our patient’s cardiac tumor did
diagnosed annually in the United States.1 extrinsic compression of the artery by tumor. not express CD117 and the drug was not a
Despite aggressive treatment with surgery, The splenic lesions noted on CT scans likely treatment option. Since metastatic sarcoma to
radiation and chemotherapy, outcomes remain represent distant emboli with infarction. the heart is a rare occurrence, no prospective
suboptimal as 3,680 (35%) soft-tissue sarcoma Finally, review of the outside hospital TTE or randomized trials exist to help guide treat-
patients die annually.1 Death secondary to abnormalities noted after the patient’s periop- ment. In fact, there are no data to show
metastases is common and sites of metastases erative MI indicated that he had cardiac metas- whether systemic treatment of unresectable
vary depending on the type of soft-tissue sarco- tases at initial presentation. A high degree of cardiac sarcomas significantly improves dura-
ma with most types showing a predilection for suspicion for cardiac involvement by sarcoma tion or quality of life. In the setting of conges-
the lungs. Metastatic involvement of the heart may have hastened a correct diagnosis. tive or restrictive heart failure, many of the
by soft-tissue sarcoma has been reported in first-line chemotherapy options are not feasi-
the literature but most cases of cardiac ble for fear of therapy worsening cardiac func-
involvement occur in the setting of widespread tion. In our case, gemcitabine/docetaxel
metastases.2 Our patient is among the first Conclusions chemotherapy was felt to be an active regimen
reported cases of an epithelioid high-grade with controllable toxicity and without potential
pleomorphic sarcoma metastatic to the heart Management of metastatic sarcoma to the devastating cardiac side effects. Tolerance to
in absence of known widespread metastases. heart remains a difficult task. Some reports the treatment regimen thus far has been
Familiarity with the unique characteristics discuss surgical resection of cardiac metastat- acceptable and the patient is continuing this
of the soft-tissue sarcomas will enable a physi- ic lesions with variable success,4,5 while others chemotherapy.
cian to identify expected patterns of metastat- report the use of cardiac transplantation.6 In
ic spread. One should be suspicious of cardiac this case, surgical excision was attempted, but
metastases in a soft-tissue sarcoma patient the extensive infiltrating nature of the tumor
who suddenly develops unexplained congestive prohibited complete debridement leaving sys- References
heart failure, new cardiac murmurs, arrhyth- temic therapy as the only viable option. There
mias or embolic phenomena. For such are several generally accepted systemic thera- 1. Jemal A, Siegel R, Ward E, et al. Cancer
patients, metastatic cardiac disease should be pies for metastatic sarcoma with most regi- statistics, 2008. CA Cancer J Clin 2008;58:
included in the differential diagnosis and fur- mens including doxorubicin as a single agent7 71-96.
ther evaluation with electrocardiograms, or in combination with other drugs. The most 2. Catton C. The management of malignant
echocardiograms, and cardiac MRI should be widely employed combination chemotherapy cardiac tumors: clinical considerations.
made. Accurate imaging of cardiac cancer is regimens are doxorubicin/dacarbazine,8,9 dox- Semin Diagn Pathol 2008;25:69-75.
very important in the multimodal medical and orubicin/ifoxfamide/mesna10,11 mesna/doxoru- 3. Yuan SM, Shinfeld A, Lavee J, et al. Imag-
surgical management of metastatic cardiac bicin/ifosfamide/dacarbazine,12 ifosfamide/epi - ing morphology of cardiac tumours. Card-
[page 2] [Rare Tumors 2009; 1:e1]

Case Report
iol J 2009;16:26-35. a Southwest Oncology Group study. J Natl tic cytotoxicity of sequential treatment with
4. Harting MT, Messner GN, Gregoric ID, Cancer Inst 1991;83:926-32. gemcitabine followed by docetaxel in the
Frazier OH. Sarcoma metastatic to the 10. Edmonson JH, Ryan LM, Blum RH, et al. treatment of sarcoma. J Clin Oncol 2004;22:
right ventricle: surgical intervention fol- Randomized comparison of doxorubicin 1706-12.
lowed by prolonged survival. Tex Heart Inst alone versus ifosfamide plus doxorubicin 16. Maki RG. Gemcitabine and docetaxel in
J 2004;31:93-5. or mitomycin, doxorubicin, and cisplatin metastatic sarcoma: past, present, and
5. Kono T, Amano J, Sakaguchi M, Kitahara against advanced soft tissue sarcomas. J future. Oncologist 2007;12:999-1006.
H. Successful resection of cardiac Clin Oncol 1993;11:1269-75. 17. Verweij J, Casali PG, Zalcberg J, et al.
metastatic liposarcoma extending into the 11. Grobmyer SR, Maki RG, Demetri GD, et al. Progression-free survival in gastrointesti-
SVC, right atrium, and right ventricle. J Neo-adjuvant chemotherapy for primary nal stromal tumours with high-dose ima-
Card Surg 2005;20:364-5. high-grade extremity soft tissue sarcoma. tinib: randomised trial. Lancet 2004;364:
6. Goldstein DJ, Oz MC, Rose EA, et al. Ann Oncol 2004;15:1667-72. 1127-34.
Experience with heart transplantation for 12. Elias A, Ryan L, Sulkes A, et al. Response to
18. Blanke CD, Demetri GD, von Mehren M, et
cardiac tumors. J Heart Lung Transplant mesna, doxorubicin, ifosfamide, and dacar-
al. Long-term results from a randomized
1995;14:382-6. bazine in 108 patients with metastatic or
phase II trial of standard- versus higher-
7. Tierney J Fea. Adjuvant chemotherapy for unresectable sarcoma and no prior
dose imatinib mesylate for patients with
localised resectable soft-tissue sarcoma of chemotherapy. J Clin Oncol 1989;7:1208-16.
unresectable or metastatic gastrointesti-
adults: meta-analysis of individual data. 13. Frustaci S, Gherlinzoni F, De Paoli A, et al.
Sarcoma Meta-analysis Collaboration. Adjuvant chemotherapy for adult soft tis- nal stromal tumors expressing KIT. J Clin
Lancet 1997;350:1647-54. sue sarcomas of the extremities and gir- Oncol 2008;26:620-5.
8. Antman K, Crowley J, Balcerzak SP, et al. dles: results of the Italian randomized 19. Demetri GD, von Mehren M, Blanke CD, et
An intergroup phase III randomized study cooperative trial. J Clin Oncol 2001;19: al. Efficacy and safety of imatinib mesylate
of doxorubicin and dacarbazine with or 1238-47. in advanced gastrointestinal stromal
without ifosfamide and mesna in 14. Hensley ML, Maki R, Venkatraman E, et al. tumors. N Engl J Med 2002;347:472-80.
advanced soft tissue and bone sarcomas. J Gemcitabine and docetaxel in patients 20. Verweij J, Casali PG, Kotasek D, et al.
Clin Oncol 1993;11:1276-85. with unresectable leiomyosarcoma: results Imatinib does not induce cardiac left ven-
9. Zalupski M, Metch B, Balcerzak S, et al. of a phase II trial. J Clin Oncol 2002;20: tricular failure in gastrointestinal stromal
Phase III comparison of doxorubicin and 2824-31. tumours patients: analysis of EORTC-ISG-
dacarbazine given by bolus versus infu- 15. Leu KM, Ostruszka LJ, Shewach D, et al. AGITG study 62005. Eur J Cancer 2007;43:
sion in patients with soft-tissue sarcomas: Laboratory and clinical evidence of synergis- 974-8.

Squamous cell carcinoma obtained. Histopathological review showed

scrotal squamous cell carcinoma with testicu- Correspondence: Jerome E. Azike, MBBS,
of the scrotum in a Nigerian: lar involvement (Figure 1). He succumbed to FWACS, Department of Surgery, College of
case report the disease after seven months. Medicine & Health Sciences, Imo State
University, Orlu, Nigeria.
Jerome E. Azike,1,2 N.O. Chukwujama,1,2 E-mail: jeazike@yahoo.com
T.C. Oguike1,2
Discussion Key words: cancer of the scrotum, occupational
1
Department of Surgery, College of cancer, automobile mechanic, used engine oil.
Medicine and Health Sciences, Imo State
The scrotum is a seven-layer pouch which Received for publication: 2 May 2009.
University, Orlu, Imo State, Nigeria;
2
invests the testes, testicular adnexae, and dis- Accepted for publication: 8 May 2009.
Imo State University Teaching Hospital,
tal spermatic cord. The scrotal lymphatics
Orlu, Imo State, Nigeria drain into the corresponding superficial This work is licensed under a Creative Commons
inguinal nodes. Anastomoses exist between Attribution 3.0 License (by-nc 3.0)
the lymphatics of the contralateral network
©Copyright J.E. Azike et al., 2009
across the median raphe. Tumors have been Rare Tumors 2009; 1:e2
Abstract reported that arise out of virtually any of the doi:10.4081/rt.2009.e2
components of the scrotal wall.1
Squamous cell carcinoma of the scrotum is Squamous cell carcinoma of the scrotum is
rare and to the best of our knowledge has now exceedingly rare. It was the first malig-
never been reported from Nigeria. We report nancy linked to occupational exposure.1-2 minimize exposure. Prognosis correlates with
on a case thought to be occupation-related in a Previously, it most commonly resulted from extent of nodal involvement with virtually no
42-year old Nigerian taxi driver who had previ- exposure to environmental carcinogens such survivors if iliac nodes are involved.3,5 Ability to
ously been an automobile mechanic and later a as chimney soot, tars, paraffin, and some achieve a negative margin at the time of initial
long-haul truck driver. He presented with a petroleum products. Currently most cases surgery is an important prognostic factor as
stage D disease and only palliation was feasi- result from poor hygiene and chronic inflam- adjunctive therapy such as radiotherapy or
ble. mation.3 chemotherapy or both has not proven useful.1
Used engine oils have elevated polycyclic In conclusion, the index patient presented very
aromatic hydrocarbons which tend to be greater late when even surgery, chemotherapy and
for petrol engines than for diesel engines. radiotherapy could not possibly offer any mean-
Case report Prolonged and repeated contact with such oils ingful improvement in terms of outcome. We
can cause skin and scrotal cancer. Car mechan- believe this case will raise the awareness in
A 42-year old taxi driver who had been a car ics are at potential risk from used engine oil.4 our environment of the existence of this dis-
mechanic for four years 25 years earlier pre- Best occupational health practices are ease and improve the index of suspicion among
sented in 2007 with a ten-year history of a invaluable at the workplace for those at risk to practicing surgeons and oncologists.
small pruritic painless nodule on his ventral
scrotal surface which had ulcerated but failed
to heal. He infrequently washed his work-out-
fit while an auto-mechanic and admitted to its
frequent soiling, sometimes up to his under-
wear, with used engine oil while at work. He
took a bath at the close of work each day; how-
ever, his personal hygiene outside the work-
place was good.
On examination he was pale, had a foul-
smelling, grotesque, fungating, ulcero-prolifer-
ative mass with rolled edges which involved
the whole scrotum and proximal third of the
penile shaft, extending 5 cm to the right thigh
antero-medially and 3 cm of the anal verge.
The scrotum was fixed to the pubis. There
were bilateral inguinal lymphadenopathy
involving both the vertical and horizontal
chains. He looked otherwise well nourished
and was ambulant. He was also rather
depressed emotionally.
Ultrasonography revealed a hepatomegaly
and para-aortic lymphadenopathy, the largest
2.8 cm in diameter. His general condition was
optimized and biopsy confirmed the diagnosis. Figure 1. a, b, c, d. Histology of the various sections of the tumor; (a) Normal skin and
He had palliative scrotectomy with bilateral contiguous areas the well differentiated squamous cell carcinoma invading the surround-
orchidectomy and subsequently cisplatinum- ing deeper tissue; (b) High magnification of the malignant squamous cells; (c) Remnants
based combination chemotherapy, after he had of the testicular tubules being invaded by the tumor; (d) The malignant squamous cells
invading the deeper testes.
been counseled and informed consent

Case Report
ME, eds. Adult and Pediatric Urology, 4. Wyre Borough Council, Lancashire U.K.,
References Philadelphia: Lippincott, Williams and Health and Safety Factsheet – No. 12
Wilkins; 2002. (internet), 2002. Available from: http://
2. Waldron HA. A brief history of scrotal can-
1. Rowland RG, Herman JR. Tumors and www.wyrebc.gov.uk (Cited 5th July, 2008)
cer. Br J Ind Med 1983;40:390-401.
Infectious Diseases of the Testis, 3. Presti JC Jr. Genital Tumors. In Tanagho EA, 5. Ray B, Whitmore WF Jr. Experience with
Epididymis, and Scrotum. In Gillenwater McAnich JW, editors. Smith’s General Carcinoma of the Scrotum. J Urol 1977;
JY, Grayhack JT, Howards SS and Mitchell Urology. New York: Mc Graw Hill 2008:375-87. 117:741-5.

Extraosseous osteosarcoma tic, osteoclastic or giant cell type, telangiectat-

ic, small cell or well differentiated forms. The Correspondence: Temitope O. Alonge,
in Ibadan: case series over immunohistochemical profile includes the Consultant Orthopedic Surgeon/Senior Lecturer,
a 20-year period expression of osteocalcin and osteonectin Department of Orthopedics and Trauma,
which are specific for osseous osteosarcomas, University College Hospital and College of
Temitope O. Alonge,1 Henry but a study by Fanburg-Smith et al.7 showed Medicine, University of Ibadan, Ibadan, Nigeria
E-mail: alonget2003@yahoo.com
A. Obamuyide,2 Gabriel Olabiyi Ogun3 that osteocalcin is highly sensitive for EOO
1
Consultant Orthopedic Surgeon/Senior neoplastic cells.1 Closely related differentials
Key words: extraosseous osteogenic sarcomas,
Lecturer, Department of Orthopedics and include calcified hematoma, myositis ossifi- Sub-Saharan Africa, histology.
cans, synovial sarcoma, epithelial sarcoma,
Trauma, University College Hospital,
liposarcoma or malignant fibrous histiocytoma. Received for publication: 3 May 2009.
and College of Medicine, University of
Accepted for publication: 5 May 2009.
Ibadan, Ibadan, Nigeria;
2
Resident in Surgery, Department of Contributions: TOA conceived, designed, super-
Surgery, University College Hospital, vised and helped to draft the manuscript and
Methods approved the final version; HAO participated in
Ibadan, Nigeria;
3
the design, gathered the data, drafted the manu-
Consultant Pathologist/Lecturer, All sarcomas recorded at our institution script and approved the final copy; GOO reviewed
Department of Pathology, College of between January 1986 and December 2005 the manuscript for critical content and approved
Medicine, and University College were compared and extraosseous variety iden- the final copy.
Hospital, Ibadan, Nigeria tified. Their charts were selected and reviewed
for relevant data. Out of 112 cases of osteosar- Attribution 3.0 License (by-nc 3.0)
coma recorded in our hospital between
January 1986 and December 2005, 5 cases ©Copyright T.O. Alonge et al., 2009
Abstract were extraosseous. This series presents the 5 Rare Tumors 2009; 1:e3
cases of EOO recorded at our institution dur- doi:10.4081/rt.2009.e3
Extraosseous osteosarcoma (EOO) is a rare ing the 20-year period from 1986-2005 and this
form of sarcoma. There have been few reports of includes one patient reported previously by
cases and outcome from an African population. Ogundiran et al.8 biopsy and histology of the initial mass at the
Out of 112 cases of sarcomas seen at the source of referral revealed an extraskeletal
UCH, Ibadan between 1986-2005, 5 were EOO. osteosarcoma.
All presented late on account of initial excision Examination revealed a 15x7 cm left fron-
without histology and outcomes were poor. Case Series toparietal mass with overlying scar. He also
EOO occurs in the black population of Sub- had a smaller temporal mass. Both were tender
Saharan Africa. The outlook for these patients
Case #1 and hemorrhagic. Skull X-ray showed an
is still bleak. extensive soft tissue swelling extending from
A 16-year-old male student who presented
with a 4-year history of progressive left ankle the left frontal to the left parietal region. There
swelling and pain. He had excision of a mass was an associated increase in the density of
in his left ankle at a private facility without the underlying subcutaneous tissue but no cal-
Introduction cifications. Routine laboratory studies were
histological evaluation a year prior to presen-
tation at the University College Hospital within normal limits. He had radiotherapy but
Extraosseous osteosarcoma (EOO) is a later represented with facial recurrence after
(UCH), Ibadan. On presentation at the UCH,
malignant mesenchymal neoplasm that pro- two months.
examination revealed a 10x7 cm mass over the
duces osteoid, bone or chondroid material and
left lateral malleolus that was tender, differen-
is located in the soft tissue without attachment
to the skeleton as determined by imaging
tially warm, with both cystic and solid areas. Case #3
No significant popliteal or inguinal lym- A 21-year-old man with a 1-year history of a
modalities or inspection during surgical oper-
phadenopathy was noted. Laboratory studies painful left upper back swelling and 4 month
ative procedure.1 EOO is a rare type of tumor
were essentially normal. history of progressive weakness of both legs
making up only 1% of all soft tissue sarcomas2,3
and 4% of all osteosarcomas.4 He had a local excision of the mass and the which progressed to paraplegia. He had a
Wilson reported the first case of EOO in operative finding was a 10x7 cm multiloculat- biopsy of the mass at a private facility five
19415 and since then fewer than 300 cases ed brownish soft tissue mass over the left lat- months before presentation at the UCH but no
have been reported in the English Language eral malleolus covered with a fibrous capsule histological evaluation of the mass was car-
literature.6 The tumor is most common in mid- with a pedicle arising from the ankle joint. ried out. Examination at the UCH revealed a
dle-aged and elderly patients. A previous study There was associated erosion of the adjoining left periscapular fluctuant mass with overlying
showed that EOO is a doxorubicin-resistant bone and the histology report revealed soft tis- hypertrophic scar which was also attached to
lesion with a poor prognosis and a form of soft sue osteosarcoma. He was lost to follow-up but underlying structures. He also had a T5 para-
tissue sarcoma that should be viewed by clini- represented two years later with recurrence. plegia. Chest X-ray showed a left paravertebral
cians as clinically and therapeutically distinct soft tissue mass lesion with evidence of
from osseous osteosarcoma.6 Case #2 destruction of the 5th rib and left sided pul-
The single most important criteria for diag- A 70-year-old man who presented with a monary effusion. Urinary Bence Jones protein
nosis of this tumor is the presence of neoplas- 1-year history of a painful scalp swelling asso- was negative, the full blood count was normal
tic osteoid and bone; sometimes with neoplas- ciated with bleeding. A similar swelling had but the ESR was elevated. Two pleural aspi-
tic cartilage.1,5 The histological variants of EOO recently grown on the right temporal region rates were hemorrhagic and CT myelography
include osteoblastic, chondroblastic, fibroblas- prior to presentation at the UCH. Incisional showed an isolated left sided isodense lesion

Case Report
in the spinal cord with extensive erosion of A common mode of presentation is as a However, if these are not possible due to the
the ribs as well as infiltration into the left swelling of insidious onset with associated anatomic location of the tumor, amputation is
pleural cavity. pain in one-third of patients but often the recommended.19
Incisional biopsy of the left chest wall lesion tumor grows to a large size before the patient In a review of 48 cases of EOO and 39 trials
revealed osteogenic sarcoma. Chemotherapy seeks medical advice.14 It may ulcerate with of chemotherapeutic agents reported by
was to be administered but the patient could growth, but that usually occurs after biopsy or Sordillo et al. they showed that no patient had
not afford it and he was subsequently lost to attempts at excision and the tumor usually a major response.14 The average 5-year survival
follow-up. occurs in middle-aged and elderly patients.15 rate in 5 previous studies ranges from 15-
The anatomic location of EOO is usually the 25%2,9 and the response to multimodality ther-
Case #4 muscles of the thigh, which are the most com- apy is not as good as for OOO.14 Tumor size (<5
A 20-year-old man who presented with an monly affected; the large muscles around the cm vs. ≥5 cm) was the major predictor of
11-month history of progressive soft tissue pelvic and shoulder girdles and the retroperi- patient survival.13
swelling of the right thigh associated with toneum, though rare locations like the thyroid Of note, the challenges of managing malig-
pain. The soft tissue mass was excised initial- gland, penis, mediastinum and the kidney are nancies and other chronic illnesses in a devel-
ly at a private facility but no histological evalu- occasionally encountered.1,12,15,17,18 oping economy like ours is exemplified by
ation of the specimen was carried out. At the Memorial Sloan-Kettering cancer these cases. The issues of late presentation,
Examination at the UCH revealed a massively center, a review of 48 cases of EOO during non-submission of biopsy specimen for histo-
swollen right thigh with multiple areas of 1950-1983 showed a median age at diagnosis logical assessment, non-affordability of treat-
of 51 years (range, 6-80 years).14 The most ment modality and default from follow-up
ulceration. Biopsy and histology at the UCH
common primary sites were the thighs and raise critical issues. These include late pres-
revealed extraosseous osteogenic sarcoma.
buttocks (54.2%) with preponderance in entation, lack of health or social insurance
The patient was given a hemostatic dose of
patients aged 50 years and above and slightly making the patient bear the full cost of their
radiotherapy but was subsequently lost to fol-
more common in males (58%) than in treatment and probably also the ignorance of
low-up.
females.12 In the report by Chung and Enzinger, the initial managing physician regarding the
EOO occurs principally as a soft tissue mass need for histological assessment of all biop-
Case #5 involving an extremity with a predilection for sies or their unwillingness to insist on this
A 40-year-old housewife who presented with the thighs (lower extremity 46.6%; upper (as a measure to reduce costs and increase
a 20-month history of painful left breast lump extremity 20.5%) and the retroperitoneum in their competitiveness). These factors may all
which had been excised previously at another 17%. In most cases, the tumor was deep seated be related to cost of treatment, and patients,
hospital without histological evaluation, but and firmly attached to the fascia, but occasion- therefore, have a significantly long delay
recurred eight months before presentation at ally they are freely movable and confined to the before presentation and would usually present
UCH. Examination revealed a globular left subcutis or dermis. The duration of symptoms in a private facility with a view to reducing the
breast mass which was warm, multinodular, prior to presentation ranges from two weeks to cost of treatment.
fixed to the pectoralis fascia and which meas- 25 years (median six months). Prior trauma to
ured 20x18 cm. There was associated ipsilater- the site was observed in 12.5% and irradiation
al axillary lymph node enlargement. Other sys- to the affected site in 5.7% of cases.12
tems were essentially normal. Although osseous osteosarcoma (OOO) Conclusions
A clinical diagnosis of locally advanced can- occurs predominantly in the first two decades
cer of the left breast was made. A core needle of life, EOO are rarely encountered under 40 In conclusion, the outlook for patients with
biopsy revealed an osteogenic sarcoma which years of age.15 However, in this case series, 3 of EOO is grave and the majority of patients with
was confirmed by the histology of the mastec- the 5 patients were aged 21 years and under in this tumor succumb to metastatic disease
tomy specimen. She was scheduled for post- keeping with other cases which have been doc- within a period of three years after the initial
operative radiotherapy but defaulted and died umented in the pediatric age group.16 diagnosis.1 Extraosseous osteosarcoma occur
six months post-mastectomy. Imaging modalities by either plain conven- in the populations of Sub-Saharan Africa and
tional radiograph, CT scan or MRI of the soft tis- the poor prognosis for EOO in our environment
sue is essential to rule out any continuity of is further compounded by the factors earlier
tumor with bone. If adjacent bone shows radio- highlighted. Since recurrence occurs mostly
Discussion logical changes of involvement by the tumors, it within two years after surgery, adjuvant
is most likely to be originating from the bone chemotherapy and radiotherapy have been
The exact cause of EOO is unknown and it is rather than from the soft tissue. A soft tissue found to be beneficial.15
presumed to be mainly an idiopathic condition. mass with spotty to massive calcification with-
Unlike osseous osteosarcoma (OOO), it has out adjacent bone involvement is one of the clas-
not been documented in siblings or in associa- sic radiographic appearances of this tumor.15
tion with hereditary retinoblastoma but risk EOO is a difficult disease to treat and the References
factors associated with the development of this optimum therapy has not been fully deter-
tumor include previous exposure to radiation, mined due to the relative rarity of these 1. Weiss SW, Goldblum J. Osseous soft tissue
such as X-rays and radioactive thorium dioxide tumors. Advances in the care of these patients tumours in Enzingers and Weiss: Soft
(Thorothrast).9 Other associated factors sug- will require disease-specific clinical trials.6 A Tissue Tumours 4th ed. Pg 1389-1417,
gested in literature in the development of EOO wide local excision, with at least 5cm margin Mosby St Loius, 2001.
include trauma, the assessment and evalua- of normal tissues should be the treatment of 2. Allan CJ, Soule EH. Osteogenic sarcoma of
tion of which is difficult and controversial.10 choice.15 The local recurrence-free survival the soft tissue: a clinicopathologic study of
Some cases have been associated with intra- rate observed in a recent study6 suggests that 26 cases and review of the literature.
muscular injection11 while some EOO have patients with extremity EOO can be treated Cancer 1971;27:1121-33.
been reported to follow myositis ossificans.12,13 with limb salvage operative procedures. 3. McCarter MD, Lewis JJ, Antonescu CR, et

Case Report
al. Extraskeletal osteosarcoma: analysis of 9. Lee WR, Laurie J, Townsend A. Fine struc- seous osteogenic sarcoma. J Chin Med
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al. Retroperitoneal extraosseous osteosar- the extraskeletal soft tissue. Cancer 1956; pediatric malignancy: Case report and
coma. J Clin Path 2002;54:77-8. 9:1027-43. review of the literature. J Pediatr Surg 1999;
5. Wilson H. Extraskeletal ossifying tumours. 11. Lee JH, Griffith WJ, Bottomley RH. Extrao- 34:1025-8.
Ann Surg 1941;113:95-112. sseous osteogenic sarcoma following an
17. Hertel V, Basten O. Extraosseous osteosar-
6. Ahmad SA, Patel SR, Ballo MT, et al. intramuscular injection. Cancer 1977;40:
coma of the thyroid gland. Laryngorhinoo-
Extraosseous osteosarcoma. Response to 3097-101.
tologie 2006;85:913-6.
treatment and long term outcome. J Clin 12. Chung EB, Enzinger F. Extraskeletal osteo-
18. Dudhat S, Desai S, Borges A, et al. Retro-
Oncol 2002;20:521-7. genic sarcoma. Cancer 1987;60:1132-42.
7. Fanburg-Smith JC, Bratthauer GL, Miettinen 13. Bane BL, Evans HL, Ro JY, et al. Extraskel- peritoneal extraosseous osteosarcoma. A
M. Osteocalcin and osteonectin immunore- etal sarcoma: a clinicopathologic review of case report and review of literature. Indian
activity in extraskeletal osteosarcoma: a 26 cases. Cancer 1990;65:2762-70. J Cancer 1999;36:186-9.
study of 28 cases. Hum Pathol 1999;30:32. 14. Sordillo PP, Hadju SL, Magill GB, et al. Ext- 19. Lewis RJ, Loiz MJ, Beazley RM. Extra-
8. Ogundiran TO, Ademola SA, Oluwatosin raosseous osteogenic sarcoma: a review of osseous osteogenic sarcoma: case report
OM, et al. Primary osteogenic sarcoma of 48 patients. Cancer 1983;51:727-34. and approach to therapy. Ann Surg 1974:40:
the breast. World J Surg Oncol 2006;4:90. 15. Lin S-Y, Chen W-M, Wu HH, et al. Extraos- 597-600.

A multimodal approach to the vitreal hemorrhage occurred 20 months after

treatment in the right eye, while the lesion Correspondence: Franco Perrone,
treatment of bilateral choroidal treated with brachytherapy remained unal- U.O. Fisica Sanitaria, Azienda Ospedaliero-
metastases from thyroid tered. Universitaria Pisana, via Roma 67, 56125 Pisa, Italy
E-mail: f.perrone@ao-pisa.toscana.it
carcinoma
Key words: choroidal metastases, thyroid carcino-
Maria Grazia Fabrini,1 ma, radiotherapy, anti-VEGF factors.
Federica Genovesi-Ebert,2 Case Report
Franco Perrone,3 Mario De Liguoro,1 Acknowledgments: the authors are grateful to the
Clara Giovannetti,4 Fausto Bogazzi,4 In October 1996, a 58-year old male patient Pisa section of the “Lega Italiana per la Lotta
in satisfactory general condition and under Contro i Tumori” for supporting the present pub-
Stanislao Rizzo,2 Enio Martino,4
medical therapy for arterial hypertension, was lication.
Luca Cionini1
treated with total thyroidectomy, parathy-
1
Divisions of Radiotherapy, 2Ophthalmic Contributions: radiotherapy treatment and fol-
roidectomy, bilateral cervical lymphadenecto-
low-up: MGF, MDL; ophthalmologic follow-up:
Surgery, 3Health Physics and my and also with resection of a single ischio-
4
FGE; radiotherapy treatment planning, data
Endocrinology and Metabolism of Pisa pubic recurrence. Histo-pathological examina- analysis and dose evaluation: FP; brachytherapy:
University Hospital, Italy tion of the thyroid gland and of the bone MGF, SR, FGE; endocrinological follow-up: CG, FB,
metastasis revealed a thyroid carcinoma (G3), EM; text editing: CG, MDL, MGF, FGE, FB, FP; text
confirmed by positive thyroglobulin immunos- reviewing: EM, LC.
taining, with solid and papillary areas of oxyfil
Abstract cell-type. No diffusion to neck lymph nodes Conflict of interest: the authors reported no poten-
tial conflict of interests.
was found. Disease was scored as T3N0M1,
A 58-year old man, affected by metastatic IVC stage following the American Joint Cancer Received for publication: 20 May 2009.
thyroid carcinoma, experienced a progressive Committee grouping. Revision received: 28 May 2009.
bilateral visual impairment. Ophthalmic exam- After surgery, the patient received a radio- Accepted for publication: 2 June 2009.
ination revealed the presence of a choroidal metabolic treatment with 131-I. During the fol-
mass with an associated exudative retinal low-up, the thyroglobulin hematic levels were This work is licensed under a Creative Commons
periodically checked. Attribution 3.0 License (by-nc 3.0)
detachment in both eyes. Twelve years before,
a diagnosis of metastatic thyroid carcinoma From 1997 to 2007, a diffusion of multiple
©Copyright M.G. Fabrini et al., 2009
had been established and the patient had been metastases was observed; the largest recur- Rare Tumors 2009; 1:e4
subject to several therapeutic procedures. rences were treated by surgical resections. In doi:10.4081/rt.2009.e4
In May 2007, he received a radiotherapy order to limit the development of recurrences,
treatment to the left eye with an episcleral other systemic 131-I radio-metabolic therapies
plaque and bilateral bulbar injection of beva- were administered (Figure 1).
In May 2007, the patient presented a pro- eter, with an associated serous retinal detach-
cizumab. The patient had a rapid and stable
gressive visual loss in both eyes; he had a past ment.
visual acuity recovery. Twenty months after
treatment, the lesion treated with radiotherapy history of retinal venous thrombosis in his left Standardized A-scan echography showed in
was still stable whereas the contra-lateral eye, with a residual best corrected visual acu- both lesions an irregular structure with a
lesion had evolved and determined a vitreal ity of 20/40. sharp initial spike and moderate-high internal
hemorrhage. Ophthalmologic examination, performed in reflectivity.
May 2007, showed that ocular adnexa, extra- Fundus fluorescein angiography evidenced
ocular movements and pupillary reactions an area of irregular fluorescence with a mild
were normal in both eyes and no exophthal- leakage in correspondence of the supero-tem-
mus was found. No pupillary defects were evi- poral arcade in the RE. A block of the fluores-
Introduction denced and the Best Corrected Visual Acuity cence due to the retinal pigment epithelium
was 20/70 in the left eye (LE) and 20/25 in the was noted in the posterior pole of the LE, in
Choroidal metastases from thyroid cancer right eye (RE). correspondence of the choroidal mass. The
are uncommon findings.1 They often occur in Slit lamp examination of the anterior seg- ischemic maculopathy, secondary to the previ-
advanced stages, and generally several years ment revealed only a light nuclear sclerosis. ous venous thrombosis, appeared as an hypo-
after the initial diagnosis. Main related symp- Intra-ocular pressure was 15 mm of Hg in both fluorescent lesion with late staining.
toms can include pain and impairment of visu- eyes. Indocyanine angiography showed the hyper-
al ability. Eye metastases may cause blindness Ophthalmoscopic examination detected a fluorescence of the lesion in the RE, especially
with a rapid degradation of the patient’s quali- solid lesion localized in the posterior pole in the intermediate phases, with wash out of
ty of life.2,3 closely to the macula in the RE and a similar the dye in the late phases. In the LE, indocya-
This paper reports a case of bilateral lesion in the posterior pole of the LE, where nine angiography revealed an atrophic area of
choroidal metastases in a patient in satisfacto- hypertrophic areas of the retinal pigment retinal pigment epithelium and of choriocapil-
ry general condition, with a long history of epithelium related to the previous venous laris in correspondence of the fovea, while the
metastatic thyroid carcinoma initially respond- branch occlusion were also evident (Figure 2). mass-lesion showed an irregular staining of
ing to radio-metabolic therapy. B-scan ultrasound examination confirmed the dye in the intermediate and late phases
A multimodal approach was adopted to treat the presence of a slightly elevated, solid (Figure 2).
the ocular lesions, in order to restore his visu- choroidal mass in both eyes: in RE it was 1.25 Optical Coherence Tomography showed a
al acuity. After a follow-up of 18 months, the mm in thickness, with an associated serous massive detachement of the neuro-epithelium
patient’s visual ability was still good, although retinal detachment, in LE it measured 3.3 mm in the RE (Figure 3); a hypertrophic hyper-
multiple metastases developed in other sites. A in height and 4.8 mm in maximum base diam- reflective area of the retinal pigment epitheli-

Case Report
um (due to the previous macular scar) and a

Figure 1. The figure
shows hematic thi- detachment of the neuro-epithelium temporal
roglobulin concentra- to the macula were also found in the LE.
tions (in ng/mL), start- Although a biopsy was not obtained from the
ing from initial thy- choroidal masses, diagnosis of presumed bilat-
roidectomy, as a func- eral choroidal metastases from thyroid carci-
tion of the follow-up
time in months (140 noma was based on the patient’s medical his-
months from October tory and on ophthalmologic findings: the
1996 to June 2008); occurrence at the posterior pole, the solid
black dots report thy- appearance, the yellow-orange color, the pres-
roglobulin hematic lev- ence of serous detachment of the sensory reti-
els in ng/mL (left black
scale); red bars show na, the moderate echographic internal reflec-
the 131-I activities in tivity of the masses showing an irregular inter-
GBq (right red scale), nal reflectivity, the absence of demonstrable
administered during vascular pulsations and the hyperfluorescence
the follow-up.
with late staining were suggestive of a sec-
ondary lesion.
At the end of May 2007, the lesion in the LE
was treated with an episcleral 106Ru plaque
Figure 2. The figure brachytherapy.
shows, from top to bot-
tom, basal B-scan ultra- The small lesion in the RE was not irradiat-
sound, fluorescein ed because of its small volume, its localization
angiography, fundus close to the macula and the risk of macular
view, intermediate radiation damage. A week after plaque
phase indocyanine
angiography and late removal, an intra-vitreal injection of beva-
phase indocyanine cizumab (Avastin; Genentech, San Francisco,
angiography of both CA) was performed in both eyes in order to
eyes before brachythera- reduce the serous retinal detachment.
py. The images on the In October 2008 an US scan indicated that
right side refer to the
left eye. the lesion in the right eye remained
unchanged and the mass in the left eye was
reduced to 2.5 mm in height. OCT showed a
marked reduction in height of the neuro-
epithelium detachement in the right eye and a
disappearance of the temporal fluid in the left
eye (Figure 3). BCVA was still 20/20 in the
right eye and 20/40 in the left eye. The other
metastases showed a generalized progression.
At the end of 2008, the patient began a
chemotherapy treatment with anthracycline.
A vitreal hemorrhage occurred 20 months
after treatment in the right eye, while the
lesion treated with brachytherapy remained
still unaltered.
Discussion
Eye metastases are an important clinical
problem, because they represent the most
Figure 3. Optical common cancer of the eye and may occur in
Coherence Tomography
before brachytherapy 12% of patients with metastatic carcinomas.4
(top) and in October Nevertheless, ocular metastases from thyroid
2008 (bottom) of macu- carcinoma are uncommon and bilateral syn-
lar region in the right chronous metastases have a rare occurrence
eye (left side) and the and represent a clinical challenge.5-8
left eye (right side),
showing the reduction Taking into account all the currently avail-
of fluid (central black able therapeutic options, a flexible approach
area). The red region in should be planned, depending on the clinical
the left eye corresponds situation.
to the area interested by The therapeutic approach should consider
a previous thrombotic
episode. the presence of painful symptomatology,
patient’s life expectancy, clinical ophthalmo-

Case Report
logic assessment and general conditions. Therefore, bevacizumab can reduce retinal Prognostic factors in differentiated carci-
Enucleation should be considered in pres- ischemia that could lead to radiation retinopa- noma of the thyroid gland. Am J Surg 1992;
ence of painful eye with secondary neovascular thy and exudative retinal detachment in order 164:658-61.
glaucoma. In all other situations, an organ to improve visual acuity and to reduce develop- 4. Bloch RS, Gartner S. The incidence of ocu-
sparing approach should be considered. ment of neovascular glaucoma. lar metastatic carcinoma. Arch
Brachytherapy is particularly effective in Macular lesions create a clinical challenge Ophthalmol 1971;85:673-5.
administering a high-dose to a single lesion of for which treatment with intra-vitreal beva- 5. Gysin P, Gloor B. Cryo- and photocoagula-
small volume. This method involves temporary cizumab seemed promising. One might theo- tion for choroidal metastases of a thyroid
placement of an episcleral radioactive device, rize that, like laser photocoagulation, beva- carcinoma. Klin Monatsbl Augenheilkd
in correspondence to the tumor, until the pre- cizumab may decrease the ocular ischemia 1979;174:978-81.
scribed dose is administered. resulting from plaque radiation or may induce 6. Arat YO, Boniuk M. Red lesions of the iris,
Generally, the treatment can be performed a decrease of vascular permeability in non- choroid, and skin secondary to metastatic
in an outpatient setting and is well tolerated, vital tissue. Clearly, testing these theories is carcinoma of the thyroid: a review. Surv
determining mild to moderate toxicity; more- beyond the scope of this study. However, clini- Ophthalmol 2007;52:523-8.
over, the results are satisfactory in terms of cal series in the literature showed encourag- 7. Bianciotto CG, Demirci HY, Shields CL,
visual function and organ preservation. ing results in treating ischemic radiation ther- Shields JA. Simultaneous eyelid and
Photocoagulation by means of xenon or argon apy. choroidal metastases 36 years after diag-
ion lasers has been used in the past as an In the present case, intra-vitreal bevacizum- nosis of medullary thyroid carcinoma.
option in selected small choroidal melanomas. ab administration probably achieved a reduc- Ophthal Plast Reconstr Surg 2008;24:62-3.
Recently, it has been replaced by TTT that has tion of serous detachment in the posterior 8. Shields CL, Cater J, Shields JA et al.
been proven to be effective in treating selected pole, thus restoring a useful visual function. Combined plaque radiotheraphy and trans-
small volume lesions. Currently, TTT is also pupillary thermotherapy for choroidal
used as a supplement to plaque radiotherapy.8 melanoma: tumor control and treatment
Bevacizumab is a full-length recombinant complications in 270 consecutive patients.
humanized monoclonal antibody directed References Arch Ophthalmol 2002;120: 933-40.
against VEGF, originally indicated for the treat- 9. Finger PT. Radiation retinopathy is treat-
ment of metastatic colorectal cancer. The 1. Shields CL, Shields JA, Gross NE, et al. able with anti-vascular endothelial growth
antiangiogenic properties of bevacizumab, Survey of 520 eyes with uveal metastases. factor Bevacizumab (Avastin). Int J Radiat
administered via intravenous infusion or Ophthalmology 1997;104:1265-76. Oncol Biol Phys 2008;70;974-7.
intravitreal injection, have been studied in 2. American Cancer Society: Cancer Facts 10. Finger PT, Chin K. Anti-vascular endothe-
patients with age-related macular degenera- and Figures 2008. Atlanta, GA: American lial growth factor bevacizumab (avastin)
tion, choroidal neovascularization, and other Cancer Society, 2008. for radiation retinopathy. Arch Ophthalmol
retino-choroidal vascular diseases.9,10 3. Shah JP, Loree TR, Dharker D, Strong EW. 2007;125:751-6.

Pleomorphic sarcoma References

metastatic to the duodenum?
1. Hawasli AH, Cayce R, Luong T, et al.
Fabio R. Tavora, Allen P. Burke Metastatic pleomorphic sarcoma to left
Armed Forces Institute of Pathology, atrium. Rare Tumors 2009;1:e1.
Washington, DC, USA 2. Burke AP, Cowan D, Virmani R. Cardiac
sarcomas. Cancer 1992;9:387-95.
We read with interest Hawasli et al. report of 3. Burke AP, Virmani R. Metastatic tumors to
a pleomorphic sarcoma metastatic to the left the heart and pericardium, in Atlas of
atrium.1 However, we suspect that the true site Tumor Pathology, Tumors of the Heart and
of origin is unknown, and may in fact be the Great Vessels. Armed Forces Institute of
heart. There are several reasons for this: Pathology Washington DC 1996.
- the histological appearance is similar to 4. Hallahan DE, Vogelzang NJ, Borow KM, et
left atrial tumors that have already been al. Cardiac metastases from soft-tissue
reported;2 sarcomas. J Clin Oncol 1986;4:1662-9.
- the left atrium, is the most common site
of cardiac pleomorphic sarcoma;
- all metastatic sarcomas to the heart have
been in the right atrium or ventricle or
have involved myocardium and/or peri-
cardium; 3,4
- the tumor appears to have been present in Correspondence: Allen P. Burke,
the heart at the time of intestinal resec- Armed Forces Institute of Pathology,
tion, as the angiographic findings suggest, Washington, DC, USA
as well as the large size of the valve tumor E-mail: allen.burke@gmail.com
(9 cm);
- tumors of such histology are very uncom- Received for publication: 24 June 2009.
mon in the duodenum; Accepted for publication: 25 June 2009.
- histopathological findings of the duodenal This work is licensed under a Creative Commons
specimen are not presented. Attribution 3.0 License (by-nc 3.0)
At the very least, we believe that it is
unknown which of the two sites is primary. For ©Copyright F.R. Tavora, A.P. Burke 2009
this reason, we believe that the very rare sce- Rare Tumors 2009; 1:e5
nario of metastatic sarcoma presenting as a doi:10.4081/rt.2009.e5
left atrial mass is still not demonstrated con-
vincingly.

Multimodality treatment of microspheres (DC Bead™, Biocompatibles UK

Ltd., Farnham, UK) pre-loaded with 100 mg of Correspondence: Guido Poggi,
unresectable hepatic doxorubicin. One day after each TACE proce- U.O Oncologia II, Fondazione S. Maugeri,
metastases from pancreatic dure we performed ultrasound guided percuta- 27100 Pavia, Italy. E-mail: guido.poggi@fsm.it
glucagonoma neous radiofrequency. The radiofrequency sys-
Key words: neuroendocrine tumors, liver metas-
tem consists of an expandable electrode with
insulated outer needle of 2.2 mm of diameter tases, hepatic transarterial, chemoembolization.
Guido Poggi,1 Laura Villani,2
that houses nine deployable curved tines
Giovanni Bernardo1 Received for publication: 15 June 2009.
(Starburst XL; Rita Medical Systems).
1
Department of Oncology, Accepted for publication: 29 June 2009.
Abdominal enhanced CT scan at one month
2
Pathology, IRCCS Fondazione Maugeri, after the last RFTA procedure showed minimal
Pavia, Italy arterial contrast enhancement in two lesions This work is licensed under a Creative Commons
of the right lobe. The pancreatic tumor was Attribution 3.0 License (by-nc 3.0)
then surgically removed and the residual vital
©Copyright G. Poggi et al., 2009
hepatic tumors were treated with four sessions
Rare Tumors 2009; 1:e6
Abstract of radiotherapy with Y-DOTATOC, a radiola- doi:10.4081/rt.2009.e6
beled somatostatin analog. Thirty-two months
Glucagonomas are pancreatic islet cell after diagnosis the patient was well, he had
tumors arising from the alpha cells which regained his normal body weight and the ery-
thema had completely disappeared. usually multiple and diffuse and therefore rad-
belong to neuroendocrine tumors. They fre-
ical resection is feasible only in 10-20% of
quently metastasize to the liver. We report the
patients.6 Surgical resection of liver metas-
case of a 52- year old man with a pancreatic
tases with curative intent is associated with 5-
glucagonoma with synchronous multiple liver
year survival rates of 73-85%7,8 but, in unre-
metastases treated by surgery, transarterial Discussion sectable disease, surgery is not useful as a pal-
chemoembolization, percutaneous radiofre-
liative tool unless more than 90% of the tumor
quency thermal ablation and long-acting
Glucagonomas are pancreatic islet cell load can be debulked.9 In this setting, systemic
octreotide. Our report confirms that a multi-
tumors arising from the alpha cells which chemotherapy and octeotide have proved more
modal approach is very effective in patients
often produce elevated levels of circulating useful in controlling the endocrine syn-
with unresectable liver metastases from pan-
glucagon.1 The characteristic feature of the drome.10,11 On the experience of the efficacy of
creatic endocrine tumors providing long-last-
glucagonoma syndrome is a skin rash termed transarterial chemoembolization (TACE) in
ing palliation and probably prolonging survival.
necrolytic migratory erythema. Other findings hepatocellular carcinoma that shares vascular
include a mild insulin-resistant diabetes, glos- findings with neuroendocrine hepatic metas-
sitis, cheilosis, weight loss, venous thrombosis tases, TACE has been effectively used in the
constipation and mood changes.2 Glucagonoma palliative management of these tumors.12-13
Case Report is a neuroendocrine tumor (NET) which fre- TACE has also been used in adjuvant settings
quently metastasize to the liver.3 The particular to reduce tumor load before hepatic resection,
A 52-year old man was referred to our hospi- biological behavior of NETs, characterized by a hepatic transplantation or tumor ablation tech-
tal because of weight loss, chronic diarrhea long natural history, even in the presence of niques.4,14,15 Preliminary results show that the
and an erythematous rash with bullae and ero- liver metastases, has important therapeutic new drug-eluting microspheres now available
sions on the feet (Figure 1), in the groin and implications.4,5 Surgical resection is to be con- seem to optimize TACE procedures. In fact,
on the face. Blood chemical analyses showed sidered when the metastases are resectable these microspheres are capable of loading the
mild anemia (hemoglobin 10.8 g/dL), and an and no extrahepatic disease is present. drugs and slowly delivering them directly into
impaired fasting glucose test. As a part of the Unfortunately, neuroendocrine metastases are the tumor, thus achieving high intratumoral
diagnostic work-up, he underwent an abdomi-
nal computed tomography which showed a
large tumor of the pancreatic tail and multiple
hepatic lesions (Figure 2). Histological exami-
nation of a specimen obtained by ultrasound-
guided percutaneous biopsy of a liver lesion
revealed a tubulo-acinar structure of moder-
ately atypical cells positive for chromogranin
(Figure 3). 111In-octreotide scan showed hepat-
ic and pancreatic uptake without evidence of
extrahepatic metastases. A high level of
glucagon in the plasma (950 pg/mL) confirmed
the diagnosis of glucagonoma. Long-acting
octreotide was started with partial improve-
ment of the symptoms. The patient was then
treated with hepatic transarterial chemoem-
bolization (TACE) combined with percuta-
neous radiofrequency thermal ablation (RFTA)
in an effort to reduce the hepatic tumor bur- Figure 1. Necrolytic
den. Two sessions of TACE, one month apart, migratory erythema on
the feet.
were performed using polyvinyl alcohol-based

Case Report
Figure 3. Liver biop-

sy reveals a tubulo-
acinar structure of
moderately atypical
cells positive for
Figure 2. Abdominal CT scan shows multi- chromogranin
ple hepatic lesions. (x100).
concentrations and low plasma concentra- 3. Plöckinger U, Rindi G, Arnold R, Eriksson ME. Hepatic arterial embolization for
tions.16,17 The results with microspheres loaded B, et al. Guidelines for the diagnosis and metastatic hormone-secreting tumors.
with doxorubicin have been promising, show- treatment of neuroendocrine gastroin- Technique, effectiveness, and complica-
ing an advantageous pharmacokinetic profile testinal tumours. Neuroendocrinology tions. Cancer 1990;65:2227-32.
and good clinical response when compared 2004; 80:394-24. 13. Ruszniewski P, Rougier P, Roche A, et al.
with conventional TACE both in patients with 4. Falconi M, Bassi C, Bonora A, et al. Role of Hepatic arterial chemoembolization in
unresectable HCC18 and in patients with liver chemoembolization in synchronous liver patients with liver metastases of
metastases from well differentiated NETs.19 metastases from pancreatic endocrine endocrine tumors. A prospective phase II
Local therapy using RFTA provides a minimal- tumours. Dig Surg 1999;16:32-8. study in 24 patients. Cancer 1993;71:2624-
ly invasive procedure that decreases tumor vol- 5. Vogl TJ, Naguib NN, Zangos S, et al. Liver 30.
ume, preserves most of the normal liver and metastases of neuroendocrine carcino- 14. Roche A, Girish BV, de Baère T, et al.
can be repeated several times.20 Nevertheless, mas: interventional treatment via transar- Trans-catheter arterial chemoemboliza-
histological data from liver specimens of HCC terial embolization, chemoembolization tion as firstline treatment for hepatic
patients who underwent RFTA showed that and thermal ablation. Eur J Radiol 2009; metastases from endocrine tumors. Eur
tumor size has a significant impact on the 72:517-28. Radiol 2003;13:136-40.
local effect of this treatment. Indeed, vessels 6. Sarmiento JM, Que FG. Hepatic surgery 15. Veenendaal LM, Borel Rinkes IH, Lips CJ,
adjacent to the tumor cause heat loss due to for metastases from neuroendocrine van Hillegersberg R. Liver metastases of
perfusion-mediated cooling.21 Balloon catheter tumors. Surg Oncol Clin N Am 2003;12: neuroendocrine tumours; early reduction
occlusion or TACE increase the efficacy of 231-42. of tumour load to improve life expectancy.
RFTA by reducing tumor arterial supply.22 In 7. Chamberlain RS, Canes D, Brown KT, et al. World J Surg Oncol 2006; 26:4-35.
our patient we performed each RFTA exactly Hepatic neuroendocrine metastases: does 16. Poggi G, Quaretti P, Minoia C, et al.
one day after the TACE to obtain an increase of intervention alter outcomes? J Am Coll Transhepatic arterial chemoembolization
the necrotic area induced by thermal ablation. Surg 2000;190:432-45. with oxaliplatin-eluting microspheres
After two procedures of both TACE and RFTA, 8. Moertel CG, Johnson CM, McKusick MA, et (OEM-TACE) for unresectable hepatic
the hepatic tumor load was considerably al. The management of patients with tumors. Anticancer Res 2008;28:3835-42.
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four sessions of somatostatin receptor mediat- carcinomas. Ann Intern Med 1994;120: Pharmacokinetic and safety study of dox-
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is capable of binding to the residual vital 9. Blonski WC, Reddy KR, Shaked A, et al. of hepatic arterial embolization. J Vasc
tumor. Our report confirms that a multimodal Liver transplantation for metastatic neu- Interv Radiol. 2006;17:1335-43.
approach is very effective in patients with roendocrine tumor: a case report and 18. Varela M, Real MI, Burrel M, et al.
unresectable liver metastases from pancreatic review of the literature. World J Chemoembolization of hepatocellular car-
endocrine tumors providing long-lasting palli- Gastroenterol 2005;11:7676-83. cinoma with drug eluting beads: efficacy
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Octreotide as an antineoplastic agent in gastroenteropancreatic endocrine tumors
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Case Report
Radiofrequency ablation of neuroen- 21. Lencioni R, Crocetti L, Petruzzi P, et al. 22. Rossi S, Garbagnati F, Lencioni R, et al.
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Complete small bowel Case Report Correspondence: Chi Pan Lau,

obstruction caused by Department of Clinical Oncology,
metastasis from primary A 58-year old man with good past health pre- Prince of Wales Hospital, The Chinese University
of Hong Kong, Hong Kong, China
nasopharyngeal carcinoma sented with a one year history of episodic epis-
E-mail: cp_lau@clo.cuhk.edu.hk
taxis in June 2007. On examination he was
Chi Pan Lau, Edwin Pun Hui, found to have bilateral cervical lymphadenopa-
Key words: small bowel obstruction, metastasis,
Anthony Tak-Cheung Chan thy. Endoscopic examination of the nasophar-
nasopharyngeal carcinoma.
ynx revealed a nasopharyngeal tumor biopsy
Department of Clinical Oncology, Prince which showed undifferentiated carcinoma. Contributions: CPL and EPH contributed to
of Wales Hospital, The Chinese Computer tomography (CT) of the head and manuscript drafting. ATC contributed to critical
University of Hong Kong, China neck region showed a tumor mass extending manuscript revision. All authors read and
up to the base of skull and down to the hard approved the final manuscript.
palate, with parapharyngeal extension and
involvement of the cervical lymph nodes bilat- Conflict of interest: the authors reported no poten-
Abstract erally. Whole-body positron emission tomogra-
tial conflicts of interests.
phy (PET) scan showed no metastatic disease Consent: written informed consent was obtained
We here report the first case in the litera- elsewhere. The patient was diagnosed to have from the patient for publication of this case
ture on a surgical emergency of complete small locally advanced nasopharyngeal carcinoma report and any accompanying images.
bowel obstruction caused by metastasis from (NPC) of UICC/AJCC (International Union
nasopharyngeal carcinoma nine months after Against Cancer and American Joint Received for publication: 19 June 2009.
the primary tumor was treated with concurrent Committee on Cancer) stage T2bN2 and he Accepted for publication: 29 June 2009.
chemoradiation. The patient achieved pro- was treated with concurrent chemoradiation
longed survival with prompt surgical treatment This work is licensed under a Creative Commons
with weekly cisplatin. He was in clinical remis-
Attribution 3.0 License (by-nc 3.0)
followed by systemic chemotherapy. sion for nine months after his treatment until
he developed symptoms of acute intestinal ©Copyright C.P. Lau et al., 2009
obstruction with abdominal pain and disten- Rare Tumors 2009; 1:e7
tion. Abdominal X-ray showed dilated small doi:10.4081/rt.2009.e7
Introduction bowel loops. He underwent urgent laparotomy
and intra-operatively he was found to have a
Cancers involving the bowel are usually pri- lesion completely obstructing the distal small
mary large or small bowel cancers, direct inva- bowel. The lesion was resected and resection
sion from primary cancers arising from other was followed by primary bowel anastomosis Discussion
abdominal organs or peritoneal carcinomato- (Figure 1). The patient recovered well one
sis. Metastatic cancer from malignancy out- month after his operation. Microscopic exami- Small bowel metastases from primary head
side the abdomen involving the intestinal nation of the small bowel lesion showed undif- and neck cancer is extremely rare. Among the
mucosa is relatively uncommon although it is ferentiated carcinoma and the tumor cells few reported cases, the majority of them were
well reported in the literature, and can be asso- were immunohistochemically positive for from cancer of the larynx.6,7 Guillem et al. ana-
ciated with multiple surgical emergencies cytokeratin and c-kit. lyzed a 10-patient series which showed that
including intestinal bleeding, perforation, or Fluorescence in situ hybridization (FISH) of small bowel metastases from head and neck
intussusception. Small bowel obstruction Epstein-Barr Virus (EBV) encoded RNA cancers occurred more commonly in old male
caused by metastatic lesion from other primary (EBER) was also positive in the tumor cells patients (mean age 71 years).8 They were usu-
cancer is a rare event. Idelevich et al. reviewed (Figure 2). The histology of the small bowel ally discovered because of occlusive, perfora-
the literature and found that between 1988 and lesion was compared to the initial nasopharyn- tive or bleeding symptoms and complications.
2005, only 36 such cases have been reported.1 geal carcinoma biopsy specimen and they were Perforation more commonly occurred at jeju-
Interestingly, the most common primary can- similar. Plasma EBV-DNA was found to be ele- nal metastases while clinical bleeding and
cer in these cases was lobular breast carcino- vated to 150,473 copies/mL and PET scan occlusion more commonly occurred at ileal
ma (47%), followed by lung cancer (11%) and showed high FDG uptake (maximum SUV metastases. In any case, the diagnosis of small
malignant melanoma (8%). 17.7) at the retroperitoneal lymph nodes con- bowel metastases from head and neck cancer
These cases can occur after patients have sistent with metastatic disease at these sites. carried poor prognosis. In these 10 patients,
been in remission for many years2-4 and can be The patient was subsequently treated with deaths occurred within eight months following
the first site of disease presentation.5 Because three cycles of combination chemotherapy diagnosis, either due to post-operative compli-
of its rarity, recurrent metastatic disease as with paclitaxel and carboplatin three-weekly. cations or cancer progression.
the cause of small bowel obstruction in Repeated whole body PET scan showed com- To our knowledge, we report the first case of
patients who have been in remission for their plete remission with no residual disease small bowel metastasis from primary nasopha-
primary cancer was not immediately suspected detectable. Plasma EBV-DNA level also ryngeal carcinoma. Nasopharyngeal carcinoma
and it was known only during pathological decreased to 900 copies/mL. Although the (NPC) is an endemic subtype of head and neck
assessment of the resected specimen. We here patient had progressive disease subsequently, cancer in South East Asia especially the south-
report a case of complete small bowel obstruc- his metastatic disease remained responsive to ern part of China. In contrast to other types of
tion caused by recurrent metastatic disease further lines of chemotherapy with capeci- head and neck cancer, NPC has a special viral
from a patient who has been treated for pri- tabine and gemcitabine and he remains well at etiology with strong association with EBV
mary nasopharyngeal carcinoma. the present time with preserved quality of life. infection.9 The other special feature of NPC is

Case Report
3. Daniels IR, Layer GT, Chisholm EM. Bowel

obstruction due to extrinsic compression
by metastatic lobular carcinoma of the
breast. J R Soc Promot Health 2002;
122:61-2.
4. Van Trappen P, Serreyn R, Elewau AE, et al.
Abdominal pain with anorexia in patients
with breast carcinoma. Ann Oncol
1998;9:1243-5.
5. Clavien PA, Laffer U, Torhos J, Harder F.
Gastrointestinal metastases as first clini-
cal manifestation of the dissemination of a
Figure 1. Specimen resected during lapa- Figure 2. Microscopic examination of the breast cancer. Eur J Surg Oncol 1990;16:
rotomy. A lesion is found completely resected specimen. Poorly differentiated 121-6.
obstructing the small bowel macroscopi- carcinoma cells stained strongly for 6. Airoldi M, Gabriele P, Succo G, et al. Small
cally. Epstein-Barr virus-encoded RNA (EBER). bowel metastasis from squamous cell car-
cinoma of the larynx. A case report.
Tumori 1993;79:286-7.
7. Buyukcelik A, Ensari A, Sarioglu M, et al.
its chemosensitivity.10 Common sites of metas- uncommon, prompt recognition and treatment Squamous cell carcinoma of the larynx
tases from primary nasopharyngeal carcinoma of an abdominal emergency secondary to these metastasized to the ampulla of Vater.
include regional lymph nodes, bone, lung, and metastases can result in good outcome, espe- Report of a case. Tumori 2003;89:199-201.
liver. Although poor prognosis and short sur- cially for a cancer that shows high response 8. Guillem P, Brygo A, Assila C, Dabrowski A.
vival was reported in small bowel metastases rate to systemic chemotherapy. Clinicians Small bowel metastases from head and
from head and neck cancer, for our patient need to be vigilant on unusual or unexplained neck cancers. Ann Chir 2004;129:422-6.
prompt surgical treatment for the abdominal abdominal symptoms arising from patients 9. Zur Hausen H, Schulte-Holthausen H,
emergency followed by systemic chemotherapy with malignancy outside the abdomen. Klein G, et al. EBV DNA in biopsies of
for residual metastatic disease resulted in Burkitt tumours and anaplastic carcino-
good outcome, as illustrated by an initial radi- mas of the nasopharynx. Nature 1970;228:
ological complete remission given that NPC is 1056-8.
a chemosensitive type of cancer. Our patient References 10. Ma BB, Chan AT. Recent perspectives in
has survived at least 22 months till the present the role of chemotherapy in the manage-
time with good quality of life. 1. Idelevich E, Kashtan H, Mavor E, Brenner ment of advanced nasopharyngeal carcino-
B. Small bowel obstruction caused by sec- ma. Cancer 2005;103:22-31.
ondary tumors. Surg Oncol 2006:15:29-32.
2. Bender GN, Maglinte DD, McLarney JH, et
Conclusions al. Malignant melanoma: patterns of
metastasis to the small bowel, reliability of
Although small bowel metastases from pri- imaging studies, and clinical relevance.
mary cancer outside the abdomen is relatively Am J Gastroenterol 2001:96:2392-400.

Diagnosis of vulvar lesions by Introduction Correspondence: Ilaria Dellacasa, Department of

non-invasive optical analysis: Gynecology and Obstetrics, Geneva University
a pilot study Vulvar squamous cell carcinoma of the Hospital, 1211 Geneva 4, Switzerland.
vulva (SCC) accounts for about 4% of all gyne- E-mail: ilydellacasa@yahoo.it
cological malignancies.1 It has an incidence of Vlastos Anne-Thérèse, Department of Gynecology
Anne-Therese Vlastos,1 Igor Charvet,2
and Obstetrics, Geneva University Hospital, 1211
Ilaria Dellacasa,1 Federica Capanna,1 about 1.8 per 100,000, which peaks at approx-
Geneva 4, Switzerland. E-mail: anne-therese.vlas-
Marie-Françoise Pelte,3 Philippe Thueler,4 imately 20 per 100,000 after the age of 75,
tos@hcuge.ch
Michel Saint-Ghislain,4 making it as common as cervical carcinoma.2,3
SCC is usually slow growing and begins as a Key words: vulvar intraepithelial neoplasia, non
Christian Depeursinge,4 Paolo Meda2
pre-malignant lesion, referred to as vulvar invasive diagnosis, optical analysis, absorption
1
Department of Gynecology and intraepithelial neoplasia (VIN).4 This lesion spectra, scattering spectra.
Obstetrics, 2Department of Cell actually comprises a spectrum of epithelial
Physiology and Metabolism, 3Department changes that range from mild to severe dyspla- Acknowledgments: the authors would like to
of Pathology and Immunology, Geneva sia, which immediately precede invasive car- gratefully thank Dr. Michele Follen at The
cinoma. Although advanced VIN lesions may University of Texas M.D. Anderson Cancer Center
University Hospital University, Genève,
appear as variably pigmented patches under for her helpful comments about this manuscript.
Switzerland; 4Institute of Applied Optics,
Swiss Federal Institute of Technology, vulvoscopy investigation, they may be difficult
Contributions: IC and ATV contributed equally to
to distinguish from a variety of benign dis-
Lausanne, Switzerland this research and should both be considered first
eases. This difficulty often leads to delayed author.
diagnosis, until the obvious stage of invading
squamous cell carcinoma.5 Presently, the stan- Funding: the Meda team is supported by grants
dard procedure for definitive diagnosis con- from the Programme Commun de Recherche en
Abstract sists in performing a biopsy of all suspected Génie Biomédical 1999-2002, the Swiss National
areas, even though only a fraction of these are Foundation (3100-067788.02), the Juvenile
A procedure that could allow an early in vivo at risk of neoplastic transformation.6 Because Diabetes Research Foundation International (1-
and non-invasive detection of vulvar lesions vulvar sampling is painful and bears infec- 2001-622), the European Union (QLRT-2001-
would be extremely useful. We tested an inno- tious risks for the patient, an alternative 01777), the Fondation Romande pour la
vative optical method (Optiprobe), which uses method that would allow for a non-invasive Recherche sur le Diabète and the National
a harmless, visible light source for the in vivo, Institute of Health (DK-63443-01), a Research
diagnosis would be of great value in the
and Development grant from the Geneva
on-line detection of minimal alterations in the screening programs of vulvar cancer. University Hospitals, le Fond National Suisse
structure of vulvar epithelium. A group of 3 Light-scattering spectroscopy is a recently pour la Recherche Scientifique (3100-
female volunteers without gynecological symp- developed optical method that relies on the in 067788.02).
toms were first screened to evaluate optical situ measurement of the light back-scattered
properties of normal vulvar tissue. Next, a (reflectance) from an illuminated tissue. The Received for publication: 29 June 2009.
group of 16 patients undergoing gynecological two underlying ideas are that light propaga- Accepted for publication: 30 June 2009.
examination for vulvar lesions was evaluated tion, and thus reflectance, is modified under
by the Optiprobe at suspected sites before conditions altering the structure and/or com-
Attribution 3.0 License (by-nc 3.0).
these sites were biopsied for histological position of a tissue,7-11 and that optical coeffi-
analysis. Adjacent, non-involved sites were cients can be derived from reflectance values, ©Copyright A.-T. Vlastos, et al., 2009
also measured to provide internal controls. which provide information on these alter- Rare Tumors 2009; 1:e8
Histological analysis of the biopsies identified ations.12-14 Thus, the absorption coefficient, doi:10.4081/rt.2009.e8
one case that did not show obvious alterations, which is thought to reflect the concentration of
4 cases of high-grade vulvar intraepithelial chromophores, and the scattering coefficient,
neoplasia (VIN), 5 cases of vulvitis, and 6 which is thought to reflect the size and numer-
ical density of cells and organelles, significant-
cases of lichen sclerosis (LS).
The optical properties of the VIN cases were
ly differ in normal and pathological tissues.15-18 Materials and Methods
We have built an optical set-up, referred to
significantly different from those of controls,
as Optiprobe, which comprises a multi-fiber
due to a decrease in the absorption spectra and
mini-probe to screen small tissue volumes of
Patient selection
an increase in the scattering spectra. In con- The study was approved by the Committee
about 1 mm3.17,19 We have found that this equip-
trast, a significant increase in the absorption ment allows for an in vivo, real-time detection for Ethics in Research of the University of
spectra and a decrease in the scattering spec- of minimal tissue lesions, like those expected Geneva Hospitals, and conducted according to
tra were observed in the cases of vulvitis. In at the beginning of inflammatory and cancer- the guidelines of this Committee. After
the LS cases, the absorption spectra were as in ous alterations.15,20 Here we have assessed informed consent, a first group of 3 healthy
controls, whereas the scattering spectra were whether the method has a sufficient sensitivi- volunteers were screened with the Optiprobe
significantly decreased. We conclude that the ty to identify alterations of vulvar tissues in technology to determine the optical properties
Optiprobe provides a useful tool for a rapid and patients undergoing vulvoscopy. We report that of normal vulvar tissue. A second group of 16
non-invasive detection of vulvar alterations. the Optiprobe method discriminated normal patients, undergoing vulvoscopic examination
The method should contribute to reduce the and pathological cases, with a sensitivity and for suspicion of vulvar lesions, were similarly
number of biopsies and to facilitate the long- specificity that compared well with those of evaluated.
term follow-up of vulvar lesions. histological analysis, while avoiding the need The very same sites were then sampled for
of invasive biopsies. standard histological analysis. Sites of non-
involved tissue from nearby regions were also

Article
measured to provide an internal control. The the number of true positive cases (i.e. cases 25-140% for the absorption spectra (Figure
optical-biopsy combined procedure did not showing positive tests in patients with abnor- 1C), and from 5-20% for the scattering spectra
imply additional discomfort for the patients, mal histology) by the number of true plus false (Figure 1D).
inasmuch as the fiber-optic probe was gently negative cases (i.e. cases showing normal
applied on vulvar surfaces for illumination tests in patients with abnormal histology). Histology set the standard for the
with a harmless visible light source. On aver- Specificity of tests was evaluated by dividing retrospective validation of the
age, the duration of the combined vulvoscopic- the number of true negative cases (i.e. cases
optical-biopsy procedure was about 10 min showing normal tests in patients with normal
optical findings
longer than that of the standard vulvoscopic- histology) by the number of true negative Immediately after the optical measure-
biopsy examination. cases plus false positive cases (i.e. cases ments, a biopsy was taken at each of the 16
showing altered tests in patients with normal suspected sites that had been investigated.
Optical measurements histology). The histopathological scoring of these samples
The optical mini-probe set-up, and the theo- resulted in the identification of one site show-
ry of the method used to collect reflectance sig- ing no detectable alteration, 4 sites showing
nals and to derive optical coefficients, have Results high-grade VIN, 5 sites with vulvitis and 6 sites
been previously described.17,19,21,22 Briefly, the tip with lichen sclerosis.
of the hand-held optical probe was applied on The optical spectra of normal
the vulvar epithelium. Once in place, a 400 vulvar tissue changes with Optical analysis distinguished
msec pulse of white-light (wavelength range normal and pathological vulvar
hormonal status
480-950 nm) provided by a halogen lamp
The optical properties of normal vulvar tis- epithelium
(Ocean Optics LS-1) was delivered through the
source fiber of the probe. Intensity of sue were first evaluated by recording the Absorption and scattering coefficients were
reflectance, i.e. light backscattered from the absorption and scattering spectra in 3 healthy determined for wavelengths between 400 and
illuminated tissue, was simultaneously record- volunteers, whose vulva was clinically normal. 700 nm, in 16 sites suspicious of vulvar lesion
ed at various distances from the source, using In each case, maximal light absorption was and in nearby sites that appeared phenotypi-
the 10 collecting fibers of the probe. Collected observed between 400 and 500 nm (Figure 1A), cally not involved and were used as controls.
reflectance was brought to a spectroscope reflecting the normal presence of chro- Non-parametric statistics confirmed that the
(Jobin-Yvon CP 200), focused on a cooled CCD mophores oxy and deoxy-hemoglobin within optical properties of VIN sites were signifi-
camera (Hamamatsu C7041) during an expo- surface tissues. In the same volunteers, the cantly (p<0.001) different from those of con-
sition time controlled by a mechanical shutter, scattering coefficient decreased as a function trols, due to a decrease in the absorption coef-
and computer digitized in 16 bits (National of increasing wavelength (Figure 1B), consis- ficient (Figure 2A) and an increase in the
Instruments PCI-MIO-16E-4). Reflectance tent with the light-scattering characteristics of scattering coefficient (Figure 3A). Thus, on
measurements were repeated 6-8 times per surface tissues. Comparison between the average, the absorption and scattering coeffi-
site and averaged. In each patient, at least one recordings from the 3 volunteers revealed sig- cients of VIN cases were 50% and 40% those of
suspicious and one control site were probed nificant (p<0.001) differences in both absorp- controls (Figures 2D and 3D). Taking these
before the surgical biopsy. tion (Figure 1A) and scattering (Figure 1B) values as optical threshold for diagnosis, we
Once the gynecological examination was coefficients. These differences were repre- calculated that the Optiprobe would detect VIN
completed, the acquired reflectance spectra sented by a variation coefficient varying from cases with a sensitivity of 75% (absorption) -
were analyzed using a Monte Carlo simulation
and a modified form of the Henyey-Greenstein
A B
phase function to compute an absorption and a
Absorption coefficient
Scattering coefficient
scattering coefficient. These optical parame-

ters are thought to reflect the interaction of
mm–1
mm–1
light with chromophores and the changes of

light propagation in small tissue volumes,
respectively.17,19,21
Histology
Biopsies of the vulvar tissue, taken at the Wavelength (mm) Wavelength (mm)
very same sites that were probed optically, C D
were fixed in 10% formol and processed for
Absorption variation
Scattering variation
standard histological analysis by an expert

pathologist. In this study, each sample was
%
assigned to a normal, lichen sclerosis, VIN or a

vulvitis group.
Statistics
Optical measurements from altered and Wavelength (mm) Wavelength (mm)
control sites were compared using appropriate
non-parametric statistics, as provided by the Figure 1. Optical spectra of normal vulvar tissue vary between healthy women. Mean
SPSS program (SPSS Inc., Chicago, USA). (bold line) and standard deviations (thin lines) of the absorption (A) and scattering coef-
Sensitivity of optical analysis (hereafter ficients (B) measured on 3-4 adjacent sites in each healthy volunteer (a, b and c are
referred to as tests) was estimated by dividing recordings from the 52-, 48- and 34-year old women, respectively.

Article
A B C
Absorption coefficient
mm–1
Wavelength (mm) Wavelength (mm) Wavelength (mm)
D E F
Absorption variation
%
Figure 2. (A-C) Absorption analysis discriminated VIN and inflammatory lesions, but not lichen sclerosis from normal tissue. (A) Mean
(bold line) and standard deviations (thin lines) of absorption spectra obtained at sites featuring histology characteristics of VIN (A),
inflammation (B) and lichen sclerosis (C). Absorption spectra of VIN and vulvitis (black) were significantly (p<0.001) different from
those of controls spectra (gray), for light wavelengths of 400-700 nm. In contrast, absorption spectra of lichen sclerosis (black) were
not different from those of controls (gray). (D-F) Mean (bold line) and standard deviations (thin lines) of percentage of change in
absorption spectra between pathological and control sites were calculated for the 4 VIN (D), the 5 vulvitis (E), and the 6 lichen scle-
rosis sites (F). Graphs show that VIN lesions induced a significant decrease of absorption between 400 nm and 500 nm, whereas a sig-
nificant increase was observed at inflammatory sites. No significant change was observed at lichen sclerosis sites.
A B C
Scattering coefficient
%

D E F
Scattering variation
coefficient %
Figure 3. (A-C) Scattering analysis discriminated VIN, inflammatory and lichen sclerosis lesions from normal tissue. Mean (bold line)
and standard deviations (thin lines) of scattering spectra obtained in women diagnosed with VIN (A), inflammation (B) and lichen
sclerosis (C). Scattering spectra of VIN sites, vulvitis sites and lichen sclerosis sites (black) were significantly (p<0.001) different from
controls spectra (gray) for light wavelengths of 400-700 nm, 400-500 nm, and 500-700 nm, respectively. (D-F) Mean (bold line) and
standard deviations (thin lines) of percentage change over control was calculated for the 4 VIN (D), the 5 vulvitis (E) and the 6 lichen
sclerosis sites (F). Graphs show significant scattering variation in VIN, vulvitis and lichen sclerosis cases, for light wavelengths of 400-
700 nm, 400-510 nm and 500-700, nm respectively.

Article
50% (scattering). revealed a slow decrease correlated to the with the standard biopsy-histology approach,
Compared to controls, sites of vulvitis fea- increase of wavelengths, as is usually observed while avoiding the tissue invasion required by
tured significantly (p<0.001) increased with surface biological tissues.23,25 Although the latter approach. This method should prove
absorption values (Figure 2B) and decreased both absorption and scattering measurements a useful complement to clinical diagnosis of
scattering values (Figure 3B). When expressed had a comparable shape in all volunteers, we vulvar lesion in directing the biopsy procedure,
as percentage of the corresponding control val- observed significant differences in their as well as in guiding invasive therapeutic acts
ues, the average absorption and scattering val- absolute values. These differences could not be (e.g. laser irradiation, excision) to only rele-
ues of vulvitis cases represented 100% and attributed to variations of the optical set-up, vant areas of the vulvar surface.
20% of control values, respectively (Figures 2E which probed stable standards with a variation
and 3E). Using these values, the test discrimi- coefficient of less than 5% for absorption and
nated normal from vulvitis cases with a sensi- scattering measurement. Thus, the variation
tivity of 80% for both absorption and scattering coefficients observed for absorption (30-140%) References
coefficients. and scattering (5-20%) measurements of nor-
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sites of lichen sclerosis were not significantly individual variation. While the reason of this genital tract. Ed. B.D.Inc London Hamilton
different from controls for all investigated light variation remains to be determined (could this 2001;1-8.
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nificant (p<0.001) decrease in scattering spec- necessity of having a proper internal control cal information on gynecological cancer.
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Discussion tion coefficients in all the three types of 43
lesions that were investigated. While the 6. Girardi F, Pickel H, Joura EA, et al.
We have developed a new optical procedure nature of the biological parameters that affect- Guidelines for diagnosis and therapy of
and equipment for a non-invasive, in vivo ed the optical coefficients remains to be deter- intraepithelial neoplasia and early inva-
analysis of small tissue volumes. The proce- mined, this method provides a new tool for a sive carcinoma of the female lower genital
dure is based on the spectroscopic measure- rapid distinction between pathological and system (cervix uteri, vagina, vulva) estab-
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Congenital giant melanocytic 40 days gestation and it is thought that con-

genital nevi develop between the 2nd and 6th Correspondence: Ghulam S. Hashmi,
nevi month of gestation. It develops from neuro Dept. of Oral & Maxillofacial Surgery,
ectodermal cell between the intra uterine life Faculty of Medicine, Aligarh Muslim University,
Ghulam S. Hashmi,1 Syed S. Ahmed,2 of the 8th to 24th week of pregnancy. Body pro- Aligarh-202002, India
Shahla Khan3 E-mail: sarwarhashmi@rediffmail.com
tein HGE/SF (hepatocyte growth factor/scatter
1
Dept. of Oral & Maxillofacial Surgery, factor) seems to be responsible for encourag- Key words: nevus, melanoma, giant, congenital.
Faculty of Medicine, Aligarh Muslim ing these neuroectodermal cells to develop,
University, Aligarh, India; migrate and scatter. In those of us with a Received for publication: 23 June 2009.
2
Dept. of Oral & Maxillofacial Surgery, nevus, it seems that we have too much or the Accepted for publication: 29 June 2009.
Faculty of Medicine, Aligarh Muslim wrong type of this body protein HGE/SF in
some cells, so we develop extra pigment and
University, Aligarh, India; Attribution 3.0 License (by-nc 3.0)
3
abnormal skin cells called nevus cells.
Dept. of Prosthodontics, Faculty of
Congenital nevi are generally seen in 1 in ©Copyright G.S. Hashmi, et al., 2009
Medicine, Aligarh Muslim University,
every 20,000 children, whereas the giant vari- Rare Tumors 2009; 1:e9
Aligarh, India ety involving much of the body surface area are doi:10.4081/rt.2009.e9
less common, possibly around one in every
200,000. While congenital nevi are typically
larger than the common acquired nevi, they nevus presenting neurological symptoms, like
Abstract cannot always be distinguished by size alone. worsening headache and vomiting, need to
They are often round or oval, clearly demarcat- have an MRI of the brain.4,7 Those with
Nevi are common skin tumors caused by ed and some times slightly intact. seizures also need to have repeated MRI per-
abnormal overgrowth of cells from the epider- Pigmentation is usually even, although some
mal and dermal layers of the skin. Most nevi formed periodically. The risk of malignant
congenital nevi have a speckled appearance. change in giant nevi is probably the most con-
are benign, but some pre-cancerous nevi must Coarse dark hair may be present. The conge-
be monitored or removed. The giant congenital tentious issue in its management. The consen-
nital nevi occur in 1-1.25% of neonates and
nevus is greater than 10 cm in size, pigmented sus is that lesions are pre-malignant, but the
with the passage time, may change from flat,
and often hairy. Between 4% and 6% of these purported incidence of malignancy varies wild-
pale, tan macules to elevated verrucous hairy
lesions will develop into a malignant ly from 0-42%. Surgical excision remains the
lesions. The head and neck area involve
melanoma. Since approximately 50% of the mainstay of treatment for large congenital
approximately 15% of all nevus. Intraoral
melanoma develop by the age of two, and 80% melanocytic nevi, and most giant nevi are
occurrence is extremely rare. In cases of
by the age of seven, early removal is recom- managed by staged excision and resurfacing
acquired nevus, junctional nevus develops at
mended. The objective of this paper is to pres- with skin grafts or tissue expanders and flaps.
the age of two years, progressing to a com-
ent a unique case of giant nevi and their sur- For facial nevi, laser treatment is one of the
pound nevus through the teenage years, and
gical management. best known options available for the removal of
then to a dermal nevus in adulthood. Conge-
giant nevi.9
nital nevi are significant because of their
Histologically, nevi are transformed
much higher incidence of melanoma transfor-
melanocytes, which are normally highly den-
mation. A Bathing Trunk nevus is a darkly pig-
Introduction dritic cells interspersed among basal ker-
mented, disfiguring, often hairy patch of skin
present at birth, which may cover an extreme- atinocytes. The genetic basis of these lesions
The word Nevus derives from the Latin word ly large area of the body. Some times the nevus is not known. Findings of a culture of
Knee-vus meaning birthmark or mole. The covers most of the trunk, the upper arm and melanocytes from such a lesion showed chro-
nevus is defined as a congenital, developmen- thigh. Bathing trunk nevi are thought to be mosome rearrangements involving 1p,12q, and
tal tumor-like malformation of the skin or caused by spontaneous mutations or other 19p. The giant nevi might be associated to sev-
mucous membrane.1 Acquired nevi are events during fetal development, but in some eral diseases: neurocutaneous melanosis, dif-
extremely common. They appear at about the families, the frequent appearance of these fuse lipomatosis, structural brain malforma-
eight month of life and increase in number lesions suggest that they may be genetically tions, hypertrophy of skull bones, limb atrophy,
with age. inherited. They may be associated with other skeletal asymmetry involving both soft tissues
Classification of nevus: birth defects.8 The distinction between con- hyper-and hypoplasia, von Recklinghausen's
1. congenital genital nevi and other forms of acquired nevi disease and vitiligo.
a. small can usually be made on clinical examination.
b. giant Any nevus larger than 1.5 cm is likely to be
2. acquired congenital. The congenital nevi are rare; they
a. intra dermal nevus (common mole) are often darkly pigmented and may be hairy Case Report
b. junctional nevus and papillary in appearance. Occasionally they
c. compound nevus cover an extensive area of skin, up to 25% or A 5-year old female presented with multiple
d. spindle cell nevus more of the body surface. They may undergo dark black colored, wart like patches, on her
e. epetheloid cell nevus malignant change even during childhood. The face, neck, shoulder, leg and entire back. No
f. blue nevus (Jadassohn-Tieche)2 life-time risk for malignant degeneration in a other abnormality was found on physical
large congenital nevus is approximately 6%.5,6 examination. Family history failed to show any
Familial tendencies exist and approximately In these cases melanoma can arise in the first other individuals with a similar lesion (Figure
1 in 20,000 new born is found to have a large few years of life and excision should be consid- 1). The concern of the present problem of the
congenital nevus.3 Melanocytes (pigment pro- ered as soon as possible. No specific investiga- patient was only esthetic. On examination
ducing skin cells) are found in utero at about tion is required for small nevi. People with extra orally, there were 5-6 small to medium

Case Report
5). An antibiotic was advised. Cefadroxil syrup

was indicated 1tsf B. D. for 7 days.
Histopathological examination revealed large
discrete cells, each with an ovoid, vesicular
nucleus and pale cytoplasm. The nevus cells
are situated within the connective tissue and
are separated from the overlying epithelium by
a well defined band of connective tissue.
(Figures 3-6).
Figure 4. Post-operative photograph of the Discussion

same patient on OT table.
Congenital nevi are generally seen in 1 in
every 20,000 children whereas giant congeni-
tal varieties involving much of the body sur-
face area are less common, possibly around 1
in 200,000. They can vary in size from being
less than 1/4 inch to covering almost the
entirebody. The cause of congenital moles
Figure 1. Pre-operative photograph of the
patient on OT table. may have recently been discovered. Abnormal
HGF/SF (hepatocyte growth factor/scatter fac-
tor) seems to develop in certain body cells
accidentally, called spontaneous autosomal
dominant genetic mutations. These muta-
tions are not hereditary. Congenital moles will
hardly ever disappear on their own. However,
they are important because they can some-
times lead to a potentially deadly skin cancer
called malignant melanoma. Malignant
changes of giant nevus can occur at any age
but most often occur in infants or toddlers.
Pregnancy increases the production of
melanin in the body. Most dermatologists rec-
ommend avoiding excess sun by wearing
Figure 5. Post-operative photograph of the
Figure 2. Intra-operative photograph of same patient. broad-brimmed hats, sunglasses, long-sleeved
the same patient. shirts, long pants or skirts, gloves and espe-
cially avoiding sunburn by staying in the
shade, but not all are true. There are cases of
melanoma occurring in a mole locating in the
arm pit, which is a part of body that receives
virtually no sun exposure whatsoever.
Complete excision should include removal of
each and every cell of melanoma. Since it is
actually impossible to totally remove every last
single cell of the nevus, the extensive surger-
ies required to nearly totally remove a nevus
can cause other severe, sometimes nearly
fatal, complications. Literature says people
with nevus in our group die of cancer after
their giant nevus had been totally removed.
Figure 6. (40x) Histopathological examina-
Figure 3. Resected specimen of the same tion shows nevi cells are separated with Other literature says that we have had mem-
patient. connective tissue layer. bers who underwent numerous surgeries to
successfully remove the entire external giant
skin nevus only to die later of brain or spinal
sized black discolored patches with coarse hair facial nevi. Routine blood examination and X- cord melanoma. Now the cultured skin auto-
grown over it present on the right side of the ray chest were in the normal range. Surgical graft are sometimes used as a reconstruction
face, neck, shoulder, both the legs and the excision of all the facial nevi was planned and of the large excised melanoma. There are a
entire back indicating Bathing Trunk nevus. it was excised under G.A. using Propofol. number of treatment options available, but
There was no history of pain, itching or dis- (Figures 2-4) Primary closure was performed they are not ideal and also have some disad-
comfort. The patient lives a normal life and the using 6-0 prolene. Since all the nevi are small vantages e.g. integra, dermabrasion, laser,
only concern was the esthetic problem of the in size, no reconstruction is required (Figure chemical peels, tissue expanders and so on.

Case Report
Nevi, Juvenile Melanoma and Malignant The incidence of malignant transforma-

References melanoma in children. Cancer 2006;7:564- tion in giant pigmented nevi. Scand J Plast
85. Reconstr Surg 1977;11:163-711.
1. Chunj C, Forte AJ, Narayan D, et al. 4. Zemtsov A, Lorig R, Bergfeld W, et al. 7. Frieden I, Williams M, Barkovich A. Giant
Magnetic resonance imaging of cutaneous
A review. J Craniofac Surg 2006:1210-15. congenital melanocytic nevi: Brain mag-
melanocytic lesions. J Dermatol Surg
2. Gosain AK, Santoro TD, Larson DL, et al. netic resonance findings in neurologically
Oncol 1989;15:854-8.
Congenital Nevi: a 20 – year experience 5. Shaw M. Malignant melanoma arising asymptomatic children. J Am Acad Derma-
and an algorithm for their management. from a giant hairy naevus. Br J Plast Surg tol 1994;31:423-9.
Plast Reconstr Surg 2001;108:622-36. 1962;15:426-31. 8. Conway H. Bathing trunk nevus. Surgery
3. McWhorter HE, Woolner LB. Pigmented 6. Lorentzen M, Pers M, Brettville-Jensen G. 1939;6:585.

Intramedullary capillary a more recent two week history of gait difficul-

ties. His past medical history is significant for Correspondence: Wilson Z. Ray,
hemangioma of the thoracic a prior left-sided intracerebral hemorrhage Washington University School of Medicine,
spine: case report and review with consequent hemiparesis three years ago. 660 S. Euclid Ave, Campus Box 8057,
St. Louis, MO 63110, USA
of the literature The patient’s baseline deficits associated
with his prior left hemisphere stroke included
Key words: intramedullary capillary hemangioma,
Rahul Kasukurthi,1 Wilson Z. Ray,2 dysarthria, right facial weakness, and a dense
dysembryogenesis.
Spiros L. Blackburn,2 Eriks A. Lusis,2 right hemiparesis. New deficits included 3-4/5
Paul Santiago2 strength of the left lower extremity and a sen- Received for publication: 20 June 2009.
1
sory level just above the nipples consistent Accepted for publication: 29 June 2009.
Division of Plastic and Reconstructive
with approximately a T3 spinal level. Reflexes
Surgery, Washington University School of were 3+ in the bilateral lower extremities. This work is licensed under a Creative Commons
Medicine, Saint Louis, MO, USA; Attribution 3.0 License (by-nc 3.0)
2
Babinski reflex was present bilaterally.
Department of Neurosurgery, MRI of the thoracic spine both before and ©Copyright R. Kasukurthi et al., 2009
Washington University School of after the administration of intravenous Rare Tumors 2009; 1:e10
Medicine, Saint Louis, MO, USA Gadolinium demonstrated what initially doi:10.4081/rt.2009.e10
appeared to be a homogenously enhancing
intradural, extramedullary lesion displacing
the cord anteriorly with significant cord defor-
Abstract mation (Figure 1). Our differential diagnosis Discussion
included: nerve sheath tumor, meningioma,
Capillary hemangiomas are benign vascular and ependymoma. Capillary hemangiomas involving the spinal
neoplasms. When associated with the spine, The patient was offered an excisional biop- cord are extremely rare, and are most fre-
these growths frequently involve the vertebral sy of the lesion. T2 and T3 laminectomies were quently extramedullary in location.1-3 We are
body, but rarely have they been reported to performed, and the lesion location was con- aware of only a handful of previously reported
occur as intradural lesions, while even more firmed using intra-operative ultrasound. cases of intramedullary spinal cord capillary
rarely occurring in a true intramedullary loca- Intradural exploration revealed a highly vascu-
tion. We report a rare case of an intrame- hemangiomas (Table 1). Notably, all but one
lar, partially encapsulated cherry-red lesion previously reported case involved the thoracic
dullary capillary hemangioma of the thoracic
that appeared to arise from the dorsal aspect of spine or the conus.
spinal cord and a review of the literature.
the spinal cord. In contrast to MRI findings, the MRI is the gold standard imaging modality
tumor was found to be intramedullary in loca- for intramedullary lesions.13-16 Many such
tion. Overlying the tumor was a region of lesions can be safely removed with proper
thickened arachnoid, but no demonstratable imaging, surgical planning and technique. In
Introduction
dural attachment. Several involved nerve roots the case of intramedullary capillary heman-
were coagulated and divided. Further dissec- giomas, however, on MRI the lesion can be
Capillary hemangiomas are benign vascular
tion revealed an extremely friable exophytic interpreted as extramedullary,5,8,10 and the orig-
neoplasms typically encountered in the skin.
tumor arising from the region of the dorsal inal differential diagnosis often fails to include
They occur most frequently in childhood as
root entry zone of T3. Intra-operative frozen capillary hemangioma,2,8,11 as was the case with
cutaneous or subcutaneous lesions character-
section was consistent with a possible heman- our patient. As previously discussed by
ized histologically by nodules of capillary-sized
giopericytoma. Post-operative MRI showed no Roncaroli et al. and Nowak et al., the treating
vessels lined by flattened endothelium.1 As the
most common primary tumor of the spine, cap- evidence of residual tumor. surgeon must be cognizant of intramedullary
illary hemangiomas are frequently encoun- On histopathology, the tumor grossly con- capillary hemangiomas to avoid misdiagnosis
tered as interosseous lesions. The occurrence sisted of a partially circumscribed lesion with a and potential excessive treatment.1,2 Although
of these tumors in the central nervous system, brownish-tan appearance. H&E staining extremely rare, capillary hemangiomas of the
however, is exceedingly rare and they are even demonstrated a hypercellular, vascular neo- spinal cord have a benign clinical course. Glial
less frequently encountered as intramedullary plasm composed of cytologically bland spindled based tumors, such as ependymomas and
lesions.2 Despite the high prevalence of verte- cells with minimal cytoplasm. These cells were astrocytomas, account for over 90% of
bral body hemangiomas, extraosseous exten- arranged in vague lobules of short irregular intramedullary tumors.17 The distinctive gross
sion causing neurological impingement spindle cells and dilated vascular spaces. appearance of capillary hemangiomas intra-
remains uncommon. Immunohistochemical findings are explained operatively often eliminates the more common
In the present case, we report an intra- in Figure 2. Further evaluation demonstrated glial based lesions from the differential diag-
medullary capillary hemangioma of the tho- dilated, compressed vascular channels and nosis. The remaining possibilities include
racic spinal cord, an exceedingly rare presen- focal extramedullary hematopoiesis. In total, lesions ranging from: hemangiopericytoma,
tation with few previously reported cases exist- the findings were consistent with capillary hemangioblastoma, cavernous angioma, heman-
ing in the literature.2-6 hemangioma. gioendothelioma, arteriovenous malforma-
Post-operatively the patient had good functions, venous angiomas, and capillary telang-
tional recovery. At three months follow-up the iectasias. Fortunately, histopathological analy-
patient had only minor residual lower extrem- sis reliably distinguishes these lesions for
Case Report ity dysesthesia with return of baseline motor diagnosis.
function. The patient has remained stable 36 Although related most closely to the catego-
The patient is a 47-year old right-handed months post resection. ry of vascular malformations, capillary heman-
man with several months of non-specific mid- giomas that appear within the spinal cord
back pain, lower extremity hyperesthesia, and parenchyma may have their origins elsewhere.

Case Report
Table 1. Cases of intramedullary capillary hemangiomas previously reported in English.2,4-12umor or/ Patient Imaging Tumor
Size/ Symptoms/ Treatment Outcome Recurrence
Author/ Patient Imaging Tumor size/ Symptoms/ Treatment Outcome Recurrence
year age/sex location deficits
Roncaroli 42 not size not reported; 1.5-year h/o abdominal surgery recovered none
2000 M reported T11 pain, leg weakness reported
50 not size not reported; 1-year h/o LBP, proximal surgery little none
M reported T11 leg weakness bilaterally, + radiotherapy improvement reported
L-1 sensory level, loss of 2 years
patellar reflex post-op
53 not size not reported; 2 year h/o UMN, LMN surgery leg weakness none
M reported conus signs bilateral lower 1.5 years post-op reported
extremities
64 not size not reported; 2 year h/o bilateral leg pain, surgery recovered none
M reported T10 leg weakness reported
Ianelli 3 months, CT: dilated size not reported; Abnormal head surgery neurologically intact none
2005 M ventricles. T 4-7 circumference; wide, full, 1 year post-op; reported
MRI: T4-7 tense anterior fontanel no focal deficits
intramedullary with diastatic sutures.
enhancing lesion Mild irritability, lethargy
apparent. No other
neurological signs
Kelleher 57 MRI: T9 & T10 2.4x1.0x0.5 cm; 7-months h/o thoracic pain; dexamethasone spastic gait none
2005 M extramedullary T9-T10 2-week h/o bilateral lower and surgery 3 months post-op reported
enhancing lesion limb weakness,
decreased lower limb DTRs
Mawk 1 month, CT: discoid mass in size not apraxia of legs, surgery rapid recovery none
1987 not stated R buttock. reported; conus hemangiomatous reported
Myelography: malformation
vascular cord lesion involving the skin and
with complete soft tissue of the buttock
myelographic block
at L1-2
Andaluz 41 MRI: intradural, 2x1 cm, 3 month h/o surgery recovered none
2002 M extramedullary conus medullaris LBP radiating to thighs. reported
enhancing mass Decreased L flexor strength
(4+/5), bilateral patellar and
Achilles areflexia
Nowak 63 MRI: intradural maximum diameter 3 year h/o intermittent surgery residual paresis none
2000 F extramedullary 1.0 cm; T12-L1 Lasègue’s sign; hypesthesia of L tibialis anterior, reported
enhancing mass and activity related 14 months post-op
lumbosciatalgia L thigh
Abe 65 not size not 2 month h/o lower limb surgery little improvement none
2004 M reported reported; T5 weakness, paraparesis 7 years post-op reported
Roncaroli 74 MRI: enhancing lower thoracic 9-month h/o bilateral surgery no changes 1 year no new
2000 M nodules on cauda cord, conus, cauda leg weakness post-op hemangiomas
equina, lower
thoracic spinal cord,
conus medullaris
Shin 66 MRI: intradural 1.3x2 cm; T8-T9 8-month h/o surgery recovered no new
2000 F mass at T8-T9; LBP, weakness of the lower hemangiomas
intramedullary and limbs, paraparesis,
extramedullary components sensory abnormality
Hida 50 MRI: Mass not reported; tetraparesis, upper surgery recovered not
1993 M from C3-T1 C3-T1 extremities hyporeflexia, to baseline reported
lower extremities flexion
spasm, decreased pain/tactile
sensation below C3, bladder/
bowel dysfunction
Although several patients had imaging studies suggesting “extramedullary” lesions, they were ultimately found to have intramedullary capillary hemangiomas.
h/o = history of; UMN = upper motor neuron; LMN = lower motor neuron; LBP = lower back pain; DTR = deep tendon reflexes; R = right; L = left.

Case Report
A Trembath EJ. Metameric capillary heman-

A
gioma producing complete myelographic
block in an infant. Case report. J Neuro-
surg 1987;67:456-9.
7. Abe M, Tabuchi K, Tanaka S, et al.
Capillary hemangioma of the central nerv-
ous system. J Neurosurg 2004;101:73-81.
8. Andaluz N, Balko MG, Stanek J, et al.
Lobular capillary hemangioma of the
spinal cord: case report and review of the
literature. J Neurooncol 2002;56:261-4.
B 9. Hida K, Tada M, Iwasaki Y, Abe H.
Intramedullary disseminated capillary
hemangioma with localized spinal cord
swelling: case report. Neurosurgery
B 1993;33:1099-101.
10. Nowak DA, Gumprecht H, Stolzle A,
Lumenta CB. Intraneural growth of a cap-
illary haemangioma of the cauda equina.
Acta Neurochir (Wien) 2000;142:463-7;
discussion 7-8.
11. Roncaroli F, Scheithauer BW, Deen HG.
Multiple hemangiomas (hemangiomato-
Figure 2. (A) Photomicrograph of H&E sis) of the cauda equina and spinal cord.
stain shows a hypervascular tumor com- Case report. J Neurosurg 2000;92:229-32.
posed of thin and irregular capillary ves- 12. Shin JH, Lee HK, Jeon SR, Park SH. Spinal
sels and minimal cytoplasm. Magni-
fication X 200. (B) Immunohisto-chemi- intradural capillary hemangioma: MR find-
cal staining revealed the tumor cells to be ings. AJNR Am J Neuroradiol 2000;21:954-
strongly and diffusely immunoreactive for 6.
CD31, CD34, and CD99. Scattered S-100 13. Brotchi J, Dewitte O, Levivier M, et al. A
Figure 1. (A) Sagittal T1-weighted MR protein and BCL-2 positive cells were
image with Gadolinium revealing a homo- survey of 65 tumors within the spinal cord:
present. Epithelial membrane antigen
geneously hyperintense mass involving the (EMA) and inhibin stains were negative surgical results and the importance of pre-
upper thoracic spine. (B) Axial T1-weight- and MIB-1 labeling was brisk, but with operative magnetic resonance imaging.
ed MR image with Gadolinium demon- rare mitoses. Magnification X 200. Neurosurgery 1991;29:651-6.
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Holland IM. Gadolinium-enhanced mag-
netic resonance imaging of spinal
tumours. Br J Radiol 1989;62:1067-74.
Similar to intramedullary lipomas (which
References 15. Scotti G, Scialfa G, Colombo N, Landoni L.
account for 1% of intramedullary lesions), cap-
Magnetic resonance diagnosis of intra-
illary hemangiomas of the spinal cord may rep-
medullary tumors of the spinal cord.
resent a form of dysembryogenesis. Rather 1. Nowak DA, Widenka DC. Spinal intradural
Neuroradiology 1987;29:130-5.
than being a true neoplasm, these lesions capillary haemangioma: a review. Eur
16. Goy AM, Pinto RS, Raghavendra BN, et al.
more likely arise from inclusion of mesenchy- Spine J 2001;10:464-72.
Intramedullary spinal cord tumors: MR
mal tissue into the neural tube during primary 2. Roncaroli F, Scheithauer BW, Krauss WE.
imaging, with emphasis on associated
neurulation.18-20 The available literature clearly Capillary hemangioma of the spinal cord.
cysts. Radiology 1986;161:381-6.
demonstrates the benign nature of Report of four cases. J Neurosurg 2000;93:
17. Miller DJ, McCutcheon IE. Hemangio-
intramedullary capillary hemangiomas, and 148-51.
blastomas and other uncommon
gross total resection appears to be curative 3. Holtzman RN, Brisson PM, Pearl RE,
intramedullary tumors. J Neurooncol 2000;
with good outcomes and no reported recur- Gruber ML. Lobular capillary hemangioma
47:253-70.
rences (Table 1). Given the rarity of this of the cauda equina. Case report. J
18. Muraszko K, Youkilis A. Intramedullary
lesion, its benign course and straightforward Neurosurg 1999;90:239-41.
spinal tumors of disordered embryogene-
therapy, surgeon familiarity is important to 4. Iannelli A, Lupi G, Castagna M, et al.
sis. J Neurooncol 2000;47:271-81.
ensure patients receive appropriate diagnosis Intramedullary capillary hemangioma
19. Tihan T, Chi JH, McCormick PC, et al.
and treatment. associated with hydrocephalus in an
Pathologic and epidemiologic findings of
infant. J Neurosurg 2005;103:272-6.
intramedullary spinal cord tumors.
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Neurosurg Clin N Am 2006;17:7-11.
O'Sullivan MG. Intramedullary capillary
20. Warf BC, Scott RM, Barnes PD, Hendren
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Pediatr Neurosurg 1993;19:25-30.

A case report of surgical gone a surgical operation ten years before his
referral, and had been diagnosed with von Correspondence: Manabu Hoshi,
debulking for a huge mass of Recklinghausen disease. This condition had Department of Orthopedic Surgery, Osaka City
elephantiasis neuromatosa been present for many years, and the tumor University Graduate School of Medicine, Japan
had continued to grow gradually. Spontaneous E-mail: hoshi@med.osaka-cu.ac.jp
Manabu Hoshi, Makoto Ieguchi, Susumu subcutaneous hemorrhages frequently
occurred. At four years before his referral, a Received for publication: 24 June 2009.
Taguchi, Shinya Yamasaki
Accepted for publication: 1 July 2009.
plastic surgeon had attempted debulking sur-
Department of Orthopedic Surgery,
gery at his previous hospital, but the operation This work is licensed under a Creative Commons
Osaka City University Graduate School of
was not completed because of massive bleed- Attribution 3.0 License (by-nc 3.0)
Medicine, Japan
ing, even with a small skin incision. During
the previous year, he had only been able to ©Copyright M. Hoshi et al., 2009
walk short distances and remained in bed in Rare Tumors 2009; 1:e11
doi:10.4081/rt.2009.e11
hospital. There was no particular familial his-
Abstract tory of neurofibromatosis. On examination at
his first visit, he had an extensive mass of neu-
Achievement of a safe outcome for an exten- rofibroma over his trunk, and café-au-lait spots disease is an autosomal dominant trait and
sive mass with hypervascularity in the extrem- were scattered around the whole body. The represents a relatively common disorder char-
ities requires a surgical team skilled in muscu- right leg below the buttock was markedly acterized by neuroectodermal and mesoder-
loskeletal oncology. We report debulking sur- enlarged, and he required great effort to go to mal tissues. The typical characteristics
gery for a huge mass of elephantiasis neuro- the toilet and could not stand up by himself. include von Recklinghausen disease of the
matosa in the right leg of a 56-year old man Dilated superficial veins and multiple skin skin, café-au-lait spots and hamartoma of the
using the novel Ligasure® vessel sealing sys- ulcerations were present on the huge mass. In iris. Plexiform neurofibroma characteristical-
tem. view of the clinical appearance, plexiform neu- ly shows diffuse irregular infiltration into the
rofibroma was easily considered as a diagno- adjacent muscle and fat, and occasionally
sis. Magnetic resonance imaging (MRI) becomes huge and acquires a grotesque clini-
revealed an extensive mass that infiltrated the cal appearance, referred to as elephantiasis
Introduction fat, skeletal muscle and adjacent bone in the neuromatosa.1,2 Radiological modalities for
lower leg. A T2-weighted sequence of MRI elephantiasis neuromatosa play important
Patients with plexiform neurofibroma rarely demonstrated dilated twisting capillaries in roles in providing anatomical data if surgery is
suffer from hypertrophy of the skin of the leg. the high-intensity region of a superficial sub- planned. Among the radiological assessments,
Plexiform neurofibroma may become very cutaneous lesion, appearing as a myxomatous CT and MRI can provide many useful advan-
large and deforming, and be referred to as ele- lesion, compatible with the histology of neu- tages for surgical planning.6,7 Elephantiasis
phantiasis neuromatosa.1,2 Owing to the cos- rofibroma. Contrast-enhanced angiographic neuromatosa may involve hypervascularity
metically grotesque appearance and functional computed tomography (CT) demonstrated a and most reported cases have exhibited mas-
loss and pain in the affected limb, surgical rich vascular supply to the extensive mass, sive spontaneous bleeding.3,7 In our case, a
treatment is usually considered. However, arising from both sides of the major external previous surgical attempt to debulk this lesion
hypervascular structures are usually involved and internal iliac arteries. Extensive capillary had resulted in massive blood loss and was not
in this disease, and these can cause sponta- pooling was also seen. After these imaging completed. Pre-operative assessment of the
neous hemorrhage and severe bleeding, espe- studies, biopsies were attempted at several vascular supply to such a huge mass seemed
cially during surgery. Removal of such huge spots to exclude the possibility of sarcomatous to be inevitable, considering the importance
masses seems impossible without massive change. The needle biopsy specimens con- of controlling intra-operative bleeding. The
bleeding. As a result, conservative treatment firmed the histology of the neurofibroma. At use of MRI enabled us to non-invasively
without surgery is usually adopted in most that time, total tumor resection was judged to assess the relationships of the lesions with
cases, and, even if surgery is selected, disartic- be impossible, and debulking surgery was the major vessels, as well as the vascular sup-
ulation or amputation of the affected limb is planned piece by piece. During surgery, reduc- ply and angiographic features of the lesions.
sometimes recommended to the patients.3-5 In tion of the mass was carried out using a novel The contrast-enhanced angiographic CT con-
the present report, we describe surgical bipolar vessel sealing device, Ligasure®. The firmed the hypertrophic nature of the abnor-
debulking for a huge mass of elephantiasis resected surgical specimen was compatible mal tissues, as well as the large drainage ves-
neuromatosa in the right leg of a 56-year old with the histology of neurofibroma and no sels and multiple tortuous collateral branches.
man using the novel Ligasure® vessel sealing malignant changes were observed. Post-opera- These modalities may assist not only in the
system (Valleylab, Boulder, CO, USA), and dis- tively, most parts of the operation scar gradual- correct diagnosis but also in understanding of
cuss how to approach an extensive mass of ele- ly healed. Re-suturing was necessary at only a the anatomy of the vasculature of elephantia-
phantiasis neuromatosa. small part of the skin fold. At one year after the sis neuromatosa. Plexiform neurofibromato-
debulking surgery, he could move by himself sis is a poorly circumscribed unencapsulated
and was extremly satisfied with the outcome. tumor, with diffusely infiltrating cutaneous
lesions. Cosmetic and functional problems
Case Report with the affected limb are the major concerns
for the patient and doctor, regarding the indi-
A 56-year old man with a huge mass below Discussion cations for surgery. Plexiform neurofibroma is
both buttocks that had gradually increased in often hypervascular and can lead to severe
size over 35 years was referred to our hospital. Neurofibromatosis is estimated to occur at bleeding during surgery.8 Surgeons and
At 20 years of age, the mass in the buttock was rates of 1 in 2,000-3,000 births and shows an patients sometimes hesitate to undertake the
the size of a baseball. The patient had under- equal sex distribution. Von Recklinghausen challenging surgery required for huge plexi-

Case Report
Figure 1. (a,b) The patient References

suffers from a huge mass of
elephantiasis neuromatosa in
the right leg. (c) A T2-weight- 1 Moore BH. Some orthopedic relationships
ed MRI sequence reveals a of neurofibromatosis. J Bone Joint Surg
high-intensity myxomatous 1941;23A:109-40.
mass and hypervascularity.
(d) Contrast-enhanced angio- 2. Westcott RJ, Ackerman LV. Elephantiasis
graphic CT shows a rich vas- neuromatosa. Arch Dermatol Syphilol
cular supply arising from 1941;55:233-41.
both sides of the major exter- 3. Stevens KJ, Ludman CN, Sully L, et al.
nal and internal iliac arteries. Magnetic resonance imaging of elephanti-
(e) The histopathological
findings at biopsy confirm asis neuromatosa. Skeletal Radiol 1998;27:
neurofibroma. 696-701.
4. Martínez-García S, Vera-Casaño A, Eloy-
García Carrasco C, et al. Elephantiasis
neuromatosa in a patient with neurofibro-
Figure 2. (a) The Ligasure®
vessel sealing device. (b) matosis type 1. J Eur Acad Dermatol
Resected surgical specimens Venereol 2008;22:103-5.
of the elephantiasis neuro- 5. Birch PD, Davies AM. The value of comput-
matosa. (c) Gross findings of ed tomography in elephantiasis neuro-
the right leg after surgery. matosa. Br J Radiol 1988;61:76-8.
6. Hertzanu Y, Hirsch M, Peiser J, et al.
Computed tomography of elephantiasis
neuromatosa. J Comput Assist Tomogr
1989;13:156-8.
7. Hourani R, Rizk T, Kung S, et al. Ele-
phantiasis neuromatosa in neurofibro-
matosis type I. MRI findings with review of
the literature. J Neuroradiol 2006;33:62-6.
8. Kuo LA, Kuo RS. Plexiform neurofibro-
matosis: a difficult surgical problem. Aust
N Z J Surg 1990;60:732-5.
9. Slakey DP. Laparoscopic liver resection
using a bipolar vessel-sealing device:
LigaSure®. HPB (Oxford) 2008;10:253-5.
10. Lee WJ, Chen TC, Lai IR, et al. Randomized
clinical trial of Ligasure versus conven-
tional surgery for extended gastric cancer
form neurofibromas because of the high risk. sealed zone, which can be safely divided.12 resection. Br J Surg 2003;90:1493-6.
Sometimes, amputation or disarticulation, Sealing is accomplished with minimal char- 11. Jayne DG, Botterill I, Ambrose NS, et al.
both of which are less invasive and not as ring, and the delivery of thermal energy is lim- Randomized clinical trial of Ligasure ver-
technically demanding, may be recommended ited to the adjacent tissues of up to 0.5-2 mm. sus conventional diathermy for day-case
to the patients. For any surgical procedure, the No foreign items are left within the body, such haemorrhoidectomy. Br J Surg 2002;89:
surgeons must try to minimize the risk of as clipping wire and ligatures, which can act 428-32.
intra-operative complications and to ensure as possible sources of infection and/or allergy. 12. Cipolla C. Ligasure in total thyroidectomy.
that the surgery proceeds as smoothly and rap- The Ligasure® system seems to be safe Surg Today 2008;38:495-8.
idly as possible. The Ligasure® vessel sealing because control of these aspects is not
system has been used in several fields of dependent on the experience of the operators.
abdominal, urological and gynecological sur- This system is expected to reduce the risks of
geries, and many clinical studies have con- intra-operative and post-operative complica-
firmed its efficiency and safety.9-11 However, lit- tions compared with traditional procedures in
tle information is available concerning the the musculoskeletal system.
clinical applications of this technology for
musculoskeletal oncology of the extremities.
This system is a hemostatic method that
offers consistent permanent autologous seal- Conclusions
ing of vessels and tissue bundles up to 7 mm
in diameter. The system is composed of an The Ligasure® system is a novel device for
electrosurgical generator and a hand piece surgical debulking of extensive hypervascular
with a ratcheted scissor mechanism. When masses in the musculoskeletal field, such as
the sacrificed tissue is grasped and com- this case with elephantiasis neuromatosa,
pressed by the instrument, sealing is automat- because of the lack of technical demands and
ically completed. After removal of the instru- the associated reductions in blood loss and
ment, the seal is visible as a translucent operating time.

Rare Tumors 2009; volume 1:12
Value of centrifugated Introduction Correspondence: Hussain Gadelkarim Ahmed,

liquid-based cytology University of University of Khartoum, 102,
by Papanicolaou and Oral Exfoliative Cytology (OXC) is a cost Faculty of Medical Laboratory Sciences,
Khartoum, Sudan
May-Grünwald in oral effective and perhaps the best procedure for
E-mail: juhina2005@gmail.com
the initial evaluation and diagnosis of oral
epithelial cells lesions.1 It is simple, safe and reliable, espe-
Key words: liquid-based, cytology, oral cells.
cially in population-based screening programs,
Hussain Gadelkarim Ahmed,1
where repeated samples might be required.2 Acknowledgments: we would like to thank the
Ali Mahmmoud Edris,1 Early detection of a pre-malignant or cancer- members of the Department of Oral Surgery at
Eneel Ahmed Mohmed,2 ous oral lesion can improve the survival and the Dental Teaching Hospital for their coopera-
Mohammed Omer M. Hussein3 the morbidity of patients suffering from these tion and assistance. We are very grateful to the
1
Department of Histopathology and conditions.3 people at the Department of Histopathology and
Cytology, Faculty of Medical Laboratory Liquid-based cytology, since its inception in Cytology, Faculty of Medical Laboratory Sciences,
Sciences, Khartoum, Sudan; the 1990s, has shown significant advantages University of Khartoum for their technical help
2 over conventional exfoliative cytology. Studies and assistance.
Faculty of Dentistry, University of
Khartoum, Sudan; in cervical cytology have shown that the LBC Contribution: HGA, assessment of the results,
3
Sudanese Cancer Society, Khartoum, reduces the problems related to sampling and statistical analysis, preparation of the manu-
preparation of better smears and reduction in script; AME, smears staining and solution prepa-
Sudan
false-negative rates.4-6 Although conventional rations; EAM, specimens collection and revision
cytology is useful when diagnosing oral PML of the manuscript; MOMH, involved in manu-
(better sensitivity and predictive positive value script writing, references editing and data entry
if compared with the cervical smear test with for analysis.
Abstract similar specificity), LBC gives better results,
Conflict of interest: the authors have no connec-
as it is not only enhances both sensitivity and tion with any company and the work was support-
For many years, liquid-based cytology specificity, but also provides material for fur- ed by the University of Khartoum.
(LBC) has been developed for cervical cancer ther investigation (AgNORs, DNA, immunohis-
screening and not oral cancer, as it requires tochemistry, etc.).7,8 LBC using a filtration Received for publication: 29 June 2009.
automated devices. The aim of this study was process and computer assisted thin layer depo- Accepted for publication: 30 June 2009.
to compare the utility of centrifugated CLBC sition of cells has been developed as a replace-
preparation with that of direct preparation in ment for cytocentrifugation and/or smearing, Attribution 3.0 License (by-nc 3.0)
oral lesions, by Papanicolaou (Pap) and May owing to its improved cell recovery capabilities
Grünwald-Giemsa's (MGG) methods. A total and better cell preservation. In most published ©Copyright H.G. Ahmed et al., 2009
of 100 consecutive cases of oral lesions were series, LBC allows a good interobserver repro- Rare Tumors 2009; 1:e12
investigated. We compared the results ducibility.9 However, LBC requires expensive doi:10.4081/rt.2009.e12
obtained by the CLBC performed by cytocen- automated devices and materials, which might
trifugation with those obtained by direct not be affordable for many cytopathology labo-
smear applying Pap and MGG methods. The ratories in countries with poor resources.
comparison between CLBC and direct smears Thus, in this study we evaluated the efficiency formed supernatant was poured off and
was based on the thickening or adequacy of of the inexpensive CLBC method relying on replaced by acid alcohol for 30 min. Then the
the smear, distribution of cells and staining cytocentrifugation. supernatant was discarded leaving only a few
quality. All smears in CLBC and direct prepa- drops which were shook vigorously with acid
ration were found adequate. For thickness of alcohol. Thereafter, a drop of coating medium
the smear, 40% and 42% were excellent, 33% (glycerin/albumin) was added. Then two
and 30% were good, and 27% and 28% were Materials and Methods smears (wet fixed and air dried) were made
acceptable by LBC and direct preparation, from each specimen on moist, clean glass
respectively. For the distribution of cells and In this descriptive comparative study, a slides. The slide was tilted and with a Pasteur
scantiness of background elements, 92 total of 100 consecutive cases of oral lesions pipette, pellet was taken and replaced at the
(92%) smears of the CLBC have revealed were investigated. Cytological materials were upper end of the slides, left to drain, and then
clear, well distributed smears, compared to obtained by scraping the surface of the lesion. left to dry overnight.
70 (70%) of those in direct preparation. For The obtained materials were used for prepara- Direct preparation and CLBC smears were
the staining quality with the Pap method, tion of two direct smears and the remaining stained using staining methods (Pap and
39% and 69% were excellent staining quality, materials were immersed in washing solution MGG). For the smears which were stained
25% and 20% were good, and 36% and 11% for CLBC. One of the direct smears was imme- using the Papanicolaou method, ethyl alcohol
were acceptable for CLBC and direct prepara- diately fixed in 95% ethyl alcohol, while it was fixed smears were hydrated in descending
tion, respectively. In MGG method, 9% and wet (for subsequent Pap Stain), and the other concentrations of 95% alcohol through 70%
22% were excellent staining quality, 23% and was air dried then fixed in methanol (for sub- alcohol to distilled water for 2 min in each
36% were good and 68% and 43% were sequent MGG stain). The scraped materials stage. Then smears were treated with Harris'
acceptable for CLBC and direct preparation for CLBC were flushed out in suspending Haematoxylin for 5 min, to stain the nuclei,
respectively. CLBC performed by cytocen- solution (suspending medium composed of rinsed in distilled water and differentiated in
trifugation is inexpensive, and reduces inad- 20 mL of 95% ethanol + 6 mL of glacial acetic 0.5% aqueous hydrochloric acid for a few sec-
equate smears and background staining. acid +74 mL normal saline (Merck, onds to remove the excess stain. They were
Darmstadt, Germany); for ten min, and then then were immediately rinsed in distilled
spun in cytospin for 10 min at 3000 rpm. The water to stop the action of discoloration. Then

Article
the smears were blued in alkaline water for a of the smear, 40% and 42% were excellent Table 1. Showing the comparison between
few seconds and dehydrated in ascending thickness, 33% and 30 were good, and 27% and direct preparation and LBC using Pap and
alcoholic concentrations from 70% through 28% were acceptable by CLBC and direct MGG methods.mor or/ Patient Direct
two changes of 95% alcohol for 2 min for each preparation, respectively. For the distribution 39 (39%) 9 (9%)
change. The smears were next treated with of cells and scantiness of background ele-
eosin Azure 50 for 4 min. For cytoplasmic ments, 92 (92%) smears of the CLBC have Direct
staining they were treated with Papanicolaou revealed clear, well distributed smears, com- Excellent 39 (39%) 9 (9%)
Orange G6 for 2 min, rinsed in 95% alcohol pared to 70 (70%) of those in direct. However, Good 25 (25%) 23 (23%)
and then the smears were dehydrated in Fair 36 (36%) 68 (68%)
8 (8%) and 30 (30%) of the CLBC and direct
absolute alcohol. The smears were then smears, respectively, have shown a disorgan- CLBC
cleared in Xylene and mounted in DPX ized pattern. Excellent 69 (69%) 22 (22%)
(Distrene polystyrene Xylene) mount. All Good 20 (20%) 36 (36%)
When comparing the staining quality
reagents used were from Thermo Electron Fair 11 (11%) 43 (43%)
between the CLBC and direct smears, with the
Corporation, UK. Pap method 39% and 69% were excellent
For the smears which were stained using staining quality, 25% and 20% were good, and
the MGG method, the air dried methanol fixed 36% and 11% were acceptable for direct prepa-
smears were transferred to a staining jar con- ration and CLBC, respectively. With the MGG
taining May Giemsa stain freshly diluted with method, 9% and 22% were excellent staining tion. CLBC showed thin uniform distribution
an equal volume of buffered water for 15 min, quality, 23% and 36% were good, and 68% and of cells, in addition to clear background due to
then transferred without washing to a jar con- 43% were acceptable for direct preparation reduction in both cell overlapping and the
taining Giemsa stain freshly diluted with nine presence of artifacts. The cells also appeared
and CLBC, respectively. When comparing the
volume of buffered water for 10 min. The well preserved in their morphology and this
staining quality between Pap and MGG in
smears were then washed rapidly in three might be due to obtaining sufficient fixation
direct preparation, 39% and 9% were excellent
changes of water and examined. and the release of artifacts by washing. In
staining quality, 25% and 23% were good, and
regard to the thickening of the smear, both
36% and 68% were acceptable by Pap and
Assessment of cytological smears techniques achieved similar appearance, and
MGG, respectively. When comparing the stain-
we think that thickening of the smear depends
for staining quality ing quality between Pap and MGG in CLBC,
to some extent on the skilful preparation of
The smears were assessed and evaluated by 69% and 22% were excellent staining quality,
the smear. However, some studies reported
an experienced cytotechnologist. For compara- 20% and 36% were good, and 11% and 43%
that the scantiness of background staining
tive analysis of both techniques, parameters were acceptable by Pap and MGG in this order,
obtained in LBC enhances sensitivity and
such as thickness, cellular distribution, leuko- as shown in Table 1.
quality.19 Not surprisingly studies of the accu-
cytes and red blood cells were evaluated, adopt- racy of liquid-based monolayer cytology report
ing criteria reported elsewhere.10,11 Also, given sensitivity of 61% to 66% and specificity of
that a good staining method must show the 82-91%.20,21 Furthermore, comparable results
shapes and sizes of the cell, provide crisp Discussion between LBC and direct preparation have
delineation of nuclear chromatin, and demon- been reported.22
strate the cytoplasm, each slide was given a Oral cancer (OC) mortality is very high in When comparing the staining quality
mark out of ten and graded as follows: (i) 10-8 the Sudan, particularly among men due to the (using Pap and MGG stains) between the LBC
excellent; (ii) 7-5 good; (iii) 5 acceptable. All habit of Toombak use [Tobacco Specific and direct smears, CLBC preparation has
parameters were compared to standard param- Nitrose amine (TSN) rich tobacco].13 Toombak shown superior staining quality compared to
eters illustrated elsewhere,12 and the degrees dippers develop a clinically and histologically that of direct preparation. Cellular details in
were given. characteristic lesion at the site of dipping. The CLBC were more clearly seen than in direct
We compared the results obtained by the risk for cancer of the oral cavity among preparation, and such findings were previous-
centrifugated liquid-based cytology (CLBC) Toombak users is high (RR 7.3-73.0-fold)14 ly reported applying automated LBC.23
diagnoses performed by cytocentrifugation Therefore, there is an urgent need for imple- However, some studies have found no signifi-
with those obtained by direct smear applying mentation of simple and cost-effective meth- cant difference between LBC and convention-
Pap and MGG methods. The comparison ods to screen the population at risk. al cytology.11 However, many studies have
between CLBC and direct smear was based on Oral exfoliative cytology is a non-aggressive reported the reliability of Pap stain compared
the thickening or adequacy of the smear, dis- procedure that is well accepted by the patient, to other cytological stains by the means of dif-
tribution of cells and staining quality. and is, therefore, a suitable choice for the ferentiating and identifying cellular details.24,25
early diagnosis of oral cancer, including When comparing the staining quality
epithelial atypia and squamous cell carcino- between Pap and MGG in CLBC and in direct
ma.15 In recent years, LBC has acquired a wide preparation, Pap stain revealed better staining
Results range of acceptance in non-cervical cytology quality. A study by James et al.26 found an
specimens,16 including oral cytology.17 This agreement between Pap and MGG stain analy-
As the comparison between CLBC and method is convenient in interpreting the ses with regard to specimen adequacy.
direct smears was based on the thickening or results since it yields optimal cellularity for Both, the liquid-based preparation and con-
adequacy of the smear, distribution of cells, evaluation, and studies have shown similar or ventional smear are diagnostically reliable;
and scantiness of background elements and even better diagnostic accuracy as compared the liquid-based method showed an overall
staining quality, all smears in CLBC and direct to the direct smear method.10,18 In this study, 92 improvement on sample preservation, speci-
preparation were found adequate, though few (92%) of the smears of the CLBC have men adequacy, visualization of cell morpholo-
5 (5%) of direct preparation showed a reduced revealed clear, well distributed smears, com- gy and reproducibility.
amount of cells. With regard to the thickening pared to 70 (70%) of those in direct prepara-

Article
J Clin Pathol 2004;57: 1208-12. diagnostic agreement in oral lesions. Med

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improved preparations for cervical screen- Application of cytology and molecular biol-
JS. Effects of the endocervical specimen
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Retroperitoneal lipoma arising medications. Upon a pelvic examination, an

ill-defined and soft mass was detected in the Correspondence: Masafumi Koshiyama,
from the urinary bladder right pelvic cavity. She had fullness in the Department of Obstetrics and Gynecology,
right adnexal region. Transvaginal ultra- Otsu Red-Cross Hospital, 1-1-35, Nagara, Otsu,
Shingo Ukita,1 Masafumi Koshiyama,1 sound sonography showed an echogenic Shiga, 520-0046, Japan
Megumi Ohnaka,1 Naoyuki Miyagawa,1 mass without any solid portions in the right E-mail: koshiyamam@nifty.com
Yukio Yamanishi,1 Fumitomo Nishimura,1 adnexal region. These observations suggest-
Key words: lipoma, retroperitoneum, ovarian
Michikazu Nagura,1 Tomoko Kim,1 ed a mature cystic tumor of the ovary con-
mature cystic teratoma, urinary bladder, magnet-
Masaya Hirose,1 Tomoyuki Shirase,2 taining fat. An MRI revealed a mass measur- ic resonance imaging.
Hisato Kobayashi,3 Hiroshi Ozasa1 ing 15 cm in the right retropelvic cavity,
1
Department of Obstetrics and which showed high intensities on T1 and T2- Contributions: SU and MK, substantial contribu-
weighted images that were the same intensi- tions to conception and design, acquisition of
Gynecology, Otsu Red-Cross, Otsu,
ty as fatty tissues (Figure 1). Another MRI data, or analysis and interpretation of data; all
Shiga, Japan; 2Department of Pathology, authors are responsible for drafting the article or
showed that the tumor was in the retropelvic
Otsu Red-Cross, Otsu, Shiga, Japan; revising it critically for important intellectual
3
cavity, because the right round ligament and
Department of Radiology, Otsu broad uterine ligament were detected over content; MK, final approval of the version to be
Red-Cross, Otsu, Shiga, Japan published; all members are medical doctors of
this tumor and the right iliac artery and vein
Otsu Red-Cross Hospital.
touched the tumor. The patient underwent
surgery with a diagnosis of a retroperitoneal Conflict of interest: the authors reported no poten-
lipoma. Macroscopically, an encapsulated, tial conflict of interests.
Abstract yellowish and soft mass lay between the uri-
nary bladder and the right iliac vessels in Received for publication: 10 July 2009.
Retroperitoneal benign lipomas are the right retropelvic space (Figure 2). The Accepted for publication: 10 July 2009.
extremely rare and represent about 2.9% of tumor penetrated the right lateral umbilical This work is licensed under a Creative Commons
all primary retroperitoneal tumors. About ligament, and had feeding vessels from that Attribution 3.0 License (by-nc 3.0)
80% of the tumors in the retroperitoneal cav- ligament. The tumor showed strong adher-
ities are malignant neoplasms. We experience to the urinary bladder but did not infil- ©Copyright S. Ukita et al., 2009
enced a case of a retroperitoneal lipoma sim- trate the surrounding organs. The tumor Rare Tumors 2009; 1:e13
ulating an ovarian mature cystic teratoma. A doi:10.4081/rt.2009.e13
was thought to be a large lipoma arising
diagnosis was correctly made by magnetic from the urinary bladder, therefore, a total
resonance imaging (MRI) prior to surgery, tumorectomy was performed.
and a total tumorectomy was performed. The Histological sections revealed a tumor
retroperitoneal lipoma was recognized to consisting of typical adipose cells without
have arisen from the urinary bladder. atypia (Figure 3). Neither lipoblasts nor
Histological sections revealed a tumor con- malignant cells were observed in the sec-
a
sisting of typical adipose cells without atypia. tions, and the histo-pathological diagnosis
These types of lipomas should be carefully was that of a lipoma. The patient had no
followed-up because they often recur and post-operative complications, experienced
undergo malignant transformations. less gluteal pain, and was discharged on
post-operative day 8. She had an uneventful
recovery during the post-operative follow-up
period.
Introduction
Primary retroperitoneal tumors represent b
about 0.2% of all neoplasms. Out of these Discussion
about 80% of the tumors are malignant neo-
plasms.1 Retroperitoneal benign lipomas are Most lipomas are superficial, and
extremely rare, and represent about 2.9% of retroperitoneal lipomas are very rare. When
all primary retroperitoneal tumors.2 Herein lipomas occur in retroperitoneal locations,
we present a case of a large retroperitoneal they are mostly renal in origin.3 A few report-
lipoma prior to resection. The tumor was ed cases have a pancreatic origin,4 and so on.
identified as having arisen from the urinary Pelvic lipomas are exceedingly rare, but can
bladder at the time of surgery. arise from the iliac vessels and paravaginal
tissues.5 One reported case with pelvic ori- Figure 1. Retropelvic mass showed very
gins demonstrated a urinary bladder outlet high intensities on T1-(a) and T2-(b)
obstruction secondary to a pelvic lipoma.6 To weighted images that were the same inten-
Case Report sity as fatty tissues. This mass was diag-
our knowledge, the present case arising from nosed as a retropelvic lipoma by observing
the urinary bladder is the first such report in the position of the uterine broad ligament
A 61-year old Japanese woman, gravida 3, the world. The lipoma presented herein was (arrow), the round ligament (arrow), the
complained of gluteal pain. She did not have characterized by the diffuse overgrowth of uterine artery (arrow) and the lateral
umbilical ligament (arrow).
a medical history of surgery or concomitant fatty tissues in the perivesical spaces, but

Case Report
the transvaginal ultrasound sonograph showed

an echogenic mass without any solid portion References
in the right adnexal region, which suggested a
mature cystic teratoma of the ovary containing 1. Armstrong JR, Cohen I. Primary malignant
fat. On the MRIs, the lipomatous components retroperitoneal tumors. Am J Surg 1965;
showed very high signal intensities on the T1- 110:937-43.
weighted and T2-weighted images. 2. Pai MR, Naik R, Raughuveer CV. Primary
Furthermore, the diagnosis of retropelvic retroperitoneal tumors: a 25 year study.
tumors is aided by observing the position of Indian J Med Sci 1995;49:139-41.
the uterine broad ligament, the round liga- 3. Cavazza A, Giunta A, Pedrazzoli C, et al.
ment, the uterine artery and the lateral umbil- Extrarenal retroperitoneal angiomyolipo-
ical ligament. Thus, we were able to diagnose ma: description of a case and review of the
Figure 2. Retropelvic lipoma after its this tumor as a retropelvic lipoma prior to sur- literature. Pathologica 2001;91:44-9.
removal. gery. Therefore, MRIs are effective for diagnos- 4. Moriki T, Ohtsuki Y, Takahashi T, et al.
ing retroperitoneal lipomas. Lipoma-like tumor mass probably arising
Benign subcutaneous lipomas and malig- in the retroperitoneal heterotopic pan-
nant liposarcomas are well-documented and creas: A previously undescribed lesion.
are characterized by chromosome 12 aberra- Pathol Int 2004;54:527-31.
tions. Recently, some retroperitoneal lipomas 5. Hull WB, Blumenfeld ML, Jacques D. Large
were shown to have no detectable rearrange- paravaginal pelvic lipoma: A case report. J
ments of chromosome 12 or its amplification.7 Reprod Med 1999;44:636-8.
On the other hand, retroperitoneal lipomas 6. Berens BM, Azavan A. Bladder outlet
have shown rearrangements in chromosomes obstruction due to pelvic lipoma: comput-
1 and 8. Therefore, there are different chromo- erized tomography, magnetic resonance
somal rearrangements between retroperi- imaging and radiographic evaluation. J
toneal lipomas and malignant liposarcomas. Urol 1991;145:138-9.
Figure 3. Histological examination reveals However, there are no significant optical dif-
an adipose tissue neoplasm without cyto- 7. Foa C, Mainguene C, Dupre F, et al.
logic atypia. ferences in CTs or MRIs observed prior to sur- Rearrangement involving chromosomes 1
gery between lipomas and well-differentiated and 8 in a retroperitoneal lipoma. Cancer
liposarcomas.8 Thus, one should consider the Genet Cytogen 2002;133:156-9.
possibility of a liposarcoma when trying to 8. Kimura N, Morita T, Murata A. et al. A case
lacked any urinary obstructions. The patient resect a retroperitoneal lipoma. Furthermore, of giant retroperitoneal lipoma. Nihon
experienced only slight gluteal pain. because these types of lipomas are known to Rinsyo Gekagakkaishi 2002;63:2030-4.
MRIs present greater diagnostic precision recur and undergo malignant transformation,
than ultrasonographies (USGs) and computer- subjects with resected retroperitoneal lipomas
ized tomographies (CTs). In the present case, must have careful follow-up.

Primary breast lymphomas into account.1 Clinically and pathologically, pri-

mary lymphomas of the breast must be distin- Correspondence: Olivier Julen, Department of
1 1 guished from both benign lymphoid infiltrates Gynecology and Obstetrics, Geneva University
Olivier Julen, Ilaria Dellacasa,
and non-lymphoid neoplasms of the breast. Hospital, 1211 Geneva 4, Switzerland
Marie-Françoise Pelte,2 Bettina Borish,2 E-mail: olivier.julen@hcuge.ch
Since the breast normally contains some lym-
Christine Bouchardy,3 Federica Capanna,1 Anne-Thérèse Vlastos, Department of Gynecology
phoid tissue and functions during lactation as
Georges Vlastos,1 Jean-Bernard part of the mucosal immune system, lym- and Obstetrics, Geneva University Hospital, 1211
Dubuisson,1 Geneva 4, Switzerland. E-mail: anne-therese.vlas-
phomas in this site may be related to lym-
Anne-Thérèse Vlastos1 tos@hcuge.ch
phomas of mucosa-associated lymphoid tissue,
1
Department of Gynecology and so-called MALT lymphoma. Primary breast lym- Key words: lymphoma, breast, cancer, bcl6, bcl2.
Obstetrics, Geneva University Hospital; phoma (PBL) can still be misdiagnosed as car-
2
Department of Pathology and cinoma, a particular point of interest for Acknowledgments: we thank the technicians of
Immunology, Geneva University Hospital, pathologists and clinicians. In addition, there the Department of Clinical Pathology for their
Genève, Switzerland; is a lack of consensus about its treatment and work with immunostaining. We also thank the
3 prognostic factors. The purpose of this study is registrars of the Geneva Cancer Registry for col-
Geneva Cancer Registry, Institute for lecting additional data on this subset of patients.
to evaluate clinical presentation and patholog-
Social and Preventive Medicine,
ical features, diagnostic difficulties and poten-
University of Geneva, Switzerland tial prognostic markers of this rare tumor. Received for publication: 30 June 2009.

Abstract Materials and Methods
©Copyright O. Julen et al., 2009
The diagnosis, prognostic factors, and opti- Rare Tumors 2009; 1:e14
The data were derived from the Geneva
mal management of primary breast lymphomas doi:10.4081/rt.2009.e14
Cancer Registry, which includes information
(PBL) is difficult. Seven patients recorded at regarding all cases of malignant neoplasms
the Geneva Cancer Registry between 1973-1998 occurring in the population of the region
were reviewed. Five patient had diffuse large B- (approximately 420,000 inhabitants). The reg- clinical information was obtained from a retro-
cell lymphoma, one a follicular lymphoma and istry collects information from various sources spective review of all the patient charts.
one a MALT-lymphoma. All patients had clinical and is considered accurate, as attested by its Pathological diagnosis of primary breast
and radiological findings consistent with breast very low percentage (<2%) of cases recorded lymphoma was based on the following strict
cancer and underwent mastectomy, which is not from death certificates only.3 Individual clinical criteria as described by Wieseman and Liao in
indicated in PBL. Diagnosis should be estab- files from all university public hospitals are sys- 1972: 1) an adequate pathological specimen;
lished prior to operative interventions, as fine tematically consulted and inquiry forms are 2) a close association of mammary tissue and
needle aspiration missed the diagnosis for one addressed regularly to physicians for patients lymphomatous infiltrate; 3) no evidence of dis-
patient and intra-operative frozen sections for 3 treated in the private sector. Trained registrars seminated lymphoma at the time of diagnosis;
patients in our study. Five-year and 10-year systematically abstract data from medical and and 4) the presence of ipsilateral axillary
overall survivals were 57% and 15%, respective- laboratory records. Physicians regularly receive nodes was acceptable if they occurred con-
ly. Of the 3 patients who died from PBL, 2 had questionnaires to secure missing clinical and comitantly with the primary lesion. Staging
tumors that were Bcl-2 positive but Bcl-6 nega- therapeutic data. Death certificates are consult- was based on the WHO classification 2001.6 In
tive. All 3 surviving patients have positive Bcl-2 ed systematically. Recorded data include socio- all patients, the pathological diagnosis was
and Bcl-6 immunostaining, which could be demographic information, method of discovery, established on excisional biopsy or mastecto-
important prognostic factors if confirmed by a type of confirmation, tumor characteristics my specimen. Original hematoxylin-eosin-
larger study. (coded according to the International stained sections and formalin-fixed, paraffin-
Classification of Diseases for Oncology),4 stage embedded tissue were available in all cases.
of disease at diagnosis, treatment during the Histological review of the microscopic slides
first six months after diagnosis, survival status, was performed by some of the authors
Introduction and cause of death. (MFP/ATV). Extensive immunohistochemical
The registry regularly assesses survival rate studies were performed.
The breast is one of the least common pri- index. In brief, it refers to the date of confirma-
mary extranodal sites for malignant lym- tion of diagnosis or the date of hospitalization if
phomas. A variety of pathological subtypes it preceded the diagnosis and was related to the
have been reported. The frequency with which disease. In addition to passive follow-up (routine Histology and immunohisto-
the different subtypes of primary lymphoma of examination of death certificates and hospital
the breast occur is difficult to determine, records), an active follow-up is performed rou- chemistry
because both terminology and classification tinely each year using the files of the Cantonal
vary among the relatively small case series that Population Office in charge of the registration of Conventional histology included hematox-
have been reported. There is general agree- the resident population. Finally, cause of death is ilin eosin, Giemsa, and silver stain of all avail-
ment, however, that these lymphomas are usu- established from clinical records and coded able tissue blocks. Immunostaining was per-
ally of Non-Hodgkin’s lymphoma (NHL) histol- according to the World Health Organization’s formed using the listed antibodies with a
ogy.1 They account for 0.04-0.5% of all breast classification.5 streptavidine-biotin peroxidase system.
neoplasms and less than 1% of all NHL.2 In this study we included all cases of PBL Antigen retrieval, if necessary, was carried out
NHL is a potentially systemic disease; there- diagnosed between January 1973 and December either by microwaving or pressure cooking in
fore, appropriate management must take this 1998 among the resident population. Additional ethylenediamine tetraacetic buffer (pH 2.5).

Article
Table 1. Clinical staging under presumption of carcinoma.

N. Age Working Clinical Side Location Size TNM Primary Secondary CR Time to D F S Cause of
yr classification presentation cm staging treatment treatment death years of death
1 86 MALT Periartritis R All breast 6.5 T4d N2 Mx Patey Rx refused Yes 5 years 5 PBL
2 78 Follicular Breast mass R UO+I NA T3 N1 Mx Patey Ch refused No 2 months progression PBL
3 74 DLBCL Breast mass L UO 5 T3 N0 Mx Mastectomy No No 15 days progression PBL
4 62 DLBCL Breast mass L UO 3 T2 N0 Mx Patey No Yes 5 years 5 Cardiac
5 71 DLBCL Breast mass R UO+I 5.4 T3 N1 Mx Patey Ch: CHOP Yes / *7,5 Alive
6 39 DLBCL Breast mass R NA 2 T2 N0 Mx LAND Rx Yes / *16,5 Alive
7 44 DLBCL Breast mass L LO 5 T3 N0 Mx Patey Ch: CHOP Yes / *4,5 Alive
UO: upper outer quadrant; UI: upper inter quadrant; LO: lower outer quadrant; R: right; L: left; TNM: classification by Tumor Node Metastasis; Age*: years; MALT: MALT lymphoma; Follicular: follicular lymphoma;
DLBCL: diffuse large B-cell lymphoma; LAND: lumpectomy and axillary dissection; Pathey: mastectomy and axillary dissection; DSF: disease free survival; CR: complete response.
Table 2. Pathological characteristics including immunochemical studies. Patient Direct

N. Age Working Keratine LCA CD3 CD20 CD79 MiB1 Bcl-2 Bcl-6 MiB1
yr classification
1 86 MALT + + - + + 60% + - 60%
2 78 Follicular - + - + + 30% - + 30%
3 74 DLBCL + + - + + 50% + - 50%
4 62 DLBCL + + - + + / - - /
5 71 DLBCL - + - + + 80% + + 80%
6 39 DLBCL - + + + + 80% + + 80%
7 44 DLBCL + + - + + 90% + - 90%
UO: upper outer quadrant; UI: upper inter quadrant; LO: lower outer quadrant; R: right; L: left; TNM: classification by Tumor Node Metastasis; Age*: years; MALT: MALT lymphoma; Follicular: follicular lymphoma;
DLBCL: diffuse large B-cell lymphoma.
The work-up included CD3, CD4, CD5, CD8, involvement and 4 (57%) right-breast involve- patients. The average tumor size at diagnosis
CD20, CD21, CD23, CD30, CD45, CD68, CD79a, ment. None had bilateral involvement. Clinical varied from 2 cm to 6.3 cm in the greatest
MIB1, pan-cytokeratine, Bcl-2 and Bcl-6. If not lesions were located predominantly in the diameter (mean, 4.5 cm) (Table 1). The sec-
otherwise mentioned, these antibodies were upper outer quadrant (UOQ) in 2 (29%) tion presented with homogeneous fish-flesh
from Dako, Copenhagen. The SPSS software patients, in the upper outer and inner quad- surface with occasional hemorrhagic or necro-
(SPSS 10 version Inc., Chicago, IL.) was used rant in 2 (29%), in the lower outer quadrant sis foci. For small tumors, margins were regu-
for statistical analysis. Descriptive statistics (LOQ) in one (14%) and involved the whole lar and pushing, for larger, irregular and stel-
were performed to assess the frequency distri- breast in one patient (14%). Four patients late. Fibrosis or sclerosis surrounding the
bution. We calculated disease-specific and dis- (57%) had no clinical axillary involvement. All tumor mass may suggest a medullary carcino-
ease-free interval probabilities using the patients sought consultation for breast related ma of the breast or a benign process. Under
Kaplan-Meier method.7 symptoms and presented with a palpable mass. light microscopy, the tumor masses were poor-
Only one patient reported pain, described as ly circumscribed, infiltrating the mammary
located in the homolateral shoulder; however, lobules, and surrounded mammary ducts.
the whole breast was involved in this case. No Diffuse large B-cell lymphoma, or DLBCL, was
Results malignant lymphoma was suspected on clinical the most common entity, (5 cases; 71%). Large
examination, nor in complementary investiga- blastic B cells replaced the normal architecture
tions. In particular, mammography examina- of the underlying breast in a diffuse pattern
Since its creation in 1970, the registry has
tion before surgery was suggestive of breast and broad or fine bands of sclerosis were
recorded over 7,800 women with breast malig-
carcinoma in all cases (100%). observed. The morphological variant was cen-
nancies. Only 9 patients were initially diag-
First diagnosis was breast carcinoma in 6 troblastic lymphoma for all of the masses. The
nosed and recorded as primary breast lym-
out of 7 cases (86%) and inflammatory breast most common DLBCL were composed of medi-
phoma, representing less than 0.1% of all malig-
carcinoma in one case (14%). Fine needle um-sized to large lymphoid cells with general-
nant breast tumors. However, there were only 7
aspiration (FNA) was performed in 2 (29%) ly basophilic cytoplasm. Nuclei were character-
true PBL after histological review. In 2 women,
cases, both suggestive of breast carcinoma. ized by oval to round vesicles, fine chromatin
clinical investigations performed at diagnosis
Primary breast lymphoma was diagnosed after and 2-4 membrane bound nucleoli. In some
were insufficient to definitively conclude that
surgical excision in all cases, with frozen sec- cases, the cells were multilobated. Centro-
the lymphoma occurred primarily in the breast.
tion diagnosis for 3 cases. Frozen section diag- blastic variant of diffuse large B-cell lymphoma
noses revealed lymphoma in 2 cases and a was monomorphic in one case and polymor-
Patients’ characteristics malignant non-differentiated tumor. phic in the remaining cases. One case was
Patients’ and tumor characteristics are diagnosed with grade III follicular lymphoma
described in Table 1. The median age at diag- Pathology (Figure 1). The remaining case was an extra-
nosis was 65 years (range 39-86); most were in nodal marginal zone B-cell lymphoma MALT
the seventh decade of life (4 patients, 57%). Table 2 summarizes pathological character- lymphoma. The characteristic marginal zone B
Three patients (43%) had left-breast istics among primary breast lymphoma cells had small to medium-sized, slightly irreg-

Article
ular nuclei with moderately dispersed chro-

matin and inconspicuous nucleoli, resembling
those of centrocytes. They had a relatively
abundant, pale cytoplasm. The glandular-
epithelium was invaded and destroyed by
aggregates of lymphoma cells resulting in so-
called lymphoepithelial lesions (Figure 2).
Four DLBCL showed additional histological
features of MALT (lymphoepithelial lesions)
(Figure 3). Our last 2 cases showed no lym-
phoepithelial lesions but clearly showed ductal
invasion by lymphoma cells (Figure 4).
Immunophenotype
Immunohistochemical studies are reported in
Table 2. As expected, DLBCL expressed the pan-
B markers CD20 and CD79. Bcl-2 was positive in
4 cases (80%) and nuclear expression of Bcl-6 in
2 cases (40%). MiB1 was highly expressed indi-
cating a high proliferative rate (up to 90%) in all
cases. The follicular lymphoma expressed the
pan-B markers CD20 and CD79 as well as Bcl-6.
Bcl-2 protein was expressed in the majority of
the reported cases, ranging from nearly 100% in
grade I to 75% in grade III however, cutaneous
follicular lymphoma is frequently Bcl-2 negative.
MiB1 was expressed in 30% of the cells. The
MALT lymphoma expressed CD20 and CD79 as
well as Bcl-2.
Treatment Figure 1. Follicular lymphoma. (a) Follicular aspect: HE (x100); (b) large transformed
cells with one to three peripheral nucleoli: Giemsa (x200); (c) B cells with follicular
Various treatment strategies were used arrangement: CD79 (x50); (d) B cells with follicular arrangement: CD79 (x100); (e) reac-
according to available data. Treatments are tive T cells surrounding the B cells with follicular arrangement: CD3(x50); (f ) Bcl-6
reported in Table 1. Surgery was initially per- staining (x200).
formed because of the initial clinical impres-
sion of mammary carcinoma. Surgeries con- condition, died two weeks after surgery. One (median age: 55-60 years).1,8-10 In our series we
sisted of mastectomies associated with an axil- relapsed after five years (skin) and subse- found an older median age: 65 years (39-86
lary lymph node dissection for 6 patients and a quently died of lymphoma. At time of the last years), as already described, whereas some
breast conserving surgery for one patient with follow-up, 3 were alive. One died of other caus- authors find a younger median age.11 The right
a small size (2 cm) lesion. The Levels I and II es (cardiovascular disease). Five and 10-year breast was reported to be most frequently
axillary lymphatics were included within the overall survival rates were 57% and 15%, involved.1,8-11 Only a few series report the oppo-
breast or chest-wall fields; 3 of the 6 performed respectively. Of the 3 patients who died from site and another had no predominant site.12 Five
were positive (50%). their PBL, 2 had positive Bcl-2 immunostain- to 25%2,13 of reported cases were simultaneously
The treatment proposed after surgery was ing (66%) but negative Bcl-6 immunostaining bilateral at presentation,8,10,12 nevertheless no
chemotherapy in 3 cases (43%), of whom one (66%). On the other hand, of the 3 patients still such case is reported in our series. We were par-
(14%) refused and radiotherapy in 2 cases alive, all had positive Bcl-2 immunostaining ticularly interested in the method by which
(29%), which was also refused by one patient and 2 positive Bcl-6 immunostaining (66%). these tumors were detected and hypothesized
(14%). The last 2 cases (29%) were treated Treatment modalities and their corresponding that increased knowledge and the current wide-
with surgery alone. One patient had a mastec- effect on mortality are presented in Table 1. spread use of mammography as a screening
tomy and axillary dissection. The second method for breast carcinoma may increase the
patient had a simple mastectomy and did not detection of breast lymphoma. Hemato-
receive adjuvant therapy because of her poor poietic neoplasms involving the breast, although
condition. None of the cases received com-
Discussion less common than breast carcinoma, are often
bined modality approaches. In the present study we evaluated all patients clinically indistinguishable from other breast
who presented with primary lymphomatous tumors. Microscopically, these tumors can
Outcome involvement of the breast over a 26-year period mimic primary carcinoma of the breast, espe-
Median follow-up was 5.8 years (range: 0.15- at our institution. Only the patients who satis- cially in limited material such as fine needle
16). Of the 7 patients, 5 achieved complete fied the strict criteria of PLB according to aspirations (FNA). In 2 patients with FNA in our
response after therapy (Table 1). Two patients Wiseman and Liao were analyzed for this study series, cytology was interpretated as carcinoma.
never achieved complete response and died of to avoid the potential inclusion of patients with In the 3 patients with frozen section diagnosis,
disease progression. In one of these patients secondary breast involvement of NHL.2 The most only one (the follicular lymphoma case) was
progression was observed to the brain and frequent clinical scenario is that of a unilateral diagnosed correctly. FNA misdiagnosis has been
skin. The other, because of her poor medical breast mass presenting in a middle-aged woman reported by several authors.12

Article
Published reports on the treatment outcome

for PBL range from equivalent to worse prog-
nosis for PBL compared to other non-Hodgkin’s
lymphomas (NHL).1,2 Confounding the matter
are the different definitions of PLB used by dif-
ferent authors. Some consider the lymphoma
to be PBL if the patient presents with com-
plaints relating to the breast or if the main
tumor mass is in the breast.1,12 Others use
more strict definitions of PBL.2,16 Different
pathological types of breast lymphoma have
also been reported by different investigators at
least partially because of different histological
criteria used.9,12
Cohen et al. studied both primary and sec-
ondary breast lymphomas with a broad panel of
T- and B-cell markers using paraffin-embedded
tissue and the avidin-biotin immunoperoxi-
dase method. Cases of PBL were further tested
to determine light and heavy chain type.
Thirty-five cases were analyzed, including 16
primary lymphomas. Diffuse large cell lym-
phoma was present in 10 of 16 primary and 14
of 18 secondary cases. Lymphoepithelial
lesions in ducts and lobules and frequent vas-
cular involvement were found in both primary
and secondary cases. Immunohistochemistry
studies on 13 tumors revealed all of the pri-
mary tumors to be B-cell in origin, except for
one case of primary T-cell lymphoma; to the
Figure 2. Destruction of the glandular tis-
sue epithelium by aggregates of lym- authors' knowledge, this represents the first Figure 4. Primary breast lymphoma with-
phoma cells. (a) Mammary gland infil- description of this entity. Fifteen of 17 second- out lymphoepithelial lesion. (a)
trated by lymphoma cells: HE (x400); (b) ary tumors exhibited B-cell markers and one of Proliferation index: MiB1 (x200) (80%
mammary gland infiltrated by B cells: 17 exhibited T-cell markers; in only one case positive); (b) HE (x100); (c) mammary
CD20 (x400); mammary gland: Keratin could lineage not be determined.17 Among pri- gland: keratin (x200).
(x400).
However, breast carcinoma is not the only

pitfall. Diabetic mastopathy (DM) may be over-
interpreted as lymphoma. DM, which has been
described in both diabetic patients and non-
diabetic patients, generally demonstrates
fibrocystic change with dense stromal fibrosis
and an extensive perivascular infiltrate of
small B-lymphocytes. However, there is no cur-
rent evidence that DM is a precursor lesion to
PBL.8,13 Traditionally a surgical approach to the
treatment of patients’ PBL has been adopted,2
even if mastectomy could be avoided in most
patients,15 and treatment confined to chemo-
therapy and radiation therapy appropriate for
the histological type. In our series, all patients
underwent a surgical treatment. It is important
to underline that all mastectomies in our
series were performed due to the initial clini-
cal and/or pathological diagnosis impression
(frozen section or FNA) of adenocarcinoma.
Similarly, although there have been reports of
radiation therapy alone for patients with PBL,16
patients with intermediate-grade and high-
grade lymphomas of the breast are best treated
Figure 3. Lymphoepithelial lesions. (a) Lymphoepithelial lesion: HE (x50); (b) lym-
with chemotherapy or with combined chemo- phoepithelial lesion: HE (x100);(c) mammary gland: keratin (x200); (d) mammary gland
therapy and radiation therapy.10 infiltrated by B cells: CD20 (x200).

Article
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most frequent heavy chain type; IgA reactivity diffuse large B-cell lymphoma.21 References
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Article
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17. Aguilera NS, Tavassoli AF, Wei-Sing C, typic studies in the diagnosis and classifi- et al. Expression and prognostic signifi-
Abbondanzo SL. T-cell lymphoma present- cation of hematopoietic and lymphoid neo- cance of survivin in de novo acute myeloid
ing in the breast: a histologic, immuno- plasms. An update. Am J Clin Pathol 1999; leukaemia. Prognostic significance of sur-
phenotypic and molecular genetic study of 111:13-39. vivin expression in diffuse large B-cell
four cases. Modern Pathol 2000;13:599- 21. Barrans SL, O'connor SJ, Evans PA, et al. lymphomas. Br J Haematol 2000;111:196-
605. Rearrangement of the BCL6 locus at 3q27 203.
18. Cohen PL, Brooks JJ. Lymphomas of the is an independent poor prognostic factor 24. Ichikawa A, Kinoshita T, Watanabe T, et al.
breast. A clinicopathologic and immuno- in nodal diffuse large B-cell lymphoma. Br Mutations of the p53 gene as a prognostic
histochemical study of primary and sec- J Haematol 2002;117:322-32. factor in aggressive B-cell lymphoma.
ondary cases. Cancer 1991;67:1359-69. 22. Hill ME, Maclennan KA, Cunningham DC, Failure of parturition in mice lacking the
19. Farinha P, Andre S, Cabecadas J, Soares J. et al. Prognostic significance of BCL-2 prostaglandin F receptor. N Engl J Med
High frequency of MALT lymphoma in a expression and bcl-2 major breakpoint 1997;337:529-34.
series of 14 cases of primary breast lym- region rearrangement in diffuse large cell 25. Brogi E, Harris NL. Lymphomas of the
phoma. Appl Immunohistochem Mol non-Hodgkin's lymphoma: a British breast: pathology and clinical behavior.
Morphol 2002;10:115-20. National Lymphoma Investigation Study. Semin Oncol 1999;26:357-64.

Neuroblastoma occurring in region are reported to be the primary sites in

these individuals.3 There are no documented Correspondence: Martin Nzegwu,
a 38-year old Nigerian man: reports of this lesion in adults from Nigeria or Head Department of Morbid Anatomy, University
a rare finding anywhere else in Africa. It has been suggested of Nigeria Medical School, Enugu, Nigeria
that the behavior of this disease may be differ- E-mail: martin_nze@yahoo.com
Martin A. Nzegwu,1 Aloy Aghaji2 ent in older patients than in young children
with a longer course, ultimately resulting in a Key words: neuroblastoma, adult.
1
Head Department of Morbid Anatomy,
poor outcome regardless of the stage.4,5 Conflict of interest: the authors reported no poten-
University of Nigeria Medical School,
Enugu, Nigeria; 2Provost, College of tial conflict of interests.
Medical Sciences, University of Nigeria
Received for publication: 11 June 2009.
Medical School, Enugu, Nigeria Case Report Accepted for publication: 1 July 2009.

A 38-year old civil servant came as a referral Attribution 3.0 License (by-nc 3.0)
to our urology clinic on the 21st of December
Abstract 2007 with a six month history of right flank ©Copyright M.A. Nzegwu and A. Aghaji 2009
dull non-radiating pain which was worse on Rare Tumors 2009; 1:e15
Neuroblastoma (NB) is a common malig- walking and relieved by rest. Three months doi:10.4081/rt.2009.e15
nancy in children, but rarely occurs in adults. later, the abdominal swelling became more
Accepted unfavorable prognostic factors generalized and tense. He had an intravenous
include age over one year, low histological pyelogram which showed bilateral hydro- The diagnosis in this case report was easy;
grade and advanced stage, MYCN amplifica- nephrosis with a possible retroperitoneal however, no diagnosis could be made from the
tion, chromosomal aberrations, elevations of malignancy. Neither family history nor social gross and clinical presentation until the histo-
neuron specific enolase and lactate dehydro- history was significant. On examination, a logical tests had been performed. These
genase, and increased catecholamine grossly distended abdomen was found tense showed sheets of small round blue proliferat-
metabolites in urine or serum. In adults, and non-tender. Tumor resection revealed a ing cells forming circular or rosette like struc-
abdomen/retroperitoneum are the primary grade III NB. The abdominal mass measured
sites and in children the adrenal gland. We 34x28 cm and was hard to touch. His hemoglo-
report a 38-year old civil servant who present- bin was 88 g/L and leukocyte count 7.3x109/L.
ed at our urology clinic on the 21 st of Chest X-ray was normal and HIV status was
December 2007 with a six month history of negative for HIV1 and 11. Abdominal ultra-
right flank dull pain which was worse on sound showed normal liver, both kidneys were
walking and relieved by rest, hypertension covered by a mass 85x65 cm with little ascites.
and a large right retroperitoneal mass. Tumor Urinary meta-epinephrine was mildly elevated.
resection revealed a grade III NB. Chemo- Figures 1, 2 and 3 show the morphological
therapy using a combination of vincristine, description and appearance of the lesion, cut
adriamycin and cyclophosphamide was start- surface and microscopy. A diagnosis of an
ed. Follow-up showed regression of the mass abdominal invasive neurofibroma was made
initially with a relapse after patient abscond- whose origin may be either from the adrenal or
ed for three months. He resurfaced with new from the sympathetic ganglia. In an adult, this
masses and he had a repeat chemotherapy is a hitherto unreported lesion not only in Figure 1. Shows partly encapsulated gray-
with disappearance of the masses and is cur- Nigeria but perhaps in the whole of Africa. ish white lobulated seemingly encapsulat-
rently undergoing further treatment. To our Hence the importance of this report is to high- ed hemorrhagic lesion altogether measur-
knowledge this is the only report of NB in an light the possibility that neuroblastoma, ing 34x28 cm. Firm in consistency and
adult registered so far in Nigeria and perhaps though a childhood malignancy, can present as superficially resembling the brain.
the whole of Africa. Currently, there are no an abdominal mass in an adult. The patient
standard treatment guidelines for patients was placed on combination chemotherapy
with NB in adulthood. This study emphasizes using vincristine, adriamycin and cyclophos-
the need for a standard treatment regime for phamide. He made a dramatic recovery but
adult onset neuroblastoma and its recogni- later absconded only to resurface three months
tion as a possible differential in intra-abdom- later with what looked like a recurrence. He
inal mass in adults. was again counseled and a repeat course of the
same cytotoxic drugs was given with disap-
pearance of the masses. He has remained com-
pliant and relatively stable since then.
Introduction
Neuroblastic tumors, of which neuroblas-
tomas are the most common, are embryonic Discussion
neoplasms of the sympathetic nervous system,
and are the most common solid neoplasms of Neuroblastoma is essentially a tumor pre-
childhood other than central nervous system senting in childhood, usually occurring before Figure 2. Cut surface shows a cystic and
tumors.1,2 Neuroblastoma rarely occurs in the age of four.2 There are only a few isolated solid lesion with several areas of necrosis.
The lesion remains grayish white in color.
adults, although abdomen and retroperitoneal reports of its occurrence in adults.1,3,4

Case Report
scanty myoxid stroma. The lesion also showed

a brisk mitosis per high-power field. In case of References
doubt and in more experienced centers, rou-
tine immunohistochemistry tests would also 1. Meltzer S. Neuroblastoma occurring in
be performed for S-100, neurone specific eno- adults. Can Med Assoc J 1926;16:647-51.
lase, neurogranin and bombesin to further 2. Ronald AD, Shamlal M. The adrenal gland
establish the diagnosis and differentiate them in Sternberg’s Diagnostic Surgical
from other lesions like rhabdomyosarcoma Pathology, Vol 1. Fourth edition. Lippincott
and lymphomas. Electron microscopy may also Williams and Wilkins, Philadelphia, USA.
be useful in centers where it is available and 2004. p 643.
will show dendritic processes, dense core 3. Maclean TW, Iskander SS, Shimada H, Hall
granules and desmosomes. MC. Neuroblastoma in an adult. Urology
Figure 3. Shows the microscopic descrip- The successful diagnosis of NB for those in 2004;64:1232.
tion. Sections show sheets of small round Africa, where ancillary investigative processes 4. Franks LM, Bollen A, Seeger RC, et al.
blue cells proliferating and forming circu- are not well established, requires awareness Neuroblastoma in adults and adolescents:
lar or rosette like structures with a central and a high index of suspicion so as to see this an indolent course with poor survival.
arranged neurofibrils directed inwards lesion as a possible differential of a malignant
(Homer Wrights rosettes). These are dis- Cancer 1997;79:2028-35.
posed in a background of a scanty myoxid abdominal lesion in an adult. Furthermore, a 5. Loraine MF, Andrew B, Robert CS, et al.
stroma. The lesion shows a brisk mitosis revision of the treatment protocol of the lesion Neuroblastoma in adults and adolescents,
per high-power field POINTER (magnifi- needs to be put in place globally as in the case an indolent course with poor survival.
cation x 40). of the same lesion occurring in children, as Cancer 2000;79:2028-35.
the disease indeed appears to differ in its bio-
logical behavior. This patient is still under
tures with central arranged neurofibrils observation and has just concluded another
directed inwards (Homer Wrights rosettes). radiological survey to ascertain the extent of
These are disposed in a background of a the disease.

Primary lymphoepithelial Case Report Correspondence: Soumaya Ben Abdelkrim,

carcinoma of the parotid gland Farhat Hached Hospital, Department of Pathology,
in a North African woman A 70-year old women presented with a left 4000 Sousse, Tunisia
sided, slowly enlarging, painless, non-tender E-mail: benabdelkrims@voila.fr
Soumaya Ben Abdelkrim,1Amel Trabelsi,1 mass in the parotid region of several months’
Key words: lymphoepithelial carcinoma, parotid,
Faten Hammedi,1 Monia Omezzine,2 duration. Her medical and surgical history was
pathology.
Soumaya Rammeh,1 Atef Ben otherwise uneventful. On physical examina-
Abdelkader,1 Badreddine Sriha1 tion, in the left parotid gland she had a volumi- Received for publication: 20 June 2009.
1
nous mass of 7 cm with a regular border that Accepted for publication: 29 June 2009.
Department of Pathology, Farhat Hached
was mobile on the superficial and deep planes,
Hospital, Sousse, Tunisia; and did not hurt upon palpation. Her facial This work is licensed under a Creative Commons
2
Department of Maxillofacial Surgery, nerve function was intact, and no enlarged cer- Attribution 3.0 License (by-nc 3.0)
Sahloul Hospital, Sousse, Tunisia vical lymph nodes were palpated. The remain-
©Copyright S.B. Abdelkrim et al., 2009
ing systemic examination did not reveal any
coexistent lesions. Magnetic resonance imag- doi:10.4081/rt.2009.e16
ing detected a 7x6x6 cm mass in the superficial
Abstract lobe of the left parotid that was interpreted as
most likely representing a pleomorphic adeno-
Lymphoepithelial carcinoma of the salivary ma (Figure 1). The patient underwent a left The surrounding cellular infiltrate were a mix-
glands is a rare neoplasm that is character- parotidectomy, and the facial nerve was left ture of CD20 and CD3 positive B and T lympho-
ized by a non-neoplastic lymphocytic infiltra- anatomically intact. Her recovery was unevent- cytes. Immunohistochemical expression of EBV
tion associated with an epithelial prolifera- ful. Macroscopically, there were multiple surgi- latent membrane protein 1 (LMP1) and in situ
tion. It involves mainly the parotid gland. cal specimens that were brownish and firm in hybridization to EBV encoded RNA were nega-
Racial and geographical factors contribute to consistency. Histological findings demonstrat- tive. These findings were consistent with the
the pathogenesis of this tumor. We report a ed a tumor located in the parotid gland that was diagnosis of primary LEC of the left parotid
case of a 70-year old woman from a non- made of irregular sheets, islands and strands of gland after excluding metastatic nasopharyn-
endemic area who presented with several poorly differentiated carcinoma richly infiltrat- geal undifferentiated carcinoma to the parotid
months history of swelling in the parotid ed by lymphocytes and plasma cells, accompa- gland by random biopsies from the nasopharyn-
region. Magnetic resonance imaging showed nied by large lymphoid follicles (Figure 2). The geal mucosa. The patient underwent an ipsilat-
a parotid mass suggestive of a pleomorphic epithelial component consisted of large cells eral radical neck dissection and there were no
adenoma. The diagnosis of lymphoepithelial with indistinct cell borders resulting in synci- lymph node metastases. She remains alive and
carcinoma of the parotid gland was performed tial appearance, eosinophilic cytoplasm and disease free five months after treatment.
on the surgical specimen. A primitive oval vesicular nuclei (Figure 3). The nuclei
nasopharyngeal carcinoma was ruled out by contained open chromatin material with promi-
random biopsies of the nasopharynx mucosa. nent nucleoli. Frequent mitotic figures were
The Epstein-Barr virus (EBV) was absent in also found. Areas of squamous differentiation Discussion
neoplastic cells. We insist that, even in non- were noted. The surrounding parotid tissue
endemic areas and when clinical and radio- showed a chronic lithiasic sialadenitis. According to the classification by Ellis and
logical characteristics are not suggestive of Immunohistochemically, most of the tumor Auclair,2 undifferentiated carcinomas of the
malignancy, intra-operative frozen section cells were positive for cytokeratin (Figure 4). salivary glands can be subtyped further into
analysis should be used in order to ensure the
appropriate treatment.
Introduction
Lymphoepithelial carcinoma (LEC) is a
specific subtype of undifferentiated carcino-
ma with characteristic dense lymphoid stro-
ma. The most frequent location is the
nasopharynx. Identical tumors have been
rarely described in the major salivary glands
where they account for approximately 0.4% of
all malignant salivary gland tumors.1 A limited
number of cases were reported from non-
endemic areas. We report a new case from a Figure 1. Magnetic
non-endemic region with an atypical clinical resonance imaging
presentation and an aspecific radiological showing a well cir-
pattern and we discuss the clinical and patho- cumscribed mass of
logical pattern and management of this the left parotid
gland.
uncommon tumor.

Case Report
genetic factors, environmental factors, and

EBV infection in the oncogenic process of
LEC of the salivary glands.9 Parotid LEC usu-
ally presents as an enlarging parotid lump,
occasionally painful and with facial nerve
Figure 2. Lympho- involvement in approximately 20% of cases.4
epithelial lesion of the Clinical features suggestive of malignancy
parotid gland (hema- are rapid-growing course, pain or tenderness,
toxylin-eosin, original progressive facial nerve palsy and obvious
magnification ×40). cervical lymphadenopathy.10 Our case is par-
Islands of neoplastic
epithelial cells (arrows) ticular for the atypical presentation suggest-
associated with lym- ing a benign lesion; in fact, our patient
phoid infiltration that showed no signs suggestive of malignancy.
occasionally form lym- On presentation, up to 40% of patients have
phoid follicles.
metastases to the cervical lymph nodes, 20%
develop local recurrence or lymph node
metastases, and 20% have distant metastases
within three years following therapy. Distant
metastases usually involve the lung, liver,
bone, and brain. 1 Macroscopically, these
tumors are firm, 1-10 cm masses, multinodu-
lar, circumscribed, or clearly infiltrative into
adjacent salivary gland, fat, muscle, or skin,
with a cut surface that varies from a grey-tan
Figure 3. The epithelial
component of the to yellow-gray.11 Histologically, it is character-
lesion have a syncitial ized by a syncitial growth pattern and a dense
appearance and shows stroma made of non-neoplastic lymphoplas-
an obvious pleomor- macytic cells; the lymphoid cells include a
phism (hematoxylin- mixture of B and C cells and are sometimes
eosin, original magni-
fication ×400). associated with germinal centers. The epithe-
lial component is composed of irregular
shaped islands, cords, trabeculae of pleomor-
phic, large, malignant cells with abundant
lightly eosinophilic cytoplasm and vesicular
nuclei.3,12 Mitotic rate is variable. Histiocytes
are abundant in the tumor islands in some
cases, imparting a 'starry sky' appearance.3
Other inconsistent findings are non-caseat-
ing granulomas with or without multinucleat-
ed giant cells and amyloid deposition.13 A def-
inite squamous differentiation with intercel-
lular bridges has been identified in several
cases.3 LEC is indistinguishable from undif-
ferentiated nasopharyngeal carcinoma which
Figure 4. Immunohi- is much more common or other LECs that
stochemical expression
of cytokeratin (×400). develop in various parts of the body. 4,10
Therefore, to confirm the diagnosis of pri-
mary LEC in the major salivary glands,
metastatic nasopharyngeal carcinoma to the
small cell undifferentiated carcinoma, large remains unknown. Among the possible etiolo- salivary glands should be eliminated through
cell undifferentiated carcinoma, and LEC. gies are a malignant transformation of the examination of the upper aerodigestive tract
LEC accounts for approximately 0.4% of glandular and ductal inclusions in the intra- with endoscopy and even random biopsy of
malignant salivary gland tumors and has a parotid lymph nodes6 and a malignant trans- the nasopharynx.3,4,10,13 In reality, the parotid
characteristic extensive and dense lymphoid formation of the epi-myoepithelial island.7 In gland is the predominant site of occurrence of
stroma.1 This tumor affects the parotid gland 1991, the presence of EBV was detected by LEC and an exceptional site of metastasis
in approximately 80% of the cases.3 Most Hamilton-Dutoit et al.8 in the malignant cells from nasopharyngeal carcinoma, which more
cases occur in the fifth decade of life and a of salivary LECs in the Eskimo population of typically metastasizes to the cervical or sub-
predilection for female patients is reported.4 Greenland. Only a few cases of EBV-negative mandibular lymph nodes.1 Histologically, the
There is a racial prevalence in Inuits LEC have been reported, and almost exclu- LEC must be distinguished from benign
(Eskimo) in the Arctic region, south-eastern sively in non-Inuit patients6 suggesting that lesions such as lymphoepithelial sialadenitis
Chinese and Japanese. Most parotid LEC the virus plays a role in the etiology of LEC. and from other epithelial malignancies, such
cases arise de novo, but they may rarely devel- The association of EBV with salivary gland as primary or metastatic poorly differentiated
op within lymphoepithelial sialadenitis.5 The LEC may also exist in non-endemic areas.4 It squamous cell carcinoma, adenocarcinoma,
exact origin and pathogenesis of parotid LEC seems there is a complex interaction between and amelanotic melanoma; another differen-

Case Report
tial diagnosis is with large cell or anaplastic 1975;85:389-99.

types of lymphoma.2 The optimal management References 8. Hamilton-Dutoit SJ, Therkildsen MH,
of LEC of the major salivary glands is com- Nielsen NH, et al. Undifferentiated carci-
plete excision with clear surgical margins fol- 1. Schneider M, Rizzardi C. Lymphoepithelial noma of the salivary gland in Greenlandic
lowed by adjuvant radiotherapy to the tumor carcinoma of the parotid glands and its Eskimos: demonstration of Epstein-Barr
bed and neck. relationship with benign lymphoepi- virus DNA by in situ hybridization. Hum
Neck dissection is reserved for patients thelial lesions. Arch Pathol Lab Med Pathol 1991;22:811-5.
who have clinically positive cervical lymph 2008;132:278-82. 9. Sheen TS, Tsai CC, Ko JY, et al. Undiffer-
nodes.10,14 Our patient underwent only surgical 2. Ellis GL, Auclair PL. Atlas of tumor pathol- entiated carcinoma of the major salivary
treatment because radiotherapy was not ogy: tumors of the salivary glands. glands. Cancer 1997;80:357-63.
available at that time. Lymphoepithelial carci- Washington, DC: Armed Forces Institute 10. Wang CP, Chang YL, Ko JY, et al. Lympho-
noma seems to have a better prognosis than of Pathology, 1996. epithelial carcinoma versus large cell
the other undifferentiated carcinomas of the 3. Saw D, Lau WH, Ho JH, Chan JK, Ng CS. undifferentiated carcinoma of the major
salivary glands, in part because of the lym- Malignant lymphoepithelial lesion of the salivary glands. Cancer 2004;101:2020-7.
phoid stroma that has a role in limiting the salivary gland. Hum Pathol 1986;17:914- 11. Jang SJ, Paik SS, Lee WM, et al. Lympho-
aggressiveness of this carcinoma. Advanced 23. epithelial carcinoma of the submandibu-
disease, the presence of metastases on diag- 4. Manganaris A, Patakiouta F, Xirou P, lar gland – a case report. J Korean Med Sci
nosis, and histological features such as high Manganaris T. Lymphoepithelial carcino- 1997;12:252-5.
mitotic rate, anaplasia, and necrosis are pre- ma of the parotid gland: is an association 12. Cleary KR, Batsakis JG. Undifferentiated
dictors of a worse prognosis.1,9 The 5-year sur- with Epstein-Barr virus possible in non- carcinoma with lymphoid stroma of the
vival rate has been reported to range from 50- endemic areas? Int J Oral Maxillofac Surg major salivary glands. Ann Otol Rhinol
87%.10 2007;36:556-9. Laryngol 1990;99:236-8.
In conclusion, it is worth underlining the 5. Gravanis MB, Giansanti JS. Malignant 13. Kuo T, Hsueh C. Lymphoepithelioma-like
diagnostic difficulty in this case caused by the histopathologic counterpart of benign salivary gland carcinoma in Taiwan: a
absence of clinical symptoms suggestive of lymphoepithelial lesion. Cancer 1970;26: clinicopathological study of nine cases
malignancy and the non-specific nature of the 1332-42. demonstrating a strong association with
radiological signs. In order to ensure a correct 6. Kountakis SE, SooHoo W, Maillard A. Epstein-Barr virus. Histopathology 1997;
therapeutic approach, intra-operative frozen Lymphoepithelial carcinoma of the 31:75-82.
section analysis of a parotid mass should be parotid gland. Head Neck 1995;17:445-50. 14. Hsiung CY, Huang CC, Wang CJ, et al.
used to exclude a malignant tumor even when 7. Batsakis JG, Bemacki EG, Rice DH, Lymphoepithelioma-like carcinoma of
dealing with a clinical and radiological pres- Stebler ME. Malignancy and the benign salivary glands: treatment results and fail-
entation suggestive of pleomorphic adenoma. lymphoepithelial lesion. Laryngoscope ure patterns. Br Radiol 2006;79:52-5.

A review of the history, scrotal tumor.1

Squamous cell carcinoma of the scrotum is Correspondence: Jerome E. Azike,
epidemiology and treatment a tumor that is of interest for clinical and his- Department of Surgery, College of Medicine and
of squamous cell carcinoma torical reasons. It has been identified as a sen- Health Sciences, Imo State University, Orlu, Imo
State, Nigeria.
of the scrotum tinel health event (occupational) [(SHE(0)].4
E-mail: jeazike@yahoo.com
Synonyms include epidermoid carcinoma of
Jerome E. Azike1,2 the scrotum, chimney sweepers cancer, mule-
Key words: cancer of the scrotum, history, epi-
spinners cancer and epithelioma of the scro-
1
Department of Surgery, College of demiology, treatment.
tum. It is customary to give priority for the
Medicine and Health Sciences, Imo State description of the disease to Bassius who Received for publication: 13 June 2009.
Universityœ, Orlu, Campus; 2Imo State described it in 1731, but it was Percivall Pott Accepted for publication: 12 July 2009.
Universitary Teaching Hospital, Orlu, Imo who in 1775 described its occurrence in chim-
State, Nigeria ney sweeps in Pott’s Chirurgical Observations, This work is licensed under a Creative Commons
thereby making him the first to attribute an Attribution 3.0 License (by-nc 3.0)
occupational cause to the disease. This also
©Copyright J.E. Azike 2009
established scrotal cancer as the first Rare Tumors 2009; 1:e17
described occupational cancer.1,2,5 Squamous doi:10.4081/rt.2009.e17
Abstract cell carcinoma of the scrotum has historically
been associated with exposure to occupational
Squamous cell carcinoma of the scrotum is (industrial) and non-occupational (environ-
a tumor that is of interest for clinical and his- mental) carcinogens. From the eighteenth
torical reasons. It was the first cancer linked to century, there have been at least three broad tact with used engine oil can cause skin and
occupational exposure when, in 1775, Perivall occupational groups with a preponderance of scrotal cancer. Car mechanics are at potential
Pott described it in chimney sweeps in the disease: chimney sweeps, people who work risk from used engine oils.7 Best occupational
England. Other occupations that had a prepon- with the distillates of coal, and men exposed to health practices are invaluable to minimize
derance of the disease included people who mineral oil. The common hazard in these occu- exposure at the work place. The establishment
worked with the distillates of coal and men pations arises from polycyclic aromatic hydro- of the concept of latent period in tumor induc-
exposed to mineral oil. Currently, the disease carbons in soots, tars and mineral oils.6 In tion in the last century helped shed light on the
is very rare and most cases are thought to these industries, improved technology or the observation by several writers that the scrotal
result from poor hygiene and chronic irrita- decline of the industry have led to less men lesion appeared many years after the man had
tion. Surgery with a negative resection margin being affected. Chimney sweep cancer was left the job associated with squamous cell can-
offers the best hope of cure as adjunctive ther- commoner in England, as cases were virtually cer or when he was in another trade altogeth-
apy has not proved useful. Prognosis correlates unknown in other parts of Europe or America; er. In this respect, Henry Earle and Curling
with the extent of nodal involvement. attention to personal hygiene had for long noted the disease appearing after intervals of
been the practice among the continental 15 years and 19 years, respectively.5 Other non-
sweeps. The introduction of protective clothing occupational factors that may be associated
at work and improved personal hygiene with the disease include prior history of can-
Introduction reduced the incidence of chimney sweep cancer, PUVA (psoralen-ultraviolet light) treat-
cer in England. ments, radiotherapy, poor personal hygiene
The scrotum is a seven-layer pouch which The first public notice that the distillation of and treatment with arsenical compounds.3,5,8,9
covers the testes, testicular adnexae, and dis- coal might induce cancer of the scrotum was Case reports exist which correlated squamous
tal spermatic cord. These layers are the epider- given by Von Volkman at the Third Surgical cell carcinoma of the scrotum with human
mis, dermis, tunica dartos, the three layers of Congress in Berlin in 1873. Tar from gas works papilloma viruses, mainly oncogenic types 16
Colles’ fascia and the parietal layer of the tuni- blast furnaces, and coke ovens was used wide- and /or 18 or 6/118,10,11 but a direct causal rela-
ca vaginalis,1 The scrotal lymphatics drain into ly from the end of the nineteenth century, both tionship has not been established. Squamous
the corresponding superficial inguinal lymph in the original state and for the distillation of a cell carcinoma of the male genitalia may be
nodes. Anastomoses to the lymphatics of the series of hydrocarbons which included cre- multifocal,12 especially when oncogenic human
contralateral network across the median raphe osote, anthracene and naphthalene. The etiol- papillomavirus types are present.10
occur. Testicular lymphatics drain to the para- ogy of the disease was unclear from the time of Patients frequently delayed seeking medical
aortic nodes. Pott until 1922, when Passey gave experimen- help,5 mainly due to embarrassment, ignorance
Tumors have been reported to arise out of tal evidence of the presence of weak carcino- or both; that the initial lesion is usually slowly
virtually any of the components of the scrotal gens in soot, as the theory of chronic irritation growing and painless may also be contributory.
wall.2 Both benign and malignant tumors of the popular at the time did not fully answer all the In a case series of 9 patients, Mc Donald report-
scrotum are rare.1 Squamous cell carcinoma of questions raised. Men exposed to mineral oil ed that the interval between patient awareness
the scrotum is now very rare; the incidence included shale oil workers and engineering of the lesion to diagnosis averaged 3.3 years.13
has been reported to be less than 10 cases per workers exposed to cutting oils. Unrefined or In a case series of 19 patients seen between
year in the United States.2 Squamous cell car- mildly refined mineral oils have substantial 1948 and 1971, Ray and Whitmore found the
cinoma is the most common malignant tumor levels of polycyclic aromatic hydrocarbons and interval before presentation was 26 months.9
of the scrotum; however, rare cases of basal their use in industries such as printing and However, in earlier reviews the interval
cell carcinoma, melanoma, Paget’s disease and metalworking in the past has led to skin can- between onset of symptoms and treatment was
sarcoma have been reported.3 Secondary cers.5 The hazard has remained but newer cir- reported to have been about 10-12 months.9
tumors of the scrotum can occur; for instance, cumstances may now be involved. Engine oils This may suggest that as the disease became
carcinoid tumor of the small bowel can metas- have elevated polycyclic aromatic hydrocarbon less common, the interval between onset of
tasize to the scrotum simulating a primary content with use; prolonged and repeated con- symptoms and presentation increased.

Review
The patients afflicted with chimney sweeps Diagnosis approach may be necessary to fully address all
cancer were generally young men. Writing in aspects of patient management.
The diagnosis is suggested clinically and is
1832, Henry Earle considered that the majority
confirmed by wedge biopsy of the edge of the
of cases were in patients between the ages of Treatment of the regional lymph
scrotal lesion. Refractory scrotal inflammatory
30 and 40. Green analyzed 36 cases pooled
lesions should be biopsied to rule out squa- nodes
from the eighteenth and nineteenth century
mous cell carcinoma. General investigations Briefly, the optimal management of patients
literature and found the mean age of presenta-
include full blood count, serum electrolytes
tion was 37.7 years.5 However in the series by with squamous cell carcinoma of the scrotum
urea creatinine estimation, liver function
Ray and Whitmore, which involved cases seen with clinically negative inguinal node is contro-
tests, urinalysis, urine culture if indicated,
between 1948 and 1971, the average age was versial and involves a decision as to whether a
wound swab culture and sensitivity if ulcera-
56 years; the majority occurred in the 5th to 7th prophylactic or therapeutic node dissection
tion is present. There is need for extensive
decade of life.9 evaluation with appropriate investigative should be performed. Some authors15,25 propose
Squamous cell carcinoma of the scrotum modalities to exclude associated internal bilateral radical groin dissection to remove
frequently present as a solitary wart or nodule malignancy. Staging investigations include micrometastasis; the rationale of the contralat-
on the scrotum. There seems to be no abdomino-pelviscrotal ultrasound, MRI of the eral groin dissection being the free communi-
predilection for any side, if patients with occu- scrotum, and chest CT. cation between the lymphatics of the two sides
pational cancer are excluded.9 Superficial of the scrotum. Dean emphasized that only 50%
ulceration may follow increase in size or the of patients with inquinal adenopathy actually
Staging
effect of scratching at the lesion. Ulcerated had metastases, suggesting that routine dis-
lesions may have a sero-sanguinous discharge Staging of scrotal carcinoma as proposed by section would be useful only in half of the
that may become profuse and foul-smelling if Ray and Whitmore:9
patients with inquinal adenopathy. He advocat-
infected. If an ulcer is present, it is a malig- Stage A
ed bilateral groin dissection only for proved
nant squamous ulcer and would have features A1 Disease localized to the scrotum
metastases.17 Ray and Whitmore based on their
expected of such. There may be ipsilateral or A2 Locally extensive disease involving
experience, advocated patient follow-up at 2-3
bilateral inguinal lymph node enlargement adjacent structures (penis, perineum,
testis and/or cord structures, pubic month intervals after excision of primary lesion
which may be inflammatory or neoplastic or
bone) by continuity but without evident and to perform an ipsilateral ilioinguinal dis-
both.9 In some cases, the growth may become
metastasis. section if there is clinical evidence of metasta-
large and grotesque. Pain is usually absent
Stage B sis proved by biopsy, and to perform an ipsilat-
until late stages of the disease. Azike,
Regional* metastasis, resectable eral ilioinguinal dissection if there is clinical
Chukwujama and Oguike reported on a recent
Stage C evidence of metastasis proved by biopsy, and to
case of squamous cell carcinoma of the scro-
Regional metastasis, non-resectable defer contralateral ilioinguinal dissection until
tum with penile and testicular involvement in
a 42-year old who presented with a 10-year his- Stage D there is clinical evidence of metastasis. Presti
tory.14 Distant metastasis (beyond regional nodes) jr. advocated observation for clinically negative
*Inguinal or ilioinguinal lymph nodes, but patients with clinically palpa-
ble nodes to be given antibiotics first. If the
Spread and metastasis
Treatment groin nodes remain clinically palpable, ilioin-
The lesion tends to remain localized to the guinal lymph node dissection is performed. But
scrotal wall, may occasionally involves the The established treatment for squamous cell
carcinoma of the scrotum is wide excision if it becomes clinically negative after broad
adjacent perineal skin but rarely involve the spectrum antibiotics, limited node sampling is
scrotal contents or penis; distant spread is with a 2-3 cm margin. Surrounding subcuta-
neous tissue should be excised with the pri- performed. If positive, ilioinguinal lymph node
rare.9 The pubic bone is occasionally involved dissection is performed; if negative observation
by direct extension.14,15 In the series of 141 mary tumor. Resection of the scrotal contents
is rarely necessary for tumor control unless is continued.3
cases, Southan and Wilson found testicular
involvement in 6 and penile in 3 cases.16 involved by tumor.3,9 Intra-operative frozen sec-
Spread is to the inquinal which may be unilat- tions may help to confirm a disease free mar- Prognosis
eral, bilateral or crossed; iliac nodes, the para gin. Primary scrotal closure is usually possible, An important prognostic factor is the ability
aortic nodes, and may reach the lungs. but may be a challenge after large tumor resec- to completely excise the tumor at the time of
Metastatic involvement has been reported as tion. Many investigators have reported various
initial surgery.2 Prognosis correlates with the
early as four months or as late as ten years.17 methods to cover a healthy testis when primary
presence or absence of nodal involvement. If
The iliac nodes may be involved when there is closure is not feasible. These include immedi-
the inguinal nodes are involved the 5-year sur-
ate use of local thigh flaps,18 myocutaneous
no recognized inguinal involvement.9 vival rate is approximately 25%. There are vir-
gracilis or adductor minimus myocutaneaus
flaps, and heterologous fascia grafts.19-21 tually no survivors if the iliac nodes are affect-
Primary tumors in other sites Other investigators place the exposed testis in ed.3,9 In a review of a series of 18 patients, Ray
Dean noted the high incidence of multiple the subcutaneous tissue of the thigh or femoral and Whitmore Jr found no correlation among
primary tumors in patients with scrotal cancer. region or do ipsilateral orchidectomy.15,22,23 Others the patient age, duration of symptoms, size,
In his series, 8 of 27 patients had other pri- do contralateral testicular transposition follow- histological type or grade of the tumor and sur-
mary tumor.17 In the series by Ray and ing a hemiscrotectomy.24 Local recurrence may vival. However, they reported that patients with
Whitmore,8 9 of 19 patients had another pri- occasionally occur and may be due to insuffi- high tumor burden had the worst prognosis; no
mary tumor.9 Weinstein, Howe and Burnett cient tumor resection or may represent new patient with non-resectable metastasis or
found that 8 out of the 19 cases had prior his- lesions.9,24 Adjunctive treatment like radiother- metastases beyond the inquinal nodes sur-
tory of cancer.4 Lione and Denholm described a apy or chemotherapy or both has not proved vived.9 Patient follow-up is for life.
patient who died of stomach cancer two years useful, and only palliation is usually feasible
after treatment for scrotal carcinoma.9 for late stage disease. A multidisciplinary

Review
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8. Burmer GC, True LD, Krieger JN. Santucci R. Extramammary Paget’s dis-
Squamous cell carcinoma of the scrotum is Squamous cell carcinoma of the scrotum ease of the penis and scrotum: excision,
now a rare clinical entity and it is given only associated with human papillomaviruses. reconstruction and evaluation of occult
scant attention in most urological textbooks. It J Urol 1993; 149:374-7. malignancy. In: Arango O, Bielsa O,
is pertinent to once again remind the medical 9. Ray B, Whitmore Wf Jr, Experience with Lorente JA, De Leon E, Mas GA. Hemi-
community of the existence of this disease and Carcinoma of the Scrotum. J Urol 1977; scrotectomy with contralateral testicular
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add to the resources available to the practising Development of Human Papillomavirus tion utilizing bilateral gracilis myocuta-
urologists and oncologists. type 16 associated squamous cell carcino- neous flaps. In: Arango O, Bielsa O,
ma of the scrotum in a patient with Lorente JA, De Leon E, Mas GA. Hemi-
Darier’s disease treated with systemic scrotectomy with cantralateral testicular
isoretinoin. J Urol 1995; 153:1940-3. transposition for scrotal cancer. J Urol
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G. A case of Scrotal Cancer with Inguinal 20. DiGeronimo EM. Scrotal reconstruction
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Tyring S.K, Pow-sang M, Dozier S, Cirelli
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R, Arany I, et al. Development of Human
3. Presti JC Jr, Genital Tumors. In Tanagho Bielsa O, Lorente JA, De Leon E, Mas GA.
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Halperin WE, Melius JM, Sestito JP. 13. Mc Donald MW. Carcinoma of the scrotum. (extra Mammary Paget’s disease): case
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Assessment of cytological opment of both OSCCs or potentially malignant

lesions are considered to be similar.1,2 Correspondence: Hussain Gadelkarim Ahmed,
atypia, AgNOR and nuclear However, social habits of tobacco use and alco- University of University of Khartoum, 102, Faculty
area in epithelial cells of hol consumption have been strongly attributed of Medical Laboratory Sciences, Khartoum,
Sudan: E-mail: Hussaingad1972@yahoo.com
normal oral mucosa exposed to development of these lesions1,2 In the Sudan,
the high incidence of OSCCs and an equally
to toombak and smoking high prevalence of potentially malignant oral Key words: toombak, smoking, oral mucosa,
AgNOR, nuclear area.
mucosal lesions have been strongly attributed
Hussain Gadelkarim Ahmed,1 to the habit of snuff use, locally known as
Abd-Elraheem Ali Babiker2 Acknowledgments: we would like to thank the
toombak.3 Toombak has been in use in the members of the Department of Histopathology
1
Department of Histopathology and Sudan for centuries and its use is wide- and Cytology, Faculty of Medical Laboratory
Cytology, Faculty of Medical Laboratory spread.3,4 A close relationship between use of Sciences, Sudan University for Science and
Sciences, University of Khartoum, toombak and development of OSCCs has been Technology for their technical help and assis-
Khartoum, Sudan; 2Department of reported.3 In addition, use of toombak has been tance.
Histopathology and Cytology, Faculty of shown to produce a variety of oral mucosal
changes such as dysplasia and hyperkerato- Financial disclosure: the authors have no connec-
Medical Laboratory Sciences, University tion with any company and the work was support-
sis.3,5 An unusually high level of the carcino-
for Science and Technology, Khartoum, ed by the authors and the Sudan University for
genic tobacco-specific nitrosamines (TSNAs)
Sudan Science and Technology.
was found in toombak.6 In the Sudanese popu-
lation, however, and due to several reasons,
both cigarette smoking and alcohol consump- Accepted for publication: 30 June 2009.
tion are uncommon.3,5 Early diagnosis is of
Abstract great importance for oral SCC, oral exfoliative This work is licensed under a Creative Commons
cytology, a simple, painless and inexpensive Attribution 3.0 License (by-nc 3.0)
The purpose of this study was to assess cel- method has become a preferred method for
lular proliferative activity of clinically healthy ©Copyright H.G. Ahmed and A.-E. A. Babiker 2009
both early diagnosis of the lesion and for
oral mucosal epithelial cells of toombak dip- Rare Tumors 2009; 1:e18
establishing quantitative techniques.7,8 The doi:10.4081/rt.2009.e18
pers and smokers by means of AgNOR counts presence of two or more of the following fea-
and nuclear areas via nuclear morphometry. tures were consistent with atypia: nuclear
Smears were collected from normal-appearing enlargement, associated with the increased
mouth floor mucosa and tongue of 75 toombak nuclear/cytoplasmic ratio, nuclear hyperchro-
dippers, 75 smokers and 50 non-tobacco users matism, chromatin clumping with prominent excluded from this study. Also individuals who
between the ages of 20 and 70 with a mean age nucleation, irregularity of nuclear membranes, had drunk any alcoholic beverage for the last
of 36 years. AgNORs were counted in the first bi- or multinucleation, increased keratiniza- ten years were not included in the study.
50 well-fixed, nucleated squamous cells and tion.9 Nucleolar organizer regions (NORs) are All cytological smears were collected by the
nuclear areas were calculated via microscopic located in the cell nucleoli during interphase. same examiner from the mucosa of the mouth
stage micrometer. Cytological atypia was They are loops of DNA in which ribosomal RNA floor and tongue (in smokers) or from the dip
ascertained in 6 tobacco users and could not be is encoded.10 They are located in the acrocen- site (in toombak dippers). Participants were
ascertained in non-tobacco users. Statistically tric chromosomes 13, 14, 15, 21 and 22.7 Their asked to rinse their mouth with saline solution
mean AgNOR numbers per nucleus in the non- number per nucleus has been shown to be cor- for a minute before collection of the samples.
tobacco users (2.45±0.30) was lower than the related with the rate of ribosomal RNA tran- The specimen collection site was dried by a
toombak dippers (3.081±0.39, p<0.004), and scription, cell proliferation and DNA ploidy.10 smooth wipe so as to avoid silver staining of
the smokers (2.715±0.39, p<0.02), and mean Nucleolar organizer regions can be demon- the mucoid material of saliva during applica-
nuclear areas of epithelial cells of toombak dip- strated with the use of AgNOR technique tion of AgNOR method to the slides. The mate-
pers (6.081±0.39, p<0.009) and smokers which is the silver staining technique for rial was collected by a smooth brush after
(5.68±10.08, p<0.01) was also significantly showing NORs as black dots inside the nucle- brushing the floor of the mouth and tongue or
higher than non-smokers (5.39±9.4). The us when examined under a light microscope.7 dip-site two times, and rinsing and cleaning
mean number of nuclei having more than 3 the brush each time in a saline solution. This
AgNORs was 28%, 19% and 7% in toombak dip- was done so as to collect cells from the inner
pers, smokers and non-tobacco users, respec-
layers of the oral mucosa. The material collect-
tively. These findings support the view that Materials and Methods ed was smeared on two slides and immediate-
toombak dipping and smoking are severe risk
ly fixed in 95% ethyl alcohol for 15 minutes.
factors for oral mucosal proliferative lesions A total of 200 clinically healthy volunteers One slide was stained according to the
and exfoliative cytology is valid for screening seen in our Dental Clinic, aged between 20 and Papanicolaou staining method7 and the other
of oral mucosal lesions. 70, with a mean age of 36 years, of which 75 was stained according to AgNOR staining
were toombak dippers, 75 were cigarette smok- method described by Ploton et al.11
ers and 50 were non-tobacco users, were ini-
tially selected for this study. All toombak dip-
Introduction pers and cigarette smokers were chosen
Papanicolaou staining method
among persons who have dipped toombak or Ethyl alcohol fixed smears were hydrated in
The prevalence of potentially malignant oral smoked cigaretteS at least for the last five descending concentrations of 95% alcohol
mucosal lesions and conditions shows wide years and at least 5 cigarettes per day. Patients through 70% alcohol to distilled water, for two
variations between developed and developing with clinically apparent oral mucosal lesions, minutes in each stage. Then the smears were
countries.1 The primary risk factors for devel- and previous benign or malignant lesions were treated with Harris’ hematoxylin for five min-

Article
utes to stain the nuclei, rinsed in distilled ties as the cells whose AgNORs were counted,
water and differentiated in 0.5% aqueous were selected and the nuclear area of each cell Discussion
hydrochloric acid for a few seconds, to remove was calculated via the microscopic stage
the excess stain. They were then immediately micrometer. In this study we have taken the smears from
rinsed in distilled water, to stop the action of the mouth floors and tongue of the study sub-
discoloration. Then the smears were blued in Statistical analysis jects. It has been found that the mean AgNOR
alkaline water for a few seconds and dehydrat- counts in smokers are the highest in epithelial
ed in ascending alcoholic concentrations from SPSS version 12 statistical software was cells of floor of the mouth when compared with
70%, through two changes of 95% alcohol for used for statistical analysis. The numeric the edge of the tongue and lower lip,7 although
two minutes for each change. The smears were results (AgNOR counts and nuclear areas) some studies have reported strong association
next treated with Eosin Azure 50 for four min- were expressed as mean±SD, and the 95% between smoking and carcinoma of the
utes. For cytoplasmic staining, they were treat- confidence intervals (CIs) of the means were tongue. Consequently, our cytological materi-
ed with Papanicolaou Orange G6 for two min- calculated. The X2 test was used to compare the als were collected from the mouth floors and
utes, rinsed in 95% alcohol and then dehydrat- differences in categorical variables between tongues of the smokers. Concerning toombak
ed in absolute alcohol. The smears were then the groups. Relationships between variables dippers we planned to take the cytological
cleared in Xylene and mounted in DPX were analyzed using Pearson’s correlation materials from the application site (dip site).
(Distrene Polystyrene Xylene) mount. All the analysis. A p<0.05 was considered statistically Generally toombak is dipped and retained
reagents used were from Thermo Electron significant. between gum and lip or cheeks or floor of the
Corporation, UK. mouth, and sucked slowly for about 10±5 min-
Atypia was assessed cytologically by using Ethical consent utes.4 Toombak dippers develop a clinically and
the criteria described elsewhere.12 The pres- histologically characteristic lesion at the site
ence of two or more of the following features Each participant was asked to sign a written
of dipping.3
were consistent with atypia: nuclear enlarge- ethical consent form during the interview,
In the present study it can also be seen that
ment associated with increased nuclear cyto- before the specimen was taken. The informed cytological atypia among the tobacco users is
plasmic ratio, hyperchromatism, chromatin ethical consent form was designed and significantly higher than the non-tobacco
clumping with moderately prominent nucleoli, approved by the ethical committee of the users, which is a similar finding with the study
irregular nuclear membranes and bi- or multi- Faculty of Medical Laboratory Research Board, of Ahmed et al.12 Their findings suggested that
nucleation, scant cytoplasm, and variation in Sudan University for Science and Technology. toombak dipping and cigarette smoking are
size and/or shape of the cells and nuclei. associated with a risk for occurrence of oral
epithelial atypia, which can be detected by use
AgNOR staining method of simple cytological methods. The findings
The smears were stained according to the
Results further suggested that tobacco components,
AgNOR staining method. Working solution was specially the TSNAs, may stimulate the epithe-
freshly prepared by mixing one volume of 2% Mean age was 36.2±10.7 in the study popu- lial cells to undergo squamous differentia-
gelatin in 1% formic acid solution and two vol- lation; 34.9±11.6 in non-tobacco users, tion/or cellular morphological changes that
umes of 50% aqueous silver nitrate solution. 34.7±8.5 in smokers and 38.5±11.8 in toombak might lead to malignancy as suggested by oth-
All smears were incubated with this silver dippers. All the population were males and ers.6,14
solution for 30 minutes at room temperature in there were no statistically significant differ- AgNOR counts have been of great value for
a dark medium and they were protected in the ences between non-smokers and toombak dip- the assessment of cellular proliferative activity
dark until each slide was analyzed. pers (p=0.09) or smokers (p=0.94) in age. that is frequently encountered in pre-malig-
Two investigators, blind to the study groups, Cytological atypia was ascertained in 6 tobacco nant and malignant changes.15 A number of
analyzed the silver-stained cells under light users and could not be ascertained in non- studies have pointed out that the AgNOR count
microscope (Olympus BX-51, Japan) at 1000x tobacco users. Among the 6 subjects with cyto- is a rapid and an easily reproducible method
magnification. All smears were screened hori- logical atypia, there were 4 (67%) toombak dip- which permits a clear distinction between
zontally from left to right and AgNORs were pers and 2 (33%) cigarette smokers. malignant and benign cells.15,16
counted in the nuclei of the first 50 non-over- There are many previous AgNOR studies of
In toombak dippers, AgNOR numbers per
lapping, inner layers, nucleated epithelial oral mucosa with benign, pre-malignant and
nucleus varied from 1 to 9, in smokers from 1
cells. Superficial cells with pyknotic nuclei malignant lesions, and only a few studies have
to 7, while the range was between 1 and 4 in
were not counted. The AgNOR count was made been conducted on exfoliative cells obtained
the non-tobacco users. The mean±SD of
adopting the method described by Crocker et from oral mucosa exposed to cigarette smoking
AgNOR numbers per nucleus in the non-tobac-
al.13 or alcohol.7,17-19 It is noteworthy that to the best of
co users (2.45±0.30) was lower than the toom- our knowledge there has been no AgNOR study
AgNORs, which were visible as black-dark
bak dippers (3.081±0.39, p<0.004), and the of normal oral mucosa exposed to toombak dip-
brown dots located within the nuclei of the
cells, were counted; overlapped black dots were smokers (2.715±0.39, p<0.02), and mean±SD ping. Mean AgNOR counts and keratinization
counted as one structure. To calibrate the nuclear areas of the oral epithelial cells of are the only parameters that are sought in most
examiners, ten smears from each group toombak dippers (6.081±0.39, p<0.009) and of these studies. Though some cytological stud-
(toombak dippers, smokers and non-tobacco smokers (5.68±10.08, p<0.01), were also sig- ies have assessed the oral epithelial atypia of
users) were counted three times in a non-con- nificantly higher than non-tobacco users toombak dippers,8,12 to the best of our knowl-
secutive way. Mean number of AgNORs and (5.39±9.4). The mean number of nuclei having edge, this is the first study including cytological
mean percentage of nuclei with more than more than 3 AgNORs was 28%, 19% and 7% in atypia, mean AgNOR counts and nuclear areas
three AgNORs was also calculated. toombak dippers, smokers and non-tobacco of oral mucosal cells exposed to toombak dip-
For calculating the nuclear areas of the users, respectively. ping and cigarette smoking, and a comparison
epithelial cells, the smears were further of all these parameters.
assessed. Fifty cells, having the same proper- However, there is no study from the Sudan

Article
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ies.10,23 Although there might be negligible dif- Histol 2004; 26:175-80. Evaluation of the nucleolar organizer
ferences in counting and calculating tech- 8. Ahmed HG, Mahgoob RM. Impact of toom- region associated proteins in exfoliative
niques, we believe that the variation in age of bak dipping in the etiology of oral cancer: cytology of normal buccal mucosa. Effect of
the study population may be an explanation for Gender-exclusive hazard in the Sudan. J smoking. Oral Oncol 2001;37:446-54.
the differences in our results from previous Can Res Ther 2007; 3:127-30. 21. Einstein TB, Sivapathasundharam B.
studies. It is well-known that the risk of cyto- 9. Ahmed HG, AI Elemirri D. Assessment of Cytomorphometric analysis of the buccal
logical atypia increases with increasing age.12 oral cytological changes associated with mucosa of tobacco users. Indian J Dent
In conclusion, our results support the view that exposure to chemotherapy and/or radio- Res 2005;16:42-6.
tobacco use is a risk factor for the develop- therapy. CytoJournal 2009;6:8 22. Schwartz JL, Muscat JE, Baker V, et al. Oral
ment of oral epithelial proliferative changes, 10. Vellappally S, Fiala Z, Smejkalová J, et al. cytology assessment by flow cytometry of
and exfoliative cytology can be the preferred Smoking related systemic and oral dis- DNA adducts, aneuploidy, proliferation
method for screening for oral mucosal lesions. eases. Acta Medica (Hradec Kralové) and apoptosis shows differences between
As oral cancer is a major health problem in the 2007;50:161-6. smokers and non-smokers. Oral Oncol
Sudan, strategy for prevention comprising 11. Ploton D, Menager M, Jeannesson P, et al. 2003;39:842-54.
comprehensive public educational program is Improvement in the staining and in the 23. Caruntu ID, Scutariu MM, Dobrescu G.
highly recommended. All those involved in the visualization of the argyrophilic proteins Computerized morphometric discrimina-
habit of toombak use should undergo a contin- of the nucleolar organizer region at the tion between normal and tumoral cells in
uous screening program. optical level. Histochem J 1986;18:5-14. oral smears. J Cell Mol Med 2005;9:160-8.

Desmoplastic small round cell management of DSRCT is little described.

We report a rare case of a metastasized Correspondence: Dorra Ben-Sellem,
tumor: impact of 18F-FDG PET abdominal DSRCT detected in a 43-year old Service de Biophysique et de Médecine
induced treatment strategy patient whose diagnostic and therapeutic Nucléaire, CHU de Hautepierre, 1, Avenue de
Molière, 67098 Strasbourg, France.
in a patient with long-term strategies were influenced by the 18F-FDG PET-
E-mail: bensellem_dorra@yahoo.fr
CT. The patient is still alive at the time of this
outcome report, ten years after the diagnosis.
Dorra Ben-Sellem,1 Kun-Lun Liu,2 Accepted for publication: 13 July 2009.
Sébastien Cimarelli,3 This work is licensed under a Creative Commons
André Constantinesco,1 Alessio Imperiale1 Case Report Attribution 3.0 License (by-nc 3.0)
1
Service de Biophysique et de Médecine
©Copyright D. Ben-Sellem et al., 2009
Nucléaire, Hôpital de Hautepierre, A 43-year old man with a history of right kid-
Strasbourg, France; 2Service d’Onco- ney cysts was referred to our Institution for doi:10.4081/rt.2009.e19
hématologie, Hôpital de Hautepierre, further evaluation of a preaortic intraperi-
Strasbourg, France; 3Service de Médecine toneal mass incidentally detected during
Nucléaire, Centre Leon Berard, Lyon, abdominal ultrasonography. Clinical examina-
tion and routine biological evaluation showed day 1-3) and etoposide (150 mg/m2 on day 1-3).
France The sequence was repeated every three weeks.
no remarkable findings. Media contrast
enhancement (mce) CT of the abdomen and No concomitant radiotherapy was performed.
pelvis showed the presence of a vascularized, Morphological imaging (CT) performed after 4
preaortic mass (7x5 cm) associated to and 6 cycles of treatment demonstrated com-
Abstract plete remission. No other radiological lesion
retroperitoneal lymphadenopathy and mesen-
teric nodules, for which the diagnosis of malig- was described.
The desmoplastic small round cell tumor nancy was evoked. Chest mce-CT showed nei- In September 2003, retroperitoneal lym-
(DSRCT) is an uncommon and highly aggres- ther pathological lymphadenopathy nor lung phadenophathy was detected on CT study and
sive cancer. The role of 18F-FDG PET in man- parenchyma abnormalities. The serum level of biopsied. Microscopic examination revealed
agement of DSRCT is little reported. We report common tumoral markers was normal. The lymphatic DSRCT relapse. Radiological partial
a case of metastasized abdominal DSRCT results of 24 h urine analysis showed normal remission was obtained after 3 cycles of VIDE,
detected in a 43-year old patient whose diag- concentrations of dopamine, epinephrine and thus 12 cycles i.v. of irinotecan (180 mg/m2 on
nostic and therapeutic approaches were influ- norepinephrine. A whole body (WB) bone scan day 1, every two weeks) were administered as
enced by 18F-FDG PET-CT. The patient is still showed no pathological foci of tracer uptake. a second-line chemotherapy. In an attempt to
alive ten years after diagnosis. 18F-FDG PET-CT An ultrasound guided needle biopsy of preaor- determine the response to therapy, the patient
seems to be a useful method for assessing tic lesion was made for pathological evalua- underwent whole-body (WB) 18F-FDG PET
therapeutic efficiency and detecting early tion. Microscopic examination revealed neo- examination (Figure 1a). A combined PET-CT
recurrences even in rare malignancies such as plastic proliferation of small cells with abun- scanner was employed (Discovery ST, GE
DSRCT. dant and clear cytoplasm. The nuclei were Medical System; Milwaukee, USA). PET-CT
slightly increased in size, oval, hyperchromat- acquisitions started 60 min after tracer injec-
ic, and with inconspicuous nucleoli. The tumor tion (5.5 MBq/kg), including a head to thighs
cells were surrounded by fibro-sclerotic stro- CT followed by a 2D PET. CT, PET (attenuation
Introduction ma. The immunohistochemical studies corrected) and fusioned PET-CT images were
revealed that the tumor cells were positive for displayed and visually interpreted. For quanti-
The desmoplastic small round cell tumor antibodies against keratin, epithelial mem- tative analysis of 18F-FDG tumoral uptake, we
(DSRCT) is an extremely rare and highly brane antigen, vimentin, desmin and focally use the maximum standardized uptake value
aggressive neoplasm mainly affecting adoles- neuron specific enolase. Tumoral proliferation (mSUV) per focus. In all of the PET studies
cents and young male adults.1,2 DSRCT origi- index, estimated with antibodies against Ki- performed, the mSUV was measured in the foci
nates predominantly in the abdominal or pelvic 67, was elevated (50%). Both the histological of highest 18F-FDG uptake within the tumor.
cavity, spreading along the peritoneum with aspect and immunohistochemical profile lead Those values were then considered for tumor
organ involvement and secondary phenome- to the diagnostic hypothesis of DSRCT. The residual viability assessment. 18F-FDG PET-CT
na.3 Despite multimodality aggressive therapy, molecular analysis found no specific gene showed several retroperitoneal lymphadenopa-
patient prognosis is unfavorable, with a medi- translocation t(11;22)(p13;q12). In October thy with pathological glucidic hypermetabo-
an survival of less than 30 months. Only a few 1999, the patient underwent surgery including lism, inducing modification of chemothera-
long-term survivors are reported.4,5 tumoral radical resection, partial sigmoidecto- peutic strategy. Three cycles of actinomicine
To our knowledge, no definitive standard my, and primitive iliac and peri-aortic lym- (2.5 mg/m2 on day 1, every three weeks) were
recommendations exist concerning DSRCT phadectomy. Microscopic analysis of the performed without any considerable effect on
treatment and patient management during fol- excised tumor confirmed biopsy suspicion; tumoral progression. Thereafter, the patient
low-up.3 X-ray Computed Tomography (CT) thus metastatic DSRCT was retained as the was treated by VIP 500, combining i.v. etopo-
remains the first choice imaging modality final diagnosis. side (100 mg/m2 on day 1-5), ifosfamide (1200
employed in patients affected by DSRCT. 18F- Treatment was carried out according to the mg/m2 on day 1-5) and cisplatine (20 mg/m2 on
fluoro-2-deoxy-D-glucose positron emission 99 EURO-EWING protocol.7 From December day 1-5). The sequence was repeated every
tomography (18F-FDG PET) is a functional 1999 to April 2000 the patient received 6 cycles three weeks. WB 18F-FDG PET-CT study was
imaging technique widely used in clinical of VIDE combining intravenous (i.v.) vin- performed after the completion of the first 2 of
oncology because of its high diagnostic accura- cristine (1.5 mg/m2 on day 1), ifosfamide (3000 6 cycles of VIP 500, to assess early response to
cy.6 However, the role of 18F-FDG PET in the mg/m2 on day 1-3), doxorubicin (20 mg/m2 on therapy. A limited area of residual abnormal

Case Report
glucidic hypermetabolism within the reduced

tumoral mass was recorded on PET-CT images.
No other abnormal hypermetabolic spots sug-
gestive of metastatic localizations were detect-
ed. The patient was considered to be a positive
responder to treatment; thus chemotherapy
was completed and followed by oral adminis-
tration of etoposide 50 mg daily. A follow-up 18F-
FDG PET-CT performed in September 2005
demonstrated complete regression of the trac-
er uptake abnormalities above retroperitoneal
lymphadenopathy detected on previous exami-
nation and morphologically unchanged, so the
treatment was stopped (Figure 1b). In
December, the PET-CT study showed no active
disease, and the patient was considered to be
in remission. Figure 1. Whole-body maximum intensity projection 18F-FDG PET-CT images in 43-year
old patient with DSRCT showing: (a) first relapse, (b) complete temporary remission
In June 2006, a follow-up PET-CT study after chemotherapy, (c) second relapse, (d) with moderate response to medical treatment.
showed pathological 18F-FDG uptake within
several retroperitoneal lymphadenopathy of
one centimeter of maximal diameter, consis-
tent with second tumoral relapse (Figure 1c).
Thus, the patient was treated by oral etoposide the predilection of these tumors to metastasize ment efficacy. 18F-FDG PET accuracy is higher
50 mg daily and corticoids 100 mg, day 1-5 through both the lymphatic and hematogenous than that of CT in the assessment of a viable
monthly. Follow-up scintigraphic examination routes.3 In our clinical observation, metastatic tumor after chemoradiation treatment, in par-
was performed in July 2007, demonstrating the proliferation was essentially lymphatic, with- ticular in lymphomas.25 Moreover, the sensitiv-
persistence of hypermetabolic retroperitoneal out soft tissue or bone involvement. ity of a sole morphological approach may be
lymphadenopathy (Figure 1d). The same DSCRT are frequently characterized by a reduced in normal-sized metastatic lymph
chemotherapy was continued including oral recurrent specific translocation t(11;22) node detection, considering size as the princi-
etoposide 50 mg daily, 3-4 days weekly accord- (p13;q12), resulting in a fusion gene between pal diagnostic criteria for tumor involvement.
ing to the hematologic results, associated to Ewing’s sarcoma gene and Wilm’s tumor gene.5 Our results are in accordance with those found
corticoids 100 mg, day 1-5 monthly. The patient Nevertheless, according to several reports,19,22 by Rosoff et al.,24 showing no pathological 18F-
is still alive at the time of this report, ten years no specific gene translocation was found in FDG uptake in PET images above stable lym-
after the diagnosis. our patient. phadenopathy on CT slices, after the comple-
Because of the rarity of this tumor, only case tion of chemotherapy. The non-invasive nature
reports and small series of patients are docu- of PET and its ability to detect early responses
mented, thus no consensus exists concerning to therapy make it an ideal modality to evalu-
Discussion standard methods for its diagnosis, treatment ate the effectiveness of chemotherapy.
and management.3 Prognosis of patients affected by DSRCT is
DSRCT is a rare and highly aggressive Although magnetic resonance imaging has extremely poor, with a median survival of less
malignancy of still unknown etiopathogenesis, been reported to be more useful than other than 30 months and a rate of 3- and 5-year sur-
first described in 1989 by Gerald and Rosai.8 In radiological techniques in delineating the vival of 29% and 15%, respectively.5,21 The long
1991, it was proposed as a distinct entity with extent of the abdominal and pelvic disease,19 survival observed in our patient is largely supe-
well-recognized histological features, kary- CT remains the radiological investigation of rior to the survival reported in the literature.
otype and immunochemical characteristics first choice. DSCRT appear as single, or multi- 18
F-FDG PET-CT played an important role in
with coexpression of epithelial, mesenchymal ple, lobulated soft tissue masses within the patient management, allowing detection of
and neural markers.1,4,9 DSRCT has a predilec- omentum, mesentery, perisplenic space, par- early recurrence of disease and consequent
tion for adolescent and young adult males, with avesical region, retroperitoneum and in the change in chemotherapeutic strategy. The rel-
a median age of 22 years.10 The majority of scrotum.4,21 atively long disease free interval of 42 months
DSCRT occurs in the abdominal cavity, includ- The usefulness of 18F-FDG PET-CT in the may be due to complete tumoral resection fol-
ing retroperitoneum, pelvis, omentum and management of patients affected by DSRCT is lowed by adjuvant chemotherapy.3,5 The inva-
mesentery as primary origin site. Some cases scarcely reported. Dimitrakopoulou-Strauss et sive and disseminated nature of the disease
had presentation sites in the scrotum, pleura, al.,23 recently suggested 18F-FDG PET-CT as a makes radical resection difficult to achieve3,9
lung, mediastenum, chest wall, thigh, intracra- valuable diagnostic tool for monitoring thera- with consequent worse patient prognosis.
nial, soft tissue, sino-nasal regions, submen- peutic effect in patients with metastasized Furthermore, chemotherapeutic agents are
tal, parotid gland and kidney.11-19 DSRCT treated by inhibitors of mammalian only temporarily effective in treating DSRCT
DSCRT are characterized by multinodular target of rapamycin (mTOR). In the report of and no consistent response to chemotherapy
growth on the serosal surface.11,20 These tumors Rosoff et al.,24 18F-FDG PET-CT was explored has been described.9 Patients who present
have a tendency to spread along the peri- with the aim of assessing the therapeutic extra-abdominal tumors that are amenable to
toneum and mesothelial-lined surfaces with effect of irinotecan in a patient with DSRCT complete surgical resection appear to have a
organ involvement and secondary phenome- showing residual mass, morphologically better prognosis.19 In the series reported by
na.3 The most frequent sites of metastasis are unchanged on CT images. PET-CT showed no Saab et al.,19 2 patients with extra-abdominal
the liver, lymph nodes, lung and bone mar- evidence of active disease, especially above tumors had no evidence of disease at eight and
row.3,9,21 This pattern of disease spread reveals pelvic tumor, demonstrating complete treat- ten years, respectively.

Case Report
assessment of intensive induction with Cancer 2005;42:78-84.

Conclusions Vincristine, Ifosfamide, Doxorubicin, and 17. Adsay V, Cheng J, Athanasian E, et al.
Etoposide (VIDE) in the treatment of Primary desmoplastic small cell tumor of
The optimal management for DSRCT Ewing tumors in the EURO-E.W.I.N.G 99 soft tissues and bone of the hand. Am J
remains to be determined. The usefulness of clinical trial. Pediatr Blood Cancer 2006; Surg Pathol 1999;23:1408-13.
non-invasive metabolic imaging modality, such 47:22-9. 18. Finke NM, Lae ME, Lloyd RV, et al. Sinosal
as 18F-FDG PET-CT, may improve the prognosis 8. Gerald WL, Rosai J. Case 2. Desmoplastic desmoplastic small round cell tumor: A
of DSRCT patients by detecting tumoral small cell tumor with divergent differenti- case report. Am J Surg Pathol 2002;26:799-
relapse earlier than conventional anatomic ation. Pediatr Pathol 1989;9:177-83. 803.
imaging. Additional prospective studies are 9. Chang CC, Hsu JT, Tseng J, et al. Combin- 19. Saab R, Khoury JD, Krasin M, et al. Desmo-
needed to confirm these results, assessing the ed resection and multi-agent adjuvant plastic small round cell tumor in childhood:
validity of a morpho-functional approach in chemotherapy for desmoplastic small the St Jude Children’s Hospital experience.
DSRCT management. round cell tumor arising in the abdominal Pediatr Blood Cancer 2007;49: 274-9.
cavity: Report of a case. World J Gastro- 20. Granja NM, Begnami MD, Bortolan J, et al.
enterol 2006;12:800-3. Desmoplastic small round cell tumor:
10. Battisti S, Renaudin K, Rigaud J, et al. Cytological and immunocytochemical fea-
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2. Jellouli M, Mekki M, Krichene I, et al. al. Desmoplastic small round cell tumors of plastic small round cell tumor. Oncology
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review of the literature. Bull Cancer 13. Parkash V, Gerald WL, Parma A, et al. P, Ströbel P, et al. A recent application of
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3. Hassan I, Shyyan R, Donohue JH, et al. pleura. Am J Surg Pathol 1995;19:659-65. tomography, treatment monitoring with a
Intraabdominal desmoplastic small round 14. Karavitakis EM, Moschovi M, Stefanaki K, mammalian target of rapamycin inhibitor:
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4. Hiralal Gamanagatti S, Thulkar S, Rao SK. of the pleura. Pediatr Blood Cancer 2007; tic small round cell tumor. Hell J Nucl Med
Desmoplastic round cell tumour of the 49:335-8. 2007;10:77-9.
abdomen. Singapore Med J 2007;48:19-21. 15. Syed S, Haque AK, Hawkins HK, et al. 24. Rosoff PM, Bayliff S. Successful clinical
5. Mingo L, Seguel F, Rollan V. Intra- Desmoplastic small round cell tumor of the response to Irinotecan in desmoplastic
abdominal desmoplastic small round cell lung. Arch Pathol Lab Med 2002;126:1226- round blue cell tumor. Med Pediatr Oncol
tumour. Pediatr Surg Int 2005;21:279-81. 8. 1999;33:500-3.
6. Gambhir SS, Czernin J, Schwimmer J, et 16. Biswas G, Laskar S, Banavali SD, et al. 25. Coleman M, Kostakoglu L. Early 18F-labeled
al. A tabulated summary of the FDG PET Desmoplastic small round cell tumor: fluoro-2-deoxy-D-glucose positron emis-
literature. J Nucl Med 2001;42:1S-93S. extraabdominal and abdominal presenta- sion tomography scanning in the lym-
7. Juergens C, Weston C, Lewis I, et al. Safety tions and the results of treatment. Indian J phoma. Cancer 2006;107:1425-8.

Epithelioid hemangioendothe- sinus rhythm with a rate of 44 beats/min,

occasional premature ventricular extrasystole Correspondence: Dina El Demellawy,
lioma of the temporal artery on ECG, mild mitral insufficiency, and mild Assistant Professor, Department of Pathology and
presenting as temporal degree of mitral valve prolapse on echocardio- Laboratory Medicine, Northern Ontario School of
Medicine, Thunder Bay, William Osler Health
arteritis: case report and gram. Her cardiac enzymes were negative and
Care, Department of Pathology and Laboratory
chest X-ray was unremarkable. Ultrasound
literature review performed on the left temporal artery showed Medicine, Brampton, Ontario, Canada.
E-mail: dina_eldemellawy@rogers.com
mild aneurysmal dilatation measuring 0.44
Dina El Demellawy,1 Ahmed Nasr,2 cm in maximum diameter. ESR was normal,
Salem Alowami3 Received for publication: 7 July 2009.
instead of being elevated as expected in cases Accepted for publication: 14 July 2009.
1
University of Northern Ontario School of of temporal arteritis. Left temporal artery
Medicine, Thunder Bay, William Osler excisional biopsy was performed. Gross exam- This work is licensed under a Creative Commons
ination showed a hemorrhagic vessel measur- Attribution 3.0 License (by-nc 3.0)
Health Care-Brampton Civic Hospital,
Department of Pathology and Laboratory ing 1.2 cm in length and 0.15 cm in diameter
©Copyright D. El Demellawy et al., 2009
Medicine, Brampton, Ontario, Canada; that harbored a focal aneurysm measuring 0.5
2 cm. Microscopic examination showed a solid doi:10.4081/rt.2009.e20
University of Toronto, Department of
neoplasm arising from the arterial wall
Surgery, Toronto, Ontario, Canada;
3
(Figure 1) partially occluding and involving
McMaster University, Department of the arterial wall. The tumor was formed of
Pathology and Molecular Medicine, sheets and anastomosing bands of plump
Hamilton, Ontario, Canada epithelioid cells that were embedded in a Gieson and Trichrome confirmed that the
myxoid stroma (Figure 1). The tumor cells tumor is originating from the arterial wall
displayed mild pleomorphism, hyperchromat- (Figures 3, 4 and 5). Immunohistochemistry
ic nuclei, and frequent intracytoplasmic lumi- showed the tumor cells to positively react with
Introduction na (Figure 2). Mitotic figures accounting for CD31 (Figure 6), CD34, Factor VIII and
2/10 HPF were identified, however necrosis Vimentin and negatively with Cam 5.2,
In general, vascular tumors encompass a was absent. Special stains using Elastic Van- AE1/AE3, EMA, Actin (Figure 7), Desmin,
spectrum of tumors with hemangiomas repre-
senting the benign group, angiosarcomas that
represent the opposite frankly malignant
group, and an intermediate group of heman-
gioendotheliomas. Hemangioendotheliomas
are classified as epithelioid hemangioen-
dothelioma (EHE), retiform hemangioen-
dothelioma, composite hemangioendothe-
lioma, Kaposiform hemangioendothelioma
(with or without Kasabach-Merritt syn-
Figure 1. Epithe-
drome), and spindle cell hemangioendothe- lioid hemangioen-
lioma. The latter two types of hemangioendothelioma show-
dotheliomas usually follow a benign course, ing epithelioid co-
in contrast to the other types of hemangioen- hesive cells oblit-
erating the lumen
dotheliomas, which are considered as a low- and most of the
grade malignant sarcoma with unpredictable arterial wall. Note
prognosis. EHEs are rare tumors, mostly residual foci of
described in the lungs and liver. Though muscularis media
endothelial in origin, EHEs reported to origi- (HEX100).
nate from arteries are extremely rare. We
report a very rare case of EHE arising from
the temporal artery showing a peculiar pres-
entation.
Case Report
A 41-year old female presented with painful
left temporal artery of one month duration of
acute onset and progressive course. The
Figure 2. Epithe-
patient’s past medical and family history was lioid hemangioen-
insignificant except for bradycardia of dothelioma show-
unknown etiology and mitral valve prolapse. ing mild pleomor-
Physical examination revealed a resting heart phism, and hyper-
rate of 40 beats/min and a thickened palpable chromatic nuclei
(HEX400).
left temporal artery. Investigations revealed a

Case Report
largest series of 137 cases. EHE is a rare vascu-

lar tumor that is intermediate in morphological
features and biological behavior between
hemangioma and conventional angiosarcoma.
EHE has been reported in the liver, lung, gas-
trointestinal tract, head and neck, central nerv-
ous system, heart, and bone.4-11 Tumor demogra-
phy and presentation is influenced by its loca-
tion but, in general, these tumors affect middle-
aged individuals. Liver and lung lesions are
more common in females, whereas tumors of
Figure 3. Elastic the bone and soft tissues have an equal sex dis-
lamina within the tribution.12 EHEs present variably with the
arterial wall high- majority of patients’ symptoms related to the
lighted by elastic tumor mass effect. Although EHEs originate
stain (Elastic Van-
Gieson X100). from endothelial cells, those originating from
small sized peripheral arteries are rarely
described.13-16 To the best of our knowledge, 5
cases of EHEs have been reported (including the
current case) (Table 1).13-16 However, none origi-
nated from the temporal arteries and only a sin-
gle case showed symptoms mimicking dissemi-
nated vasculitis16 associated with an elevated
ESR. In the current case, several differentials
were considered including those of endothelial
cell origin such as Masson hemangioma (papil-
lary endothelial hyperplasia), epithelioid
hemangiomas, and angiosarcoma. The non-
endothelial cell origin differentials were
metastatic carcinoma, mesenchymal tumors
Figure 4. Elastic
lamina within the such as intra-vascular fasciitis, myxoid chon-
arterial wall high- drosarcoma and epithelioid sarcoma, metastatic
lighted by elastic malignant melanoma and pecomas. The pres-
stain (Elastic Van- ence of the myxoid matrix, cellular atypia, tumor
Gieson X400). infiltration into the media and adventitia, and
the absence of thrombosis excluded heman-
gioma and papillary endothelial hyperplasia. The
absence of profound atypia, brisk mitoses,
necrosis and intercommunicating channels
excluded the possibility of angiosarcomas and,
in addition, the long uncomplicated follow-up of
the patient did not suggest angiosarcoma. The
immunoprofile of the tumor with diffuse and
intense expression of CD31, CD34 and
Vimentin, and the absence of Keratin, as well as
melanoma, muscle and histiocytic markers is
classic for a vascular tumor, excluding tumors of
Figure 5. Epithe-
lioid hemangioen- non-endothelial origin. EHE is a well-differenti-
dothelioma with ated endothelial tumor with unpredictable
elastic trichome behavior. Unlike angiosarcoma, the histological
highlights stromal grading system is not useful for predicting its
reaction (Elastic prognosis. As a result, the treatment options are
Trichrome X400).
still controversial. For excised tumors, radia-
tion17 and interferon therapy may be used in an
attempt to restrain growth of incompletely
S100, Melan A, HMB 45, and CD 68. The case removed tumors.18 In addition, the former may
was diagnosed as EHE of the temporal artery. Discussion sclerose the blood vessels. In our case, the
patient received no further therapy because
The patient underwent thorough investiga-
thorough imaging showed no evidence of resid-
tion by imaging which documented the EHE is a distinct entity that was first
ual disease. In conclusion, we report a remote
absence of any suspicious lesion or residual described by Weiss and Enzinger in 1982,1 and case of EHE involving the temporal artery and
tumor. The patient was followed up for three studied in detail by Ishak et al.2 in 1984, who presenting as temporal arteritis. To the best of
years, during which symptoms and signs of described 32 cases. However, a decade and a half our knowledge, this is the first case report of
recurrence or/and metastasis were absent. later in 1999, Makhlouf et al.3 reported the EHE in this location and with such presentation.

Article
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dothelioma infil- year follow-up. Cardiovasc Pathol 2007;
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wall with residual 16:183-6.
foci of muscularis 11. Kleer CG, Unni KK, Mcleod RA. Epithelioid
media highlight- hemangioendothelioma of bone. Am J
ened by actin. Surg Pathol 1996;20:1301-11.
(X400).
12. Weiss SW, Goldblum J, Enzinger FM.
Enzinger and Weiss' Soft Tissue Tumors
(4th ed). Philadelphia, PA: Mosby, 2001:
891-914.
Table 1. Reported cases of epithelioid hemangioendothelioma of small arteries.
13. Koh YC, Yoo H. Epithelioid haemangioen-
Case report Age in Gender Presentation and Artery Laterality Follow-up dothelioma of the sphenoid bone. J Clin
years clinical diagnosis of origin Neurosci 2001;8:63-6.
14. Tayeb T, Bouzaiene M. Epithelioid heman-
Koh et al. 26 Female Progressing Middle Left Not stated
gioendothelioma mimicking an occipital
(2001)13 exophthalmos meningeal
artery artery aneurysm. Rev Stomatol Chir
Maxillofac 2007;108:451-4.
Tayeb & 29 Female Scalp nodule, Occipital Right No recurrence 15. Akashi K, Yasuda M, Suto R, et al. A case of
Bouzaeine clinically occipital or metastasis
epithelioid hemangioendothelioma asso-
(2007)14 artery aneurysm
ciated with an artery. Tokai J Exp Clin Med
Akashi et al . 67 Female Elbow lump Branchial Left No recurrence 1997;22:65-9.
(1997)15 or metastasis
16. Castello P, Caronno R, Piffaretti G, Tozzi
Castello et al. 26 Male Forearm Radial Right Not stated M. Epithelioid hemangioendothelioma of
(2005)16 Painless mass the radial artery. J Vasc Surg 2005;41: 151-
El Demellawy et al. 41 Female Painful temple, Temporal Left No recurrence 4.
(unpublished data, clinically temporal or metastasis 17. Kubota T, Sato K, Takeuchi H, Handa Y.
2009) arteritis Successful removal after radiotheraphy
and vascular embolization in a huge tento-
rial epithelioid hemangiendothelioma: a
2. Ishak KG, Sesterhenn IA, Goodman ZD, et case report. J Neurooncol 2004;68:177-83.
References al. Epithelioid hemangioendothelioma of 18. Palmieri G, Montella L, Martignetti A,
the liver: a clinicopathologic and follow-up Bianco AR. Interferon alpha-2b at low dose
1. Weiss SW, Enzinger FM. Epithelioid study of 32 cases. Hum Pathol 1984;15839- as long-term antiangiogenic treatment of
hemangioendothelioma: a vascular tumor 52. a metastatic intracranial hemangioen-
often mistaken for carcinoma. Cancer 3. Makhlouf HR, Ishak KG, Goodman ZD. dothelioma: a case report. Oncol Rep 2000;
1982;50:970-81. Epithelioid hemangioendothelioma of the 7:145-9.

Retrorectal epidermoid cyst sented with urinary discomfort and constipa-

tion from one month. She had not been able to Correspondence: Masaru Hayashi,
with unusually elevated serum urinate for a few days previously without Department of Obstetrics and Gynecology,
SCC level, initially diagnosed as pressing herself. She consulted a previous hos- Dokkyo Medical University, 880 Kitakobayashi,
Mibu-chou, Shimotsuga-gun, Tochigi 321-0293,
an ovarian tumor pital’s department of obstetrics and gynecolo-
Japan. E-mail: ma-haya@dokkyomed.ac.jp
gy. In that hospital, the diagnosis was an ovar-
Masaru Hayashi,1 Shigeki Tomita,2 ian tumor, and she was introduced to our
Key words: developmental cysts, retrorectal epi-
Takahiro Fujimori,2 Hitoshi Nagata,3 department for curative surgery. In the inter-
dermoid cyst, SCC-antigen, serum SCC, ovarian
nal and rectal examination, a hard, cystic, non- tumor.
Keiichi Kubota,3 Akiko Shoda,1
removable, mass larger than a fist was palpat-
Kazumi Tada,1 Nobuaki Kosaka,1
ed in the left side of rectum and the posterior Acknowledgments: we would like to thank Ms.
Ichio Fukasawa,1 Noriyuki Inaba1 of the uterus. We could not insert a speculum Chiaki Matsuyama, Department of Surgical and
1
Department of Obstetrics and and a probe for transvaginal sonography into Molecular Pathology, Dokkyo Medical University
Gynecology, Dokkyo Medical University, her vagina because of the tumor’s strong com- for her skillful technical assistance.
Mibu, Tochigi, Japan; 2Department of pression. MRI revealed a unilocular cystic
Surgical and Molecular Pathology, tumor measuring 11x11x12 cm in the bottom Contributions: MH, mainly took charge of this
of the pelvic cavity, compressed rectum, uter- patient as a gynecologist, and conceived,
Dokkyo Medical University, Mibu, Tochigi,
ine cervix, vagina and urinary bladder (Figure designed and supervised this manuscript; AS, KT
Japan; 3Department of Surgery 2, Dokkyo and NK, also took charge of this patient; IF and
Medical University, Mibu, Tochigi, Japan 1). The contents of this cyst consisted of two
NI, reviewed this manuscript; ST and TF, diag-
different kinds of fluid, and there was a border- nosed this tumor pathologically,and performed
line between them. The content in the back immunohistochemical study; HN and KK, took
side had T1 weighted-low intensity, T2 weight- charge of this patient as a surgeon.
Abstract ed-high intensity signal. The abdominal side
showed T1 weighted-iso intensity, T2 weight- Conflict of interest: the authors report no con-
ed-moderately high intensity signal. There flicts of interest. The authors alone are responsi-
Retrorectal epidermoid cyst is one of the ble for the content and writing of the paper.
were some heterogeneous contents in both flu-
developmental cysts which arise from rem-
ids (Figure 1). Given the fat suppressive condi-
nants of embryonic tissues. We report a rare Received for publication: 2 July 2009.
tion, this T1 weighted-iso intensity area slight- Accepted for publication: 3 July 2009.
case of retrorectal epidermoid cyst, initially
ly reduced its signal. The content in the center
diagnosed as an ovarian tumor. Serum SCC This work is licensed under a Creative Commons
of the abdominal fluid had much reduced its
value as tumor marker was elevated to the Attribution 3.0 License (by-nc 3.0)
signal by this condition. This means the
high level. Laparoscopy revealed ovaries,
abdominal side of this cyst contains a fat ele-
uterus and other pelvic organs were all normal. ©Copyright M. Hayashi et al., 2009
ment. The wall in this cyst was thin and Rare Tumors 2009; 1:e21
This tumor existed in the retroperitoneal cavi-
smooth. There was neither solid part in the doi:10.4081/rt.2009.e21
ty and compressed the rectum. Later, complete tumor nor signs of invasion into surrounding
tumor resection was performed by laparotomy. tissues. White blood cell (10.5×109/L) and C-
Histological study revealed the epithelium of reactive protein (2.05 mg/dL) were slightly ele-
this tumor consisted of only squamous cells vated. Other laboratory data were within nor-
without atypia, and the diagnosis of this tumor mal limits. In these clinical findings, the diag- tumor adhered to the posterior wall of the rec-
was retrorectal epidermoid cyst. Retrorectal nosis before the operation was an ovarian tum, but complete resection was possible and
epidermoid cyst is very rare, and difficult to tumor, and in particular, a mature cystic ter- was performed. Both intra-operative frozen
diagnose before surgery. However, if we have- atoma of the ovary was suspected from image section analysis and the cytology of the tumor’s
knowledge of developmental cysts, and by care- diagnosis. Laparoscopy was performed for liquid contents did not show any malignant
ful digital examination and image diagnosis, a diagnosis and treatment in the same day. finding. The resected-tumor measured 12×10
differential diagnosis can be made. However, it revealed ovaries, uterus and other cm, and it was light gray-colored, elastic, hard
intra-peritoneal pelvic organs were all normal. and unicystic. The cyst wall was thin and
This tumor was in the retroperitoneal cavity, degenerated. It weighed approximately 500
and compressed the rectum to the right and grams as a whole tumor. The content of this
Introduction anterior side (Figure 2). Since we could not cyst was filled with 300 mL of dense muddy and
make a diagnosis of this retroperitoneal tumor, fatty fluid, which partially curdled.
Retrorectal epidermoid cyst is one of the we consulted the department of surgical gas- The cytology of this content showed abun-
developmental cysts which arise from remnants troenterology, and we abandoned the sequen- dant white blood cells and squamous cells
of embryonic tissues. Because of the rarity of tial curative operation by laparoscopy. More without any atypia (Figure 3). Histological
these tumors in adults, the differential diagno- clinical examinations were performed after study revealed that this tumor had a unicystic
sis is very difficult before surgery. We report a laparoscopy including colonoscope, 3D CT. structure, and the epithelium of this cyst wall
rare case of retrorectal epidermoid cyst which Serum tumor markers were also proven out consisted of only keratinized, stratified squa-
showed the elevated serum SCC level, and was after laparoscopy. SCC value was elevated to mous cells (Figure 4A and B). Some portion of
initially diagnosed as an ovarian tumor. 30.4 ng/mL (cut-off value is 1.5 ng/mL). Other squamous epithelium almost maintained a
tumor markers such as CA125, CA19-9, CEA, stratified layer structure (Figure 4A), another
AFP, CA72-4, CA15-3 and TPA were all within portion of these peeled off from their outer
normal limits. On the following days, laparoto- surface (Figure 4B). There was no atypia of
Case Report my was performed for curative excision of this squamous epithelium. According to these
tumor with some malignant possibilities pathological findings, this tumor was diag-
A 22-year old woman, gravida 1, para 0, pre- because of the elevated serum SCC level. This nosed as an epidermoid cyst, which was one of

Case Report
resection of this tumor, serum SCC level was

A B normalized. This case has been free of recur-
rence and her serum SCC level also has
remained within normal range for two years
after surgery.
Materials and Methods

Immunohistochemical study was performed
by the common avidin-biotin complex method
C using anti-CEA antibody (Histofine SAB-
PO(M) Kit®; Nichirei Bio Science, Japan),
anti-CA19-9 antibody (DAKO, USA) and anti-
SCC-antigen antibody (Hepa-Ab®; XEPTAGEN,
Italy). Hepa-Ab® recently became available for
the detection of SCC-antigen in the immuno-
Figure 1. Pre-operative diagnosis of the histochemical study.
retrorectal epidermoid cyst by magnetic reso-
nance imaging (MRI); Open arrowhead indi-
cates uterine cervix, and closed arrowhead
indicates vaginal cavity. Open arrow indicates
rectum. Closed arrow indicates some hetero- Discussion
geneous contents in both fluids. (A) T1-
weighted transverse MRI. (B) T2-weighted
transverse MRI. (C) T2-weighted sagittal Retrorectal cysts are rare in adults. The inci-
MRI. dence of these tumors is estimated at 1/40,000-
63,000 admissions to large referral centers.1
The etiology of these cysts is classified into
five categories,2 which are congenital, neuro-
genic, inflammatory, osseous and miscella-
neous. Most cases of 16 retrorectal cysts are
congenital for 55-70%,1-3 and most of congeni-
tal retrorectal cysts are developmental cysts,
Figure 2. Laparoscopic finding which are 60% of them.1,2 The term “develop-
in the pelvic cavity; open mental cysts” was initially proposed and
arrowhead indicates rectum, defined by Hawkins in 1953.4 These are
which was compressed and thought to arise from caudal embryonic ves-
shifted to the right and anterior tiges,4 and occur mostly in middle-aged women
side by the retrorectal epider-
moid cyst. Arrow indicates the and in 3:1 female:male ratio.5 Originally, these
retrorectal epidermoid cyst as a are classified into the three subtypes by histo-
retroperitoneal tumor. logical findings, which are epidermoid cyst,
dermoid cyst, and tailgut cyst.4 Both epider-
moid cyst and dermoid cyst are lined with
stratified squamous epithelium, but dermoid
cyst also contains skin appendages, such as
hair follicle, sweat glands and tooth buds. Both
cysts result from closure defects of the ectoder-
mal tube with skin inclusion. Tailgut cyst, also
known as retrorectal cystic hamartoma or
mucus secreting cyst, is lined with various
epitheliums such as columnar cells, squamous
cells, and transitional cells, often in combina-
tions of these. This cyst arises from the rem-
Figure 3. Cytology of the con- nants of the embryonic postnatal gut.4-7 The
tents in the presacral epider- clinical presentation of retrorectal develop-
moid cyst; Papanicolaou stain
(x800). ment cysts is often non-specific, and half of
them are asymptomatic, which are incidental-
ly discovered during routine physical examina-
the developmental cysts. Immunohisto- tive in the peeled and peeling keratinized tion. The most common symptom is related to
chemical studies using anti-CEA, CA19-9, and epithelium (Figure 5A2). SCC-antigen was tumor effect arisen by compression to the rec-
SCC-antigen antibodies were performed. strongly positive in the stratified squamous tum and lower urinary tract, such as constipa-
CA19-9 was negative. On the other hand, CEA epithelium (Figure 5B1). Especially in the tion and urinary frequency.5-9 The other com-
was weekly positive in the stratified squamous peeled and peeling keratinized epithelium, it mon symptom is pain when these cysts are
epithelium (Figure 5A1) and moderately posi- was intensively positive (Figure 5B2). After infected or generate malignant transforma-

Case Report
A B Figure 4. Patholo-
gical features of the
retrorectal epider-
moid cyst; H.E.
stain (x200). (A)
Stratified squamous
epithelium. (B)
Peeling and peeled
squamous epitheli-
um.
A1 A2 Figure 5. Immuno-
histochemical stud-
ies of the retrorectal
epidermoid cyst.
(A) Immunostaining
for CEA (x200).
(A1) Stratified squa-
mous epithelium.
(A2) Peeling and
peeled squamous
epithelium.
(B) Immuno-stain-
ing for SCC antigen
(x200).
(B1) Stratified squa-
mous epithelium.
(B2). Peeling and
peeled squamous
B1 B2 epithelium.
tion.6,9 Chronic infection occurs in 30-50% of reported including our case. Malignant trans- there is no report that the serum tumor mark-
developmental cysts.10 Infected cysts are source formation occurred in 4 cases (6.9%) of these; er is positive as far as we know in the English
of a perianal abscess or a draining sinus. How all were squamous cell carcinoma.13 For the language literature. Nagano reported SCC,
infection originates is unknown, but trauma treatment of developmental cysts, complete CA19-9, CA125 and CEA levels in the aspirated
and infection by the lymphatics or a congenital surgical resection is recommended so as not to fluid of one malignant retrorectal epidermoid
sinus have been suggested.7 Malignant trans- cause infection, recurrence or generate malig- cyst case (squamous cell carcinoma) were all
formation of developmental cysts is rare. Abel nant transformation.5,7,9 If the patients do not extensively elevated; however, all serum levels
reported an incidence of 8% in developmental have any clinical17 symptom or sufficient clini- were within the normal limit. We did not meas-
cysts.10 Hjermstad reported one case of malig- cal findings present any possibilities of malig- ure the tumor marker level of its contents.
nant transformation, which histology con- nancy, surgical resection should be performed From the result of immunohistochemical study
firmed was poorly differentiated mucinous because of the difficulties of operating once and this case’s clinical course, we supposed
adenocarcinoma, in 53 cases of tailgut cysts.11 infection has occurred in the developmental elevated serum SCC level was the cause in this
Killingstone reviewed 43 cases of tailgut cyst. cysts.7 Regarding serum tumor markers of the case. Subacute inflammation on her epider-
The malignancy arose in 17 cases of these; developmental cysts, there were some reports moid cyst occurred due to physical stimuli or
adenocarcinoma in 11 cases, carcinoid in 5 that serum CEA and/or CA19-9 level were ele- unknown cause, and then squamous cell of
cases and neuroendocrine in one case.12 In vated in the malignant tailgut cases.14-16 epithelium in the epidermoid cyst degenerated
Japan, 58 cases of epidermoid cysts have been However, in the retrorectal epidermoid cyst, and peeled off. Consequently, the SCC-antigen

Case Report
was released into the blood circulation. presentation and management of pre- 12. Killingsworth C, Gadacz TR. Tailgut cyst
Because of the rarity of developmental cysts, sacral tumors. Br J Surg 1986;73:153-5. (retrorectal cystic hamartoma): report of a
they are very frequently misdiagnosed and 4. Hawkins WJ, Jackman RJ. Developmental case and review of the literature. Am Surg
inappropriate surgery is performed.6 If a gyne- cysts as a source of perianal abscesses, 2005;71:666-73.
cologist initially finds a retrorectal cyst, most sinuses and fistulas. Am J Surg 1953;86: 13. Tsukamoto Y, Samizo M, Takahashi T,
cases will be misdiagnosed as an ovarian 678-83. Maekawa T, Miyashita M. A case of adult
tumor. Retrorectal epidermoid cyst contains 5. Dahan H, Arrivé L, Wendum D, et al. Retro- presacral epidermoid cyst. Jpn J Gastro-
fatty elements such as desquamated debris, rectal developmental cysts in adults: clini- enterol Surg 2008;41:705-10.
cholesterol, keratin, and water.18 A gynecologist cal and radiologic histopathologic, differ- 14. Maruyama A, Murabayashi K, Hayashi M,
confuses these elements in the epidermoid ential diagnosis, and treatment. et al. Adenocarcinoma arising in a tailgut
cyst with that of mature cystic teratoma, which Radiographics 2001;21:575-84. cyst: report of a case. Surg Today 1998;28:
is a common ovarian tumor. However, if we 6. Singer MA, Cintron JR, Martz JE, et al. 1319-22.
have knowledge of the developmental cysts, by Retrorectal cyst: a rare tumor frequently 15. Schwarz RE, Lyda M, Lew M, Paz IB. A car-
careful digital examination and image diagno- misdiagnosed. J Am Coll Surg 2003;196:
cinoembryonic antigen-secreting adeno-
880-6.
sis, it is possible to make a differential diagno- carcinoma arising within a retrorectal
7. Theuerkauf FJ Jr, Hill JR, ReMine WH.
sis, since developmental cysts exist between tailgut cyst: clinicopathological considera-
Presacral developmental cysts in mother
the presacral and retrorectal space, not in the tions. Am J Gastroenterol 2000;95:1344-7.
and daughter: report of cases. Dis Colon
Douglas pouch like an ovarian tumor.18 16. Cho BC, Kim NK, Lim BJ, et al. A carci-
Rectum 1970;13:127-32.
8. Hobson KG, Ghaemmaghami V, Roe JP, et noembryonic antigen-secreting adenocar-
al. Tumors of the retrorectal space. Dis cinoma arising in tailgut cyst: clinical
Colon Rectum 2005;48:1964-74. implications of carcinoembryonic antigen.
References 9. Mentes BB, Kurukahvecioglu O, Ege B, et Yonsei Med J 2005;46:555-61.
al. Retrorectal tumors: a case series. Turk 17. Nagano Y, Yoshimoto N, Nakajima S,
1. Jao SW, Beart RW Jr, Spencer RJ, et al. J Gastroenterol 2008;19:40-4. Hosoi H. Squamous cell carcinoma arising
Retrorectal tumors: Mayo Clinic experi- 10. Abel ME, Nelson R, Prasad ML, et al. Para- from presacral epidermoid cyst in an adult,
ence, 1960-1979. Dis Colon Rectum 1985; sacrococcygeal approach for the resection report of a case. Nihon Rinsho Geka
28:644-52. of retrorectal developmental cysts. Dis Gakkai Zasshi 1998; 59: 2695-9.
2. Uhlig BF, Johnson RI. Presacral tumors Colon Rectum 1985;28:855-8. 18. Hannon J, Subramony C, Scott-Conner CE.
and cysts in adults. Dis Colon Rectum 11. Hjermstad BM, Helwig EB. Tailgut cysts. Benign retrorectal tumors in adults: the
1975;18:581-9. Report of 53 cases. Am J Clin Pathol 1988; choice of operative approach. Am Surg
3. Stewart RJ, Humphrevs WG, Parks TG. The 89:139-47. 1994;60:267-72.

Metastatic rectal cancer Case Report Correspondence: Sergio Huerta,

to the breast Assistant Professor of Surgery, Surgical Services
A 54-year old African American female pre- (112), 4500 S. Lancaster Road, Dallas, TX 75225,
Hsiao C. Li,1 Prapti Patel,1 Payal Kapur,2 sented with nausea, vomiting, and abdominal USA. E-mail: sergio.huerta@utSouthwestern.edu
Sergio Huerta3 pain. A computed tomography scan of the
Key words: metastatectomy, palliative surgery,
University of Texas Southwestern abdomen and pelvis showed diffuse wall thick-
fine needle aspiration, colonoscopy.
Medical Center/Dallas VA Medical Center ening of the small bowel, colon, and rectum
Departments of 1Medical Oncology, with ascites (Figure 1A). An exploratory Received for publication: 12 July 2009.
2
Pathology and 3Surgery, Dallas, TX, USA laparotomy revealed a massive amount of Accepted for publication: 24 July 2009.
purulent fluid and multiple loculated abscesses
as well as a rectal mass. A rigid proctoscopy This work is licensed under a Creative Commons
showed the mass to be 3-4 cm from the anal Attribution 3.0 License (by-nc 3.0)
Abstract verge with an obvious perforation. Drains were

©Copyright H.C. Li et al., 2009
placed and a diverting colostomy was per-
formed. Pathological evaluation of a surgical doi:10.4081/rt.2009.e22
Rectal cancer metastatic to the breast is an specimen taken from the rectum showed an
exceedingly rare event with around 15 cases invasive poorly differentiated adenocarcinoma
reported in the literature. A metastatic breast (Figure 2A, B, and C). A CT scan performed two
deposit from the rectum signifies diffuse dis- weeks after this operation showed a large het- ill-defined margins as well as an oval hypoe-
seminated disease or a highly aggressive erogeneous soft tissue mass that distended the choic solid mass measuring 2.4 cm in the right
tumor such that surgical intervention other rectum to 8 cm with no evidence of metas- axilla. An ultrasound guided core biopsy of
than palliation has a limited role. In the pres- tases. She was clinically staged as having both the right breast mass and the right axil-
ent report, we discuss a patient who present- cT4NxM0 adenocarcinoma of the rectum. She lary lymph node showed poorly differentiated
ed with rectal cancer and developed a breast remained in the hospital for two months due to invasive adenocarcinoma with no normal
metastatic deposit. She soon developed pro- infectious complications then received pre- breast parenchyma or in situ breast carcinoma.
gressive metastatic involvement of the lungs operative radiation to a dose of 5040 cGy over When compared to the specimen from the pre-
and the soft tissues and succumbed to the a period of 44 days. Concurrent chemotherapy vious rectal mass, the poorly differentiated
malignant course of this disease 12 months was recommended, but not delivered because areas of the rectal biopsy showed a similar
after the diagnosis of the primary rectal tumor. the patient missed multiple appointments with morphology to the tumors in the breast and
medical oncology. After the completion of her right axilla. Immunostains showed the breast
radiation therapy, however, she did receive and right axillary tumors to be negative for
three cycles of capecitabine and oxaliplatin estrogen receptor, progesterone receptor, Her-
Introduction with a partial response in the rectum. A total 2/neu, CK7, mammoglobin, BRST-2, and
mesorectal excision was planned, but the MUC2, focally positive for monoclonal CEA and
Rectal cancer is expected to affect 40,870 patient then developed a firm 3 cm mass in the CDX2, and positive for MUC1. Fluorescent in
Americans in 2009.1 Up to 30% of patients with upper outer quadrant of the right breast at situ hybridization for Her-2/neu was non-
attempted curative surgical intervention will 10:00 with a 2 cm firm mobile lymph node in amplified (Figure 3A, B, and C). A repeat com-
eventually develop regional recurrence.2 the right axilla. Mammographic examination puted tomography scan showed new pul-
Further, nearly 70% of these patients have local showed a 3.2 cm indistinctly marginated mass monary nodules. Thus, systemic chemotherapy
recurrence as well as distant metastases.3 (Figure 1B). An ultrasound of the right breast with capecitabine and oxaliplatin was
Nineteen percent of patients newly diagnosed showed a 3.7 cm hypoechoic, round mass with resumed. After one cycle, she developed a new
with colorectal cancer present with distant
metastasis at the time of diagnosis4,5 and col-
orectal cancer patients treated for cure will
develop metastatic disease of some form in
nearly 40% of cases.6 Colorectal cancers most
typically metastasize to regional lymph nodes.
The liver is the most common site of distant
metastasis followed by the lungs and bone. Up
to one quarter of liver metastases present syn-
chronously, but most commonly liver lesions
develop metachronously following treatment of
the primary colorectal tumor. Metastases from
rectal cancer to multiple organs have been
reported either as synchronous lesions or
metachronous events.7-11 In either setting,
metastatic disease from the rectum to unusual
sites such as the spleen, skin or breast carries
a substantially poor prognosis. In the following
report, we present a patient with rectal cancer
metastatic to the breast whose aggressive Figure 1. Computed tomography of the abdomen and pelvis. (A) Demonstrated a thick-
ened bowel with a mass in the rectum (arrow). This study was obtained prior to treat-
tumor led to her demise within a year follow- ment. A mammogram of the breast (B) demonstrated a lesion shown by the arrow.
ing the initial diagnosis of rectal cancer.

Case Report
5 cm soft tissue mass at the level of the skull

base that displaced the cervical right internal
carotid artery interiorly, encased the right ver-
tebral artery, and compressed the right inter-
nal jugular vein. She received palliative radia-
tion therapy to this area. Unfortunately, she
soon developed a new mass adjacent to the pri-
mary rectal cancer that caused right hydro-
dronephrosis for which she had a right percu-
Figure 2. Photomicrograph of rectal mass showing a poorly differentiated adenocarcino-
ma with focal better-differentiated component (right). (A) Hematoxylin and eosin stain taneous nephrostomy tube placed. Two weeks
(H&E), x200. (B) Cytokeratin 20 (CK20) immunoreactivity in more differentiated com- after this insult, she developed a small bowel
ponent only, x200; (C) CDX2 immunoreactivity in more differentiated area, x200. obstruction. Following aggressive systemic
chemotherapy, she was unable to overcome the
aggressive metastatic course of the primary
tumor and expired one year after her initial
diagnosis.
Discussion
The management of disseminated metastat-
Figure 3. Photomicrograph of breast mass showing morphology and immunoprofile sim- ic colon cancer remains a clinical challenge
ilar to the poorly differentiated adenocarcinoma in the rectum with associated dirty and surgical intervention has a limited role,
necrosis. (A) Hematoxylin and eosin stain, x200. (B) Focal CDX2 immunoreactivity,
x200. (C) Focal villin immunoreactivity, x200. typically performed exclusively for palliation.
Metastatic spread from rectal cancer occurs
both by lymphatic and hematogenous routes.
Rectal metastasis to various organs
Owing to the venous drainage into the portal
system from the superior hemorrhoidal vein,
Liver the liver is the most common site of distant
Lung metastasis from rectal cancer.12 Systemic
Bone drainage into the inferior vena cava from the
Pancreas
inferior hemorroidal plexus may lead to
metastatic involvement to the lung and bone.
Adrenal glands Unusual metastatic lesions from the rectum
Cutaneous to the pancreas (~ 7%)7,8 and adrenal glands
Breast have been reported (2-17%).9 Even more
unusual sites of metastasis originating from
the rectum have been documented to the skin
(<4%)10 and the breast (Figure 4).11
Involvement of the skin or breast from rectal
Figure 4. Frequency of rectal metastasis to various organs. The most common sites are the cancer signifies disseminated metastatic dis-
liver and lungs. ease and the prognosis for these patients is
exceedingly poor with less than a 20% 1-year
Results of 32 FNAs with metastatic deposits to the breast survival. The breast is an unusual site for
metastatic deposits. The most common
Melanoma metastatic deposit of the breast is the result of
Lung (SCC) a contralateral primary breast carcinoma.13
Lung (Adenoca.) Fine needle aspiration will identify extra-
mammary malignancy metastatic to the breast
Lung (Carcinoid)
with a range of 0.5-5%.14 The three most com-
NHL mon extra-mammary malignancies are bron-
Colon chogenic carcinoma, melanoma, and lym-
Sarcoma phoma.13-15 A wide array of rare metastatic
Gyn (endometrial, ovarian) deposits might also occur with much less fre-
Other quency and these include: papillary cancer of
the ovary, squamous carcinoma (SCC) of the
nasal cavity, SCC of the cervix, endometrial
adenocarcinoma, gastric cancer, and bladder
(Figure 5).13-15 Extra-mammary metastatic
Lung
deposits originating from the rectum is an
Figure 5. Thirty-two fine needle aspiration specimens with mestatatic deposits to the exceedingly rare event. Metastases from the
breast in 31 women and 1 man (age 61±3 years old) [range 14-91 years]. The most com- colon to the breast were first reported by
mon origin was cutaneous melanoma.14
McIntosh16 and from the rectum by Lal in

Case Report
1999.17 Around 15 reports of rectal metastases 2. Wanebo HJ, Koness RJ, Vezeridis MP, et al. 11. Sanchez LD, Chelliah T, Meisher I, et al.
to the breast have been documented since ini- Pelvic resection of recurrent rectal cancer. Rare case of breast tumor secondary to
tially described.11 As in the case in the present Ann Surg 1994;220:586-95. rectal adenocarcinoma. South Med J 2008;
report, most patients succumb to the aggres- 3. Chari RS, Tyler DS, Anscher MS, et al. 101:1062-4.
sive course of the disease within a year after Preoperative radiation and chemotherapy 12. Yoo PS, Lopez-Soler RI, Longo WE, et al.
the diagnosis of the primary tumor. The man- in the treatment of adenocarcinoma of the Liver resection for metastatic colorectal
agement of disseminated metastatic rectal rectum. Ann Surg 1995;221:778-86. cancer in the age of neoadjuvant
cancer remains a clinical and multidisciplinary 4. Foster JH. Treatment of metastatic disease chemotherapy and bevacizumab. Clin
challenge. In the past, patients would receive of the liver: a skeptic's view. Semin Liver Colorectal Cancer 2006;6:202-7.
systemic chemotherapy until their ultimate Dis 1984;4:170-9. 13. Muttarak M, Nimmonrat A, Chaiwun B.
demise. However, metastatectomies are 5. Jemal A, Siegel R, Ward E, et al. Cancer Metastatic carcinoma to the male and
becoming increasingly common. Traditionally, statistics, 2008. CA Cancer J Clin 2008; female breast. Australas Radiol 1998;
metastatectomies have been performed for col- 58:71-96. 42:16-9.
orectal liver and lung metastases as this has 6. Wolpin BM, Meyerhardt JA, Mamon HJ, et
14. Wood B, Sterrett G, Frost F, et al. Diagnosis
clearly improved the survival of patients whose al. Adjuvant treatment of colorectal cancer.
of extramammary malignancy metastatic
primary disease has been controlled.12,18 CA Cancer J Clin 2007;57:168-85.
to the breast by fine needle biopsy.
Metastatectomies for adrenal9 and pancreatic 7. Bachmann J, Michalski CW, Bergmann F,
Pathology 2008; 40:345-51.
tumors7,8 have also been performed with suc- et al. Metastasis of rectal adenocarcinoma
cessful outcomes. However, metastasis to the 15. Domanski HA. Metastases to the breast
to the pancreas. Two case reports and a
breast from rectal cancer signifies disseminat- from extramammary neoplasms. A report
review of the literature. JOP 2007;8:214-
ed metastatic disease or a highly aggressive 22. of six cases with diagnosis by fine needle
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ting have a limited role other than palliation. Rectal cancer metastasis to the head of the 1293-300.
The main form of treatment for these patients pancreas treated with pancreaticoduo- 16. McIntosh IH, Hooper AA, Millis RR, et al.
is systemic chemotherapy. denectomy. J Hepatobiliary Pancreat Surg Metastatic carcinoma within the breast.
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225-49. Nurs 2003;15:131-2. metastases. Eur J Cancer 2006;42:2212-21.

Plexiform neurofibroma in the Case Report

Correspondence: Sojun Hoshimoto,
hepatic hilum associated with A 24-year old woman who had been diag- Department of Surgery, Fujita Health University
neurofibromatosis type 1: nosed with NF-1 during childhood was referred School of Medicine, 1-98 Dengakugakubo,
Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
a case report to Fujita Health University Hospital in
E-mail: sojunh@yahoo.co.jp
September 2004 for evaluation of an upper
Sojun Hoshimoto,1 Zenichi Morise,1 abdominal mass found on abdominal comput- Key words: plexiform neurofibroma, neurofibro-
Chinatsu Takeura,1 Masahiro Ikeda,1 ed tomography (CT) at another hospital and matosis, hepatic hilum.
Tadashi Kagawa,1 Yoshinao Tanahashi,1 progressive aggravation of intermittent upper
abdominal pain. There was no relevant family Conflict of interest: the authors reported no poten-
Yasuhiro Okabe,1 Yoshikazu Mizoguchi,2
history. Physical examination revealed numer- tial conflict of interests.
Atsushi Sugioka1
ous café-au-lait spots and cutaneous tumors.
1
Department of Surgery and 2Department In addition to the skin lesions, there was a his- Received for publication: 20 July 2009.
of Pathology, Fujita Health University Accepted for publication: 23 July 2009
tory of surgical treatment for scoliosis. All lab-
School of Medicine, Toyoake, Aichi, Japan oratory test results obtained at admission were This work is licensed under a Creative Commons
all within normal limits. Abdominal CT Attribution 3.0 License (by-nc 3.0)
revealed a multilobulated low-attenuation non-
enhancing mass involving the celiac trunk and ©Copyright S. Hoshimoto et al., 2009
Abstract the common hepatic artery, extending to the Rare Tumors 2009; 1:e23
doi:10.4081/rt.2009.e23
hepatic hilum through the hepatoduodenal lig-
We present an extremely rare case of plexi- ament (Figure 1). Hepatic angiography
form neurofibroma involving the hepatic showed a normal caliber of the hepatic artery
hilum. A 24-year old woman who had been without any irregularity, and portography as
diagnosed with neurofibromatosis type 1 was visualized through the superior mesenteric nance cholangiopancreatography (MRCP), the
referred to our hospital for evaluation of an artery revealed a patent portal vein without common bile duct and the left hepatic duct
abdominal mass found on computed tomogra- encasement. On magnetic resonance imaging were slightly depressed, without dilatation of
phy and progressive aggravation of intermit- (MRI), the lesion was visualized as a the intrahepatic bile duct. Based on these
tent abdominal pain. Abdominal computed hypointensity on T1-weighted images and as a imaging findings, the patient was diagnosed to
tomography revealed a multilobulated non- hyperintensity on T2-weighted images, and have a neurofibroma, although sarcomatous
enhancing mass involving the celiac trunk was found to extend along the intrahepatic differentiation could not be excluded.
and hepatic artery, that extended to the hepat- Glisson’s sheath (Figure 2). On magnetic reso- Although MRI findings suggested that the
ic hilum through the hepatoduodenal liga-
ment. Magnetic resonance imaging showed
the lesion extending along the intrahepatic
Glisson’s sheath. Based on the imaging find-
ings, the patient was diagnosed to have a neu-
rofibroma, although sarcomatous differentia-
tion could not be excluded. The tumor was
resected, leaving behind the intrahepatic
extension, with the aim of alleviating the
abdominal pain and preventing obstructive
jaundice. Histopathological examination
revealed the diagnosis of plexiform neurofi-
broma. At present, three years after the sur-
gery, the patient remains symptom-free, with-
out any evidence of recurrence.
Figure 1. Contrast-enhanced computed tomography showing a low-attenuation lesion

involving the celiac axis (CA), the common hepatic artery (CHA), and the portal vein
(PV), and extending into the hepatic hilum (arrows).
Introduction
Plexiform neurofibroma, which is consid-
ered pathognomonic of neurofibromatosis
type 1 (NF-1), usually occurs in the neck,
pelvis, and extremities. Plexiform neurofibro-
ma in the hepatic hilum is an unusual mani-
festation of NF-1 and is extremely rare. We
present the case of a 24-year old woman with
NF-1 diagnosed to have plexiform neurofibro-
ma involving the celiac trunk, the common
hepatic artery, the hepatoduodenal ligament Figure 2. Abdominal MRI (T2-weighted image) showing a hyperintense tumor involving
and the hepatic hilum that showed extension the hepatoduodenal ligament and the hepatic hilum (arrows), extending along the intra-
hepatic Glisson’s sheath (arrow heads).
along the intrahepatic Glisson’s sheath.

Case Report
Figure 3. Laparotomy revealed a whitish Figure 4. (A) Multiple nerve fascicles are expanded by proliferation of tumor cells embed-
firm tumor involving the hepatoduodenal ded in a prominent myxoid matrix. (HE stain, x 40). (B) At high magnification, the
ligament and the hepatic hilum (arrows). tumor was chiefly composed of elongated spindle-shaped cells having wavy nuclei, with
a myxoid matrix. (HE stain, x 400).
tumor was unresectable owing to its intrahep- nant tumors.1 The average life expectancy of predominantly in the head or neck in NF-1
atic extension, the tumor was removed in patients with NF-1 is probably reduced by 10-15 patients,5 in approximately 40% of patients
February 2005, leaving behind the intrahepatic years, and malignancy is the most common with NF-1, lesions are detected by abdominal
extension, with the aim of alleviating the cause of death.2 The most characteristic or pelvic CT.9 Internal plexiform lesions in the
abdominal pain and preventing obstructive tumors in patients with NF-1 are neurofibro- abdomen or pelvis are commonly located in the
jaundice. Laparotomy revealed a whitish firm mas which arise from cells of the nerve sheath paraspinal space, sciatic nerve, or perirectal
tumor involving the celiac trunk, the common and consist of a mixture of Schwann cells, space.9 Therefore, extension of a plexiform
hepatic artery, and the hepatoduodenal liga- fibroblasts, perineurial cells, and mast cells.3 neurofibroma involving the retroperitoneum
ment, extending through the hepatic hilum Plexiform neurofibroma is a benign nerve and hepatoduodenal ligament into the hepatic
(Figure 3). Since skeletonization of the hepa- sheath tumor, which is virtually pathognomon- hilum is an unusual manifestation in cases of
toduodenal ligament was feasible, the tumor ic of NF-1. It consists of the same cell types as NF-1. A search of PubMed using the terms
was resected piecemeal, without any need for a cutaneous fibroma but has an expanded “liver”, “hilum”, “hilar”, or “porta hepatis”,
combined resection of the vessels or ducts. extracellular matrix, and its presence is one of and “neurofibroma” revealed only 9 cases of
On examination of the cut surface, the the clinical criteria for the diagnosis of NF-1.3 plexiform neurofibroma in the hepatic hilum
tumor was whitish, firm, solid, and partially The incidence of plexiform neurofibroma in reported to date in the English language litera-
encapsulated. Pathological examination patients with NF-1 has been reported to be 15- ture.10-17 All of the 10 cases, including the pres-
revealed expansion of the nerve fascicles, with 30%.4,5 It may be present superficially or be ent case, showed retroperitoneal involvement
a multilobulated appearance. The tumor was located internally, and consists of proliferation or intrahepatic extension along the Glisson’s
chiefly composed of elongated spindle-shaped of cells in the nerve sheath extending across sheath. Therefore, the imaging features of the
cells having wavy nuclei, with a myxoid matrix the length of a nerve, involving multiple fasci- present case are closely similar to those of the
(Figure 4A and B). Mucinous change in the cles and branches.6 Although it tends to grow previously reported cases. Rodriguez et al.
stroma was prominent. These findings were slowly, growth spurts are seen, particularly in reported a case with diffuse intrahepatic peri-
consistent with the diagnosis of benign plexi- early childhood and during puberty or pregnan- portal plexiform neurofibroma and described
form neurofibroma. No evidence of malignant cy.6 Plexiform neurofibromas are at an the non-enhancing low-attenuation lesions
transformation was seen. increased risk of developing into malignant surrounding central and peripheral periportal
The post-operative course was uneventful. peripheral nerve sheath tumors (MPNSTs). spaces as the “periportal collar sign”, which
At present, three years after the surgery, the MPNSTs arise predominantly from pre-exist- was initially described as a finding of rejection
patient remains symptom-free, and shows no ing plexiform neurofibromas and metastasize in liver transplantation.18
evidence of recurrence. widely and often presage a poor outcome.3 The Internal plexiform neurofibromas can per-
lifetime risk of MPNSTs in patients with NF-1 sist for many years without causing clinical
is estimated to be about 10%.7 problems and they usually remain undetected
On CT, plexiform neurofibromas are visual- until incidental detection by an imaging study
Discussion ized as multilobulated low-attenuation masses, or following the development of clinical symp-
usually within a major nerve distribution.8 On toms.6 When patients have substantial neuro-
NF-1, also known as von Recklinghausen’s MRI, the tumors are seen as conglomerate logical deficits or disfigurement, removal of
disease, is a systemic, autosomal dominant hyperintense masses consisting of innumer- plexiform neurofibromas poses challenging
neurocutaneous syndrome occurring at a able neurofibromas with central hypointense problems because of infiltration by the tumors
prevalence of one case in 3,000 live births.1 It regions, known as the “target sign” on T2- of the surrounding tissues and nerves,19
is caused by mutations of the NF1 gene, which weighted images.8 However, malignant trans- although the current treatment of first choice
is located on chromosome 17q11.2.2 Although formation of internal plexiform neurofibromas for plexiform neurofibromas remains surgery.
many cases are heritable, approximately 30- into MPNSTs is difficult to assess by imaging Therefore, there is controversy regarding the
50% of cases arise from spontaneous muta- alone. Thus, the diagnosis of MPNSTs requires optimal timing for surgical intervention. Some
tions.1 NF-1 is characterized by café-au-lait biopsy, but there is substantial potential for authors advocate early surgery to prevent the
spots, cutaneous neurofibromas, bone malfor- sampling error in large plexiform neurofibro- development of major cosmetic and functional
mations, Lisch nodules, and sometimes, malig- mas.6 Although plexiform neurofibromas occur impairment, whereas there is a counter argu-

Case Report
ment that even small plexiform neurofibromas 2000;151:33-40. Radiol 1998;53:389-90.

can rarely be removed entirely and regrowth 3. Theos A, Korf BR. Pathophysiology of neu- 12. Ghalib R, Howard T, Lowell J, et al. Plexi-
after surgery may occur.6 Although in the pres- rofibromatosis type 1. Ann Intern Med form neurofibromatosis of the liver: case
ent case, based on the MRI findings, the tumor 2006;144:842-9. report and review of the literature.
was deemed as difficult to remove in its entire- 4. Huson SM. The different forms of neurofi- Hepatology 1995;22:1154-7.
ty owing to its intrahepatic extension, removal bromatosis. Br Med J (Clin Res Ed) 1987; 13. Gossios KJ, Guy RL. Case report: imaging
of the tumor was nonetheless attempted in an 294:1113-4. of widespread plexiform neurofibromato-
attempt to alleviate the abdominal pain and 5. McGaughran JM, Harris DI, Donnai D, et
sis. Clin Radiol 1993;47:211-3.
prevent obstructive jaundice. To the best of our al. A clinical study of type 1 neurofibro-
14. Kakitsubata Y, Kakitsubata S, Sonoda T, et
knowledge, this is the first reported case of matosis in north west England. J Med
plexiform neurofibroma in the hepatic hilum Genet 1999;36:197-203. al. Neurofibromatosis type 1 involving the
in which successful resection was carried out. 6. Korf BR. Plexiform neurofibromas. Am J liver: ultrasound and CT manifestations.
In conclusion, we have reported an unusual Med Genet 1999;89:31-7. Pediatr Radiol 1994;24:66-7.
case of plexiform neurofibroma, unique in 7. Evans DG, Baser ME, McGaughran J, et al. 15. Malagari K, Drakopoulos S, Brountzos E, et
terms of its location at the hepatic hilum. Malignant peripheral nerve sheath al. Plexiform neurofibroma of the liver:
Thus, the presence of this tumor at this tumours in neurofibromatosis 1. J Med findings on mr imaging, angiography, and
uncommon location should also be borne in Genet 2002;39:311-4. CT portography. AJR Am J Roentgenol
mind, especially in complaints of abdominal 8. Lin J, Martel W. Cross-sectional imaging of 2001;176:493-5.
discomfort, and it is essential to periodically peripheral nerve sheath tumors: charac- 16. Partin JS, Lane BP, Partin JC, et al.
monitor patients with NF-1 for the develop- teristic signs on CT, MR imaging, and Plexiform neurofibromatosis of the liver
ment of this tumor because of the possibility of sonography. Am J Roentgenol 2001; 176: and mesentery in a child. Hepatology 1990;
serious clinical presentations and malignant 75-82. 12:559-64.
transformation. 9. Tonsgard JH, Kwak SM, Short MP, et al. CT 17. Vilas-Ferrol I, Hernandez-Gimenez M,
imaging in adults with neurofibromatosis-
Moya-Garcia MI, et al. Intrahepatic plexi-
1: frequent asymptomatic plexiform
form neurofibroma in neurofibromatosis
lesions. Neurology 1998;50:1755-60.
References 10. Fenton LZ, Foreman N, Wyatt-Ashmead J. 1. Pediatr Radiol 1998;28:733.
Diffuse, retroperitoneal mesenteric and 18. Rodriguez E, Pombo F, Rodriguez I, et al.
1. Lee MJ, Stephenson DA. Recent develop- intrahepatic periportal plexiform neurofi- Diffuse intrahepatic periportal plexiform
ments in neurofibromatosis type 1. Curr broma in a 5-year-old boy. Pediatr Radiol neurofibroma. Eur J Radiol 1993;16:151-3.
Opin Neurol 2007;20:135-41. 2001;31:637-9. 19. Ferner RE. Neurofibromatosis 1 and neu-
2. Rasmussen SA, Friedman JM. NF1 gene 11. Gallego JC, Galindo P, Suarez I, et al. MR of rofibromatosis 2: a twenty first century
and neurofibromatosis 1. Am J Epidemiol hepatic plexiform neurofibroma. Clin perspective. Lancet Neurol 2007;6:340-51.

Cystadenofibroma of the the abdomen. There was no lymphadenopathy.

The CA-125 was raised to 933 u/mL. She was Correspondence: Manisha Ram,
rete ovarii: a case report subsequently taken in for surgery. At laparoto- Department of Cellular Pathology, Basildon
with review of literature my, the findings were of a large cystic mass Hospital, Basildon & Thurrock University
with smooth external surface, originating from Hospitals NHS Foundation Trust, Nethermayne,
Manisha Ram,1 Abdel Abdulla,1 the right ovary and extending to the upper Basildon, SS16 5NL, United Kingdom
abdomen. There were no adhesions to sur- E-mail: pathologist.manisha@gmail.com
Khalil Razvi,1 Ivilina Pandeva,1
Awatif Al-Nafussi2 rounding organs. The rest of the pelvis and
Key words: ovary, rete ovarii, cystadenofibroma,
abdominal cavity were normal. The ovarian
1
Department of Cellular Pathology, rete testis, immunohistochemistry.
mass was sent for frozen section, which sug-
Basildon Hospital, Basildon & Thurrock gested a borderline tumor. In view of this, a
University Hospitals NHS Foundation Acknowledgments: we would like to thank Kerry
staging laparotomy with total abdominal hys- Hughes for her assistance in typing this manu-
Trust, Basildon, UK; 2Department of terectomy, bilateral salpingo-oophorectomy, script.
Cellular Pathology, Royal Infirmary of infracolic omentectomy and right pelvic lymph
Edinburgh, Edinburgh, Scotland, UK node dissection was performed. Macrosco- Contributions: MR, AAl-N, conception, design,
pically, a circumscribed whitish spongy mass acquisition of data, analysis and interpretation of
occupied the whole right ovary, which weighed data, drafting article and revising critically for
500 grams and measured 18x12x8 cm. The cut important intellectual content, final approval of ver-
Introduction surface revealed “honey-comb” like solid cystic sion to be published; AA, interpretation of data,
areas, with the cysts ranging in size from 0.2 revising critically for important intellectual content,
final approval of version to be published; KR, revis-
The rete ovarii (RO), the homolog of the cm to 2.5 cm and containing clear fluid (Figure
ing critically for important intellectual content, final
rete testis (RT), is present in the hilus of all 1). Microscopically, there was diffuse replace-
approval of version to be published; IP, acquisition
ovaries.1 It is composed of irregularly anasto- ment of the ovarian parenchyma, from hilus to of data, final approval of version to be published.
mosing tubules lined by flat, cuboidal or cortex, by a cellular proliferation of epithelial
columnar non-ciliated cells with scanty and stromal cells (Figure 2). The epithelial Conflict of interest: the authors reported no poten-
eosinophilic or clear cytoplasm. Some authors cells were arranged as tubular and slit-like tial conflict of interests.
state that the RO contains ciliated cells.1 The spaces (Figure 3), with numerous variably
sized cystic spaces having an irregular outline. Received for publication: 22 July 2009.
tubules generally lack a basement membrane,
as judged by the absence of PAS staining The tubules had an irregular branching config-
beneath the epithelial lining. The histological uration reminiscent of an “antler-horn” pat- This work is licensed under a Creative Commons
description of RO in humans is generally sim- tern. The areas of prominent cystic change had Attribution 3.0 License (by-nc 3.0)
ilar to that of the mouse, including a network scattered tiny papillae, projecting into the cysts
of irregular tubules, sometimes communicat- (Figures 4 and 5). The cyst lumens contained ©Copyright M. Ram et al., 2009
amorphous, granular, proteinaceous, eosino- Rare Tumors 2009; 1:e24
ing with mesonephric tubules in the mesovar-
doi:10.4081/rt.2009.e24
ium, and lined by epithelium varying from flat- philic material along with occasional foamy
tened to columnar and occasionally ciliated.2
However, in contrast to the apparent com-
moness of cysts and tumors of the RO in mice,
these lesions are described rarely in humans.2
Lesions of the human RO have been infre-
quently described, with the largest series to
date comprising under 20 cases.3 Similarly,
there are only a few reports of benign epithe-
lial tumors of the RT.4 We describe another
rare lesion of the RO: “cystadenofibroma” of
the RO in a 75-year old female, along with a
literature review. Figure 1. Gross photograph
showing bi-valved specimen
depicting solid- cystic appea-
rance.
Case Report
A 75-year old patient presented with sudden
onset of severe abdominal pain. Her past med-
ical and surgical history was unremarkable.
The physical examination revealed a distended
abdomen and the presence of a tender, round,
mobile right sided pelvic mass, measuring
approximately 20 cm in size. Her blood results
were within normal limits. A Computerized Figure 2. Microphotograph
Tomography (CT) scan of the abdomen and showing diffuse replacement
pelvis showed a large, complex mass with solid of ovary by epithelial and
and cystic areas, occupying the entire pelvis. stromal proliferation (H&E
There was a moderate amount of free fluid in X 40).

Case Report
macrophages. The lining throughout was

bland, monolayered, non-ciliated cuboidal to
columnar, with moderate amount of pale
eosinophilic cytoplasm (Figure 6). Nuclei were
basally orientated, monomorphic, round to
oval, containing dispersed chromatin and
small nucleoli. Focally, especially in areas with
marked cystic dilatation, the lining cells were
flat. The cores of the papillae and intertubular Figure 3. Microphotograph
stroma consisted of fibrovascular tissue, con- showing variably sized irreg-
taining spindle-shaped cells with monomor- ular slit-like spaces lined by
phic elongated nuclei (Figure 7). Smooth mus- monolayered bland cuboidal
epithelium and intervening
cle fibers were very occasional in the stroma mature fibrotic stroma
(Figure 8). There were no Leydig-like cells in (H&E X200).
the stroma, which was further confirmed by
negative immunostaining for Inhibin. Neither
nuclear atypia nor conspicuous mitotic figures
were seen in the epithelial or stromal cells.
Necrosis was not evident. Normal background
ovarian parenchyma was not seen (in spite of
embedding the whole specimen). The
labyrinthine channels, slit-like spaces and
mature fibrous mesenchymal type of stroma,
were all very reminiscent of RO. On immuno-
histochemistry, mesothelial markers (CK5/6,
Calretinin, WT-1, thrombomodulin) were nega-
tive. The epithelial lining cells were positive Figure 4. Microphotograph
for CK7, ER, PR, Vimentin and CD10 (Figures showing a markedly dilated
9-12). Considering the glandular and stromal cyst with papillae projecting
pattern and the immunohistochemistry into the cyst lumen (H&E
results, a diagnosis of cystadenofibroma of the X200).
RO was made. The uterus showed a benign
intramural leiomyoma along with cystic atro-
phy of the endometrium. The left ovary and
omentum were histologically unremarkable.
The right common iliac, external iliac, internal
iliac and right obturator lymph nodes showed
reactive hyperplasia only, with no evidence of
metastasis.
Discussion
Figure 5. Microphotograph
There is considerable debate regarding the showing high power view of
histogenesis of the RO. Most investigators bland cuboidal lining of
consider the RO to be of mesonephric ori- papillae (H&E X400).
gin.1,5-7 Upadhay et al.8 favor a mesonephric
origin in mice, but Nogales et al.8 state that
these results may not be transferable to
humans because of the considerable differ-
ences in gonadal development between
species. Nogales5 suggested that the RO repre-
sents a structure intermediate between the
mesonephric duct and ovarian sex cords.
Satoh9 elaborated how, during embryogenesis,
remnants of primordial sex cords in the basal
portion of the ovary give rise to the rete.
“Coelomic-epithelial” and “gonadal blaste-
mal” origins have also been advanced.1 Amidst
all this argument, Nogales et al.8 state that the Figure 6. Microphotograph
RO and RT are anatomical structures of uncer- showing bland cuboidal lin-
ing of tubules with occasion-
tain histogenesis. The position of the RO al ciliated cells (H&E X600).
varies between species. It is found most com-

Case Report
monly in the hilus of the ovary, but may be rep-

resented by tubules or cords extending
through the medulla, or may be completely
outside the ovary, in the mesovarium, adja-
cent to the hilus.7 Age-related changes have
been described in the RO. In the human fetus,
the RO enlarges and a columnar network of
tubules extends along the length of the ovary
in the hilar regions, so that at birth, the RO is
described as strongly developed.7 The so-called
urogenital union between the rete and the
mesonephric tubules (transverse ductules in Figure 7. Microphotograph
showing cellular fibrotic
the female, homologous with the efferent duc- stroma, reminiscent of rete
tules in the male) which was lost during the ovarii (H&E X200).
morphogenesis of the gonad is regained in the
male to form the excretory pathway. Hence, in
males, the RT is fully developed and function-
al. On the other hand, the reunion in the
female may not occur or is imperfect,7 hence
the RO is said to be a vestigial structure of
unknown function.8,10 The RO seems to play an
important role in early gonadal embryogene-
sis, being related to primitive sex cord forma-
tion.10 From birth through puberty, the RO
comes to occupy less of the volume of the
ovary. The rete tubules become more separat-
ed by increasing amounts of connective tis-
sue. In adults, the RO is described to be vari- showing focal smooth mus-
able in its appearance, from almost lacking to cle fibers (highlighted by
abundant. Though the RO is usually found SMA immunostaining) in
within the ovary, the position is variable and it the stroma (H&E X200).
may be found almost completely outside in the
mesovarium. With advancing age, it tends to
become more atrophic and may become solid,
adenomatous, cystic or polycystic.7 Tumors of
the RO proper are most unusual.1,10,11 In the lit-
erature, only one report has dealt with cysts,
adenomas and carcinomas of this structure.1
Khan et al.11 have tried to explain the reason of
the comparative rarity of benign and malig-
nant tumors arising in this structure, as com-
pared to other sites in the female genital tract
(FGT). They found lower levels of estrogen
receptor (ER) and progesterone receptor (PR)
in the rete, suggesting a lesser degree of showing intense and diffuse
responsiveness to hormone stimulation in ER positivity in epithelial
this structure, which consequently explains cells (H & DAB X 200).
the low proliferation rate in the RO. This low
proliferation rate, detected using antibody to
Ki-67, suggests a lower growth rate in this tis-
sue than in other tissues of the FGT. They
advance the theory that this low proliferation
is responsible for the rarity of RO tumors. The
major importance to recognize the RO and its
lesions is that they can be confused with other
conditions such as endometriosis.6 A detailed
description and characterization of this
unique structure (RO) may help in difficult
differential diagnoses between benign and
malignant ovarian lesions, analogous to tes-
ticular lesions.12 Recognition of benign lesions Figure 10. Microphotograph
is important so that unnecessary and poten- showing intense and diffuse
tially morbid therapies are avoided.13 The CK7 positivity in epithelial
cells (H & DAB X200).
majority of the rete cysts are thought to repre-

Case Report
sent non-neoplastic dilatations, since they are

lined by a single layer of bland epithelium and
appear to be exaggerations of microscopic
rete dilatations.1 Rutgers and Scully1 state that
although rete cysts have been rarely described
in the literature, they are not that uncommon.
They found 16 cases of RO cysts (cystadeno-
mas), 7 of which were found in a retrospective Figure 11. Microphotograph
review of 126 ovarian cysts. Rete cyst forma- showing no staining in
tion is more common in older than younger epithelial cells for thrombo-
women.1 The age range in the 16 cases modulin (right), whereas the
described by Rutgers and Scully1 was from 23- normal ovarian surface
epithelial lining (left) is pos-
80 years, (mean age 59 years), most of whom itive for it, acting as an inter-
were post-menopausal. Similarly, our case is nal control (H & E X200).
also that of a 75-year old post-menopausal
patient. A plethora of RT lesions have been
described,4,14 including:
1. non-neoplastic and developmental abnor-
malities, which include rete hyperplasia,
nodular proliferation of calcifying connec-
tive tissue, cystic dysplasia, acquired or sec-
ondary cystic changes in the rete, rete
changes in cryptorchidism;
2. benign neoplasms, which include cystade-
noma of usual type and sertoliform cystade- Figure 12. Microphotograph
noma; showing lack of a distinct
basement membrane, high-
3. adenocarcinoma of the rete. lighted by negative staining
Strict criteria4 have been proposed in diag- for laminin (H & DAB
nosing a primary tumor of the RT, which X400).
include:
1. absence of histologically similar extra-scro-
tal tumor; Table 1. Antibodies used in the study.
2. tumor centered on the testicular hilus; Antibodies Source Dilution Type Pre-treatment Result in our case
3. morphology incompatible with any other
type of testicular or paratesticular tumour; CK5/6 Leica Pre-dilute Monoclonal ER2, 10 min - ve
4. demonstration of a transition between the ER Leica Pre-dilute Monoclonal ER2, 20 min + ve
unaffected RT and the tumor; PR Novastra 1/200 Monoclonal ER1, 20 min Patchy + ve
5. a predominantly solid appearance. SMA Leica Pre-dilute Monoclonal No pre-treatment Focal + ve
The last criterion should not be applied too Desmin Leica Pre-dilute Monoclonal ER2, 20 min Focal + ve
rigidly, since although most cystic “carcino- S100 Biogenix 1/400 Monoclonal ENZ 1, 10 min - ve
mas of the rete” are compatible with a serous CA-125 Nocacastra 1/100 Monoclonal ER2, 20 min + ve
tumor, RT carcinomas with cystic growth pat- Cam 5.2 BD Bioscience 1/20 Monoclonal ENZ 1, 10 min + ve
tern have also been encountered. Similarly, a EMA Dako 1/400 Monoclonal ER2, 20 min + ve
transition with the unaffected RT may be dif- CEA Dako 1/25 Monoclonal ENZ 1, 10 min - ve
ficult to demonstrate, but if all other criteria
CK7 Leica Pre-dilute Monoclonal ER2, 20 min + ve
are met, a diagnosis of a primary RT tumor is
CK20 Dako 1/50 Monoclonal ER1, 20 min - ve
acceptable. Although there are no such crite-
ria for diagnosing a primary tumor of the RO, E-cadherin Dako 1/50 Monoclonal ER2, 20 min + ve
certain distinguishing features of RO tumors Vimentin Dako 1/200 Monoclonal ER1, 20 min + ve
have been described.1,2 MNF-116 Dako 1/200 Monoclonal ENZ 1, 10 min + ve
They include: Ber-EP4 Dako 1/100 Monoclonal ENZ 1, 10 min + ve
1. apparent location in the hilus of the ovary; CK19 Dako 1/200 Monoclonal ER2, 20 min + ve
2. occasional ciliated cells; Ki-67 Dako 1/200 Monoclonal ER2, 20 min < 2% cells + ve
3. crevice formation of the inner surface (of PLAP Dako 1/50 Monoclonal ER2, 20 min - ve
the tubules/glands) which recapitulates the CD10 Leica Pre-dilute Monoclonal ER2, 20 min + ve
irregular outlines of the normal rete; Thrombomodulin Dako 1/10 Monoclonal No pre-treatment - ve
4. other resemblance to the normal rete;
Inhibin Dako 1/100 Monoclonal ER2, 20 min - ve
5. normal rete adjacent to some lesions;
Laminin Dako 1/40 Polyclonal ENZ1, 10 min - ve
6. a wall of fibromuscular connective tissue.
Most of the previously reported cases have WT-1 Dako 1/1000 Monoclonal ER2, 20 min - ve
involved the hilus alone or the hilus and part AFP Dako Pre-dilute Monoclonal ER1, 10 min - ve
of the medulla.1 In our case, the ovarian ER1, enzyme retrieval (low pH); ER2, enzyme retrieval (high pH); ENZ1, enzyme 1 (BondMax); ENZ2, enzyme 2 (BondMax); CK, cytokeratin;
involvement was diffuse and extensive, from WT, Wilms’ Tumour; ER, oestrogen receptor; PR, progesterone receptor; SMA, smooth muscle actin; EMA, epithelial membrane antigen;
the hilus to the cortex. Although the definite CEA, carcinoembryonic antigen; PLAP, placental alkaline phosphatise; AFP, alpha feto protein.

Case Report
relation to the hilus was obscured, the cyst the absence of localization within the rete, or uterus did not show any such features.
walls were composed of fibrovascular tissue continuity with the RO epithelium are find- However, RUTROSCT has been shown to have
with few irregularly arranged fascicles of ings that indicate a diagnosis of mesothe- consistent positivity for Cam5.2, CK7,
smooth muscle. The intervening stroma was lioma, rather than RO carcinoma.4 Our case vimentin, calretinin, PR and apical CD10.
cellular and in places very much reminiscent had very bland epithelium, which was nega- CD56 and inhibin positivity has been found in
of RO. Normal ovarian tissue was not seen, in tive for mesothelial markers (calretinin, half of the cases. EMA, desmin, SMA and
spite of embedding and examining the whole thrombomodulin, WT-1, CK5/ 6) and positive calponin have been found to be negative.10 RO
specimen. Similar absence of ovarian tissue for epithelial markers (Cam5.2, MNF-116, Ber- and its tumors have been found to be positive
has been noted in large rete cysts of CD-1 EP4). Metastatic adenocarcinoma is another for EMA, CA- 1256,8,10 CK7, calretinin (cytoplas-
mice.2 The possible explanations put forth by differential for RO carcinomas, though not in mic), CD56 (membranous), CD10 (apical).10
Long2 are that ovarian tissue could have atro- our case. Bilaterality, multifocality and micro- They have been found to be focally positive for
phied secondary to compression, or could have scopic evidence of an interstitial growth pat- vimentin and negative for CA19.9, CEA, S-100
had amyloidosis or other degenerative tern with lymphatic or vascular permeation and PR.8 However, our case was positive for
changes not directly associated with the for- are good clues that one may be dealing with a EMA, CA-125, vimentin, CK7, ER, PR, CD10,
mation of the cyst. Another postulated expla- metastasis.4 Cystic dilatation/ transformation Cam5.2, MNF-116, BerEP4, CK-19, ECadherin
nation is that of minimal remaining ovarian of the RT has been described,4,12 but no such and CD56. Our case was negative for WT-1,
tissue, which could be missed due to limited entity has been described for the RO. ORSLCT CK5/6, calretinin, inhibin, CEA, AFP, S-100,
sectioning of the sample. But the complete has Leydig cells (inhibin and calretinin posi- thrombomodulin and PLAP. Focal smooth mus-
sectioning of our sample abolishes this possi- tive) in the stroma. Positivity for inhibin and cle in the stroma was positive for desmin and
bility. Mesonephric and rete remnants have calretinin, along with negativity for EMA and SMA. Thus, on the basis of the histological
been described in the vicinity of the lesions in CK7 favors the diagnosis of ORSLCT. However, and immunohistochemical features of the
2 cases.8 Our case also showed rete remnants the findings in our case were the reverse: EMA ovarian tumor reported here, and after exclu-
in the vicinity of the main tumor and also positive, inhibin and calretinin negative. sion of other differential diagnoses, the diag-
admixed with it. Tumors of the RO often Morever, there were no Leydig cells in the nosis of a cystadenofibroma of the RO can be
exhibit stromal luteinization or Leydig-like stroma. Even clinically, there were no hormon- established in this case. To summarize, to the
cells in the stroma, reproducing the normal al manifestations in the patient. Yolk sac best of our knowledge, this is a rare case of
relations between hilar epithelial vestiges and tumors are known for their retiform architec- cystadenofibroma of the rete ovarii in a 75-
steroid-producing cells of the hilum.1,8,10 ture.16 However, the complete absence of α year old woman.
However, in our case, there was neither stro- fetoprotein (AFP) in our case and the lack of
mal luteinization nor Leydig-like cells, making placental alkaline phosphatase (PLAP), which
the diagnosis quite difficult. Nogales et al.10 occurs in about 50% of yolk sac tumors,15
concluded that the retiform structures of makes a diagnosis of the latter most unlikely. References
Uterine Tumor Resembling Ovarian Sex Cord An ovarian adenomatoid tumor also has to be
Tumor (UTROSCT) have a similar, if not iden- considered in the differential diagnosis 1. Rutgers JL, Scully RE. Cysts (cystadeno-
tical immunophenotype to that of the RO and because of some morphological features. mas) and tumours of rete ovarii. Int J
the Wolffian Adnexal Tumor (WAT). They have However, in the absence of CK5/6, calretinin Gynec Pathol 1988;7:330-42.
been regarded as different from Ovarian and thrombomodulin expression, such a diag- 2. Long GG. Apparent mesonephric duct (rete
Retiform Sertoli Leydig Cell Tumor (ORSLCT), nosis cannot be entertained. Female adnexal anlage) origin for cysts and proliferative
probably since these ovarian tumors seem to tumor of probable Wolffian origin (FATWO) is epithelial lesions in the mouse ovary.
recapitulate early embryogenesis reproducing characterized by prominent tubule formation Toxic Pathol 2002;3:592-8.
the early RO and its connection with the prim- and peritubular basement membranes.17 3. Heatley MK. Adenomatous hyperplasia of
itive sex cords.10 Probably, they have an imma- Laminin immunostaining accentuates a the rete ovarii. Histopathol 2000;36:383-4.
ture phenotype with a different antigen prominent peritubular basement membrane, 4. Jones EC, Murray SK, Young RH. Cysts and
expression. In our case, a number of differen- and often unmasks a tubular pattern in what epithelial proliferations of the testicular
tial diagnoses were entertained. Inclusion may appear to be a solid proliferation.5 A reti- collecting system (including rete testis).
cysts could not be a possibility, since firstly, form pattern may also be seen in FATWO or Semin Diagn Pathol 2000;17:270-93.
they would not be so extensive so as to replace WAT.9 These rare tumors are also positive for 5. Devouassoux-Shisheboran M, Silver SA,
and involve the whole ovarian parenchyma. keratins, inhibin and vimentin, with variable Tavassoli FA. Wolffian Adnexal Tumor, so
Secondly, they were not stained by WT-1, ER/PR positivity. Inhibin positivity has been called female adnexal tumour of probable
which normally stains ovarian surface epithe- reported in 68%9 and 90%9 of FATWO, but it is Wolffian origin (FATWO): immunohisto-
lium and ovarian inclusion cysts.15 Rete hyper- patchy and weak. They are often non-reactive chemical evidence in support of a Wolffian
plasia, on low power examination, reveals a for EMA.5 Although our case was positive for origin. Hum Pathol 1999;30:856-63.
proliferation of irregularly sized anastomos- vimentin, keratins and EMA, inhibin was 6. Woolnough E, Russol L, Khan MS, Heatley
ing channels and glands within the rete, characteristically negative. RO has been MK. An immunohistochemical study of the
which do not form a circumscribed mass. The shown to have focal positivity for CK7, patchy rete ovarii and epoophoron. Pathol 2000;
proliferation is often vaguely lobular with and weak staining for inhibin, 8% of cases 32:77-83.
smaller glands surrounding larger cystic and being positive for ER and PR.5 Our case was 7. Wenzel JGW, Odend’hal S. The mam-
elongated forms.4 Adenomatous hyperplasia of diffusely positive for CK7, ER and PR, while malion rete ovarii: a literature review.
the rete testis (AHRT) is a benign lesion char- being negative for inhibin. EMA has been Cornell Vet 1985;75:411-25.
acterized by solid/ glandular, papillary or crib- found to be negative,5 whereas our case was 8. Nogales FF, Carvia RE, Donné C, et al.
riform proliferation of the epithelium with diffusely positive for EMA. Retiform uterine Adenomas of the rete ovarii. Hum Pathol
self-limited growth. It can appear at any time tumor resembling ovarian sex cord tumor 1997;28:1428-33.
during life.14 Mesothelioma may have elongat- (RUTROSCT) is another differential. But this 9. Mooney EE, Nogales FF, Bergeron C, et al.
ed slit-like tubules with papillary growth. But was not entertained in our case, since the Retiform Sertoli-Leydig cell tumours: clin-

Case Report
ical, morphological and immunohisto- 12. Fridman E, Skarda J, Moravsky EO, et al. 15. O’Neil CJ, Deavers MT, Malpic A, et al. An
chemical findings. Histopath 2002;41:110- Complex multilocular cystic lesion of rete immunohistochemical comparison
7. testis, accompanied by smooth muscle between low grade and high grade ovarian
10. Nogales FF, Stolnicu S, Harilal KR, et al. hyperplasia, mimicking intratesticular serous carcinomas: significantly higher
Retiform uterine tumours resembling Leydig cell neoplasm. Virchows Arch expression of p53, MIB-1, Bcl-2, Her2/nell,
ovarian sex cord tumours. A comparative 2005;447:768-71.
and C-KIT in high grade neoplasms. Am J
immunohistochemical study with retiform 13. Hartwick RWJ, Ro JY, Srigley JR, et al.
Surg Pathol 2005;29:1034-41.
structures of the female genital tract. Adenomatous hyperplasia of the rete
16. Rosai J. Rosai and Ackerman's Surgical
Histopath 2009;54:471-7. testis. A clinicopathologic study of nine
11. Khan MS, Dodson AR, Heatley MK. Ki-67, cases. Am J Surg Path 1991;15:350-7. Pathology, 9th ed. India, Elsevier; 2004.
oestrogen receptor and progesterone 14. Nistal M, Castillo MC, Regadera J, et al. Chapter 19, Ovary; pp 1649-736.
receptor proteins in the human rete ovarii Adenomatous hyperplasia of the rete 17. Young RH, Scully RE. Ovarian tumours of
and in endometriosis. J Clin Pathol testis. A review and report of new cases. probable Wolffian origin. A report of 11
1999;52:517-20. Histol Histopathol 2003;18:741-52. cases. Am J Surg Pathol 1983;7:125-35.

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Angiomyomatous hamartoma: sisted of spindle shaped cells with regular

elongated nuclei and eosinophilic cytoplasm, Correspondence: Manisha Ram,
a rare case report with review dispersed haphazardly around vascular struc- Department of Cellular Pathology, Basildon
of the literature tures (Figures 3, 4 and 5). A few interspersed Hospital, Basildon & Thurrock University
islands of adipocytes were also seen (Figures 6 Hospitals NHS Foundation Trust, Nethermayne
Manisha Ram, Nazar Alsanjari, and 7). Cellular pleomorphism, conspicuous Basildon SS16 5NL, UK
E-mail: pathologist.manisha@gmail.com
Naseem Ansari mitoses and necrosis were absent. Immuno-
Department of Cellular Pathology, histochemistry (Streptavidinbiotin- complex), Key words: angiomyomatous hamartoma, lymph
Basildon Hospital, Basildon & Thurrock showed a strong reactivity for alpha smooth node, inguinal, popliteal, cervical, lymphedema.
muscle actin (ASMA) and Desmin in the spin-
University Hospitals NHS Foundation
dle shaped cells dispersed throughout the Acknowledgments: we would like to thank Dr.
Trust, Basildon, UK
fibrous tissue and highlighted the muscular Adu-Poku Kwame and Toni-Ann Robinson for
nature of the blood vessels, especially present their assistance.
in the LN hilum (Figure 8). The blood vessels
were decorated by CD 34 (Figure 9). The histo- Contributions: MR, conception, design, acquisi-
Introduction logical appearances, supported by immunohis- tion of data, analysis and interpretation of data,
drafting article and revising critically for impor-
tochemistry, led to the diagnosis of AMH of LN.
Angiomyomatous hamartoma (AMH) of the tant intellectual content, final approval of version
On account of the entirely benign nature of to be published; NAl, interpretation of data, revis-
lymph node (LN) is a benign vascular disorder this condition extensive resection was not
of unknown etiology, first described by Chan et ing critically for important intellectual content,
required and the patient is doing well six final approval of version to be published; NAn,
al. in 1991, as a distinctive lesion of LN char-
months after the surgery, although the lym- acquisition of data, analysis, revising critically
acterized by parenchymal replacement by
phedema did not regress completely. for important intellectual content, final approval
blood vessels, smooth muscle and fibrous tis- of version to be published.
sue in the absence of cellular fascicle forma-
tion.1 This rare disease particularly involves Conflict of interest: the authors report no con-
inguinal and femoral lymph nodes,1-6 however, flicts of interest.
Discussion
one report of cervical LN involvement has been
reported.7 A single case of popliteal LN involve- Received for publication: 21 July 2009.
In a study conducted to investigate the mor- Accepted for publication: 23 July 2009.
ment has also been reported.8 To the best of
phological and clinical findings of various pri-
our knowledge, only 17 cases of AMH of LN This work is licensed under a Creative Commons
mary vascular tumors of lymph nodes other
have been reported in the literature.2 We pres- Attribution 3.0 License (by-nc 3.0)
than Kaposi’s sarcoma, Chan et al. used the
ent a case of AMH of the inguinal LN in an 82-
year old male. term “angiomyomatous hamartoma” to ©Copyright M. Ram et al., 2009
describe a distinctive clinico-pathological Rare Tumors 2009; 1:e25
lesion occurring in lymph nodes.1 AMH seems doi:10.4081/rt.2009.e25
to be a rare nodal condition as only 17 cases
Case Report have been reported in the literature so far.1,5,7
There is a tendency for AMH to occur in
inguinal LN in an 82-year old male. We re-con-
inguinal lymph nodes, although a few cases
An 82-year old male patient presented with a firm the predilection of this lesion to occur in
have been reported in femoral lymph nodes.1-6
left inguinal mass and associated ipsilateral inguinal lymph nodes, which may be related to
Isolated cases (one each) have also been
lower limb edema of two years duration. the fact that this is also the most frequent site
reported in the cervical and popliteal lymph
Computerized tomography (CT) revealed mul- of other nodal mesenchymal tumors.9,10
nodes.7,8 Laeng et al. were the first to report an
tiple enlarged lymph nodes throughout the Histologically, it was characterized by an
angiomyomatous hamartoma with a heman-
abdomen. Macroscopically, the inguinal mass extensive replacement of nodal parenchyma,
giomatoid component and vascular transfor-
measured 3x2x1 cm. On cut section, it had a
mation of sinuses in the same LN.7 Their from hilum to cortex, by a haphazard mixture
firm gray-white appearance. Microscopically, it
report of a cervical LN was also the first report of smooth muscle cells, adipose tissue and
represented a lymph node, the parenchyma of
of an AMH outside of the inguinal or femoral blood vessels within a fibrous stroma.
which was almost completely replaced from
hilum to cortex by fibrous tissue containing nodes. We report another case of AMH of the Differential diagnoses include nodal lymphan-
numerous irregular blood vessels, interspersed
spindle cells and few lobules comprised of
benign adipocytes. These changes gradually
extended from the hilum to the convex surface
of the LN (Figure 1), leaving only a thin rim of
cortical lymphoid tissue containing a few
residual atrophic follicles (Figure 2). The cap-
sule was thickened and no subcapsular or Figure 1. Microphotograph show-
medullary sinuses were found. While the ing low power view of angiomy-
hilum contained thick-walled muscular ves- omatous hamartoma, including
smooth muscle bundles admixed
sels, the cortex was mainly rich in capillary with fibrous tissue and blood ves-
like vessels. Towards the cortex, the vessels sels, extending from the lymph
became more dispersed and associated with node hilum (lower part) to cortical
smooth muscle cells, eventually splaying into lymphoid follicles (upper and
the sclerotic stroma. The fibrous tissue con- right side) (H&E X40).

Case Report
giomyomatosis, leiomyomatosis and angiomy-

olipoma of the LN.1,11 Nodal lymphangiomy-
omatosis occurs exclusively in women,
involves thoracic and abdominal lymph nodes
and is histologically characterized by the pres-
ence of smooth muscle cells forming fascicles
and sheets around anastomosing ectatic vas-
cular spaces, resulting in a pericytomatous
pattern.11 Moreover, in nodal lymphangiomy-
Figure 2. Microphotograph show-
omatosis, smooth muscle cells are plumper, ing a few residual lymphoid folli-
with lighter/clear cytoplasm and sclerosis is cles (upper part) with underlying
absent.1 Nodal leiomyomatosis, which affects smooth muscle (lower part) (H&E
intra-abdominal lymph nodes morphologically X200).
resembles extensive leiomyoma and is com-
posed of a proliferation of compact bundles of
smooth muscle cells with an insignificant vas-
cular component.11 An association with HIV/
immunodeficiency has also been reported.12
Angiomyolipoma of the LN usually affects
retroperitoneal lymph nodes and is considered
as being a manifestation of multicentricity of
angiomyolipoma of the kidney.11 The smooth
muscle cells of angiomyolipoma usually show Figure 3. Microphotograph show-
an epithelioid appearance, hypercellularity, ing all the elements of angiomyo-
pleomorphism, prominent perivascular matous hamartoma: smooth mus-
cle, fibrous tissue, adipose tissue
arrangement and positivity for melanoma and blood vessels with a disorgan-
associated antigen HMB-45.13 The histogenesis ised growth pattern (H&E X200).
of AMH of LN is still unclear.3 In the original
description, the hamartomatous nature was
postulated on the basis of a disorganized
growth pattern of smooth muscle cells and
blood vessels.1 A significant adipose tissue
component within a mixture of smooth muscle
cells and blood vessels in AMH of LN may pro-
vide morphological evidence of the hamar-
tomatous nature of the lesion. The close asso-
ciation of adipose tissue with smooth muscle Figure 4. Microphotograph show-
cells and muscular blood vessels from the hilar ing smooth muscle fibres contain-
region to the cortex indicates that adipose tis- ing benign spindle cells, together
sue may be a true component of hamartoma,5 with variably sized blood vessels in
a background of fibrous tissue
further supported by the fact that AMH is a (H&E X200).
pathological condition starting in the hilum
and extending towards the cortex.1 Adipose
cells are known to occur as a significant com-
ponent in a number of vaso-proliferative
lesions, such as nodal hemangioma, intramus-
cular hemangioma (infiltrative angiolipoma)
and angiolipomatous hamartoma associated
with Castleman’s disease.1,14,15 It has been sug-
gested that all cases of AMH of the LN with a
signficant adipose tissue component should be
termed angiomyolipomatous hamartoma.3
Figure 5. Microphotograph show-
However, the possibility that the lesion may ing high power view of benign
represent a hemangioma with a prominent spindle cells in the smooth muscle,
smooth muscle component or a reparative with a large benign adipocyte
reaction to nodal inflammation cannot be ruled (upper right) (H&E X400).
out.1 Some peculiar alterations of the lymph
node vascular supply have been described,
including increased numbers of small blood
vessels with thickened walls and formation of dered angiogenic process arising from hilar the affected lymph node, explaining the occur-
plexiform or glomeruloid structures, such as in blood vessels, presumably the hilar vein and its rence of lymphedema in some patients.1,6
primary pulmonary hypertension and glioblas- branches.6 Further, the destruction of nodal Sukarai et al. suggested that impairment of
toma multiforme.6 Such similarities suggest sinuses by all these vascular and stromal alter- lymphatic flow may be one factor related to the
that AMH of LN actually represents a disor- ations impairs the lymphatic circulation across pathogenesis of AMH.4 According to them, the

Case Report
lymphatic flow results in the development of

an AMH.2 The abnormal lymphatic flow has
been revealed by examination of the radionu-
clide lymphoscintigram.6 There are specula-
tions about whether the interference of lymph
flow is the cause or the effect of AMH, which
have to be determined.4 The unique features of
our case are as follows: 1) to the best of our
knowledge, this is only the eighteenth case of
Figure 6. Microphotograph show- AMH reported so far in the literature;2 2) it is
ing benign adipocyte lobules the fourth case in the literature in which the
amidst smooth muscle (H&E patient presented with a left inguinal mass,
X200). ipsilateral lymphedema of the leg and AMH; 3)
all the previous 17 cases have been reported in
the age range from 10-80 years (mean age, 47
years)1,3,4,7 whereas our patient is 82-years old.
To conclude, although AMH of lymph node is
very rare, its recognition is important for dif-
ferential diagnoses from angiomatous benign
and malignant tumors of lymph nodes.
Recurrences and metastases of AMH have not
been reported,1,3,5,7 except for a single occur-
rence of a secondary lesion after tumor resec-
tion, which was presumably due to impaired
Figure 7. Microphotograph show- lymphatic transport.4 Hence, keeping in mind
ing high power view of benign the hamartomatous nature of AMH, in our
adipocyte lobules (H&E X400).
patient extensive resection was not needed.
Our patient is doing well, six months after the
LN excision.
References
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a third case in the literature in which a patient represent a localized malformation in a con- myomatous hamartoma of a cervical lymph
presented with a left sided inguinal mass, ipsi- genitally damaged lymphatic system. An alter- node combined with haemangiomatoids
lateral lymphedema of the leg and AMH.2 Our native possibility is that chronic impairment of and vascular transformation of sinuses.

Case Report
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Malignant neuroectodermal meninges. A small number of metastatic

melanomas present with no clearly identifiable Correspondence: Brian P. Rubin,
tumor with melanocytic and primary site. Because of its ability to metasta- Departments of Anatomic Pathology and
rhabdomyoblastic size to a wide variety of sites as well as its wide Molecular Genetics, Taussig Cancer Center and
Lerner Research Institute, Cleveland Clinic
differentiation histological spectrum, its ability to mimic
Foundation L25, 9500 Euclid Avenue, Cleveland,
other neoplasms is well recognized. Although
spindle cell melanomas often lose immunore- OH 44195, USA. E-mail: rubinb2@ccf.org
Munir R. Tanas and Brian P. Rubin
activity for melanocyte-specific markers
Department of Anatomic Pathology, Key words: malignant peripheral nerve sheath
(HMB-45, Melan-A, tyrosinase, MiTF), they are
Pathology and Laboratory Medicine tumor, malignant melanoma, melanocytic differ-
virtually all positive for S-100 protein.2 MPNST entiation, rhabdomyoblastic differentiation,
Institute, The Cleveland Clinic and The comprises five to ten percent of all soft tissue malignant neuroectodermal tumor.
Cleveland Clinic Lerner College of sarcomas with a peak incidence in the third to
Medicine, Case Western Reserve sixth decades of life. Approximately twenty- Contributions: MRT and BPR, contributed to the
University, Cleveland, OH, USA five to fifty percent of MPNST are associated concept and design of the study, as well as the
with neurofibromatosis-1.3,4 MPNST often aris- analysis and interpretation of the data. They both
es in a pre-existing neurofibroma but can helped draft/revise the article and gave final
involve practically any anatomic site in the approval of the version to be published.
Abstract body. In general, they are considered to be Conflict of interest: the authors report no con-
high-grade sarcomas with a high likelihood of flicts of interest.
Malignant melanoma can metastasize wide- local recurrence and distant metastasis.
ly and vary significantly in its histological The typical conventional MPNST is a fascic- Received for publication: 26 July 2009.
appearance; it rarely presents as a deep-seated ular, spindle cell sarcoma with variable Accepted for publication: 5 August 2009.
mass without an obvious primary site else- immunoreactivity for S-100 protein; it is not
where. Malignant peripheral nerve sheath uncommon for conventional MPNST to be only
tumor (MPNST) is a high-grade sarcoma char- focally positive for S-100 or lack staining for
acterized by conventional and epithelioid sub- the antigen altogether. Of particular interest is ©Copyright M.R. Tanas and B.P. Rubin, 2009
types. MPNST can demonstrate heterologous the tendency for MPNST to contain areas with Rare Tumors 2009; 1:e26
differentiation, usually in the form of osteosar- heterologous differentiation, most commonly doi:10.4081/rt.2009.e26
comatous, chondrosarcomatous, or rhabdo- osteosarcomatous, chondrosarcomatous, or
myosarcomatous differentiation. MPNST does rhabdomyosarcomatous differentiation
not harbor true melanocytic differentiation, (malignant Triton tumor).4 Epithelioid MPNST
paraffin-embedded tissue by the avidin-biotin-
although epithelioid MPNST typically is dif- accounts for five percent of all MPNST. In con-
peroxidase complex technique using commer-
fusely S-100 protein positive and superficially trast to the conventional subtype, these neo-
cially available antibodies to the following anti-
can resemble malignant melanoma. An unusu- plasms have a nested growth pattern, an
gens: S-100 (polyclonal; 1:8000; DAKO,
al intra-abdominal mass was recently encoun- epithelioid cytomorphology with prominent
Carpinteria, CA, USA), HMB-45/50 (HMB 45/50
tered with features of both melanoma and con- nucleoli, as well as strong and diffuse positivi-
ty for S-100 protein; thus bearing a superficial cocktail, 1:50/1:250 A. Gown), tyrosinase
ventional or epithelioid MPNST containing a
resemblance to melanoma. Many epithelioid (T311, 1:100, Novocastra, Norwell, MA),
fascicular spindle cell component, an epithe-
lioid component with melanocytic differentia- MPNST also have a minor spindle cell compo- Melan-A (A103, 1:200, DAKO, Carpinteria, CA,
tion, as well as a rhabdomyosarcomatous com- nent which resembles conventional MPNST. USA), and microphthalmia transcription factor
ponent. The terminology “malignant neuroec- Significantly, epithelioid MPNST is negative (D5, 1:25, R. Schmidt).
todermal tumor with melanocytic and rhab- for melanocyte-specific markers (e.g. HMB-45,
domyoblastic differentiation” is proposed to Melan-A, etc.).4
describe this neoplasm, reflecting the unusual An exceptional intra-abdominal neoplasm
concomittant lines of differentiation as well as was recently encountered in consultation with Results
offering a possible rationale for nosologically features of both MPNST and melanoma includ-
challenging aspects of this neoplasm. ing a fascicular spindle cell component consis- Clinical features
tent with conventional MPNST, extensive rhab- The patient was a 67-year old man who pre-
domyosarcomatous differentiation, as well as sented with a large mass in the abdomen
an epithelioid component reminiscent of requiring resection of the spleen, a portion of
Introduction epithelioid MPNST but showing melanocytic
the pancreas, as well as a segment of colon and
differentiation. Review of the English lan-
small bowel. Approximately one year subse-
The neural crest, derived from embryonic guage literature revealed one other similar
quent to diagnosis of the abdominal mass, the
neuroectoderm, is thought to give rise to sev- case, a case of an MPNST with divergent
patient presented with a brain metastasis.
eral cell types within the human body includ- melanocytic and rhabdomyoblastic differentia-
ing melanocytes and Schwann cells.1 The pro- tion.5
totypic malignant neoplasms arising from or
Pathological features
showing differentiation toward these cell types Grossly, the intra-abdominal mass was 20
are malignant melanoma and malignant cm in greatest dimension. Histologically, it was
peripheral nerve sheath tumor (MPNST), Materials and Methods characterized by a proliferation of spindle cells
respectively. Malignant melanoma is a rela- with enlarged hyperchromatic nuclei with
tively common neoplasm arising predominant- This case was received in consultation by tapered ends and faintly eosinophilic cyto-
ly in the skin, but also the eye, oral and one of the authors (BPR). Immunohisto- plasm arranged in intersecting fascicles. A
anogenital mucosal surfaces, esophagus, and chemistry was performed on formalin-fixed, prominent herring-bone pattern could be

Case Report
observed in several fields (Figure 1A). Other

areas consisted of epithelioid cells with a mod-
erate amount of eosinophilic cytoplasm and
enlarged vesicular nuclei with prominent
nucleoli (Figure 1B). A third pattern was char-
acterized by rhabdomyoblasts containing
abundant eosinophilic cytoplasm with eccen-
trically placed, enlarged nuclei and prominent
nucleoli, representing rhabdomyosarcomatous
heterologous differentiation (Figure 1E).
Mitotic activity was brisk throughout the neo-
plasm and tumor necrosis was present.
S-100 protein was only focally positive in the
fascicles of spindle cells, but strongly and dif-
fusely positive in the epithelioid areas
(Figure1C). Melanocytic markers including
HMB-45/50 (Figure 1D), Melan-A, tyrosinase,
and MITF were strongly and diffusely positive
in the epithelioid component but were absent
from the spindle cell component. Fontana-
Masson staining did not demonstrate any
melanin pigment in either the epithelioid or
spindle cell components. Skeletal muscle dif-
ferentiation was confirmed in the rhabdomy-
oblasts by strong and diffuse immunoreactivity
for desmin (Figure 1F) and myogenin.
The brain metastasis was characterized by a
morphological appearance similar to the
epithelioid component of the abdominal mass,
including epithelioid cells with eosinophilic
cytoplasm, enlarged vesicular nuclei, and
prominent nucleoli (Figure 2A). The brain
metastasis was focally positive for S-100 pro-
tein, and variably positive for Melan-A (Figure
2B) and HMB-45.
Figure 1. Abdominal mass. (A) Fascicular spindle cell component; (B) epithelioid compo-
nent with prominent nucleoli; (C) strong and diffuse immunoreactivity for S-100 protein
Discussion in the epithelioid component; (D) uniform staining for HMB-45 in the epithelioid com-
ponent; (E) rhabdomyoblasts in areas of rhabdomyosarcomatous heterologous differenti-
ation; (F) strong and diffuse immunoreactivity for desmin in rhabdomyoblasts.
The chief differential diagnoses in this case
are malignant melanoma and MPNST. One pos-
sibility is that the neoplasm is a melanoma with
a significant spindle cell component and het-
erologous rhabdomyosarcomatous differentia-
tion. Melanocytic neoplasms displaying rhab-
domyosarcomatous differentiation have been
reported in the literature. Four case reports
have described rhabdomyosarcomas arising
within congenital melanocytic nevi, demon-
strating that cells with committed melanocytic
differentiation can undergo differentiation
toward a skeletal muscle phenotype.6-8 There is
also a report of two patients with congenital
melanocytic nevi who subsequently developed
Figure 2. Metastasis to brain. (A) Epithelioid neoplasm similar in appearance to the pri-
melanomas within their nevi showing areas of mary neoplasm shown in Figure 1B, (B) immunohistochemistry showing positivity for
rhabdomyoblastic differentiation.9 In addition, Melan-A.
the metastasis involving the brain is both clin-
ically and pathologically more suggestive of
malignant melanoma than MPNST. nent (reminiscent of epithelioid MPNST) that known primary), though possible, are rare. On
Another possibility is that this tumor repre- happens to show evidence of melanocytic dif- the other hand, MPNST commonly occurs in a
sents an MPNST with a conventional spindle ferentiation. This diagnosis is supported by deep-seated location. Furthermore, the spindle
cell component, heterologous rhabdomyoblas- the following features. First, deep-seated pri- cell component was only focally positive for S-
tic differentiation, and an epithelioid compo- mary melanomas (this patient had no other 100 protein and was negative for melanocyte-

Case Report
specific markers, which is much more typical Masson stain.17 Furthermore, melanin-contain- et al. Rhabdomyosarcoma in a congenital
of MPNST than spindle cell melanoma (which ing nerve sheath tumors have been described pigmented nevus. Pediatric Pathol 1992;
is often strongly positive for S-100 protein, as in a neurofibromatosis rat model (induced by 12:93-8.
mentioned previously). In addition, the phe- transplacental administration of ethylnitro- 8. Zuniga S, Heras JL, Benveniste S. Rhabdo-
nomenon of rhabdomyoblastic differentiation surea).18 myosarcoma arising in a congenital giant
is a relatively common occurrence in MPNST, Because both MPNST and melanoma are nevus associated with neurocutaneous
compared to its case-reportable status in thought to arise from or show differentiation melanosis in a neonate. J Pediatr Surg
melanoma. The feature of this case that is toward neural crest-derived cells, it is not sur- 1987;22:1036-8.
most difficult to reconcile with the diagnosis of prising that rare cases of melanoma might 9. Cohen MC, Kaschula RO, Sinclair-Smith
MPNST is the epithelioid component, which show rhabdomyoblastic differentiation while C, et al. Pluripotential melanoblastoma, a
showed evidence of melanocytic differentia- rare cases of MPNST might demonstrate unifying concept on malignancies arising
tion. Although epithelioid MPNST can be melanocytic differentiation. However, as dis- in congenital melanocytic nevi: report of
strongly positive for S-100 protein, melano- cussed previously, a rigid rendering of the two cases. Pediatric Pathol Lab Med 1996;
cyte-specific markers such as HMB-45 and diagnosis of either melanoma or MPNST to the 16:801-12.
Melan-A should be negative. There are rare exclusion of the other in this case is not easily 10. Imoto K, Yamazak Y, Kawahara E, et al.
cases, however, of MPNST that have been done, nor does it capture its diagnostic Malignant melanocytic schwannoma of
noted to demonstrate melanocytic differentia- nuances. Instead of forcing this neoplasm into the nasopharynx. J Otorhinolaryngol Relat
tion.10-15 the diagnostic category of melanoma or Spec 1991;53:48-51.
With the difficulties definitively classifying MPNST, a more encompassing nomenclature 11. Murakami T, Kiyosawa T, Murata S, et al.
the neoplasm as either a melanoma or MPNST, such as malignant neuroectodermal tumor Malignant schwannoma with melanocytic
we propose that an alternative term be used: may be appropriate. In the end, cases such as differentiation arising in a patient with
malignant neuroectodermal tumor with this help us to re-evaluate our diagnostic crite- neurofibromatosis. Br J Dermatol 2000;
melanocytic and rhabdomyoblastic differentia- ria and highlight possible relationships 143:1078-82.
tion. As alluded to earlier, the term “neuroecto- between different entities. 12. Roth MJ, Medeiros J, Kapur S, et al.
dermal tumor” is used to refer to the fact that Malignant schwannoma with melanocytic
both Schwann cells and melanocytes are and neuroepithelial differentiation in an
derived from the neural crest, which in turn is infant with congenital giant melanocytic
derived from embryonic neuroectoderm.1 References nevus: a complex neurocristopathy. Hum
Neoplasms with features of melanocytic and Pathol 1993;24:1371-5.
schwannian differentiation are not difficult to 1. Hamilton WJ, Mossman HW. The fate of 13. Schadendorf D, Haas N, Worm M, et al.
find. Nevi with so-called “neurotization” of the germ layers and the formation of the Amelanotic malignant melanoma present-
dermal nevomelanocytes are one example. essential (primary) tissues including ing as malignant schwannoma. Br J
Melanotic schwannoma is a well-described blood. In: Human Embryology, 4th ed. Dermatol 1993;129:609-14.
entity that occurs sporadically and in the set- Cambridge: W Heffer and Sons Ltd, 1972; 14. Shimizu S, Teraki Y, Ishiko A, et al.
ting of Carney’s complex (cardiac and cuta- 162-73. Malignant epithelioid schwannoma of the
neous myxomas, pigmented nevi, endocrine 2. Ohsie SJ, Sarantopoulos GP, Cochran AJ, skin showing partial HMB-45 positivity.
abnormalities, and melanotic schwannomas), et al. Immunohistochemical characteris- Am J Dermatopathol 1993;15:378-84.
and can on occasion metastasize (10-20%). tics of melanoma. J Cutan Pathol 2008;35: 15. Thewes M, Jungfer-Weber B, Wiebecke B,
The neoplastic cells in melanotic schwannoma 433-44. et al. Malignant epithelioid schwannoma
can be epithelioid to spindled, and can contain 3. Ducatman BS, Scheithauer BW, Piepgras with melanocytic differentiation: a rare
prominent nucleoli. In addition to being DG, et al. Malignant peripheral nerve tumor with an unusual feature. Acta Derm
strongly S-100 protein positive and HMB-45 sheath tumors. A clinicopathological study Venereol 1997;77:493-4.
positive, melanotic schwannomas contain true of 120 cases. Cancer 1986;57:2006-21. 16. Weiss SW, Goldblum JR. Enzinger and
melanin pigment, which stains positively with 4. Weiss SW, Goldblum JR. Enzinger and Weiss’s. Soft Tissue Tumors, 5th ed.
Fontana-Masson stain. Ultrastructurally, they Weiss’s. Soft Tissue Tumors, 5th ed. Philadelphia: Mosby, 2008;870-2.
are noted to contain premelanosomes and Philadelphia: Mosby 2008;904-25. 17. Fetsch JF, Michal M, Miettinen M. Pig-
melanosomes.16 Melanin-containing neurofi- 5. Ooi A, Nakanishi I, Kojima M. Malignant mented (melanotic) neurofibroma: A clin-
bromas have been described also. Fetsch et al. schwannoma with rhabdomyoblastic and icopathologic and immunohistochemical
(2000) characterized a series of 19 pigmented melanocytic differentiation. Path Res analysis of 19 lesions from 17 patients. Am
“melanotic” neurofibromas including diffuse, Pract 1992;188:770-4. J Surg Pathol 2000;24:331-43.
plexiform, diffuse/plexiform combined, and 6. Hoang MP, Sinkre P, Albores-Saavedra J. 18. Spence AM, Rubinstein LJ, Conley FK, et
intraneural epithelioid morphologies, which Rhabdomyosarcoma arising in a congeni- al. Studies on experimental malignant
exhibited immunopositivity for S-100 protein, tal melanocytic nevus. Am J Dermato- nerve sheath tumor maintained in tissue
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melanin pigment, confirmed with Fontana- 7. Schmidtt FC, Bittencourt A, Mendonca N, pathol 1976;35:27-45.

Malignant Triton tumor in the Case Report Correspondence: Sojun Hoshimoto, Department
retroperitoneal space of Surgery, Fujita Health University School of
associated with A 21-year old man, who had been diagnosed Medicine, 1-98 Dengakugakubo, Kutsukake-cho,
Toyoake, Aichi 470-1192, Japan.
neurofibromatosis type 1: to have NF-1 by a dermatologist when he was
E-mail: sojunh@yahoo.co.jp
about a year old, was referred to Fujita Health
a case study University Hospital in November 2004,
Key words: malignant Triton tumor, malignant
because of a left lower abdominal mass and
Sojun Hoshimoto,1 Zenichi Morise,1 peripheral nerve sheath tumor, neurofibromato-
gradually increasing pain in the same region. sis, retroperitoneal tumor.
Chinatsu Takeura,1 Masahiro Ikeda,1 Physical examination revealed many café-au-
Tadashi Kagawa,1 Yoshinao Tanahashi,1 lait spots, subcutaneous masses of various Conflict of interest: the authors report no con-
Yasuhiro Okabe,1 Yoshikazu Mizoguchi,2 sizes, scoliosis, and a firm fixed mass in the flicts of interest.
Atsushi Sugioka1 left lower abdomen the size of a baby’s head.
1 The left lower extremity was markedly swollen Received for publication: 20 July 2009.
Department of Surgery and 2Department Accepted for publication: 5 August 2009.
of Pathology, Fujita Health University and the patient had difficulty in walking.
Laboratory examination revealed slight ane- This work is licensed under a Creative Commons
School of Medicine, Toyoake, Aichi, Japan
mia and elevated serum CRP; however, other Attribution 3.0 License (by-nc 3.0)
serum chemistry data were within normal lim-
its. Abdominal computed tomography revealed ©Copyright S. Hoshimoto et al., 2009
a huge heterogeneous tumor approximately 17 Rare Tumors 2009; 1:e27
Abstract cm in diameter occupying the left retroperi- doi:10.4081/rt.2009.e27
toneal space (Figure 1). Numerous other
We report an extremely rare case of malig- tumors, which seemed to be metastatic
nant Triton tumor developing in the retroperi- lesions, were found between the left psoas shaped cells with wavy nuclei and slightly
toneal space in a patient with neurofibromato- muscle and the left thigh with dissolution of eosinophilic cytoplasm, showing dense prolif-
sis type 1. A 21-year old man who had been the left hip joint (Figure 2). On magnetic reso- eration and forming storiform structures, with
diagnosed with neurofibromatosis type 1 was nance imaging, the tumor was visualized as a a myxomatous stroma (Figure 4A). On
admitted to our hospital with the chief com- low intensity signal on T1-weighted images immunostaining, the spindle-shaped tumor
plaint of a palpable abdominal mass. Abdominal and as a high intensity signal on T2-weighted cells showed a positive response for S-100 pro-
computed tomography revealed a huge hetero- images. tein and NSE, with sporadic distribution of
geneous tumor measuring approximately 17 After the diagnosis of retroperitoneal malig- rhabdomyoblastic cells that showed positive
cm in diameter occupying the left retroperi- nant neurogenic tumor associated with NF-1, a staining for myoglobin and desmin (Figure
toneal space, and numerous metastatic lesions laparotomy was performed. A giant, firm, 4B). Immunohistochemical staining with S-
between the left psoas muscle and the left thigh whitish, well-capsulated tumor was found 100 and desmin indicated that the tumor cells
with dissolution of the left hip joint. After the occupying the left abdomen (Figure 3). originated from Schwann cells and showed
diagnosis of a retroperitoneal malignant neuro- Although the main tumor appeared to be tight- rhabdomyosarcomatous differentiation. Based
genic tumor, resection of the tumor with recon- ly adherent to the psoas muscle and to involve on these findings, a diagnosis of MTT associat-
struction of the abdominal aorta was conduct- the abdominal aorta, there was no gross inva- ed with MPNST was made.
ed, followed by postoperative transarterial infusion of other adjacent organs. Resection of the After surgical treatment, transarterial infu-
sion chemotherapy. The histopathological diag- main tumor and of the nodules in the sion chemotherapy was administered via the
nosis was malignant peripheral nerve sheath retroperitoneal space that were suspected to left common iliac artery for the remnant
tumor with rhabdomyosarcomatous differentia- be metastatic lesions and reconstruction of the tumors in the left hip joint and the left thigh,
tion, namely malignant Triton tumor. abdominal aorta were conducted. and the patient was discharged five months
Postoperative chemo-therapy was in vain and Macroscopically, the extirpated main tumor after the surgery. However, eight months after
the patient died 14 months after the surgery as measured 19x15x13 cm in size and was encap- being discharged, the patient was readmitted
a result of lung metastasis. sulated. The cut surface of the tumor revealed for dyspnea found to be caused by lung metas-
solid and yellowish tissue in the peripheral tasis. Despite administration of transarterial
portion and foci of hemorrhage and necrosis in chemotherapy, the tumors increased greatly in
the central portion of the tumor. Histo- size, and the patient died 14 months after the
Introduction pathological examination revealed spindle- surgery. An autopsy was not performed.
Malignant Triton tumor (MTT) is a histolog-

ical variant of malignant peripheral nerve
sheath tumors (MPNSTs) with rhabdomyosar-
comatous differentiation. Although MPNSTs
have been known to develop in cases of neu-
rofibromatosis type 1 (von Recklinghausen’s
disease, NF-1) and sometimes to occur in the
retroperitoneal space, there are few reports of
MTTs developing in the retroperitoneal space.
We report an extremely rare case of MTT devel-
oping in the retroperitoneal space in a patient Figure 1. Abdominal computed tomography showing a huge tumor occupying the left
with NF-1 and describe the clinicopathological retroperitoneal space and a metastatic mass in the left psoas muscle (arrows).
features of this tumor.

Case Report
associated with a worse prognosis than

MPNSTs, regardless of whether or not they are
associated with NF-1,7,8 with a five-year sur-
vival rate of 12-26%.6,7
The reason for the more aggressive behav-
ior of MTTs than classic MPNSTs still remains
unclear. MTTs occur predominantly in the
trunk, head and neck, and lower extremities.8
According to a review of 75 cases of MTTs by
Yakulis et al. (1996), the tumor was located in
the retroperitoneum in only one case (1.3%).6
Figure 3. At laparotomy, a well-capsulated Subsequent to the publication of this review,
tumor was found occupying the left we could identify only one case of retroperi-
abdomen.
toneal MTT by a PubMed search of the English
language literature using the terms “retroperi-
toneum” or “retroperitoneal” and “Triton.”9 All
the three cases of MTTs developing in the
retroperitoneal space reported so far, including
the present case, presented with a huge
abdominal mass,6,9 since these retroperitoneal
tumors are often asymptomatic in the earlier
stages.
Like most soft-tissue sarcomas, MTTs tradi-
tionally are insensitive to chemotherapy and
Figure 2. Multiplanar reformation images
revealed lateral depression of the abdomi- radiotherapy. However, several authors have
nal aorta by the main tumor (arrow reported recently that repeated resection com-
heads), and numerous metastatic lesions bined with chemotherapy and/or radiotherapy
between the left psoas muscle and the left against recurrent MTTs might prolong the sur-
thigh, with dissolution of the left hip joint vival in patients with MTTs.10,11 Because
(arrows).
MPNSTs and MTTs have a high malignant
potential, patients with NF-1 should be fol-
lowed by periodic check-ups, including com-
puted tomography for early detection of such
tumors as these, and multidisciplinary treat-
ments including complete resection are
required for patients with MTTs.
Discussion
NF-1 is an autosomal dominant disorder
characterized by café-au-lait spots, cutaneous Figure 4. (A) Spindle-shaped cells showing References
neurofibromas, skeletal dysplasias, Lisch nod- dense proliferation and forming storiform
structures (H-E stain, x200), (B) staining
ules, and sometimes malignant tumors, and it for desmin was strongly positive in the 1. Lee MJ, Stephenson DA. Recent develop-
occurs with an incidence of approximately one area of MTT (peroxidase-antiperoxidase ments in neurofibromatosis type 1. Curr
in 3000 live births.1 MPNSTs are well known to technique, x100). Opin Neurol 2007;20:135-41.
arise from major and minor peripheral nerves 2. Ducatman BS, Scheithauer BW, Piepgras
or within pre-existing neurofibromas, and DG, et al. Malignant peripheral nerve
approximately 50 percent of patients with sheath tumors. A clinicopathologic study
MPNSTs have NF-1.2,3 The World Health of 120 cases. Cancer 1986;57:2006-21.
Organization coined the term MPNST in place fied in approximately 12 percent of patients 3. Wanebo JE, Malik JM, VandenBerg SR, et
of the previously used, often confusing, termi- with MPNSTs.2 al. Malignant peripheral nerve sheath
nology such as “malignant schwannoma,” Woodruff et al. (1973) reported a series of tumors. A clinicopathologic study of 28
“malignant neurilemmoma,” “neurogenic sar- 10 cases of malignant schwannoma with rhab- cases. Cancer 1993;71:1247-53.
coma,” and “neurofibrosarcoma.”4 The precise domyoblastic differentiation, which they were 4. Gupta G, Maniker A. Malignant peripheral
cell of origin of MPNSTs has not yet been con- the first to refer to as MTTs.5 Immunohi- nerve sheath tumors. Neurosurg Focus
clusively identified, although the Schwann cell stochemical staining for skeletal muscle mark- 2007;22:E12.
is thought to be the major candidate cell for ers such as myoglobin or desmin is essential 5. Woodruff JM, Chernik NL, Smith MC, et al.
this. The overall five-year survival rate in for making a correct diagnosis of MTT, because Peripheral nerve tumors with rhab-
patients with MPNSTs has been reported to be of the histological variations of MPNSTs. The domyosarcomatous differentiation (malig-
34-44%, and the association of these tumors average age of patients with MTTs is 31.7 nant "Triton" tumors). Cancer 1973;32:
with NF-1 is predictive of a poor prognosis.2,3 years and these tumors occur with approxi- 426-39.
The capacity of MPNSTs to undergo focal mately equal frequency in males and females.6 6. Yakulis R, Manack L, Murphy AI, Jr.
divergent differentiation is well known, and The reported incidence of MTTs occurring in Postradiation malignant triton tumor. A
tumors showing rhabdomyosarcomatous dif- association with NF-1 is in the range of 44-69. case report and review of the literature.
ferentiation, referred to as MTTs, are identi- Several authors have reported that MTTs are Arch Pathol Lab Med 1996;120:541-8.

Case Report
7. Brooks JS, Freeman M, Enterline HT. tumor). Arch Pathol Lab Med 2006;130: 2003;10:533-5.
Malignant "Triton" tumors. Natural history 1878-81. 11. Lang-Lazdunski L, Pons F, Jancovici R.
and immunohistochemistry of nine new 9. Murtaza B, Gondal ZI, Mehmood A, et al. A Malignant "Triton" tumor of the posterior
cases with literature review. Cancer 1985; huge malignant triton tumour. J Coll mediastinum: prolonged survival after
55:2543-9. Physicians Surg Pak 2005;15:728-30. staged resection. Ann Thorac Surg 2003;
8. Stasik CJ, Tawfik O. Malignant peripheral 10. Kostler WJ, Amann G, Grunt TW, et al. 75:1645-8.
nerve sheath tumor with rhabdomyosarco- Recurrent malignant Triton tumour: first
matous differentiation (malignant triton report on a long time survivor. Oncol Rep

A case of primary renal an abdominal aortic aneurysm, and angina

pectoris. He had been employed until the age Correspondence: Fumio Ito, Department of
angiosarcoma of 60 years old in the production of plastic auto Urology, Tokyo Women's Medical University
parts, such as those made from polyethylene Medical Center East, 2-1-10, Nishiogu, Arakawa-
Kazuhiko Yoshida,1 Fumio Ito,1 and acrylonitrile-butadiene-styrene copo- ku, Tokyo, Japan
Hayakazu Nakazawa,1 Yoshiko Maeda,1 lymer. E-mail: fitour@dnh.twmu.ac.jp
Hikaru Tomoe,1 Motohiko Aiba In May 2006, the patient noticed a bruise on
Received for publication: 3 August 2009.
1
Department of Urology, 2Department of his back after falling and become aware of per-
Accepted for publication: 5 August 2009.
Surgical Pathology, Tokyo Women's sistent pain in his left flank. He consulted a
family doctor, who diagnosed the condition as This work is licensed under a Creative Commons
Medical University Medical Center East,
a hemorrhage from a left renal cyst and pre- Attribution 3.0 License (by-nc 3.0)
Nishiogu, Arakawa-ku, Tokyo, Japan
scribed conservative treatment. However, the
symptoms remained and the patient was ©Copyright K. Yoshida et al., 2009
referred to our hospital three months later. Rare Tumors 2009; 1:e28
doi:10.4081/rt.2009.e28
Routine blood tests showed the presence of
Abstract anemia and an IAP value that increased to
1060, while other parameters were within the
A 78-year old man was diagnosed with a left normal range and a urine test showed no
bleeding renal cyst from CT scan results. Serial abnormal findings including hematuria. An initial pathological diagnosis was a chronic
CT scans revealed the left kidney mass to be abdominal CT scan demonstrated a distinctly hematoma with no evidence of malignancy.
increasing in size and a new lesion in the liver. bordered mass located on the upper pole of the Two months after the operation, follow-up
Renal cell carcinoma with liver metastasis was left kidney that measured approximately 14 cm CT scans showed the hepatic lesion to be
diagnosed and a radical nephrectomy per- in maximum diameter. The images also increasing in size and multiplying; however,
formed. The initial pathological diagnosis was showed that the distribution of contrast mate- we were not able to perform a liver biopsy
a benign chronic hematoma. However, the rial was limited to the margin of the mass because of the high risk of bleeding or rupture.
liver mass increased in size and multiplied, without focal pooling, which suggested that Four months after the operation, spinal paraly-
while another mass emerged in the twelfth the central part was hemorrhagic or necrosis developed suddenly, and MR imaging
thoracic vertebra with spinal paralysis and was tized, while the periphery had no obvious revealed a new tumor that had destroyed the
immediately removed. Pathological findings tumor formation (Figure 1). Additionally, CT twelfth thoracic vertebra and compressed the
for that specimen showed malignancy of stro- scanning depicted a newly developed low den- adjacent spinal cord. The tumor was removed
mal cell origin but low atypia. The renal speci- sity area with poor contrast in the sixth seg- immediately by orthopedic surgeons.
men was re-evaluated using whole cross-sec- ment of the liver (Figure 1). Therefore, we According to the pathological report, the tumor
tion analysis and immunohistochemistry, and considered that the lesions located in the left in the thoracic vertebra was composed of spin-
diagnosed as a primary renal angiosarcoma. kidney and liver corresponded, respectively, to dle cells with mildly atypical nuclei and a
Recombinant interleukin-2 therapy was start- primary renal and metastatic hepatic lesions of sheet-like appearance, and which were prolif-
ed immediately; however, the patient died of renal cell carcinoma. We performed a radical erating and infiltrating the surrounding area.
metastatic disease 13 months after the initial nephrectomy in August 2006 in order to Following the second surgery, cross-sections of
operation. Although contrast imaging depicted achieve tumor cytoreduction. The excised kid- the total kidney specimen were prepared and
the primary lesion as a non-specific hematoma ney was 960 g in weight, while the tumorous subjected to re-evaluation, which demonstrat-
with little focal pooling, and low-grade cytolog- lesion was approximately 18x11x7 cm in size, ed spindle-shaped tumor cells, the same as
ical atypia was shown pathologically, the and composed of a non-specific hematoma and those seen in the thoracic vertebra (Figure 3).
angiosarcoma was extremely aggressive. surrounding fibrous capsule (Figure 2). The Immunohistochemistry findings showed
Introduction
Angiosarcomas comprise only two percent of
all soft tissue sarcomas.1 The large majority
originate from the skin of the scalp and face,
while those with a visceral origin including the
kidneys are extremely rare.2 Recently we treat-
ed a case of primary renal angiosarcoma, in
which a prompt and exact diagnosis was diffi-
cult to obtain. We report here a brief review of
the literature and the clinical course of this
Early phase Late phase
malignancy.
Plain Enhanced
Figure 1. Abdominal CT scan findings obtained before the initial operation. An approx-
Case Report imately 14 cm-sized mass with a distinct border was found located on the upper pole of
the left kidney (A). The distribution of contrast material was limited to its margin with-
The patient was a 78-year old Japanese man, out pooling. A new lesion that later developed in the sixth segment of the liver was shown
as a low density area with poor enhancement (B).
who was treated previously for a peptic ulcer,

Case Report
that the neoplastic cells were not positive for

cytokeratin, a marker of epithelial cells, but
rather for vimentin, a marker of mesenchymal
cells. The neoplastic cells were positive also for
factor VIII-related antigen, CD31, and CD34,
which are markers of endothelial cells, and for
VEGF and its receptor, Flk-1. These immuno-
histochemical findings supported a final diag-
nosis of angiosarcoma. Immediately after the
final diagnosis, recombinant interleukin-2
monotherapy (35~70 C x 104 IU three times a
week for a total dose of 22x106 IU) was started
for the liver metastases in February 2007.
However, the patient died of metastatic dis-
ease 13 months after the initial operation.
Exterior view Cross-sectional view
Figure 2. Macroscopic appearance of affected kidney. The mass was located on the upper
Discussion pole of the left kidney. The majority of the lesion was occupied by a non-specific
hematoma and its periphery was composed of fibrous tissue. No neoplastic lesions were
Angiosarcomas comprise only two percent of observed in macroscopic observations.
all soft tissue sarcomas,1 while those deeply
located including a primary renal angiosarco-
ma are extremely rare.2 To the best of our
knowledge, 25 cases of primary renal angiosar-
coma have been reported in the English litera-
ture until the end of 2007, and the outcome for
nearly all of the affected patients has been
extremely poor.3-6 The main cause for poor prog-
nosis is the difficulty of prompt and accurate
diagnosis, especially for angiosarcomas in deep
organs such as the kidneys. In the present case,
because the actual tumor size was extremely
small, CT scanning failed to exhibit the exact
tumor shape with abnormal contrast pooling,
while a pathological examination also failed to
provide an accurate diagnosis without cross-
sections from the entire specimen. In addition,
a precise pathological diagnosis required
immunohistochemistry analysis,7 as the tumor
cells lacked some particular features, such as a
vascular architecture. In patients with an
angiosarcoma of the kidney, a prompt and exact
diagnosis is not easy to obtain in the early
stage, because clinical symptoms generally do
not develop at that point, and the disease often
shows rapid growth and metastasis. Therefore, Figure 3. Microscopic findings of the primary renal lesion. Most areas of the specimens
effective systemic treatments as standard ther- were occupied by the non-specific hematoma, whereas the tumor was located in the
apies are needed, although they have yet to be periphery of the hematoma (A). Spindle-shaped tumor cells with low-grade atypia had
established. In recent years, new treatments proliferated and invaded the adjacent parenchyma, which exhibited a sheet-like forma-
such as immunotherapy, including recombi- tion with no vascular architecture (B). The tumor cells were positive for CD31 (C), and
VEGF (D).
nant interleukin-2 (rIl-2) administration,8 and
molecular targeting therapies using beva-
cizumab9 and sorafenib10 have been utilized
increasingly. However, the long-term and large- administration.
scale effectiveness of these therapies remains In conclusion, the present case confirmed References
to be assessed. We applied rIl-2 therapy to the the aggressive biological behavior of a primary
liver metastasis in our patient via intravenous angiosarcoma of the kidney, regardless of its 1. Fata F, O’Reilly E, Ilson D, et al. Paclitaxel
administration. The patient showed good toler- relatively gentle features in imaging and patho- in the treatment of patients with angiosar-
ance for the drug; however, the metastatic logical examinations. It is important to be coma of the scalp or face. Cancer 1999;86:
lesions did not show a response, possibly aware of the possibility of angiosarcoma as well 2034-7.
because the drug was given as monotherapy as more well-known malignancies such as 2. Fletcher CDM, McKee PH. Angiosarcoma.
and in a low dose, and also because the disease renal cell carcinoma when treating a patient In: McGee JO’D, Isaacson PG, Wright NA,
was well advanced at the time of the initial with an unusual hematoma of the kidney. editors. Oxford Textbook of Pathology,

Case Report
Oxford: Oxford University Press 1992, coma: a case report and literature review. interleukin-2 immunotherapy. Int J Radiat
p936. Can J Urol 2007;14:3471-6. Oncol Biol Phys 2005;61:1446-53.
3. Akkad T, Tsankov A, Pelzer A, et al. Early 6. Souza OE, Etchebehere RM, Lima MA, et 9. Koontz BF, Miles EF, Rubio MA, et al. Pre-
diagnosis and straight forward surgery of al. Primary renal angiosarcoma. Int Braz J operative radiotherapy and bevacizumab
an asymptomatic primary angiosarcoma of Urol 2006;32:448-50. for angiosarcoma of the head and neck:
the kidney led to long-term survival. Int J 7. Meis-Kindblom JM, Kindblom, L-G. Angio- Two case studies. Head Neck 2008;30:262-
Urol 2006;13:1112-4. sarcoma of soft tissue: a study of 80 cases. 6.
4. Cranero LB, Fernández PI, Carrasco AJA, Am J Surg Pathol 1998;22:683-97. 10. Wunder JS, Nielsen TO, Maki RG, et al.
et al. Renal primary angiosarcoma. Clin 8. Ohguri T, Imada H, Nomoto S, et al. Opportunities for improving the therapeu-
Transl Oncol 2007;9:806-10. Angiosarcoma of the scalp treated with tic ratio for patients with sarcoma. Lancet
5. Lee TY, Lawen J, Gupta R. Renal angiosar- curative radiotherapy plus recombinant Oncol 2007;8:513-24.
A legacy of tinnitus: multiple sis revealed a germline heterozygous mis-

sense mutation (p.Pro81Leu) in exon 3 of the Correspondence: Jeremy J. Turner, Elsie Bertram
head and neck paragangliomas succinate dehydrogenase subunit D (SDHD) Diabetes Centre, Norfolk and Norwich University
gene. Therefore she was diagnosed with Hospital, Norwich, NR4 7UY, UK
Tricia M.M. Tan,1 Emma C.I. Hatfield,1 familial paraganglioma syndrome type 1 E-mail: Jeremy.turner@nnuh.nhs.uk
Rajesh V. Thakker,2 Eamonn R. Maher,3 (PGL1).
Karim Meeran,1 Niamh M. Martin,1 Contributions: TMMT, ECIH, KM, NMM, JJT, all
Jeremy J. Turner1 were involved in the clinical care of the patient
described; RVT, ERM, provided and interpreted
the genetic studies.
1
Department of Investigative Medicine,
Discussion
Conflict of interest: the authors report no con-
Division of Investigative Science, Imperial flicts of interest.
Paragangliomas are neuroendocrine
Healthcare NHS Trust, London, UK;
2
tumors of the autonomic nervous system. Received for publication: 4 July 2009.
Nuffield Department of Clinical
Abdominal and thoracic paragangliomas are Revision received: 9 August 2009.
Medicine, University of Oxford, Oxford,
derived from sympathetic tissue and secrete Accepted for publication: 10 August 2009.
UK; 3Department of Medical and catecholamines, like pheochromocytomas,
Molecular Genetics, Institute of This work is licensed under a Creative Commons
which are derived from the adrenal medulla.
Biomedical Research, University of Attribution 3.0 License (by-nc 3.0).
Head and neck paragangliomas are derived
Birmingham, Edgbaston, Birmingham, UK from parasympathetic tissue and usually do ©Copyright T.M.M. Tan et al., 2009
not secrete catecholamines.1 Up to a third of Rare Tumors 2009; 1:e29
paragangliomas and pheochromoctyomas are doi:10.4081/rt.2009.e29
associated with hereditary causes; i.e., muta-
Abstract tions in VHL, RET (causing multiple endo-
crine neoplasia type 2A-MEN2A), NF1, and the
We describe the case of a patient who pre- SDH complex genes SDHB, -C and -D.2 hypoxia-inducible pathways, producing a
sented with a right-sided glomus jugulare The SDH complex is bound to the inner pseudohypoxic state similar to that seen in
tumor and bilateral glomus vagale tumors. mitochondrial membrane and participates in tumors from patients with VHL disease.3,4 The
These proved to be nonmalignant paragan- both the electron-transport chain and the HIF-1 and HIF-2 transcription factors are
gliomas on histopathological analysis. Genetic Krebs cycle as part of complex II. It consists of major mediators of the hypoxic gene response
analysis revealed a germline heterozygous four subunits A-D. Mutations in subunits B, C, and the HIF-α subunits are rapidly degraded
missense mutation (Pro81Leu) in the succi- and D are associated with hereditary in normoxic cells via a VHL protein (pVHL)-
nate dehydrogenase subunit D (SDHD) gene. pheochromocytomas and paragangliomas: the dependent mechanism.5 Activation of HIF
We discuss the clinical presentations of the PGL1 syndrome with mutations in SDHD, pathways with SDH subunit inactivation has
familial paraganglioma syndrome type 1, PGL3 with mutations in SDHC, and PGL4 with been linked to accumulation of succinate and
which is caused by mutations in SDHD, and mutations in SDHB. resulting inhibition of the prolyl hydroxylase
the implications for the clinical diagnosis and Multiple mechanisms have been implicated enzymes that are necessary for HIF-α subunit
care of such patients. in the pathogenesis of SDH subunit-related modification and proteosomal degradation, as
tumors. These include abnormal activation of pVHL is unable to bind the unmodified sub-
Case Report
A 35-year old lady presented with right- Figure 1. Magnetic resonance
sided pulsatile tinnitus, conductive deafness, image scan of the neck. Fast
T2-weighted MRI scan
and a vascular lesion in the floor of the right demonstrates the right glomus
external auditory meatus. Magnetic reso- jugulare tumor (adjacent to
nance imaging revealed a right-sided glomus right cochlea, arrow), and
jugulare tumor and bilateral glomus vagale bilateral glomus vagale tumors
tumors (Figure 1). Both her paternal grandfa- (arrows).
ther and her father had undergone neck sur-
gery for tumors. She was an only child and had
a two-year-old son. She was normotensive,
with no clinical features of von Hippel-Lindau
(VHL) syndrome or neurofibromatosis type 1
(NF1). Serum calcium, urine catecholamine
excretion, and serum calcitonin were within
normal limits. Radiolabeled metaiodobenzyl-
guanidine scanning and MRI imaging of her
abdomen did not demonstrate any intra-
abdominal paragangliomas. She underwent
partial excision of her right glomus jugulare
tumor, with complete excision of both the glo-
mus vagale tumors. Histology showed nonma-
lignant paragangliomas. Genomic DNA analy-

Case Report
units.4 In addition, animal models of SDH testing. In addition, individuals with

inactivation suggest that reactive oxygen apparently sporadic pheochromocytoma or References
species may be increased and also might pro- paraganglioma disease will require genetic
voke a pseudohypoxic state.6 Therefore screening if risk factors such as extra- 1. Lenders JW, Eisenhofer G, Mannelli M, et
SDHB/D mutations may predispose to a failure adrenal sympathetic paraganglioma, al. Phaeochromocytoma. Lancet 2005;366:
of normal developmental apoptosis of sympa- malignant paraganglioma, or young age at 665-75.
thetic neuronal cells leading to persistence of diagnosis (e.g., below 40 years) are pres- 2. Gimenez-Roqueplo AP, Lehnert H, Man-
“pheochromocytoma precursor cells”.5 PGL1/ ent.2 Depending on the clinical presenta- nelli M, et al. Phaeochromocytoma, new
SDHD disease is inherited as an autosomal tion, mutation analysis of VHL, SDHB, genes and screening strategies. Clin
dominant trait, but demonstrates parent-of- SDHC, SDHD, and/or RET genes may be Endocrinol 2006;65:699-705.
origin effects in that tumors only develop indicated. 3. Pollard PJ, El-Bahrawy M, Poulsom R, et al.
when the mutation is inherited from the • Secondly, the relatives of patients in whom Expression of HIF-1alpha, HIF-2alpha
father, with possible rare exceptions.6 a pathogenic mutation is detected should (EPAS1), and their target genes in para-
Typically, head and neck paragangliomas are be offered genetic screening, even if they ganglioma and pheochromocytoma with
found, but pheochromocytomas and abdomi- are asymptomatic, because of the age- VHL and SDH mutations. J Clin Endocrinol
nal or thoracic paragangliomas can develop dependent penetrance. The inheritance Metab 2006;91:4593-8.
also. The tumors often are multiple, and tend pattern of PGL1-related disease will influ- 4. Selak MA, Armour SM, MacKenzie ED, et
to develop early, with a median age of first ence the screening program (see follow- al. Succinate links TCA cycle dysfunction
presentation of 31 years. In addition, there is ing) and the counseling given to patients to oncogenesis by inhibiting HIF-alpha
an age-dependent penetrance, with 48 per- and their relatives. In our patient’s case, prolyl hydroxylase. Cancer Cell 2005;7:77-
cent, 73 percent, and 100 percent being diag- her son is not likely to develop tumors 85.
nosed by the ages of 30, 40, and 70 years, because of the parent-of-origin effect on 5. Lee S, Nakamura E, Yang H, et al.
respectively.7 In contrast to PGL4/SDHB dis- penetrance. However, he will require Neuronal apoptosis linked to EglN3 prolyl
ease, where metastatic disease is common, genetic screening when he is older, hydroxylase and familial pheochromocy-
the tumors in PGL1 tend to be benign.7 because if he is a carrier of the SDHD toma genes: developmental culling and
mutation, then his children may be at risk. cancer. Cancer Cell 2005;8:155-67.
• Thirdly, carriers of these mutations will 6. Pigny P, Vincent A, Cardot Bauters C, et al.
require regular, lifelong, clinical, biochem- Paraganglioma after maternal transmis-
Conclusions ical, and radiological screening. In order to sion of a succinate dehydrogenase gene
reduce the lifetime exposure to ionizing mutation. J Clin Endocrinol Metab 2008;
The clinical data accumulated regarding radiation, it is necessary to use imaging 93:1609-15.
familial paraganglioma syndromes raise sev- modalities such as MRI or ultrasound. 7. Benn DE, Gimenez-Roqueplo AP, Reilly JR,
eral important implications for their clinical Optimum clinical management requires et al. Clinical presentation and penetrance
management. the multidisciplinary expertise of sur- of pheochromocytoma/paraganglioma syn-
• Firstly, patients with familial disease or geons, endocrinologists, clinical geneti- dromes. J Clin Endocrinol Metab 2006;
multiple tumors should be offered genetic cists, and radiologists. 91:827-36.

Soft tissue mixed tumor enlargement compatible with the physical

examination, but there was no calcification or Correspondence: Michiro Susa,
of the hand bone erosion. On magnetic resonance imaging Sarcoma Molecular Biology Laboratory,
(MRI), there was a 4×4×2 cm circumscribed Massachusetts General Hospital, 70 Blossom
Hiroshi Shimosawa,1 Michiro Susa,1* mass in the subcutaneous region. T1- and T2- Street, MGR J 1115, Boston, MA 02114, USA.
Takayuki Honma,1 Eiichi Hiraishi,1 weighted images depicted a heterogeneous E-mail: msusa@partners.org
Hiroshi Sakihara1 lesion with intermediate intensity, slightly
Key words: mixed tumor, soft tissue, hand,
higher than in the muscle (Figure 1 A, B).
1 immunohistochemistry.
Department of Orthopaedic Surgery, Eiju Incisional biopsy was performed followed by
General Hospital, Tokyo, Japan marginal resection. The tumor was well encap- Contributions: HS, analyzed the data and wrote
*Current address: Sarcoma Molecular sulated with slight adhesion to the palmar the first draft of the paper; MS, TH, EH, HSa,
Biology Laboratory, Massachusetts aponeurosis (Figure 2 A, B). edited the manuscript.
General Hospital, 70 Blossom Street, On histopathology, the tumor consisted of a
MGR J 1115, Boston, MA 02114, USA circumscribed lesion with a yellowish-tan Conflict of interests: the authors report no con-
appearance grossly. Hematoxylin and eosin flicts of interest.
staining demonstrated a lobulated architec-
ture, composed of epithelioid cells and myoep- Received for publication: 10 August 2009.
ithelial elements in the chondromyxoid and Accepted for publication: 13 August 2009.
Abstract collagenous stroma. There was adipocytic dif- This work is licensed under a Creative Commons
ferentiation with evidence of ductal differenti- Attribution 3.0 License (by-nc 3.0).
Mixed tumors are relatively common in the ation (Figure 3A, B). Nuclear atypia was mild,
skin and salivary glands, but extremely rare in and although there were sporadic mitoses, ©Copyright H. Shimosawa et al., 2009
soft tissues, often resulting in diagnostic prob- atypical mitotic figures were not identified. Rare Tumors 2009; 1:e30
lems. The occurrence of these tumors in the Immunohistochemical examination demon- doi:10.4081/rt.2009.e30
hand is especially limited. In this article we strated positivity for cytokeratin, S-100, and
report the clinical, radiological, and histologi- CD10. Cytokeratin and CD 10 were positive in
cal features of a mixed tumor of the both spindle and epithelioid cells. S-100 pro- show a spectrum of cellular and architectural
hypothenar region of the right hand. tein was focally positive in the spindle cells morphologies. Myoepithelial cells may be spin-
(Figure 3C, D, E). dled, plasmacytoid, ovoid, or epithelioid, and
The postoperative period was uneventful. By can express a wide variety of cytoplasmic fila-
her 18-month follow-up, no recurrence or ments. The growth pattern may be solid, myx-
Introduction metastasis had developed. oid, or reticular, and each individual tumor
includes areas with more than one growth pat-
Mixed tumors of the soft tissues were recog- tern or cell subtype.4,5
nized as a separate entity only recently, and Myoepithelial tumors of soft tissue occur
there is a limited number of case reports to Discussion equally in male and female patients. They have
date. Mixed tumors, along with myoepithe- been reported in a wide age range with a peak
liomas, which constitute myoepithelial tumors, Mixed tumors and myoepitheliomas are well in the third to fifth decades, most commonly
are composed of myoepithelial cells predomi- characterized in salivary glands, but were rec- occurring in the limbs and the limb girdles.2,5
nantly and they are relatively common in major ognized to occur in soft tissue only recently.2,3 The vast majority of cases arise in the subcuta-
and minor salivary glands. Because fewer than Histological patterns are analogous to that of neous or deep subfascial soft tissue. Most
25 soft tissue mixed tumors have been report- the salivary gland counterpart. The tumors patients present with painless swelling rang-
ed so far, their characterization has been
scarce.1,2 To our knowledge, there has not been
a report of a mixed tumor of the soft tissue of
the hand. In this report, we present a rare case
of a soft tissue mixed tumor of the hand.
Case Report
A 79-year old woman presented with a slow-
growing mass of the hypothenar region of her
right hand with a history of several years.
There was no particular incidence of trauma or
any relevant medical history. The tumor meas-
ured 4×4 cm in size and the overlying skin was
smooth and nonadherent with slight redness.
The patient did not complain of any pain or
tenderness. Physical examination of the cervi- Figure 1. (A) Axial T1-weighted magnetic resonance imaging scan revealing
cal and axillary region showed no lymph- a 4×4×2 cm intermediate intensity mass in the subcutaneous region of the
adenopathy. right hand. (B) Sagittal T2-weighted image showing a similar heterogeneous
finding. The intensity was slightly higher than in the surrounding muscle.
On plain radiography, there was soft tissue

Case Report
ing in duration from a few weeks to several

years.5 MRI appearance of soft tissue mixed
tumors varies in accordance with the hetero-
geneity of the tumor. Depending on the
amount of hemorrhage, chondromyxoid and
fibrous stroma, it is possible for the tumor to
present various findings. Preoperative diagno-
sis based on the MRI should be performed pru-
dently, and incisional biopsy should be per-
formed at all times.
There is a debate still as to whether mixed
tumors and myoepithelioma should be distin-
guished as separate entities or considered as
the same spectrum of tumors with overlapping Figure 2. (A, B) A 4×4×2 cm soft tissue mixed tumor of the hypothenar region of the
hand.
histological appearances and similar clinical
behavior. Those tumors either lacking or with
very limited ductal differentiation generally
are classified as myoepitheliomas. Current
classification simply separates those tumors
with ductal differentiation into the mixed
tumor categories.6,7 Whereas some investiga-
tors allow up to five percent or ten percent duc-
tal differentiation in myoepitheliomas,4,8-10 oth-
ers classify tumors with any ducts as mixed
tumors. In the present case, the tumor showed
distinct duct formations; therefore we diag-
nosed it in accordance with the strict criteria.
The absence of clear-cut histopathological
clues for the diagnosis of myoepithelial tumors
is hampered further by the wide variability in
their immunohistochemical characteristics.
Immunoreactivity for the S-100 protein and
muscle actins seems to be the most constant
immunophenotype, whereas immunoexpres-
sion for epithelial markers such as cytoker-
atins and EMA, or neural markers such as
GFAP, is somewhat erratic and variable from
case to case. The same immunophenotype has
been described in salivary gland myoepithelial
tumors, which usually coexpresses immunore-
activity for S-100 protein, muscle actins, and
GFAP, with variable immunoexpression for
EMA and cytokeratins.8,11-16 Figure 3. (A, B) Photomicrograph of the soft tissue mixed tumor, showing a lobulated
Although the majority of morphologically architecture with epithelioid cells and myoepithelial elements in the chondromyxoid and
benign-looking mixed tumors of soft tissue collagenous stroma, and evidence of ductal differentiation (H&E stain). Immuno-
behave in a benign fashion, there is approxi- histochemical examination demonstrated positivity for cytokeratin (C) and CD10 (E) in
both spindle and epithelioid cells, and S-100 protein in the spindle cells (D).
mately a twenty percent risk for local recur-
rence. The malignant potency of myoepithelial
tumors varies, and it is difficult to differentiate
myoepithelial tumors into benign and malig-
nant categories on histological grounds locations, with breakpoints on 8q12, 3p21, and the tumor displays a reticular architecture
only.17,18 For the diagnosis of malignant myoep- 12q14-15 have been described in myoepithelial with chondromyxoid or hyalinized stroma,
ithelioma in salivary glands, an invasive tumors of the salivary gland.22 It is interesting extraskeletal myxoid chondrosarcoma and
growth pattern has been considered as the to note that the malignant myoepithelial tumor ossifying fibromyxoid tumor should be consid-
most important feature, because the immuno- has been reported to show different chromoso- ered as differential diagnoses. Solid spindle
histochemical features are similar for the mal abnormalities such as gains of 1p31~p34, cell myoepithelial tumors can resemble
benign and malignant forms.18 In addition, 1q21~q23, and 16q22, and loss of 15q.23 leiomyomas and schwannomas. Furthermore,
cytological atypia and mitotic rate have been Nevertheless, it is difficult to establish prog- if the tumor shows significant cytological atyp-
reported to be useful.19,20 However, in the case nostic indicators for soft tissue myoepithelial ia, metastatic carcinomas, metastatic melano-
of soft tissue myoepithelial tumors, there has tumors until further reports are available. mas, and epithelioid sarcomas should be con-
been no association between the degree of Because there is considerable morphologic sidered as well.
nuclear pleomorphism or mitotic activity and heterogeneity of soft tissue myoepithelial The mixed tumor should be considered as
clinical behavior.21 Recurrent chromosome tumors, the differential diagnosis should be one of the differential diagnoses of soft tissue
rearrangements, particularly reciprocal trans- based on the dominant histological pattern. If tumors of the hand. The rarity of this tumor

Case Report
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6. Ellis GL, Auclair PL. Atlas of Tumor expression of vimentin, cytokeratin and S- with cytogenetic findings. Cancer Genet
Pathology: Tumors of the Salivary Glands, 100 in monomorphic adenoma of salivary Cytogenet 2008;183:121-4.
3rd series, fascicle 17. Washington, DC: gland: value of marker studies in the dif- 23. Bullerdiek J, Wobst G, Meyer-Bolte K, et al.
Armed Forces Institute of Pathology, 1996. ferential diagnosis of salivary gland Cytogenetic subtyping of 220 salivary
7. Seifert G, Sobin LH. World Health tumours. Cytopathology 1992;3:303-9. gland pleomorphic adenomas: correlation
Organization International Histological 15. Nishimura T, Furukawa M, Kawahara E, et to occurrence, histological subtype, and in
Classification of Tumours: Histological al. Differential diagnosis of pleomorphic vitro cellular behavior. Cancer Genet
Typing of Salivary Gland Tumours. Berlin, adenoma by immunohistochemical Cytogenet 1993;65:27-31.

Rare Tumors 2009; volume 1:e31 Rare Tumors 2009; volume 1:e31
Primary sarcoma of the liver ed in some cases of EHE because of a favorable

long term outcome,1,3 it is absolutely not advised Correspondence: Sébastien Dharancy,
and transplantation: for AS owing to a high risk of early local or gen- Service des Maladies de l’Appareil Digestif et de
a case study and literature eral recurrence after LT.4 We report the case of a la Nutrition, Hôpital Huriez, CHU, Lille 59037,
France. E-mail: s6@chru-lille.fr
review young woman who underwent LT for a infiltra-
tive hepatic tumor, of which some characteris-
tics and the clinical presentation were sugges- Key words: angiosarcoma, epithelioid heman-
Benjamin Bismuth,1 Hélène Castel,1 gioendothelioma, liver transplantation
Emmanuel Boleslawski,2 David Buob,3 tive of EHE. However, the histological analysis of
the explanted liver revealed AS. The preventive
Marc Lambert,4 Nicole Declerck,2 Received for publication: 23 June 2009.
use of an immunosuppressive drug with antipro- Accepted for publication: 8 August 2009.
Valérie Canva,1 Eli-Serge Zafrani,5
liferative properties belonging to the mam-
Philippe Mathurin,1 François-René malian target of rapamycine (mTOR) inhibitors This work is licensed under a Creative Commons
Pruvot,2 Sébastien Dharancy1 led to the usual two years’ survival after LT, Attribution 3.0 License (by-nc 3.0)
1
Service des Maladies de l’Appareil despite a local recurrence of AS.
©Copyright B. Bismuth et al., 2009
Digestif et de la Nutrition; 2Service de Rare Tumors 2009; 1:e31
Chirurgie Digestive et de Transplantation, doi:10.4081/rt.2009.e31
Hôpital Huriez; 3Anatomie et Cytologie
Pathologique, Centre de Biologie - Case Report
Pathologie; 4Service de Médecine Interne, The patient underwent a second liver biopsy. A
Hôpital Huriez, CHRU Lille, France; A 41-year-old woman was admitted in April vascular disease predominant in the pericen-
5
Département d’Anatomie Pathologique, 2002 for acute hepatitis of unknown etiology. trolobular zone was observed, with congestive
Previous liver function tests, performed in sinusoids, centrolobular vein thickening, and
Hôpital Henri Mondor,
March 2002, were normal. The only remarkable
AP-HP, Créteil, France necrosis. The abdominal magnetic resonance
medical history was obesity with a body mass
imaging (MRI) showed a diffuse nodular infiltra-
index of 31.5. There was no history of excessive
tion of the liver (Figure 1). Because of the inef-
alcohol consumption (30 g/wk), medication, or
fectiveness of corticotherapy, methotrexate (15
toxic exposure. Biological testing excluded viral,
Abstract bacterial, and autoimmune hepatitis. The com-
mg/wk) was introduced.
In October 2005 she was referred for jaundice,
puterized tomography (CT) scan revealed a
Primary sarcomas of the liver are rare tumors ascitis, and edema. Prothrombin time was 50%,
homogeneous hepatomegaly and excluded a
and their diagnosis is difficult to assess, particu- thrombosis of the sus-hepatic veins. A liver biop- bilirubin was 90 mg/L, and α-fetoprotein was
larly on percutaneous liver biopsy. Epithelioid sy showed a granulomatous infiltration of the normal. A third liver biopsy was performed,
hemangioendothelioma (EHE) is an infrequent liver, with histiocytes but no centrolobular necro- showing a proliferation of CD31– and CD34+
indication for liver transplantation, and sis, as well as a steatosis (30% of the parenchy- cells, compatible with the diagnosis of EHE or
angiosarcoma (AS) is a widely recognized con- ma). The diagnosis of acute hepatitis related to AS. A second MRI (November, 2005) revealed a
traindication because of its poor prognosis. We a vascularitis was made. Between 2002 and 2005 hepatomegaly with diffuse, hypervascular and
report the case of a young woman who under- she was hospitalized for several episodes of nodular infiltration of the liver (Figure 2). The
went liver transplantation (LT) for an infiltrative acute disease, associated fever, maculopapulous measurement of the portal pressure revealed
hepatic tumor with several features suggestive eruption, elevation of liver enzymes (AST = 5 x portal hypertension with a portosystemic gradi-
of EHE, although the analysis of the native liver ULN, ALT = 11 x ULN), and cholestasis (alkaline ent of 16 mmHg. The upper endoscopy found a
revealed AS. Everolimus was used as the main phosphatases = 20 x ULN, γGT = 10 x ULN). portal hypertensive gastropathy and esophageal
immunosuppressive drug. More than two years Because of the lack of success of the previous varices (grade 1). Clinical presentation orients
after LT, her physical condition remained stable therapy, a systemic corticotherapy (dexametha- the diagnosis toward a diffuse EHE with portal
despite a local recurrence at 10 months. In this sone = 250 mg IV) was begun in 2005, followed hypertension and hepatocellular insufficiency.
setting, the ranking of new immunosuppressive by oral prednisone (1 mg/kg/day). In May 2005 a Thus, LT was considered.
agents belonging to the family of the prolifera- low platelet count (99000/mm3) was observed. The patient underwent LT in December 2005.
tion signal inhibitors will need to be precise, but
their intrinsic properties suggest a potential use
in treatments after LT for atypical malignancies.
Introduction
Primary sarcomas of the liver are rare tumors
(approximately 1% of liver cancers) and an
exceptional indication for liver transplantation Figure 1.
(LT).1 The two main histological forms are Abdominal mag-
epithelioid hemangioendothelioma (EHE) and netic resonance
imaging in June
angiosarcoma (AS).2 Those tumors, which share 2005 (T1 without
the same mesenchymal origin (endothelial cells gadolinium injec-
edging the sinusoid), have very different natural tion) showing dif-
history and prognosis, and require different fuse nodular infil-
treatments (Table 1). Although LT can be indicat- tration of the liver.

Review
Despite the preoperative suspected diagnosis,

AS was confirmed finally at the pathological Figure 2. Abdominal
magnetic resonance
analysis of the explant, consisting of a diffuse AS imaging in November
with necrosis and invasion of the centrolobular 2005 (T1 with gadolin-
veins (Figure 3). The initial immunosuppressive ium injection) showing
regimen included prednisone (20 mg/day), hepatomegaly related
to hypervascular tumo-
mycophenolate mofetyl (1 g x 2/day), and ral infiltration of the
tacrolimus (6 mg x 2/day). Tacrolimus and pred- liver.
nisone were decreased, then withdrawn in July
2006, and changed to everolimus (3 mg/day).
Residual concentrations ranged from 10-14 µg/L.
Mycophenolate mofetyl was withdrawn in
October 2006. A postoperative CT scan per-
formed at month 10 revealed a local recurrence
with a multimicronodular infiltration of the
transplant (Figure 4). Systemic chemotherapy
with paclitaxel was begun but had to be discon-
tinued in February 2007 owing to neurological Figure 3. Transversal
and mucous toxicity. Nevertheless, the CT scan section of the native
at month 16 showed a partial response, while the liver showing diffuse
patient was under everolimus and taxane thera- tumoral infiltration.
py. At month 24, the patient was under
monotherapy with everolimus (3 g/day). She had
no biological toxicity to everolimus and was
managing quite well, despite a progression of
the disease with asymptomatic vertebral metas-
tasis. At month 30 her general health status
quickly decreased with terminal liver failure
leading to death.
Figure 4. Injected com-

puterized tomography
Discussion scan (postoperative
month 10) showing
We report an atypical clinical observation, local recurrence of liver
which is especially interesting in that it illus- sarcoma.
trates the difficulty in distinguishing the two
forms of primary sarcoma of the liver. It also
underlines the potential interest in the use of an
immunosuppressive regimen with the new
antiproliferative agents (mTOR inhibitors) in
this very particular setting. Our report is not to
promote LT for AS, based on this unusual case
study, but rather to provide some ways to opti-
mize the management of such patients. The
diagnosis of primary sarcoma of the liver is made
often at an advanced stage, because of its rarity
and the fact that it is asymptomatic for a long
time in patients with a normal nontumoral liver.2 edge of the sinusoids, often causing vascular mortality rate of 90% in the year of the diagno-
The diagnosis is confirmed by the pathological dilatations (cavernous type), or more rarely sis.2 Some authors consider EHE as a low-grade
analysis of the tumoral tissue. Although its mes- nodular solid tumors. In both histological forms, sarcoma, more frequent among women aged 30
enchymal origin is assessed easily by panen- tumoral cells are CD31– and CD34+. Hepatic AS is to 40 years. It is a particular form of sarcoma in
dothelial markers, the distinction between EHE a rare vascular tumor (<1/106 persons) predomi- that it has an intermediate malignant potential
and AS remains a delicate issue, particularly on nant in men (sex ratio, 4:1). The mean age is and a slow rate of progression.7 The radiological
a percutaneous liver biopsy. The main histologi- around 60 years.4 The known risk factor for AS is examinations reveal a unique tumor, sometimes
cal criteria to assess the diagnosis of EHE are exposure to a carcinogen such as arsenic and difficult to distinguish from other liver cancers.8
nodes formed by a hyaline stroma, and particular vinyl chloride. Metastases are found frequently In AS the panendothelial markers are positive.
epithelioid cells with intracytoplasmic red blood at the time of the diagnosis, mainly located in The gold-standard treatment is partial hepatecto-
cell inclusions, and sometimes calcifications the lung, spleen, and bones. The radiological my but, in a large number of the patients, a com-
(which are not present in AS). At the edge of the characteristics of AS are not unequivocal. MRI or plete resection is impossible owing to the infil-
nodes, sinusoids and hepatic veins are invaded CT scans may show a multinodular tumor, a trative pattern of the lesion.7 In this very particu-
by tumoral cells, but the architecture of the liver mass syndrome, or more rarely a diffuse infiltra- lar situation, LT can be discussed, because post-
is preserved.5 The histological characteristic of tion of the liver.6 The outcome of AS is very poor, transplant survival is similar to that in other liver
AS is the presence of atypical tumoral cells at the regardless of the kind of therapy, with an overall disease.1,3 Our patient had several characteristics

Review
Table 1. Comparison of the characteristics of HA and epithelioid hemangioendothe- 6. Koyama T, Fletcher JG, Johnson CD, et al.
lioma. Primary hepatic angiosarcoma: findings at
Characteristics HA Epithelioid hemangioendothelioma CT and MR imaging. Radiology 2002;222:
667-73.
Sex Male Female 7. Makhlouf HR, Ishak KG, Goodman ZD.
Mean age 60 40 Epithelioid hemangioendothelioma of the
Risk factors Carcinogenes - liver: a clinicopathologic study of 137 cases.
Cancer 1999;85:562-82.
Clinical presentation Aspecific Aspecific
8. Kim KA, Kim KW, Park SH, et al. Unusual
Radiological findings Unique Unique mesenchymal liver tumors in adults: radio-
Multinodular logic-pathologic correlation. AJR Am J
Diffuse infiltration Calcifications
Roentgenol 2006;187:W481-9.
Anatomopathology No calcifications Preservation of the 9. Hidalgo M, Rowinsky EK. The rapamycin-
Disappearance of the architecture of the acini sensitive signal transduction pathway as a
architecture of the acini target for cancer therapy. Oncogene
Gold-standard therapy Symptomatic Surgery (hepatectomy, 2000;19:6680-6.
liver transplantation) 10. Huang S, Shu L, Easton J, et al. Inhibition of
Post-transplant outcome Poor (<5%) Good (70%) mammalian target of rapamycin activates
(two-years' survival, %) apoptosis signal-regulating kinase 1 signal-
ing by suppressing protein phosphatase 5
Table 2. Review of the cases of primary sarcomas of the liver reported in the literature. activity. J Biol Chem 2004;279: 36490-6.
11. Kristof AS, Pacheco-Rodriguez G, Schrem-
Type Number of cases References mer B, et al. LY303511 (2-piperazinyl-8-
phenyl-4H-1-benzopyran-4-one) acts via
Angiosarcoma 13 ELTR register (1)
7 UNOS register (4) phosphatidylinositol 3-kinase-independent
pathways to inhibit cell proliferation via
Leiomyosarcoma 1 (18)
mammalian target of rapamycin (mTOR)-
Epithelioid hemangioendothelioma 66 ELTR register (1) and non-mTOR-dependent mechanisms. J
7 (7) Pharmacol Exp Ther 2005;314:1134-43.
12. Panwalkar A, Verstovsek S, Giles FJ.
suggestive of EHE: gender, age, absence of toxic explained, at least in part, by the antitumoral Mammalian target of rapamycin inhibition
exposure, and a slow progression of the tumor. properties of everolimus. Finally, primary sarco- as therapy for hematologic malignancies.
Nevertheless, the fact that the tumor presented mas of the liver are very rare tumors. EHE is an Cancer 2004;100:657-66.
as a hypervascular and multinodular lesion was exceptional indication for LT, although AS is a 13. Sekulic A, Hudson CC, Homme JL, et al. A
less indicative of EHE, and the findings of the widely recognized contraindication. The belief of direct linkage between the phosphoinosi-
liver biopsy performed before LT were compati- mTOR inhibitors having antiproliferative and tide 3-kinase-AKT signaling pathway and
ble with the diagnosis of AS. Only 16 patients antiangiogenic properties needs to be deter- the mammalian target of rapamycin in
who had LT for AS and 66 for EHE were recorded mined in those cases of misdiagnosed AS in mitogen-stimulated and transformed cells.
by the ELTR European Register between 1988 order to delay or slow down the recurrence of the Cancer Res 2000;60:3504-13.
and 2001, representing 0.2% of the indications sarcoma. 14. Tirado OM, Mateo-Lozano S, Notario V.
for LT.1 Some isolated case reports have been Rapamycin induces apoptosis of JN-DSRCT-
published about LT for other forms of sarcoma of 1 cells by increasing the Bax: Bcl-xL ratio
the liver (Table 2). Taking into account the high through concurrent mechanisms dependent
risk of early locoregional recurrence of the dis- References and independent of its mTOR inhibitory
ease after LT, we introduced everolimus at six activity. Oncogene 2005;24: 3348-57.
months after LT. Everolimus is an immunosup- 1. Adam R, McMaster P, O'Grady JG, et al. 15. Yu K, Toral-Barza L, Discafani C, et al.
pressive and antiproliferative agent belonging to Evolution of liver transplantation in Europe: mTOR, a novel target in breast cancer: the
the family of the mTOR inhibitors. This molecule report of the European Liver Transplant effect of CCI-779, an mTOR inhibitor, in pre-
has a specific cytostatic effect on tumoral cell Registry. Liver Transpl 2003;9: 1231-43. clinical models of breast cancer. Endocr
proliferation in vivo and in vitro, and has been 2. Weitz J, Klimstra DS, Cymes K, et al. Relat Cancer 2001;8:249-58.
evaluated as an antioncogenic therapy.9-15 Management of primary liver sarcomas. 16. Seeliger H, Guba M, Kleespies A, et al. Role
Everolimus also has an antiangiogenic action, Cancer 2007;109:1391-6. of mTOR in solid tumor systems: a thera-
and is able to increase the antitumoral effect of 3. Lerut JP, Orlando G, Sempoux C, et al. peutical target against primary tumor
chemotherapy.16 Moreover, the use of mTOR Hepatic haemangioendothelioma in adults: growth, metastases, and angiogenesis.
inhibitors has been associated with a significant excellent outcome following liver transplan- Cancer Metastasis Rev 2007.
decrease in the risk of developing de novo can- tation. Transpl Int 2004;17:202-7. 17. Kauffman HM, Cherikh WS, Cheng Y, et al.
cers after renal transplantation.17 These findings 4. Maluf D, Cotterell A, Clark B, et al. Hepatic Maintenance immunosuppression with tar-
promoted an interest in using everolimus after angiosarcoma and liver transplantation: get-of-rapamycin inhibitors is associated
LT in our patient in order to delay or decrease the case report and literature review. Transplant with a reduced incidence of de novo malig-
recurrence of AS. A local recurrence occurred at Proc 2005;37:2195-9. nancies. Transplantation 2005;80: 883-9.
month 10 but, after more than two years of fol- 5. Soslow RA, Yin P, Steinberg CR, et al. Cyto- 18. Saint-Paul MC, Gugenheim J, Hofman P, et
low-up, the outcome for our patient is better than pathologic features of hepatic epithelioid al. Leiomyosarcoma of the liver: a case treat-
that previously described in the literature. This hemangioendothelioma. Diagn Cytopathol ed by transplantation. Gastroenterol Clin
unusual survival after LT for AS may be 1997;17:50-3. Biol 1993;17:218-22.

Pitfalls in neuroendocrine drome (1), and sarcoidosis (1). Relying on this

limited but significant occurrence rate, we Correspondence: Emilio Bajetta, Medical Oncology
tumor diagnosis deem that some key points should be argued. Unit 2, Fondazione IRCCS Istituto Nazionale
Primarily, a frequent mistake concerns the Tumori, Via G. Venezian 1 - 20133 Milano, Italy.
Emilio Bajetta, Marco Platania interpretation of abnormal CgA plasma values: E-mail: emilio.bajetta@istitutotumori.mi.it
Medical Oncology Unit 2, Reference this marker, expressed in both functioning and Conflict of interest: the authors report no con-
Center for the Study and Treatment of non functioning NET tumors, shows a thresh- flicts of interest.
Carcinoids and Neuroendocrine Tumors, old of sensitivity and specificity depending on
Fondazione IRCCS Istituto Nazionale dei tumor histology, extension of the disease, and Received for publication: 31 July 2009.
Tumori, Milan, Italy biological tumor activity.3 Additionally, the Accepted for publication: 14 August 2009.
methods used to measure CgA levels are not
standardized yet, as appears from the compar-
Carcinoids, originating from cells of the dif- ison of the three commercially available kits,
fuse endocrine system (DES), account for 0.7% the outcomes of which may disagree consider- ©Copyright et al., 2009
of all malignancies and are characterized by a ably.4 Other pathological conditions may hin- Rare Tumors 2009; 1:e32
slow growth rate and the presence of nonspe- der the specificity because CgA elevations can doi:10.4081/rt.2009.e32
cific signs and symptoms often making their be detected in some instances in patients with
detection rather difficult. Gastroente ropancre- renal and hepatic failure, untreated hyperten-
atic neuroendocrine tumors (GEP-NETs) rep- sion, inflammatory bowel disease, and even in mandatory. Notwithstanding the fact that
resent the majority (~70%) of DES tumors. the presence of nonendocrine tumors.5 octreoscan is carried out routinely in hospitals
Historically they account for about 2% of all Lastly, the use of proton-pump inhibitors equipped with nuclear medicine units, the
gastrointestinal tumors but their incidence may be responsible for the elevations of CgA experience of the operators and the adoption
and prevalence have increased recently, likely values, and long-term acid inhibition is a well of a correct procedure for the image acquisi-
owing to the advances accomplished with new known cause of CAG with related ECL cell tion represent the major issues to achieve
endoscopy procedures and diagnostic tools, hyperplasia.6 On the basis of CgA values, it reliable results. Based on the largest Italian
and to the achievement of long survival rates would be best for clinicians to discriminate experience carried out in three hospitals and
fostered by the indolent evolution of the dis- patients affected by carcinoids from healthy involving 253 patients, a comparison of differ-
ease. Currently, according to the algorithm subjects and from those whose abnormal find- ent procedures of octreoscan has demonstrat-
proposed by Modlin1 for diagnosis and manage- ings depend on hyperplastic lesions of ed that the best specificity (88%) was
ment of GEP-NETs normally accepted by clini- endocrine cells in the context of a CAG. obtained when a semiquantitative evaluation
cians in routine clinical practice, the first According to our experience,7 the threshold was employed.11 In addition, this procedure
action after clinical suspicions of a NET com- value of CgA for identifying patients with NETs showed that bowel preparation is not essen-
prises the measurement of circulating mark- should be 36 U/L, which gives a specificity of tial; conversely, when the 24-hour image
ers such as CgA, NSE, serotonin, gastrin, or 83-91%. More recently, however, it has been acquisition shows accumulation in the
urinary 5-hydroxyindoleacetic acid (5-HIAA). highlighted that there is a need to change the abdomen possibly because of the radioactive
In the case of positive findings, the subse- current cutoff CgA values to exclude patients bowel content, it is extremely important to
quent action lies in the octreoscan, which in whom levels are elevated as a result of non- repeat scintigraphy after 48 hours.12 The capa-
allows the topographic localization of the pri- neoplastic conditions.8 The authors set a 95% bility of recognizing all uptake of physiological
mary lesion or of metastatic disease. Finally, specificity, corresponding to cutoff values of tracers and other pathological aspects result-
the diagnosis is completed through the surgi- 84-87 U/L, arguing that this is essential to ing in a false positive octreoscan response can
cal resection of the primary tumor or the biop- exclude patients showing false positive CgA reduce the false positive results to 3% only.13 It
sy of the reachable metastases. However, nei- increases from unnecessary examinations should be highlighted that the hypophysis,
ther laboratory tests nor octreoscans are com- specific for endocrine tumors. In our experi- thyroid, liver, spleen, kidneys, bladder, gall-
pletely reliable diagnostic tools because other ence, when a borderline or doubtful value is bladder, and intestinal tract represent areas of
clinical disorders or atypical radiological find- observed, before proceeding to the workup we physiological uptake of 111In-DTPA-octreo-
ings may mimic a carcinoid, hence leading to repeat the plasma assay with the addition of tide, and that somatostatin receptors are
an erroneous NET diagnosis. Consequently, the detection of NSE plasma dosage and of uri- found even in activated leukocytes in granulo-
the distinct possibility of false positive find- nary 5-HIAA: the latter, particularly, appears matosis processes (sarcoidosis, tuberculo-
ings exists, being the lack of experience with extremely useful and crucial to this purpose.9 sis)14 and chronic inflammatory processes
the disease the major reason for an incorrect Another issue critical in making the NET (inflammatory bowel disease, ulcerative coli-
diagnosis. Indeed, with the exception of some diagnosis easier is the correlation between tis, rheumatoid arthritis).15
sporadic case reports,2 it does not seem that marker serum values and referred symptoms In conclusion, despite a better general
the matter of the occurrence of false positive at presentation. It should be highlighted that understanding of neuroendocrine disease in
NETs has been taken into consideration sys- at diagnosis the classical carcinoid syndrome terms of natural history, biology, and clinical
tematically. Based on two years’ experience, of flushing, sweating, diarrhea, abdominal behavior, differential diagnosis of NETs should
we report the occurrence of eight cases previ- pain, bronchospasm, and right-sided heart be extremely extensive and accurate, needing
ously clinically diagnosed as NETs elsewhere, failure represents a fairly infrequent event additional and more definite investigations.
and then referred to our specialized reference occurring in less than 10% of NETs,10 because Awaiting more specific diagnostic tests, clini-
center for pathological substantiation. After it may depend on the secretion rate of tumor cal data and radiological findings should be
investigation, the following diagnoses were mediators, tumor size, its anatomical location interpreted always by taking the clinical set-
made: chronic atrophic gastritis (CAG) with and, chiefly, the extent of liver metastases. ting, particularly, into consideration. A knowl-
enterochromaffin-like cell (ECL) hyperplasia Additionally, octreoscan findings should be edge of conditions that could mimic a NET is a
(4 cases), estrogen-deprivation syndrome (1), related to the clinical setting always; conse- key factor in the approach to the disease, and
hypochondriac disorder (1), metabolic syn- quently, the need of reliable evidence is close cooperation among dedicated physicians,

Letter
pathologists, nuclear medicine specialists, and Accuracy and clinical correlates of two dif- reported cases. J Exp Clin Cancer Res
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define the optimal diagnostic protocol. in neuroendocrine tumors. Int J Biol 11. Chiti A, Briganti V, Fanti S, et al. Results
Therefore, to save medical resources and to Markers 2004;19:295-304. and potential of somatostatin receptor
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aged in highly experienced centers with the Clin Inv 1998;28:431-40. Somatostatin receptor scintigraphy with
support of a greatly integrated multidiscipli- 6. Modlin IM, Lye KD, Kidd M. A 50-year indium-111-DTPA-D-Phe-1-octreotide in
nary team. analysis of 562 gastric carcinoids: small man: metabolism, dosimetry and compari-
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Nucl Med 1992;33:652-8.
7. Bajetta E, Ferrari L, Martinetti A, et al.
13. Gibril F, Reynolds JC, Chen CC, et al.
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Hepatic angiosarcoma Introduction Correspondence: Laurence E. McCahill, Lacks

five years following Cancer Center, 200 Jefferson SE, Grand Rapids,
spontaneous intraperitoneal Primary hepatic angiosarcoma is a rare dis- MI 49503, USA. E-mail: mccahillj_l@comcast.net
bleed of a hepatic mass ease with a poor life expectancy. It is believed
Key words: hepatic angiosarcoma, hepatic mass,
to be highly lethal, with near 100% mortality by
spontaneous intraperitoneal bleed.
Jessica L. Cioffi-Pretti,1 one year. We present the highly unusual iden-
Alexandra N. Kalof,2 George Ebert,3 tification of a high-grade angiosarcoma in an
Contributions: JC-P, AK, LM, manuscript writing;
Laurence E. McCahill4 adult male five years following his initial pres- AK, GE, LM, manuscript editing/revisions.
1
entation with a spontaneously bleeding hepat-
Department of Surgery, University of ic mass. Conflict of interest: the authors report no con-
North Carolina at Chapel Hill, Chapel Hill; flicts of interest.
2
Department of Pathology, Fletcher, Allen
Health Care/University of Vermont, Received for publication: 21 July 2009.
Burlington; 3Department of Radiology, Case Report Accepted for publication: 27 August 2009.
Fletcher Allen Health Care/University of
Vermont, Burlington; 4Lacks Cancer The patient is a 32-year-old man with a his- Attribution 3.0 License (by-nc 3.0)
Center, St. Mary’s Health Care, Grand tory of Crohn’s disease, who presented febrile
Rapids, Michigan, USA and tachycardic, with a falling hematocrit ©Copyright J.L. Cioffi-Pretti, et al., 2009
(40.0-27.7%), and leukocytosis (23 K/cm) in Rare Tumors 2009; 1:e33
2003. An abdominal CT scan demonstrated a doi:10.4081/rt.2009.e33
12.0x11.0 cm hyperdense, highly attenuated,
Abstract heterogeneous mass in the lateral segment of
the left hepatic lobe, with a free intraperi- cm in maximum dimension, but with newly
Primary hepatic angiosarcoma is a rare toneal hemorrhage (Figure 1A). The patient identified asymptomatic esophageal varices
and rapidly fatal disease. We present the became stable hemodynamically after a trans- and thrombosis of the left portal vein. Over the
highly unusual identification of this lesion fusion with two units of blood. In addition to following eight months, the lesion increased in
five years after the initial clinical presenta- Crohn's disease, his past medical history was size from 3.0 cm to 4.8 cm, and developed
tion. notable for splenomegaly since the age of 18 prominent intralobular septations (Figure 1C).
In 2003, a 32-year-old man presented with years and persistent thrombocytopenia A malignant process was considered and
abdominal pain, tachycardia, and evidence of (platelet count, 40,000-50,000). He denied repeat core biopsies demonstrated an atypical
hemorrhage. A CT scan showed a hepatic drinking alcohol and subsequent hepatitis vascular proliferation with features suggestive
mass with intralesional hemorrhage, intra- serology tests were negative. of an epithelioid hemangioendothelioma.
peritoneal blood, and splenomegaly. The A fine needle aspiration of the left hepatic Subsequently the patient underwent a left
patient was stabilized clinically. Laparoscopic mass was performed and demonstrated rare hepatic lobectomy (Couinaud segments 2-4)
core biopsies demonstrated no malignancy, clusters of atypical cells with a background of that revealed a highly vascular lesion involving
only findings consistent with an old hemor- necrotic debris, suggestive of malignancy. The the left lateral and left medial lobes with fibro-
rhage. Contralateral lobe biopsies revealed paucity of cells present, however, precluded sis of the porta hepatis. Pathologic examina-
normal liver tissue. A metastatic workup was immunohistochemical workup and a definitive tion demonstrated a high-grade primary hepat-
negative and the decision was made to diagnosis. Laparoscopic needle core biopsies ic angiosarcoma with negative histological
observe the patient clinically with radiograph- were performed subsequently and revealed an margins. The patient’s postoperative course
ic follow-up, given his suspected portal hyper- organizing hematoma without evidence of was complicated by the development of signif-
tension based on thrombocytopenia and malignancy. Biopsies of the contralateral lobe icant ascites. He recovered well from surgery,
splenomegaly. demonstrated normal liver parenchyma with- and the ascites resolved. A three-month follow-
Sequential imaging demonstrated a out cirrhosis. A full metastatic workup was up CT scan demonstrated a single pulmonary
decrease in the size of the mass from 12.0 cm negative. Hepatic angiography was performed lesion suggestive of metastasis. The patient
in 2003 to 3.0 cm in 2007. Subsequent newly and demonstrated a rounded hypovascular underwent a video-assisted thoracoscopy pro-
identified esophageal varices prompted a re- lesion without a characteristic tumor blush. cedure, with the pathologic examination
evaluation of the case. A repeat biopsy Hepatic venous wedge pressures (8 torr) failed demonstrating a 1 cm focus of a high-grade
demonstrated a neoplasm of vascular etiology to support a diagnosis of portal hypertension. A metastatic epithelioid angiosarcoma. He rapid-
and uncertain malignant potential. By early bone marrow biopsy was unremarkable and ly developed a port site chest wall recurrence,
2008 the lesion had increased to 4.8 cm and platelet function assays were normal. A deci- for which he has received systemic taxane-
was resected via a left hepatic lobectomy. An sion for close observation was made secondary based chemotherapy, with a durable partial
extremely vascular lesion with surrounding to the patient’s long-standing splenomegaly response of twelve months. Currently he
dense fibrosis was identified and pathologic and thrombocytopenia and the concern for his remains free of disease in the liver.
examination demonstrated a high-grade suitability for resection.
angiosarcoma. The patient was monitored closely every
We are unaware of any previous reports four to six months with radiographic imaging,
Pathologic findings
suggesting such a prolonged natural history which documented an interval decrease in the Grossly, the resected liver specimen con-
of hepatic angiosarcoma. This case may rep- size of the lesion (Figure 1B). He remained tained a tan, hemorrhagic well-demarcated
resent the possibility of malignant transfor- asymptomatic, fully active, and otherwise mass (6.0x5.5x5.0 cm), with a peripheral rim
mation of a lower grade vascular neoplasm healthy. A surveillance CT scan performed four of fibrous tissue and approximately 60% tumor
such as hepatic epithelioid hemangioen- years after the initial presentation (April 2007) necrosis (Figure 2). The mass abutted on the
dothelioma to an angiosarcoma. demonstrated the lesion had diminished to 3.0 capsular surface with adjacent fibropurulent

Article
serositis. Surgical resection margins were nor- Acute abdominal bleeds occur spontaneously common at the time of presentation, with the
mal tissue. or following percutaneous biopsy in 15-27% of most usual metastatic sites being the lung and
Microscopically, the liver mass revealed a cases, and thus hepatic angiosarcoma should spleen. Unenhanced CT images of these mass-
high-grade malignant neoplasm composed of be considered in the differential workup of a es are observed to be hypodense when com-
epithelioid cells exhibiting marked cellular patient with spontaneous hemoperitoneum. pared to normal hepatic parenchyma, while
pleomorphism, brisk mitotic activity (>50 Associated laboratory findings tend to be non- lesions observed with contrast-enhanced CT
mitotic figures/10 high power fields) and specific, although more than half of the may be either hypo- or hyperdense, depending
extensive geographic tumor necrosis (Figure patients have unexplained thrombocytopenia on the presence of hemorrhage within the
3). The cells were arranged in cohesive sheets, and elevated alkaline phosphatase levels. The tumor. Optimal imaging techniques for the
focally forming anastomosing vascular chan- remaining liver function tests are normal and diagnosis of hepatic angiosarcoma include
nels with prominent hob-nailing and scattered tumor markers are negative. To date, there has unenhanced, multiple-phase enhanced, and
intracytoplasmic lumina. The tumor infiltrated not been any association with known viral delayed CT or MR imaging to adequately cap-
the surrounding hepatic parenchyma with markers identified.3 ture all phases of the tumor and eliminate
entrapment of benign bile ducts and hepato- Radiographically, hepatic angiosarcomas potentially benign mimickers.4
cytes. Lymphovascular invasion was not identi- have a varying appearance. There may be one Pathologically, hepatic angiosarcomas of the
fied. Positive immunohistochemical stains dominant focus or multiple masses that corre- deep soft tissue and in visceral locations gen-
included: CD31, CD34, Podoplanin (D2-40), late with the gross appearance. Metastases are erally are high-grade malignant neoplasms
EMA, and Factor VIII Ag, while Keratin CAM
5.2, Keratin MAK 6, Keratin AE1-AE3, and
HepPar1 were negative. The immunohisto-
chemical findings support vascular differentia-
tion with high-grade morphology, extensive
necrosis, and epithelioid morphology charac- A
teristic of an epithelioid angiosarcoma.
Discussion
Angiosarcomas are rare, malignant vascular
tumors that may occur in any area of the body,
but are most common in the region of the head
and neck. Sarcomas of the soft tissues consti-
tute less than 1% of all cancers, with angiosar-
comas compromising approximately 2% of soft
tissue sarcomas. Predisposing factors include
a prior history of radiation therapy, chronic
lymphedema, exposure to Thorotrast (thorium
dioxide, a radiologic contrast medium), use of B
anabolic steroids or synthetic estrogens, insec-
ticide exposure, and long-term exposure to
vinyl chloride. Typically angiosarcomas are
high-grade, aggressive tumors that tend to
recur and metastasize despite treatment.
Current therapies include surgical resection,
with radiation therapy and/or adjuvant
chemotherapy depending on the anatomic
location and size. Overall prognosis is poor for
soft tissue angiosarcomas, with a five-year
survival reported in the range of 10-35%.1
Hepatic angiosarcoma is very rare, consti-
tuting 2% of all primary hepatic cancers. The C
average incidence of hepatic angiosarcoma is
estimated to be 25 cases per year in the United
States. There is a male to female predomi-
nance of 3:1 with the majority of patients diag-
nosed in their sixth decade of life. Figure 1. CT images
showing regression
Approximately 60% of patients have evidence rather than progression
of metastatic disease at the time of diagnosis.2 of the liver lesion, (A)
Clinical presentation is nonspecific typical- initial presentation in
ly, with presenting symptoms including 2003, (B) diminished
abdominal pain, weakness, fatigue, and weight to 3.0 cm in 2007, and
(C) progression in
loss; while physical examination findings may 2008.
include hepatomegaly, ascites, and jaundice.

Article
that have an epithelioid to spindled appear-

ance. As in the current case, angiosarcomas of Figure 2. Gross liver
resection specimen.
the liver are characterized by nests and solid
sheets of malignant cells of high nuclear grade
that form irregular vascular channels and
exhibit invasion of the adjacent liver parenchy-
ma. Tumor necrosis is a common finding.
Grossly, the tumor may appear with one of four
different growth patterns: multiple nodules, a
single dominant mass, mixed patterns of a
dominant mass with smaller nodules, or an
infiltrating micronodular tumor.2
For the past 40 years, a link has been estab-
lished between hepatic angiosarcoma and
environmental toxins, including Thorotrast,
vinyl chloride, arsenic, radiation, and exoge-
nous estrogens or anabolic steroids. However,
in nearly 75% of cases, no causative agent is
identified. In all cases of environmental expo-
sure, a prolonged latency period has been Figure 3. Hepatic mass
established of 20-30 years on average, yet the and adjacent liver
gross and microscopic pathology of idiopathic parenchyma with asso-
angiosarcomas and those caused by environ- ciated capsular disrup-
tion and inflammatory
mental toxins remain identical.5 reaction (H&E stain,
Treatment for hepatic angiosarcoma is 40x magnification).
delayed often owing to the nonspecific symp-
toms with which the tumor typically presents.
The average time until diagnosis is six months
from the initial presentation to a health care
professional; however, many patients do not
seek medical attention for several months fol-
lowing the onset of symptoms. Thus, a large
tumor size and the presence of metastases are
common on diagnosis. Median survival time
following diagnosis is six months, with near
100% mortality by one year. Improved progno-
sis has been observed with a single tumor
mass, a smaller tumor size, lack of metastases,
a low-grade lesion, and negative surgical
resection margins; however, owing to the clinical diagnosis of portal hypertension por- to have primary hepatic angiosarcoma.8 In the
infrequent nature of the tumor, this still has to tends a worse prognosis. Pathologic examina- case of our patient, liver biopsies of the unin-
be quantified.2 Given the poor prognosis for tion results including high-grade nuclear fea- volved liver in 2003 failed to demonstrate char-
patients diagnosed with hepatic angiosarco- tures with epithelioid morphology are addi- acteristic periportal fibrosis, but this was iden-
ma, surgical resection is the only definitive tional unfavorable findings. Paradoxically, the tified on repeat liver biopsies in 2007, after the
treatment; however, this is not possible in radiographic finding of a tumor mass that had patient developed esophageal varices.
many cases either because of multifocal dis- been present for the previous five years in our We are unaware of any previous reports sug-
ease or the extent of the liver involvement.6 patient would suggest a less aggressive clinical gesting such a prolonged natural history of a
Adjuvant treatment remains undefined owing course of the disease. hepatic angiosarcoma. This case may repre-
to the rarity of the tumor. Chemotherapy has In hindsight, this patient’s splenomegaly sent the possibility of malignant transforma-
not been well studied except on a case report appears to be a result of periportal fibrosis and tion of a lower grade vascular neoplasm, such
basis, and in general angiosarcomas are the splenomegaly and thrombocytopenia were as hepatic epithelioid hemangioendothelioma,
resistant to radiation therapy. Liver transplan- long standing. These clinical findings have to a more aggressive angiosarcoma. While
tation has been attempted, but the tumor been reported previously as precursors to the angiosarcoma may present with spontaneous
recurrence rate remains high (64%) and long- development of angiosarcoma in other and often catastrophic intraperitoneal bleed-
term survival has not been observed (average patients. An analysis of patients with signifi- ing, this patient’s spontaneous intraperitoneal
survival time, 23 mth).7 If definitive resection cant polyvinyl chloride exposure by Lee et al. bleed was five years prior to eventual resection
can be achieved prior to microscopic spread of (1996)8 described a patient with a history of of the tumor. The patient had well-documented
the disease, long-term survival is possible. splenomegaly and thrombocytopenia, who later radiographic gradual reduction in size of the
This has been reported in three adult cases presented with esophageal varices and presi- lesion over four and a half years, before its
that were without evidence of recurrence at 64 nusoidal hypertension via a screening pro- rapid enlargement just prior to excision; a very
months, 38 months, and 10 years.3 gram. Ultimately a core needle biopsy lead to unusual progression in the natural history of a
Although our patient’s tumor was amenable the diagnosis of presinusoidal hepatic fibrosis. high-grade angiosarcoma, thus raising the
to resection, the associated hepatic fibrosis The patient later sustained a fatal gastroin- possibility of malignant transformation of a
documented by previous core biopsies and the testinal hemorrhage, and at autopsy was found benign precursor.

Article
festations of primary hepatic angiosarco- in hepatic angiosarcoma. J Hepatobiliary

References ma. Dig Dis Sci 2003;48:677-82. Pancreat Surg 2003;10:250-2.
4. Koyama T, Fletcher JG, Johnson CD, et al. 7. Maluf D, Cotterell A, Clark B, et al. Hepatic
1. Mark RJ, Poen JC, Tran LM, et al. Primary hepatic angiosarcoma: findings at angiosarcoma and liver transplantation:
Angiosarcoma. A report of 67 patients and CT and MR imaging. Radiology 2002;222: case report and literature review.
a review of the literature. Cancer 1996; 667-73. Transplant Proc 2005;37:2195-9.
77:2400-6. 5. Louagie YA, Gianello P, Kestens PJ, et al. 8. Lee FI, Smith PM, Bennett B, et al.
2. Mani H and Van Thiel DH. Mesenchymal Vinylchloride induced hepatic angiosarco- Occupationally related angiosarcoma of
tumors of the liver. Clin Liver Dis 2001;5: ma. Br J Surg 1984;71:322-3. the liver in the United Kingdom 1972-
219-57, viii. 6. Ozden I, Bilge O, Erkan M, et al. Five years 1994. Gut 1996;39:312-8.
3. Molina E and Hernandez A. Clinical mani- and 4 months of recurrence-free survival

Colonic cancer in adolescents. genetic predisposition, including hereditary

polyposis and non-polyposis syndromes.4,7,11 Correspondence: M.A.C. Odike, Ambrose Alli
A report of three cases Three cases of colonic cancer amongst University, Ekpoma, Edo State, Nigeria.
Nigerian adolescents aged 17 and 19 years are E-mail: maxodike@yahoo.com
M.A.C. Odike,1 A.E. Dongo,2 E.F. Alufohai,2 presented. These are uncommon findings, and
A.I. Odike3 hence should be of interest to clinicians to Key words: colon cancer, adolescents.
1 2
Departments of Pathology, Surgery and increase their index of suspicion as early cases
Pediatrics, Ambrose Alli University, are potentially curable.
Revision received: 17 July 2009.
Ekpoma, Edo State, Nigeria Accepted for publication: 30 July 2009.
Case #1
OS, a 19-year old male student presented to This work is licensed under a Creative Commons
the surgical out-patient (SOP) department of Attribution 3.0 License (by-nc 3.0).
Abstract the Irrua Specialist Teaching Hospital (ISTH) ©Copyright M.A.C. Odike et al., 2009
with complaints of passage of bloody and Rare Tumors 2009; 1:e34
Colorectal cancer is a common malignant watery stools, abdominal pain, lower abdomi- doi:10.4081/rt.2009.e34
neoplasm in adults, with a peak incidence of nal distension and vomiting of between one
60-79 years. About 1 million cases of the dis- week and three months duration. The abdomi-
ease and half a million deaths associated with nal pain was intermittent and colicky. He ered and was discharged home. Two months
it are reported world-wide each year. Colorectal reported mild weight loss. There was no family post-operation, she developed a nodule on the
cancer, however, is very uncommon in children history of similar illness. Physical examination anterior abdominal wall over the laparotomy
and adolescents. This is a presentation of 3 showed a mildly dehydrated young man with scar. This was thought to be a pyogenic granu-
cases of colon cancer in Nigerians aged 17 and tense and distended abdomen, visible peri- loma. A repeat abdominal ultrasound reported
19 years. Two of them were adenocarcinoma staltic waves, and hyperactive bowel sounds.
an anterior abdominal wall mass and enlarged
and the other leiomyosarcoma. The pathogen- He was admitted, and after one week the
inguinal lymph nodes, and made an impres-
esis and aspects of management are dis- abdominal distension worsened and he devel-
sion of rhabdomyosarcoma. The lump was
cussed. oped constipation. Digital rectal examination
excised and sent for histopathology examina-
and proctoscopy showed an empty rectum with
tion, together with the hemi-colectomy speci-
a circumferential and fungating irregular, firm
men. Both of them showed similar histologic
mass about 5 cm from the anal verge.
features composed of malignant glands and
Introduction An impression of intestinal obstruction sec-
cells within fibro-cellular stroma. A diagnosis
ondary to rectal tumor was made, and incision-
of colonic adenocarcinoma with metastasis to
Colon cancers are the second most common al biopsy taken for histology. The histopatholo-
the anterior abdominal wall was made. The
cancer in both men and women in America.1,2 gy diagnosis was adenocarcinoma. The patient
patient was commenced on 5-FU and referred
World-wide they are the third major cause of was offered a dysfunctioning (loop) sigmoid
colostomy after decompression of the dilated for radiotherapy, after receiving 5 courses of
cancer for men and the fourth most common chemotherapy. She died about two and a half
cause of cancer for women.2,3 They are the sec- sigmoid colon. He was commenced on 5-
flurouracil (5FU) and adriamycin following years after diagnosis
ond most common causes of cancer-related
deaths in developed countries and the most confirmation of mesenteric lymph node
common gastro-intestinal carcinoma.4-6 The involvement in the colostomy biopsy specimen. Case #3
incidence is highest in the westernized coun- He received 5 courses of chemotherapy and A 19-year old male, PO, presented to the
tries of North America, Northern Europe, was referred to another center for radiothera- emergency room of Joe Alufohai Medical
Australia, and New Zealand. Intermediate py. The patients has responded well to this. Center, Sabongida-Ora on 26/10/07 with a two-
rates are found in Southern Europe, and low week history of abdominal pain and vomiting.
rates in Africa.2,4 Reports have shown that close Case #2 On examination he was found to be in painful
to 1 million new cases of colo-rectal cancer and EB was a 17-year old student. She presented distress and to have moderate rebound tender-
nearly half a million deaths associated with to the SOP of ISTH, six weeks after appen- ness and guarding. This was worse over the
colorectal cancer are reported world-wide each dicectomy in a private hospital, with colicky right lower quadrant of the abdomen. A diagno-
year.4,7 About 98% of them are primary adeno- abdominal pain, vomiting, weakness, and dis- sis of acute appendicitis was made and the
carcinomas.4,8,9 The remaining 2% are made up charge from the appendicectomy scar of about patient taken in for emergency appendicectomy.
of carcinoid, mesenchymal and lymphoid two weeks duration. Family and social history Findings at surgery included a dilated,
tumors. These figures have decreased in the was not significant. Physical examination longish and coiled appendix; dilated terminal
West due to increased rate of screening and revealed a fixed and firm, non-fluctuant mass ileum; and an atrophic cecum with a localized
polyp removal.10 of about 10x11 cm in the right iliac fossa firm mass. In view of these findings, an addi-
The peak incidence for colorectal carcinoma region of the abdomen. Abdominal ultrasound tional intra-operative impression of congenital
is put at between ages 60 and 79 years, with found a large intra-abdominal mass, and sug- hypertrophy of the ileo-cecal valve was consid-
fewer than 20% occurring before the age of 50 gested retained foreign body, to rule out infect- ered and a limited right hemi-colectomy per-
years.8 According to another author, 90% of ed appendix stump. At exploratory laparotomy, formed. The specimen was sent for histology.
patients are older than 50 years; with highest an infected appendicectomy wound and a firm The patient did well and was discharged to the
incidence rates in individuals aged 70 to 85 to hard cecal pole mass were observed. The out-patient clinic two weeks after surgery.
years.4 Very occasionally, it may affect much mass measured about 15x12 cm and was asso- The histopathology diagnosis was leio-
younger adults from the age of 20 years.6 ciated with about 20 mls of abscess. Right myosarcoma, together with acute appendicitis.
The risk factors for development of colo-rec- hemi-colectomy was done and histopathology The patient has yet to honor his out-patient
tal cancer include age, a diet rich in fat and examination requested. The request was never appointment, six months after discharge.
cholesterol, inflammatory bowel disease, and received by the laboratory. The patient recov-

Case Report
(the adenoma-carcinoma sequence). The sec- ble increased risk among lower socioeconomic
Discussion ond pathway (microsatellite instability path- groups especially in the third world has been
way) is characterized by inheritance of a suggested.23,24 This is related to poor nutrition
Almost all bowel cancers arise in the colo- mutation in one of several genes involved in or chronic gastro-intestinal infections, such as
rectum, since the small intestine is strikingly DNA mismatch repair, which are MSH2, MLH1, amoebiasis and schistosomiasis, which are
free from cancer risk.6 Colon cancer is a silent MSH6, PMS1 and PMS2. It is involved in 10- thought to be associated with an increased
killer, often causing no recognizable symptoms 15% of sporadic cases of colon cancer and in incidence of malignancy. All three cases being
until it is too late.3 Most of them occur sporad- the hereditary non-polyposis colonic cancer presented belonged to the lower socioeconom-
ically in the absence of well-defined familial (HNPCC or Lynch) syndrome.6-8 Inheritance in ic group. None of them was immunosup-
syndromes. Regardless of the inciting event, a this type of cancer is autosomal dominant. pressed. Their exposure to chronic gastro-
well-described set of genetic alterations occurs Affected patients also carry an increased risk intestinal infestations was not determined.
that ultimately leads to colorectal malignancy.8 of cancers of the stomach, ovaries, breast and Colon cancers progress slowly and may be
Fitzgibbons et al. described a genetic factor uterus. The colon cancers in this syndrome asymptomatic for as many as five years or until
found in young patients belonging to tend to develop as flat lesions rather than as a much later phase.9 However, patients usually
Scandinavian families with the Lynch syn- polyps. Cancers arising through this pathway have occult blood losses from their tumor.4 It is
drome.12 occur at a younger age, usually before 45 likely that the index tumors started while the
The vast majority of colorectal cancers are years.6 Unlike in the adenoma-carcinoma patients were still in the pediatric age group.
adenocarcinomas, which arise from pre-exist- sequence, this pathway does not produce iden- Most studies suggest a delay in diagnosis with
ing adenomatous polyps.6 This adenoma-carci- tifiable morphologic correlates. an associated deleterious effect on outcome.
noma sequence is a well-characterized clinical These pathogenic pathways, which involve This is because many of the clinical features
and histopathologic series of events with stepwise accumulation of mutations, explain are similar to those found in common child-
which discrete molecular genetic alterations why colorectal cancer is a disease of adults. It hood problems such as intussusception,
have been associated.7 However, about 30% of is rare in patients under 40 years of age, and appendicitis, gastro-enteritis and simple con-
colorectal carcinomas arise from flat lesions even rarer in younger age groups.17 Of the stipation.23 Two of the presented cases were
without evidence of adenomatous precursors.6 1,250 cases seen by Sebbag et al. over a 25-year initially thought to be appendicitis. This is
These suggest that some dysplastic lesions can period, only 3 (0.24%) were under 19 years.13 It understandable considering the rarity of colon
degenerate into malignancy without passing is said that when colorectal cancer is found in cancer in children/adolescents.
through a polypoid stage.8 This particularly a young person, pre-existing ulcerative colitis Treatment must be aggressive and include a
occurs with cancers of the proximal colon and or one of the polyposis syndromes must be sus- combination of surgery and adjuvant chemo-
rectum.6 Two of the cases being reported were pected.8 None of our cases had any of these. therapy. The surgical resection must be as rad-
in the proximal colon; the third was in the rec- Environmental factors, especially dietary prac- ical as feasible for growth.13 Both systemic and
tum. Sebbag et al. did not consider heredity to tices, have been implicated in the observed loco-regional chemotherapy, such as intra-
be involved in the pathogenesis of colon can- striking geographic contrasts in incidence. hepatic, intra-arterial for liver metastasis,
cer.13 More recently though a known genetic People who eat high calorie, high fat have a role.7 Where technically feasible, resec-
link was described in first degree biological (Western) diets are at higher risk than people tion of metastatic deposits in the lungs or liver
family members of persons with colon cancer.3 who eat balanced low fat, high fiber (Eastern) is advisable.25,26 The chemotherapeutic agents
They have 3 times greater risk of developing diets.3,18 This is partly because fiber increases in use include 5-FU, irinotecan, leucovorin,
colon cancer than the general population. the bulk and the transit time of stool. This does and the more recent anti-vascular endothelial
However, 80% of colon cancers strike people not allow enough time for both bacterial break- growth factor, bevacizumab.7 Radiotherapy
without genetic connection to the disease.3 No down of bile salts into carcinogenic lithocholic finds use in cases of rectal cancer to reduce
family history of similar illness was obtained and deoxycholic acids, and their contact with the risk of local recurrence.
from any of the index patients. Vogelstein and colonic mucosa.2 It had been mentioned that When tumors are detected early, 90% of
colleagues identified a number of very impor- low fecal pH had a role to play in the genesis of patients survive at least five years after diag-
tant genetic alterations that contribute, colon cancer. Also the role of obesity in colorec- nosis and treatment.27 This is not the case for
through their multiplicity over the years, to the tal cancer has been discussed.20 There is a adolescents where it carries an extremely poor
eventual development of colorectal cancer.14,15 well-known link between obesity and a prognosis, owing to late diagnosis and aggres-
These are grouped into two pathogenetically Western diet. Japanese and Polish families sive tumor biology.23
distinct pathways that are believed to be who migrated from their low risk areas to the
responsible for the development of colon can- US acquired, over the course of 20 years, the
cer.16 Both pathways involve the stepwise accurate prevailing in their new environment.6
mulation of multiple mutations. The first path- They had adopted the dietary practices of their Conclusions
way (APC/β-caterin pathway) is characterized hosts.8 Dietary factors account for 90% of the
by chromosomal instability that results in risks for bowel cancer.21 A Western-type dieting Colorectal cancer remains a leading cause
accumulation of mutations in a series of onco- has become very common with us in Africa, of death from cancer in adults, especially in
genes and tumor suppressor genes. These even without migrating. This may account for the Western world. It is a very rare disease in
include mutations of the adenomatous polypo- why the incidence in black Africans is increas- children and adolescents. Even so, colon can-
sis coli (APC) gene and K-RAS gene, and loss ing, especially in the major urban cities.2 Its cer in the young is of great concern, especially
of SMAD4 (formerly called DPC4 – deleted in introduction to our children very early in life since screening strategies are focused on older
pancreatic cancer – gene) and p53 genes.7,8 may be an important influence when combined patients.17 Progress has been made in under-
The morphologic evolution of the lesion is with other environmental/racial/social factors standing the molecular basis of its predisposi-
through a localized colon epithelial prolifera- peculiar to us, which have not been studied. tion and progression. Efforts are being made
tion to formation of small adenoma that pro- After all, black Americans are said to be more on to develop better treatment and preventive
gressively enlarge, become more dysplastic, prone to developing colon cancer than their approaches, and better screening strategies.
and ultimately develop into invasive cancer white counterparts.22 Apart from this, a possi- Such screening strategies must incorporate

Case Report
children and adolescents since they are not Fausto N (eds). Robbins and Cotran 19. Walker AR, Walker BF, Walker AJ. Fecal pH,
immune to colorectal cancers, as demonstrat- Pathologic Basis of Disease. 7th ed. dietary fiber intake and proneness to colon
ed by this report. As Sebbag et al. put it, the Elsevier Saunders, Philadelphia 2004; 857- cancer in four South African population.
distribution pattern of colorectal carcinoma 68. Br J Cancer 1986;53:4895-8.
appears to have changed.13 There is no point 9. National Cancer Institute. http://www.can- 20. Siegel RL, Jemal A, Ward EM. Increase in
waiting until older age to check for risks. cer.gov.
incidence of colorectal cancer among
10. Johnson RW. Colorectal cancer.
young men and women in the United
http://www.rwjuh.edu/health_information.
11. Desai PB. Carcinoma of the colon. States. Cancer Epidemiol Biomarkers Prev
http://www.indiansurgeons.com. 2009;18:1695.
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Tumors and tumor-like lesions Patients and Methods Correspondence: Hua Jing, Department of
of the heart valves Cardiothoracic Surgery, Jinling Hospital, School
The records from January 2004 to June of Clinical Medicine, Nanjing University, Nanjing
Shi-Min Yuan,1,2 Hua Jing,2 Jacob Lavee1 2008 for tumors and tumor-like lesions involv- 210002, Jiangsu Province, People’s Republic of
1 ing the heart valves were reviewed. The China. E-mail: dr.jing@163.com
Department of Cardiac and Thoracic
Jacob Lavee, Department of Cardiac and Thoracic
Surgery, The Chaim Sheba Medical lesions mainly included valvular papillary
Surgery, The Chaim Sheba Medical Center, Tel
Center, Tel Hashomer Israel; 2Department fibroelastoma, valvular myxoma, valvular
Hashomer 52621, Israel.
thrombus and valvular calcification. The diag-
of Cardiothoracic Surgery, Jinling E-mail: jacob.lavee@sheba.health.gov.il
noses of the tumors and tumor-like lesions
Hospital, School of Clinical Medicine,
were made by echocardiography before opera- Key words: cardiac myxoma, cardiac papillary
Nanjing University, Nanjing, Jiangsu tion and confirmed by surgery and fibroelastoma, differential diagnosis, heart valve,
Province, People’s Republic of China histopathology. Vegetations of the heart intracardiac thrombus, surgical resection.
valves subjected to infective endocarditis
were easily distinguished from the tumors Received for publication: 20 August 2009.
and tumor-like lesions, and were, therefore, Accepted for publication: 24 August 2009.
Abstract excluded from this study. Size of the valvular
lesions was expressed as mean ± SD. Attribution 3.0 License (by-nc 3.0).
Valvular tumors and tumor-like lesions may
have similar morphological and clinical char- ©Copyright S-M Yuan et al., 2009
acteristics, and may place the patients at a Rare Tumors 2009; 1:e35
high risk of stroke in different ways. From Results doi:10.4081/rt.2009.e35
January 2004 to June 2008, 11 patients under-
went surgery for a suspected valvular tumor. Clinical presentation
Valvular tumor and tumor-like lesions From January 2004 to June 2008, 11 4 females, aged 50.91±15.21 (31-78) years. All
accounted for 0.32% of adult cardiac opera- patients underwent surgery in this institute patients had a good left ventricular function
tions. Five (45.5%) valvular lesions were papil- for a suspected valvular tumor, covering 32% with an ejection fraction of 61.82±5.13 (55-
lary fibroelastomas, one (9.1%) was myxoma, 2 of 3,412 adult cardiac surgical patients in the 75) percent. One patient (9.1%) was asympto-
(18.2%) were organized thrombi, and 3 same period. Patients’ clinical characteristics matic, 5 (45.5%) manifested shortness of
(27.3%) were calcification lesions. There was were listed in Table 1. There were 7 males and breath, fatigue and weakness, 2 (18.2%) pre-
a total of 5 (45.5%) atrioventricular valve
lesions, 4 arising from the atrial side of the
leaflets, and one from the ventricular side. All
5 (45.5%) semilunar valvular lesions were Figure 1. Case #5. Aortic
from the aortic valve. One (9.1%) lesion origi- valvular papillary fibroelas-
toma. (A) Long-axis view,
nated from the chorda tendinea of the mitral and (B) short axis view of
valve. All leaflet lesions were resected by a sim- transesophageal echocar-
ple shave technique, and all the patients recov- diography showed a dense,
ered favorably. Valvular tumor and tumor-like lobulated, highly mobile
mass (arrow) extending 1.2
lesions are rare. Pre-operative differential cm attached to the non-
diagnoses among these valvular lesions pose coronary cusp.
important clinical implications for appropriate
treatment for the underlying diseases. Prompt
therapeutic measures in view of the underly-
ing diseases of the valvular lesions are essen-
tial to prevent potential embolic events.
Introduction
Cardiac valve tumors are rare. Fibro-

elastoma is the most common valvular tumor,
followed by myxoma. Atypical valvular lesions,
such as organized thrombus,1 valvular calcifi-
cation2 and valvular abscess3 may develop
symptoms and present morphological fea-
tures similar to those of the valvular tumors.
We report on 11 patients who underwent a
valvular lesion resection in this institute, and
discuss the clinical implications.

Article
sented with vertigo or dizziness, 2 (18.2%) Diagnosis (Figure 3). All 6 tumors (54.5%), including 5
had chest pain, one (9.1%) had lumbago. The papillary fibroelastomas and one myxoma were
Diagnoses were made by echocardiography
symptomatic patients had a disease course of pre-operatively in all cases, and none of them pedicled by a short stalk, and both patients
3.11±7.36 (0.25-24) months. The 2 patients were noted incidentally by surgical investiga- with a valvular thrombus (18.2%), and 3
who had valvular thrombus were associated tion. There was a total of 10 (90.9%) left-sided patients with a valvular calcification (27.3%)
with cardiac or non-cardiac diseases. One had lesions, and one (9.1%) right-sided lesion. were sessile. Trivial mitral valve regurgitation
a history of cheek squamous cell carcinoma, Echocardiographic appearances of these was noted in 2 of the 4 patients with mitral
and polycythemia vera associated with severe lesions were round, soft, lobulated and highly valve lesions: one was mitral papillary fibro-
aortic valve stenosis and coronary artery dis- mobile in 4 papillary fibroelastomas (Figure 1) elastoma and the other was mitral thrombus.
ease, and the other had a history of peripher- and one myxoma, round and dense in one pap- Mild aortic regurgitation was associated with
al embolic events, carotid artery stenting for illary fibroelastoma, thick, dense and less both aortic valvular papillary fibroelastomas.
carotid artery stenosis, patent foramen ovale mobile in both thrombi (Figure 2), and thick, Mild tricuspid regurgitation was present in the
and coronary artery disease. dense and non-mobile in 3 calcification lesions patient with tricuspid valve myxoma. The 3
Table 1. Patients’ clinical characteristics and valvular mass.

Case Sex Age Diagnosis Associated Presentation Location Appearance Associated
disease
1 F 34 Papillary No Weak, Atrial side of Lobulated, No

fibroelastoma fatigue 1 posterior round
month mitral
leaflet
2 F 65 Papillary No Fatigue 2 Vessel Lobulated, round No
fibroelastoma weeks side, right.
cusp of aortic
valve
3 M 33 Papillary No Vertigo, Vessel side, Dense, round No
fibroelastoma taxia non-coronary
Diplopia cusp of aortic
one week valve
5 M 31 Papillary No Chest Vessel side, Lobulated, round No
fibroelastoma pain 3 weeks non-coronary
cusp of aortic
valve
6 M 43 Myxoma No Asymptomatic Atrial side of Lobulated, round No
septal tricuspid
leaflet
7 M 78 Thrombus Coronary artery Dizziness Ventricular side Thick, dense Coronary artery
disease, aortic 10 days of posterior mitral disease, aortic
valve stenosis, leaflet valve stenosis,
polycythemia vera, polycythemia vera,
atrial fibrillation atrial fibrillation
8 M 53 Thrombus Coronary artery Lumbago Atrial side of the Thick, dense Coronary artery
disease, patent 2 weeks posterior mitral disease, paten
foramen ovale, leaflet foramen ovale,
peripheral embolic peripheral embolic
events, carotid artery events, carotid artery
stenosis stenosis
9 F 45 Calcification Aortic valve regurgitation, Shortness of Edge of the Dense, Aortic valve regurgitation,
oral and vaginal candidosis breath and left cusp of thick, oral and vaginal candidosis
weakness 1 year non-mobile
aortic valve
10 M 64 Calcification Aortic valve regurgitation, Shortness of Atrial side of Dense, Aortic valve regurgitation,
mitral valve regurgitation, breath and anterior mitral thick, mitral valve regurgitation,
hypertension, peripheral weakness 2 leaflet non-mobile hypertension, peripheral
vascular disease months vascular disease
11 M 53 Calcification Mitral valve regurgitation, Shortness of Vascular side of the Dense, Mitral valve regurgitation,
hypothyroidism breath 3 weeks right coronary cusp thick, hypothyroidism
of the aortic valve non-mobile

Article
patients with valvular calcification presented

dominantly with severe valvular dysfunction, Figure 2. Case #7. Mitral
with either mitral or aortic regurgitation, valve thrombus. Four-
chamber view of transtho-
which required valve replacement. racic echocardiography
showed a thick, dense,
Surgery less mobile mass (arrow)
attached to the ventricu-
Eight patients (80%) underwent convention- lar side of the anterior
al cardiopulmonary bypass with cardioplegic mitral leaflet.
arrest. One patient with mitral fibroelastoma
and the patient with tricuspid valve myxoma
(20%) were operated on via port access under
femoral cardiopulmonary bypass, with the for-
mer having cardioplegic arrest, and the latter, a
beating heart. All leaflet lesions were resected
by a simple shave technique as described by
Gowda et al.,4 followed by leaflet plication with
Figure 3. Case #11. Mitral
direct suture. None had impairment of the valve calcification. Long-
valvular leaflet function. The patient with fibro- axis view of transthoracic
elastoma of the mitral chord had trivial mitral echocardiography showed
regurgitation after tumor resection which was a thick, dense, non-
repaired successfully by implanting two artifi- mobile mass (arrow)
attached to the vascular
cial chordea. Simultaneous coronary artery side of the right coronary
bypass, aortic valve replacement, and closure of cusp of the aortic valve.
foramen ovale were carried out. The cardiopul-
monary bypass time and cross-clamp time were
68.36±29.57 (38-113) and 48.9±24.29 (21-98)
min, respectively. There was a total of 5
(45.5%) atrioventricular valve lesions, with 4
arising from the atrial side of the leaflets, and
one from the ventricular side. Five (45.5%)
semilunar valvular lesions were all from the
aortic valve. Three aortic papillary fibroelas-
tomas and one aortic valve calcification lesion these valvular masses were papillary fibroelas- coronary cusps in 2, 1, and 2 patients, respec-
were from the vascular side of the leaflets, and tomas, one (9.1%) was myxoma, 2 (18.2%) tively. Three of them were papillary fibroelas-
another aortic calcification lesion was from the were organized thrombi, and 3 (27.3%) were tomas, and 2 were calcification lesions. One
edge of the left cusp. Besides, one (9.1%) calcification lesions. Five (45.5%) lesions were (9.1%) originated from the atrial aspect of the
lesion originated from the chorda tendinea of located in the mitral valve leaflets. Of them, 2 septal leaflet of the tricuspid valve, which was
the mitral valve. A solitary lesion was presented were papillary fibroelastomas, 2 were thrombi, proved to be a myxoma.
in 10 (90.9%) patients and multiple lesions in and one was calcification. Three of them were Similar to pre-operative echocardiographic
one (9.1%), and originated from the midportion on the atrial side of the posterior leaflets, one findings, gross appearances of these lesions at
of the valve leaflet away from the margin or the was on the ventricular side of the anterior surgery were round, soft, lobulated and frond-
annulus of the leaflet in 9 (81.8%), from the leaflet, and one attached to the mitral chorda like in all valvular tumors except in one aortic
edge of the leaflet in one (9.1%), and from the tendinea. There were 5 (45.5%) aortic valvular valvular papillary fibroelastoma which were
chorda tendinea in one (9.1%). Five (45.5%) of lesions, arising from the left, right and non- round and dense. Both thrombi from the mitral
Table 2. Surgery and size of the tumor.

Case Surgery Size (cm) z-score of the size
1 Valvular tumor resection (port access) 1x0.5x0.5 0.102
2 Valvular tumor resection 0.5 -0.918
3 Valvular tumor resection, artificial chorda 0.7 -0.510
4 Valvular tumor resection 0.5 -0.918
5 Valvular tumor resection 1.2 0.510
6 Valvular tumor resection (port access) 1.5 1.327
7 Valvular tumor resection, coronary artery bypass, aortic valve replacement 1.8x0.7 1.735
8 Valvular tumor resection, coronary artery bypass, closure of foreman ovale 1.4x1.1x0.8 0.918
9 Aortic valve replacement 0.4 -1.222
10 Aortic valve replacement, resection of small mass from anterior mitral leaflet 0.4 -1.222
11 Valvular mass resection, mitral valve repair Multiple 0.3-1.0 -1.444~0.111

Article
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Treatment outcome of 3% of head and neck cancers and 0.5% of all

malignant diseases. The annual incidence of Correspondence: Jin-Hyoung Kang, Division of
maxillary sinus cancer maxillary sinus cancer is 0.5-1.0 case per Oncology, Department of Internal Medicine,
100,000 of the population.1 Squamous cell car- Seoul St. Mary's Hospital, The Catholic
Hye Sung Won,1,7 Sang Hoon Chun,1,7 cinoma is the most common histologic type, University of Korea, 505 Banpo-Dong, Seocho-Gu,
Bum-soo Kim,1,2 So Ryoung Chung,1,2 accounting for approximately 70-80% of the Seoul 137-701, Korea.
Ie Ryung Yoo,1,3 Chan-Kwon Jung,1,4 cancers. The other histologic types of maxillary E-mail: jinkang@catholic.ac.kr
Yeon-Sil Kim,1,5 Dong-il Sun,1,6 sinus cancer include adenoid cystic carcino-
Key words: maxillary sinus cancer, induction
Min Sik Kim,1,6 Jin-Hyoung Kang,1,7 mas, adenocarcinomas, mucoepidermoid car-
chemotherapy, intra-arterial chemotherapy,
1
Head and Neck Cancer Interdisciplinary cinomas, sarcomas, and lymphomas. Smoking organ preservation.
and histories of chronic sinusitis are the most
Team, Departments of 2Diagnostic
common risk factors for maxillary sinus can- Conflict of interest: the authors report no con-
Radiology, 3Nuclear Medicine, 4Hospital
cer. In addition, occupational exposure to flicts of interest.
Pathology, 5Radiation Oncology,
6
chemical substances, such as formaldehyde,
Otorhinolaryngology, 7Medical Oncology, chromium, nickel, and air pollution is associat- Received for publication: 11 August 2009
The Catholic University of Korea, College ed with an increased risk for malignant tumors Revision received: 16 September 2009.
of Medicine, Seoul, Korea of the maxillary sinus.2 Accepted for publication: 17 September 2009.
Most patients with maxillary sinus cancer This work is licensed under a Creative Commons
have no symptoms in the early stage and, Attribution 3.0 License (by-nc 3.0).
therefore, many of these patients are diag-
Abstract nosed in the advanced stage of the disease. ©Copyright H.S. Won et al., 2009
The complexity of the anatomy and the proxim- Rare Tumors 2009; 1:e36
The standard treatment in the early stage of ity of the eyes, brain, and cranial nerves render doi:10.4081/rt.2009.e36
maxillary sinus cancer is surgical resection complete surgical resection difficult, which
followed by postoperative radiation therapy. leads to local recurrence, a major cause of
However, for locally advanced maxillary sinus treatment failure.3 The other issues pertaining to poor performance status, and seven patients
cancer, a multimodality treatment approach is to maxillary sinus cancer include the function- with a history of prior surgery or chemothera-
strongly recommended to improve the survival al aspects of eyesight and the cosmetic aspects py were excluded. In addition, fourteen
rate and quality of life of the patient. We deter- of facial contours, which make patients avoid patients with malignant lymphomas or soft tis-
mined the treatment outcomes of induction surgical resection. sue sarcomas were excluded. Finally, 44
chemotherapy, concurrent chemoradiation The standard treatment for maxillary sinus patients were analyzed and reviewed on the
therapy, and surgical resection for locally cancer has been surgical resection with or basis of their medical records, pathology slides
advanced maxillary sinus cancer. Forty-four without orbital exenteration, followed by post- and interpretation reports, and imaging stud-
patients with locally advanced maxillary sinus operative radiation therapy. However, in the ies. The following data were collected: age,
cancer, who had been treated between January advanced stages, tumor control and survival gender, performance status, histopathologic
1990 and April 2008 at Kangnam St. Mary's rate are still considered to be unsatisfactory, diagnosis, tumor staging, orbital invasion,
Hospital, were retrospectively analyzed. The with a local control rate of 50-60% and a five- treatment modalities, recurrences, and sur-
objective response rates were 70%, 53%, and year disease-specific survival rate of 30-50%.3,4 vival rates.
57% in the intra-arterial induction chemother- Since the late 1970s, multimodality treatments A detailed assessment of the tumor extent
apy, intravenous induction chemotherapy, and have been investigated for the treatment of was performed in all patients, based on CT
concurrent chemoradiation therapy groups, locally advanced maxillary sinus cancer, with scans and/or MRI including the maxillary sinus
respectively. The orbital preservation rates the purpose of improvement in tumor control and skull base. The orbital invasion was deter-
were 83%, 100%, and 75% in the intra-arterial rate and reduction of functional impairment. mined on these findings: contact of the mass
induction chemotherapy, intravenous induc- Notably, induction chemotherapy (ICT) and with the lamina papyracea, erosion or destruc-
tion chemotherapy, and surgical resection concurrent chemoradiation therapy (CCRT) tion of the medial and/or inferior orbital wall,
groups, respectively. In seven of nine patients are the most common multimodality treat- and invasion of the periorbital soft tissue
in whom the orbit could be preserved after ments for stages III and IV locally advanced including the optic nerves and extraocular
induction chemotherapy, the primary tumors maxillary sinus cancer. We investigated the muscles. Tumor staging was done using the
were removed completely. However, although treatment outcomes including orbital preser- 2006 edition of the American Joint Committee
the orbits were preserved in three patients vation, complete resection, pathologic down- on Cancer (AJCC) classification, and retro-
who underwent surgical resection as a primary staging, and relapse patterns in patients with spective restaging was done in previously diag-
treatment, all three cases were confirmed to be locally advanced maxillary sinus cancer who nosed patients. The performance status was
incomplete resections. We found that active underwent ICT, CCRT, and surgical resection. evaluated according to Eastern Cooperative
induction chemotherapy for locally advanced Oncology Group (ECOG) criteria.
cancer of the maxillary sinus increased the
possibility of complete resection with orbital Chemotherapy
preservation as well as tumor down-staging. Materials and Methods One of four different treatment modalities,
including intra-arterial (IA)-ICT, intravenous
Patients (IV)-ICT, CCRT, and surgical resection, was
Seventy-five patients who had been diag- selected as a primary treatment based on the
Introduction nosed with maxillary sinus cancer at Kangnam TNM stage, performance status, age, and co-
St. Mary's Hospital between 1 January 1990 morbidity. ICT was administered through the
Malignant tumors of the maxillary sinus are and 30 April 2008 were reviewed. Among these IA or IV route. Superselective IA infusion of
rare neoplasms that account for approximately patients, 10 received only palliative care owing chemotherapeutic drugs was attempted via a

Article
series of processes. The contrast-enhanced Evaluation of treatment outcomes of diagnosis to the date of death or date of last
tumor mass and tumor feeding vessels were The primary end point of our study was the follow-up. The adverse events occurring during
confirmed via diagnostic angiographic proce- response rate of the primary treatment modal- ICT and CCRT were graded according to the
dures of the internal and external carotid ities (IA-ICT, IV-ICT, and CCRT). For the evalu- National Cancer Institute Common Toxicity
arteries by means of transfemoral access. The ation of tumor response, a physical examina- Criteria (NCI-CTC, version 2.0).
internal maxillary artery was superselected tion, nasal endoscopy, and CT or MRI were per-
with a microcatheter, and then the chemother- formed. Tumor response was assessed accord- Statistical analysis
apeutic drug was administered via a micro- ing to the RECIST criteria (version 1.0). An For categorical outcomes, between-group
catheter into the tumor-supplying artery. The objective tumor response was defined as more comparisons were done using either the
transfemoral catheter was removed on comple- than partial response (PR). When recurrence Fisher’s exact test or a Chi-square test. The
tion of the infusion. Cisplatin (100 mg/m2) was or distant metastasis was suspected, PET-CT overall survival curve was estimated using the
administered via a microcatheter into the and other imaging studies of suspicious Kaplan-Meier method, and the log-rank test
internal maxillary artery over two hours on day lesions were performed and, if needed, con- was applied to assess statistical significance.
1, and then 5-FU (1000 mg/m2/day) was contin- firmed by biopsy. All statistical analyses were performed using
uously infused from day 1 to day 5 over 120 The secondary end points were the complete the SPSS program (version 13.0) and a p value
hours through the IV route. A standard hydra- resection and orbital preservation rates in of <0.05 was considered as statistically signif-
tion and mannitol diuresis regimen were patients who underwent surgical resection icant.
applied. The entire procedure was repeated 2- after ICT and surgical resection as a primary
3 times every 3-4 weeks. treatment. Complete resection was defined as
The IV-ICT was performed 2-3 times every where there were no microscopic residual
four weeks as well. Cisplatin (100 mg/m2) was tumor cells on the resection margin, and Results
administered intravenously over two hours on incomplete resection was defined as where
day 1, and 5-FU (1000 mg/m2/day) was infused there were residual tumors on the resection Patient characteristics
continuously from day 1 to day 5 over 120 margin, identified by gross and/or microscopic The clinical characteristics of the 44
hours through the IV route. All patients who examination. Orbital preservation was defined patients are summarized in Table 1. The medi-
received ICT were re-evaluated for tumor as when a case underwent total maxillectomy an age was 60 years (range 33-89 years) and
response with CT and/or MRI at least 4-6 without orbital exenteration, among the 93% of patients were ECOG 0-1. The most com-
weeks after the completion of ICT. The deci- patients with the evidence of orbital invasion mon histopathologic subtype was squamous
sion to perform surgery after ICT was based on on physical examinations and/or imaging stud- cell carcinoma (n=31; 70%). Of the 44
the tumor response. ies at the time of diagnosis. patients, 12 patients (27%) underwent surgi-
The chemotherapeutic agent used in the The tertiary end points were overall survival, cal resection as a primary treatment, and
CCRT group was cisplatin. During radiation recurrence rate, and the toxicity profile. among these patients there were six (50%)
therapy, cisplatin (30 mg/m2) was adminis- Overall survival was defined as from the date with stage III, five (42%) with stage IV, and one
tered by a weekly schedule on days 1, 8, 15, 22,
29, 36, 43, and 50, or cisplatin (100 mg/m2) was
administered every 3 weeks on days 1, 22, and
43. All patients treated with CCRT were re- Table 1. Patient characteristics.
evaluated for tumor response, and then the Patient characteristics (n=44) n (%)
next treatment modality, surgical resection or
salvage chemotherapy, was determined. The Gender (male/ female) 30(68)/14(32)
periodic follow-up was done at least 6-8 weeks Median age (years, range) 60(33-89)
after the completion of radiation therapy. ECOG performance
0/1/2 17(39)/24(54)/3(7)
Surgical resection and radiation Histologic type
therapy Squamous cell carcinoma 31(70)
In most cases, a total maxillectomy with orbital Adenoid cystic carcinoma 6(14)
preservation was carried out. However, if the Adenocarcinoma 4(9)
tumor mass extended to the lamina papyracea Myoepithelial carcinoma 1(2)
and invaded the orbit and muscles, an orbital Undifferentiated carcinoma 2(5)
exenteration with a total maxillectomy should be TNM stage
performed. The patients with metastatic cervical II/III/IVa/IVb 1(2)/10(23)/10(23)/23(52)
lymphadenopathy underwent a modified radical Tstage
neck dissection. Three-dimensional conformal T2/T3/T4a/T4b 1(2)/10(23)/10(23)/23(52)
radiation therapy (3DCRT) was applied as an Nstage
external radiation therapy technique. The total N0/N1/N2 36(81)/5(11)/3(8)
dose of 55-60 Gy with 1.8-2.0 Gy daily fractions Orbit invasion
five times per week was given to the clinical tar- yes/ no 31(70)/13(30)
get volume (CTV) in postoperative adjuvant radi- Treatment modalities
ation therapy. In the case of CCRT, the total dose †
IA-ICT/‡IV-ICT 10(23)/15(34)
of 70-75 Gy in 35-40 fractions was given with a §
CCRT/Surgical resection 7(16)/12(27)
shrinking-field technique; 50 Gy was given to the
CTV with daily fractions of 1.8 Gy five times per
†
week, and followed by 20-25 Gy to the gross IA-ICT: intra-arterial induction chemotherapy, ‡IV-ICT: intravenous induction chemotherapy, §CCRT:
tumor volume (GTV). concurrent chemoradiation therapy.

Article
Article
(8%) with stage II tumors. Eleven patients

with stage III-IV tumors received postoperative Table 2. Tumor response according to treatment modalities.
adjuvant radiation therapy after surgical resec-
tion. Ten (23%), 15 (34%), and 7 (16%) Treatment modalities Tumor response p
†
patients received IA-ICT, IV-ICT, and CCRT, CR(n) ‡
PR(n) §
ORR(%)
respectively. Of the 25 patients who received
Induction chemotherapy 60 0.521
ICT, there were 21 (84%) with stage IV and 3
IA-ICT 0 7 70 0.311
(16%) with stage III tumors. All patients treat- IV-ICT 2 6 53
ed with CCRT were stage IV. The median dura-
CCRT 1 3 57
tion of follow-up was 16 months.
†
CR: complete response, ‡PR: partial response, §ORR: overall response rate.
Tumor response and toxicity

The objective response rates of ICT and
CCRT were 60% and 57%, respectively
(p=0.521). The objective response rates of IA- Figure 1. Orbital preserva-
ICT and IV-ICT were 70% and 53%, respective- tion and complete resection
ly (p=0.311) (Table 2). In the 10 patients who rate according to treatment
modalities. IA-ICT: intra-
received IA-ICT, no complete response (CR) arterial induction
was achieved, seven patients (70%) had a PR, chemotherapy, IV-ICT: intra-
one patient had stable disease (SD), and one venous induction chemother-
patient had progressive disease (PD). The apy.
intended chemotherapy was interrupted in one
patient because of acute, severe toxicity. In the
15 patients treated with IV-ICT, two (13%) had
a CR, six (40%) had a PR, three (20%) had SD,
and three (20%) had PD. One patient was lost
to follow-up. The most common acute toxicity
associated with these treatment modalities
was nausea and vomiting. The frequency of
nausea and vomiting in the IA-ICT, IV-ICT, and
CCRT groups was 70%, 87%, and 86%, respec-
tively (p=0.927). The patients treated with IA- 100 Figure 2. Overall survival
ICT experienced other adverse events: three curve of 44 patients with
patients had facial swelling, three had perior- maxillary sinus malignancies
80 by the Kaplan-Meier
bital pain, one had severe mucositis, and one method.
had transient dizziness.
Survival (%)
60
Orbital preservation and complete
resection rate 40
Seven (70%) of 10 patients in the IA-ICT
group and seven (47%) of 15 patients in the IV- 20
ICT group underwent surgical resection with
curative intent. Of these patients, those in
whom orbital invasion had been confirmed by 0
imaging studies at diagnosis were six and four 0 30 60 90 120 150 180
patients in the IA-ICT and IV-ICT groups, Time (months)
respectively. Orbital preservation was possible
in five (83%) of six patients treated with IA-
ICT and in all four (100%) patients treated
with IV-ICT. On the other hand, orbital inva- was achieved in the patients who underwent Overall survival and recurrence rate
sion was doubtful in four of 12 patients who surgical resection after ICT (Figure 1). The overall survival curve of the 44 patients
underwent surgical resection as a primary is shown in Figure 2. The overall survival rate
treatment, and orbital preservation was possi- Pathologic down-staging by ICT for these 44 patients was 60% at three years
ble in three (75%) of four patients. Therefore, Of the 14 patients who underwent ICT fol- and 53% at five years.
there were no statistically significant differ- lowed by surgical resection, the 10 patients The three-year survival rate was 57% and
ences in the orbital preservation rates between with T4 tumors were available for pathologic 50% in the IA-ICT and IV-ICT group, respective-
the ICT and surgical resection groups tumor response. Nine (90%) of 10 patients ly (p=0.665). The most common cause of death
(p=0.505). Seven (78%) of nine patients with were shown to have pathologic down-staging was disease progression. Two of 10 patients in
orbit preservation in the ICT group had com- of the primary tumor after ICT. Among the 10 the IA-ICT group died; one patient owing to
plete resections. However, all three patients patients with clinical T4, five had pT3, three disease progression and the other patient
with orbital preservation in the primary surgi- had pT1, and one had a pathologic CR (pT0). because of infectious disease after relapse
cal resection group had incomplete resections. All cases with remarkable down-staging to pT1 with lung metastasis. Five of 15 patients in the
Therefore, a higher complete resection rate and pT0 were observed in the IA-ICT group. IV-ICT group died; three as a result of disease

Article
progression and two owing to infectious dis-

ease accompanied by disease progression. Of
A B
the 12 patients in the surgical resection group,
eight were still alive without recurrence for
more than two years, but three of four patients
with recurrences died of disease progression
and one person was lost to follow-up.
The recurrence patterns were as follows: in
seven patients who received IA-ICT followed by
surgical resection, no local recurrences were
identified except for one pulmonary metasta-
sis. In nine patients who received IV-ICT fol-
lowed by surgical resection, three local recur-
rences and two distant metastases were
detected during the follow-up period. Hence,
the recurrence rates were 17% and 56% in the
IA-ICT and IV-ICT group, respectively. In the C
surgical resection group, local recurrences
occurred in four (33%) of 12 patients.
In the ICT group, two patients with a posi-
tive resection margin died of local recurrence
within two years. In contrast, one of seven
patients with a tumor-free resection margin
died of local recurrence, and the six remaining Figure 3. A case of a T4b maxillary sinus
patients with squamous cell carcinoma had cancer patient with: (A) magnetic reso-
long-term disease-free survival. In the surgical nance imaging at diagnosis; (B) magnet-
ic resonance imaging after completion
resection group, one of three patients with a of three cycles of intra-arterial induction
positive resection margin died of a local recur- chemotherapy with cisplatin and intra-
rence, and the remaining two patients with venous 5-FU; (C) magnetic resonance
adenoid cystic carcinoma are alive still. Most imaging six months after total maxillec-
recurrences occurred within the first two years tomy with flap reconstruction.
after surgical resection or complete clinical
response to ICT, and those who had no recur-
rences within the first two years had a long-
term survival of more than five years. radiation therapy alone.5 Harrison et al. report- fore, more potent antitumor efficacy with
ed a three-year local control rate of 78% and a lower systemic toxicity was expected.7 IA
three-year survival rate of 42% in 12 patients chemotherapy may be more effective when it is
with paranasal sinus carcinomas treated with administered as an initial treatment. Because
Discussion cisplatin-based CCRT.6 In this study, seven prior surgery or radiation impairs the blood
patients with stage IV maxillary sinus cancer supply to the tumor bed, it makes local delivery
The prognosis of maxillary sinus cancer is received CCRT as a primary treatment, and the of chemotherapeutic drugs difficult. Although
disappointing, despite aggressive treatments. objective response rate was 57%. However, the the majority of head and neck cancers are
For successful treatment outcomes, it is neces- assessments of recurrence and survival rate diagnosed at advanced stages of the disease,
sary to acquire complete surgical resection and were impossible because of small sample size distant metastases are rarely detected at the
to secure adequate resection margins. and loss to follow-up. time of presentation. Moreover, maxillary
However, maxillary sinus cancers usually are The most commonly used ICT in locally sinus cancers are confined to the territory of
diagnosed at advanced stages, and the proximi- advanced head and neck cancer is IV cisplatin the terminal branch of the internal maxillary
ty of important organs such as the eyes and cra- combined with a 5-FU continuous infusion. In artery; therefore, they are suitable for the local
nial nerves makes complete surgical resection several studies, ICT produced an objective infusion of chemotherapeutic drugs.8,9
difficult. In addition, functional impairments response rate of 60-90% with a clinical CR of Robbins et al. reported a higher objective
after surgical resection are the major cause of a 20-50%.5 However, the antitumor efficacy of response rate of 92%, with a CR of 88% in 76
decreased quality of life. Therefore, surgical ICT did not lead to a prolongation in overall patients with head and neck cancers treated
resection with a curative intent should be con- survival in every case. with IA cisplatin and concomitant radiation
sidered as a primary treatment only in the early To improve the antitumor efficacy, the addi- therapy.10 In another study, a five-year survival
stages of the disease. In the advanced stages, tion of potent cytotoxic drugs such as docetax- rate of 53% was reported, with a local recur-
multimodality treatment strategies should be el to a standard chemotherapy regimen or rence rate of 15% in 19 patients with locally
arranged for prolongation of survival and development of new drug delivery methods has advanced paranasal sinus cancers who under-
improvement in the quality of life. been investigated actively. As one of the drug went surgical resection after IA chemotherapy
CCRT is regarded as the more effective delivery methods, a superselective IA infusion combined with concomitant radiation therapy.
treatment because of the radiosensitizing effi- of chemotherapeutic drugs has been proposed Orbital preservation was possible in three of
cacy of cisplatin compared with radiation ther- as an ICT in locally advanced head and neck four patients with orbital invasion.4 Lee et al.
apy alone. Several studies have demonstrated cancers. Direct infusion of chemotherapeutic presented their clinical experiences with
that CCRT has a higher tumor control rate and drugs to the feeding vessels exposed a high superselective IA cisplatin combined with IV 5-
survival rate in head and neck cancers than concentration of drug to the tumor cells; there- FU in advanced paranasal sinus cancers.11

Article
Forty-three percent of 21 evaluated patients IA-ICT and IV-ICT groups. However, the local points for new agents in induction
had a CR and 48% of the patients had a PR, recurrence rate was lower in the IA-ICT group chemotherapy for locally advanced head
with an objective response rate of 91%. In our than in the IV-ICT group. and neck cancers. Ann Oncol 2002;13:995-
study, either IA-ICT or IV-ICT was performed as The limitation of this study is that it is a ret- 1006.
an ICT. The objective response rate in the IA- rospective, relatively small sample size evalua- 6. Waldron JN, O'Sullivan B, Gullane P, et al.
ICT group was 70%, which was similar to pre- tion. Additionally, a discrepancy in clinical Carcinoma of the maxillary antrum: a ret-
vious results, and the objective response rate characteristics between groups existed. rospective analysis of 110 cases. Radiother
in the IV-ICT group was 53%. There were no Patients diagnosed with a more advanced Oncol 2000;57:167-73.
statistically significant differences in the staged tumor or orbital invasions were more 7. Fujishiro Y, Nakao K, Watanabe K, et al. A
response rate and toxicities between the two likely to receive ICT than surgery; therefore, new aspect of tri-modal therapy with
groups. comparing survival according to treatment superselective intra-arterial chemothera-
The orbital preservation rates in the modalities was difficult. However, clinical py in maxillary sinus carcinoma. Acta
patients with paranasal sinus tumors, who characteristics between the IA-ICT and IV-ICT Otolaryngol Suppl 2007;559:151-6.
received the ICT followed by surgical resection groups were comparable and the comparison 8. Forastiere AA, Baker SR, Wheeler R, et al.
or CCRT, have been reported to be approxi- of these two groups may bear significance. Intra-arterial cisplatin and FUDR in
mately 50-70%.12,13 In this study, orbital preser-
advanced malignancies confined to the
vation was possible in five of six patients in
head and neck. J Clin Oncol 1987;5:1601-6.
the IA-ICT group and all four patients in the IV-
ICT group. Although orbital preservation was 9. Wilson WR, Siegel RS, Harisiadis LA, et al.
Conclusion High-dose intra-arterial cisplatin therapy
possible in three of four patients who under-
went surgical resection as a primary treat- followed by radiation therapy for advanced
From our study we conclude that ICT in squamous cell carcinoma of the head and
ment, incomplete resection with a positive locally advanced maxillary sinus cancers
resection margin was finally ascertained in neck. Arch Otolaryngol Head Neck Surg
increased the possibility of tumor down-stag- 2001;127:809-12.
these three patients. On the other hand, in
ing and complete resection with orbital preser- 10. Rabbani A, Hinerman RW, Schmalfuss IM,
nine patients who underwent ICT followed by
vation. Although there were no significant dif- et al. Radiotherapy and concomitant intra-
surgical resection with orbit preservation,
ferences in response rate and toxicity profile
incomplete resection was confirmed in only arterial cisplatin (RADPLAT) for advanced
between the two groups of ICT, IA-ICT was
two patients. Most of the patients with a posi- squamous cell carcinomas of the head and
superior to IV-ICT with respect to tumor down-
tive resection margin experienced a local neck. Am J Clin Oncol 2007;30:283-6.
staging and local tumor control. In the future,
recurrence during the follow-up, which led to a 11. Lee YY, Dimery IW, Van Tassel P, et al.
a large-sized, prospective randomized study to
disease progression and then death. Superselective intra-arterial chemothera-
compare ICT followed by surgical resection
A case of a patient with locally advanced py of advanced paranasal sinus tumors.
with surgical resection alone is warranted clin-
maxillary sinus cancer is shown in Figure 3. Arch Otolaryngol Head Neck Surg 1989;
ically as a primary treatment for locally
This patient was diagnosed with T4b maxillary 115:503-11.
advanced maxillary sinus cancers.
sinus cancer with orbital invasion in May 12. Kerber CW, Wong WH, Howell SB, et al. An
2007. She received three cycles of IA-ICT with organ-preserving selective arterial
cisplatin and IV 5-FU, and then underwent chemotherapy strategy for head and neck
total maxillectomy with orbital preservation
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and flap reconstruction. On the pathologic 13. Urba SG, Forastiere AA, Wolf GT, et al.
reports, the tumor was removed nearly com- 1. Dulguerov P, Jacobsen MS, Allal AS, et al.
Nasal and paranasal sinus carcinoma: are Intensive induction chemotherapy and
pletely but close to a margin. She received radiation for organ preservation in
postoperative radiation therapy. She has we making progress? A series of 220
patients and a systematic review. Cancer patients with advanced resectable head
remained disease free to date.
2001;92:3012-29. and neck carcinoma. J Clin Oncol 1994;
Several studies have demonstrated that a
2. Spiro JD, Soo KC, Spiro RH. Squamous 12:946-53.
pathologic CR has a closer relationship than a
carcinoma of the nasal cavity and 14. Nazar G, Rodrigo JP, Llorente JL, et al.
clinical CR with survival.14 In the current study,
paranasal sinuses. Am J Surg 1989;158: Prognostic factors of maxillary sinus
the pathologic down-staging of the primary
tumor in the patients treated with ICT followed 328-32. malignancies. Am J Rhinol 2004;18:233-8.
by surgical resection was evaluated. In 10 3. Nishino H, Ichimura K, Tanaka H, et al. 15. Gouyette A, Apchin A, Foka M, et al.
cases of T4 tumors, pathologic down-staging Results of orbital preservation for Pharmacokinetics of intra-arterial and
after the ICT was identified in nine cases with advanced malignant maxillary sinus intravenous cisplatin in head and neck
one pathologic CR. In addition, IA-ICT was tumors. Laryngoscope 2003;113:1064-9. cancer patients. Eur J Cancer Clin Oncol
more effective with respect to pathologic 4. Samant S, Robbins KT, Vang M, et al. Intra- 1986;22:257-63.
tumor down-staging compared with IV-ICT. It is arterial cisplatin and concomitant radia- 16. Sileni VC, Fosser V, Maggian P, et al.
thought that the first-passage effect and expo- tion therapy followed by surgery for Pharmacokinetics and tumor concentra-
sure to higher local concentrations during IA advanced paranasal sinus cancer. Arch tion of intra-arterial and intravenous cis-
cisplatin have a major role in effective down- Otolaryngol Head Neck Surg 2004;130:948- platin in patients with head and neck
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Invasive neuroendocrine tumor United States for a second opinion.

On presentation, she was an otherwise Correspondence: Ephrem O. Olweny, Department
of the kidney: a case report healthy thin woman with a palpable minimally of Urology, University of California, Box 0738 400
tender mass in her left flank. A CT scan of the Parnassus Avenue, San Francisco, CA 94143, USA
Ephrem O. Olweny,1 Michael H. Hsieh,2 abdomen and pelvis (Figure 1) showed a 16 cm E-mail: eolweny@gmail.com
Jill C. Buckley,3 Jack W. McAninch1 necrotic renal mass invading into the tail of
the pancreas, spleen, and omentum, with Key words: neuroendocrine tumors, kidney,
Departments of Urology: 1University of
surgery.
California, San Francisco, 2Stanford marked displacement of intraabdominal
University School of Medicine, 3Lahey organs. No metastatic lesions were identified. Contributions: EOO primary author and partici-
Clinic, Burlington, MA, USA Clinical staging by chest CT and bone scan was pating surgeon; MHH and JCB co-authors and
negative for metastases. A magnetic reso- participating surgeons; JWM supervising partici-
nance imaging (MRI) of the abdomen showed pating surgeon and consultant on manuscript
no evidence of renal vein or IVC thrombus. preparation and submission; EOO primary author
Abstract She undwerwent uncomplicated en bloc and participating surgeon; MHH and JCB co-
resection, through a thoracoabdominal authors and participating surgeons; JWM super-
approach, of the left kidney, left adrenal, cuff of vising participating surgeon and consultant on
Neuroendocrine tumors (NETs) involve the manuscript preparation and submission.
diaphragm, spleen, tail of pancreas and part of
genitourinary system in less than 1% of cases,
the left colon, with a primary colocolostomy
with primary renal carcinoids comprising only Conflict of interest: the authors report no con-
(Figure 2). The diaphragm was closed primari-
19% of reported genitourinary NETs (56 cases flicts of interest.
ly and a tube thoracostomy placed. Her post-
worldwide). We report a case of a renal NET
operative recovery was unremarkable, with Received for publication: 14 September 2009.
presenting as a large renal mass with exten-
discontinuation of the chest tube and advance- Accepted for publication: 16 September 2009.
sive local invasion, requiring definitive radical ment to a regular diet by post-operative days 3
en bloc resection via a thoracoabdominal and 6, respectively. Pathological diagnosis was This work is licensed under a Creative Commons
approach. a low-grade neuroendocrine tumor of Attribution 3.0 License (by-nc 3.0).
unknown primary, but with total replacement
©Copyright E.O. Olweny et al., 2009
of the left kidney and involvement of all resect- Rare Tumors 2009; 1:e37
ed organs except for the adrenal gland and the doi:10.4081/rt.2009.e37
Introduction wall of the left colon (but the colon mesentery
was involved). Resection margins were nega-
The neuroendocrine cell system is divided tive. There was histological variation, with a
into gland-forming cells, such as the pituitary, dominant multinodular pattern composed of Previous case reports have described resec-
parathyroids, adrenal medulla etc., and dis- nests and trabeculae (Figure 3A and B) with tion of renal carcinoids up to 30 cm in size by
seminated neurodendocrine cells, such as focal spindled morphology (Figure 3C). Tumor partial or radical nephrectomy.7-10 However,
those found in the lung, gastrointestinal tract cells were small, with small nuclei and moder-
and genitourinary tract among other organs. ate cytoplasm. Immunohistochemistry was
Tumors arising from the disseminated neu- positive for keratin, chromogranin (Figure 3D
roendocrine sytem within the genitourinary and E), neuron-specific enolase, and synapto-
tract are referred to as carcinoids by the WHO physin (consistent with neuroendocrine carci-
classification.1 In a recent comprehensive noma), and negative for markers of fibroblasts
review of the world’s literature, Romero et al. and smooth muscle. An octreotide scan one
reported on 56 cases of primary renal carci- month post-operatively was limited, but was
noids, extirpated by partial or radical nephrec- negative for evidence of residual or recurrent
tomy.2 To our knowledge, we report the first disease.
case of a renal NET exhibiting wide local inva-
sion (diaphragm, pancreas, spleen and left
colon mesentery), requiring en bloc radical
resection through a thoracoabdominal Discussion
approach.
Disseminated neuroendocrine cells are also
known as enterochromaffin cells or amine pre-
cursor uptake and decarboxylation (APUD)
Case Report cells. They are rare in the genitourinary tract,
but have been identified in the bladder trigone,
A 61-year old woman, an immigrant from prostate, and the renal collecting system. They
Panama, presented in her home country with are absent in the renal parenchyma.3,4 Tumors
vague abdominal pain. She was diagnosed arising from these cells are extraordinarily
with diverticulitis in lieu of imaging, and was rare, particularly within the kidney. Indeed, to
treated conservatively. Six months subse- date, only 56 reported cases of primary renal
quently, she had progressively worsened carcinoid tumors have been described.
abdominal pain as well as a 20lb weight loss. Pathogenesis is controversial,5 and there is a
An abdominal ultrasound and follow-up CT common association between the presence of
Figure 1. CT scan of the abdomen and
scan revealed a large left renal mass which these tumors and renal anomalies, particularly pelvis.
was deemed unresectable. She traveled to the horseshoe kidneys.6

Care Report
A B
C D
Figure 2. Surgical specimen.
although liver and lymph node metastases

were commonly observed with larger tumors,
extensive local invasion in the absence of
metastatic disease, as described in the above
case, has not been previously reported. Within E
the gastrointestinal tract, invasive behavior of
carcinoid tumors is rare, and is associated
with poorly differentiated or sporadic tumors,
with angioinvasion and metastatic spread at
time of diagnosis commonly identified.11 As
demonstrated in the case reported, extensive
local invasion in the absence of metastatic
spread does not preclude complete surgical Figure 3. (A) Trabeculated pattern in kid-
resection. Evidence of complete extirpation ney. (B) Representative nested pattern in
was negative by octreotide scintigraphy one pancreas. (C) Representative spindled pat-
month post-operatively. Octreotide scintigra- tern in kidney. (D) Keratin stain. E.
Chromogranin stain.
phy has been described as a useful adjunctive
diagnostic tool in detecting residual or occult
metastatic carcinoid tissue following surgical
resection.9 However, long-term follow-up is histochemical and ultrastructural studies classification is needed. Pathology 2003;
required as metastatic disease up to seven of five patients. Cancer 1993;72:2660-6. 35:353-5.
years following treatment has been reported. 4. di Sant'Agnese PA. Neuroendocrine cells 8. Kojiro M, Ohishi H, Isobe H. Carcinoid
of the prostate and neuroendocrine differ- tumor occurring in cystic teratoma of the
entiation in prostatic carcinoma: a review kidney: a case report. Cancer 1976;38:
of morphologic aspects. Urology 1998;51: 1636-40.
References 121-4. 9. McCaffrey JA, Reuter VV, Herr HW, et al.
5. Murali R, Kneale K, Lalak N, Delprado W. Carcinoid tumor of the kidney. The use of
1. Kloppel G. Tumour biology and histo- Carcinoid tumors of the urinary tract and somatostatin receptor scintigraphy in
pathology of neuroendocrine tumours. prostate. Arch Pathol Lab Med 2006;130: diagnosis and management. Urol Oncol
Best Pract Res Clin Endocrinol Metab 1693-706. 2000;5:108-11.
2007;21:15-31. 6. Krishnan B, Truong LD, Saleh G, et al. 10. Schlussel RN, Kirschenbaum AM, Levine
2. Romero FR, Rais-Bahrami S, Permpong- Horseshoe kidney is associated with an A, Unger P. Primary renal carcinoid tumor.
kosol S, et al. Primary carcinoid tumors of increased relative risk of primary renal Urology 1993;41:295-7.
the kidney. J Urol 2006;176: 2359-66. carcinoid tumor. J Urol 1997;157:2059-66. 11. Akerstrom G. Management of carcinoid
3. Raslan WF, Ro JY, Ordonez NG, et al. 7. Quinchon JF, Aubert S, Biserte J, et al tumors of the stomach, duodenum, and
Primary carcinoid of the kidney. Immuno- Primary atypical carcinoid of the kidney: a pancreas. World J Surg 1996;20:173-82.

Rare
RareTumors
Tumors2009;
2009;volume
volume1:exxxx
1:e38
Bilateral angiosarcoma of the Case Report Correspondence: A.N. van Geel, Department of
breast in a fourteen-year-old Surgical Oncology, Erasmus Medical Center/
child A 14-year-old girl was admitted to our hospi- Daniel den Hoed Cancer Center, Groene Hilledijk
tal with a rapidly enlarging mass in the right 301 3075, EA Rotterdam, The Netherlands.
E-mail: a.n.vangeel@erasmusmc.nl
Albertus N. van Geel,1 breast. Histological findings of a needle biopsy
Michael A. den Bakker2 specimen were consistent with AS. Further Keywords: angiosarcoma, infancy, breast.
Departments of 1Surgical Oncology and investigation did not reveal distant metastases
2 and a simple mastectomy was performed. A Received for publication: 29 May 2009.
Pathology, Erasmus Medical Center/
complete resection was achieved with very Revision received: 13 August 2009.
Daniel den Hoed Cancer Center,
close margins (Figure 1), and for that reason Accepted for publication: 2 September 2009.
Rotterdam, The Netherlands the chest wall was irradiated with a dose of 60
Gy in 33 fractions. The histology of the mastec- Attribution 3.0 License (by-nc 3.0).
tomy specimen showed the typical features of
AS composed of ramifying irregular vascular ©Copyright A.N. van Geel et al., 2009
Abstract structures in the breast tissue parenchyma Rare Tumors 2009; 1:e38
(Figure 2A). Atypical endothelial cells with doi:10.4081/rt.2009.e38
Malignant vascular tumors are rare and hyperchromatic nuclei varying in size lined the
angiosarcomas of the breast in patients under vascular structures. Occasional multilayering
21 years of age are exceedingly uncommon. In was present, with mitoses readily identified.
this report an angiosarcoma in the breast of a Focal solid areas of tumor cells were evident.
14-year-old girl is described. She died nine Immunohistochemical staining confirmed the
months after mastectomy with recurrent dis- endothelial nature of the tumor cells with
ease in the bones and the contralateral breast. strong staining for CD31, CD34, D2-40 (Figure
The etiology of most primary angiosarcomas is 2B), and FVIII (not shown). After extensive
unknown. Secondary angiosarcomas can discussion with the pediatric oncology group
develop after radiotherapy and chronic lym- she received adjuvant therapy of six courses of
phedema. The histology of this angiosarcoma paclitaxel (175 mg/m2). Five months after sur-
is illustrated. gery she developed several bone metastases Figure 1. Gross appearance of the complete
resection of the right breast.
and the left humerus was irradiated. One
Introduction
A
Malignant vascular tumors are extremely
rare in patients under 21 years of age. Among
228 vascular tumors in 222 children and ado-
lescents observed in a 25-year period, only
four (2%) were malignant [three angiosarco-
mas (AS) and one Kaposi sarcoma].1 In a
series of 99 AS from all sites, only a single 3-
year-old patient is described.2 The largest
series of malignant vascular tumors in the
English literature is reported by the Italian
and German Soft Tissue Cooperative Group.3
Among 18 patients with malignant vascular
tumors, 12 patients ranging from one to 16
years of age were diagnosed with AS. The
most frequent sites of AS in childhood are the
head and neck region, liver, and skin.2-4 They
have been reported also in the brain,5 heart,6 B
thoracic cavity,7 and mesentery.8 Primary sar-
comas of the breast are extremely rare and
only a few patients under the age of 21 years
have been described in an overview series.9,10
The ages were 13 and 16 years, but in one
series it is clear that the 15-year-old patient Figure 2. (A) Histological section of the right breast illustrating typi-
cal features of AS: ramifying irregular vascular structures, focal solid
had AS.11 To our knowledge our study is of the areas of tumor cells, and multilayered cells with hyperchromatic
second youngest patient to be reported with nuclei. Note (arrows) residual normal ductal structures embedded
AS in both breasts.12 within angiosarcoma tissue. Hematoxylin and eosin stain; 100X mag-
nification. (B) Immunohistochemical staining of the tumor cells for
CD31 (left), CD34 (middle), and D2-40(right); 50X magnification.

Case Report
phangectasia: a case report. Pediatr Dev

Figure 3. Extensive Pathol 2008;11:482-6.
local recurrence 9. Bousquet G, Confavreux C, Magne N, et al.
after bilateral mas- Outcome and prognostic factors in breast
tectomy and radio-
therapy on the sarcoma: a multicenter study from the rare
right side. cancer network. Radiother Oncol 2007;85:
355-61.
10. Rainwater LM, Martin JK Jr, Gaffey TA, et
al. Angiosarcoma of the breast. Arch Surg
1986;121:669-72.
11. Sher T, Hennessy BT, Valero V, et al.
Primary angiosarcomas of the breast.
Cancer 2007;110:173-8.
12. Kumar A, Gupta S, Chopra P, et al. Bilateral
angiosarcoma of the breast: an overview.
Aust NZ J Surg 1990;60:341-5.
13. Kirova YM, Gambotti L, De Rycke Y, Vilcoq
et al. Risk of second malignancies after
month later the left breast showed a rapidly AS, like other non-small cell soft tissue sarco- adjuvant radiotherapy for breast cancer: a
enlarging tumor and subsequently multiple mas, are very insensitive to chemotherapy.18,19 large-scale, single-institution review. Int J
local recurrences appeared on the right side. A The prognosis is very poor, with a five-year Radiat Oncol Biol Phys 2007;68:359-63.
palliative simple mastectomy of the left breast survival rate of 20% or less.2,20,21 14. Offori TW, Platt CC, Stephens M, et al.
was performed (Figure 3). Three months later Angiosarcoma in congenital hereditary
and nine months after the first diagnosis she lymphoedema (Milroy's disease)--diag-
died with bone metastases and an extensive References nostic beacons and a review of the litera-
local recurrence of the disease. ture. Clin Exp Dermatol 1993;18:174-7.
1. Coffin CM, Dehner LP. Vascular tumors in 15. Cancellieri A, Eusebi V, Mambelli V, et al.
children and adolescents: a clinicopatho- Well-differentiated angiosarcoma of the
logic study of 228 tumors in 222 patients. skin following radiotherapy. Report of two
Discussion Pathol Annu 1993;28:97-120. cases. Pathol Res Pract 1991;187:301-6.
2. Naka N, Ohsawa M, Tomita Y, et al. Angio- 16. Marcon I, Collini P, Casanova M, et al.
AS is a rare tumor and the etiology is sarcoma in Japan. A review of 99 cases. Cutaneous angiosarcoma in a patient with
unclear in most cases. Prior irradiation after Cancer 1995;75:989-96. xeroderma pigmentosum. Pediatr Hematol
conservative therapy for breast cancer is a 3. Ferrari A, Casanova M, Bisogno G, et al. Oncol 2004;21:23-6.
well-known risk for developing mammary AS.13 Malignant vascular tumors in children and 17. Kirchner SG, Heller RM, Kasselberg AG, et
AS also occurs after chronic lymphedema fol- adolescents: a report from the Italian and al. Infantile hepatic hemangioendothe-
lowing axillary and inguinal lymph node dis- German Soft Tissue Sarcoma Cooperative lioma with subsequent malignant degen-
section.14 In children AS has been described Group. Med Pediatr Oncol 2002;39:109-14. eration. Pediatr Radiol 1981;11:42-5.
following radiotherapy for vascular disorders 4. Lezama-del Valle P, Gerald WL, Tsai J, et al. 18. Boucher LD, Swanson PE, Stanley MW, et
at a very young age.15 Other documented risk Malignant vascular tumors in young al. Cytology of angiosarcoma. Findings in
factors include: xeroderma pigmentosum,16 patients. Cancer 1998;83:1634-9. fourteen fine-needle aspiration biopsy
neurofibromatosis I,7 and exposure to vinyl 5. Lach B, Hassounah M, Khafaga Y. Primary specimens and one pleural fluid specimen.
chloride.17 The diagnosis of AS in the breast angiosarcoma of the brain in a child. Fetal Am J Clin Pathol 2000;114:210-9.
may be suspected on clinical examination Pediatr Pathol 2008;27:175-83. 19. Chui CH. Nonrhabdomyosarcoma soft tis-
when red-blue discoloration of the skin is pres- 6. Booth AM, LeGallo RD, Stoler MH, et al. sue sarcoma (NRSTS). Surg Oncol 2007;
ent; in later stages nodular tumor growth Pediatric angiosarcoma of the heart: a 16:187-93.
appears. The diagnosis may be supported fur- unique presentation and metastatic pat- 20. Koscielniak E, Jurgens H, Winkler K, et al.
ther by fine needle aspiration, in particular tern. Pediatr Dev Pathol 2001;4:490-5. Treatment of soft tissue sarcoma in child-
when combined with immunocytochemistry.18 7. Elli M, Can B, Ceyhan M, et al. Intra- hood and adolescence. A report of the
A tissue biopsy provides confirmation of the thoracic malignant peripheral nerve German Cooperative Soft Tissue Sarcoma
diagnosis of AS. The treatment of choice is sheath tumor with angiosarcoma in a child Study. Cancer 1992;70:2557-67.
surgery whether or not in combination with with NF1. Tumori 2007;93:641-4. 21. Mark RJ, Poen JC, Tran LM, et al.
radiotherapy. In contrast to small cell sarcomas 8. Costa da Cunha Castro E, Galambos C, Angiosarcoma. A report of 67 patients and
in children (Ewing’s sarcoma or primitive neu- Shaw P, et al. Primary mesenteric angio- a review of the literature. Cancer 1996;
roectodermal tumor, and rhabdomyosarcoma), sarcoma in a child with associated lym- 77:2400-6.

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Primary extrauterine an overgrowth of endometrial-like stromal

cells with scattered benign-appearing Correspondence: Gunjal Garg, 3980 John R,
endometrial stromal sarcoma: endometrial-type glands. Stromal cells Detroit, MI, 48201, USA.
response to hormone therapy showed mild to moderate cytological atypia. E-mail: gunjalgarg@yahoo.com
The tumor was positive for both estrogen and
Gunjal Garg,1 Awoniyi O. Awonuga,1 progesterone receptors. The differential diag- Key words: extrauterine, endometrial stromal
nosis included polypoid endometriosis; how- sarcoma, rectovaginal septum, hormone therapy
Eugene P. Toy2
1 ever, stromal overgrowth with atypia and
Department of Obstetrics and Contributions: ET conception and design; GG, AA
mitosis favored a low-grade Mullerian
Gynecology, Wayne State University, and ET manuscript writing; ET final approval of
adenosarcoma. Gastrointestinal stromal the manuscript.
Detroit, MI; 2Division of Gynecologic tumor (GIST), though a strong possibility
Oncology, Department of Obstetrics and when masses are encountered in this loca- Conflict of interest: the authors report no con-
Gynecology, University of Rochester, tion, was ruled out effectively by morphology. flicts of interest.
Rochester, NY, USA Additionally, immunohistochemical staining
with CD117 (not performed in our case) is Received for publication: 12 July 2009.
considered valuable in the diagnosis of GIST. Revision received: 16 September 2009.
Given that the tumor was hormone receptor Accepted for publication: 16 September 2009.
Introduction positive, megestrol acetate was prescribed
initially for the patient in an attempt to shrink Attribution 3.0 License (by-nc 3.0).
Endometrial stromal sarcomas (ESS) of the the mass in the RVS. Despite hormone thera-
uterus are hormone-sensitive tumors. There py progression of the tumor with increased ©Copyright G. Garg et al., 2009
have been reports in the literature confirming vaginal bleeding was noted. Therefore, the Rare Tumors 2009; 1:e39
the regression of ESS with progestins, patient underwent a posterior exenteration doi:10.4081/rt.2009.e39
gonadotropin analogues, and aromatase with end-sigmoid colostomy four months after
inhibitors. We report a case of primary her initial presentation. Pathological exami-
extrauterine ESS of the rectovaginal septum nation revealed a low-grade endometrial stro-
(RVS), which was poorly responsive and, in mal sarcoma (ESS). Subsequently, the patient Discussion
fact, progressed on progestin therapy. The also received adjuvant radiation because of
question arises: is the evident lack of copious mucoid material being present on Endometrial stromal sarcoma is a rare mes-
response to oral progestin in our case an debulking, and she has remained disease free enchymal neoplasm that usually occurs as a
exception or a trend more commonly seen in at 18 months follow-up. primary tumor of the uterus. However, it rarely
primary extrauterine, extraovarian ESS? To
the best of our knowledge, there has been no
report in the literature to address this ques-
tion. Therefore, we conducted a review of the
literature to evaluate the response of these
Table 1. Response to hormone therapy in primary extrauterine endometrial stromal sarco-
ma.
tumors to hormone therapy in relation to
their estrogen and progesterone receptor sta- Author Site Treatment Treatment ER/PR status
tus. of tumor response
*Kusaka et al. Cul-de-sac GnRH analogue, danazol Disease progression Strongly positive
Lacroix-Trilki et al. Sciatic nerve GnRH analogue Disease progression Strongly positive
Case Report Present case Rectovaginal Megestrol acetate Disease progression Strongly positive
septum
A 45-year-old G3P0030 African American Only case reports of patients with extrauterine extraovarian ESS with follow-up data were included in the review. ER, estrogen receptor; PR, prog-
woman underwent a supracervical hysterecto- esterone receptor; GnRH, gonadotropin releasing hormone *High-grade tumor arising from endometriosis (all other cases had low-grade tumors).
my and bilateral salpingo-oophorectomy for
chronic pelvic pain. The pathology report of
the surgical specimen confirmed the pres-
ence of endometriosis. Subsequently, six
years later, the patient presented with vaginal
bleeding, lower abdominal pain, dyspareunia,
and difficult defecation. Vaginal examination
showed active bleeding from an exophytic
polypoid mass in the posterior vaginal fornix.
Rectovaginal examination revealed a 4x3 cm
mass in the rectovaginal septum (RVS) and a
smooth rectal mucosa. Narrowing was noted
on proctoscopy at 8 cm distance owing to
extrinsic compression from the mass. The Figure 1. High power view (magnification: Figure 2. Arrow indicating the area of
vaginal polyp was removed and biopsies were 400X) of endometrial stromal sarcoma extensive endometriosis. (Stain: hema-
obtained from the adjacent normal-appearing with an entrapped benign gland (indicated toxylin and eosin; magnification: 200X.)
vaginal mucosa at the base of the mass. On by the arrow) (Stain: hematoxylin and
eosin.)
pathological examination, the lesion showed

Case Report
originates in sites other than the uterus and endometriosis. Two other patients3,4 received
ovaries. The role of hormone therapy is well hormone therapy in conjunction with References
documented in primary low-grade ESS of the chemotherapy; however, it is not feasible to
uterus, in patients with no evidence of resid- assess independently the role of hormone ther- 1. Kusaka M, Mikuni M, Nishiya M. A case of
ual disease after surgical treatment as well as apy in these cases. One explanation for the high-grade endometrial stromal sarcoma
in patients with advanced and recurrent dis- observed lack of response may be that, in spite arising from endometriosis in the cul-de-
ease. It has been shown to be effective, partic- of the hormonal receptorship, not all low-grade sac. Int J Gynecol Cancer 2006;16:895-9.
ularly in tumors that express both estrogen ESS respond to hormone therapy. Various fac- 2. Lacroix-Triki M, Beyris L, Martel P, et al.
and progesterone receptors and which have tors have been shown to influence hormone Low grade endometrial stromal sarcoma
demonstrable evidence of concomitant responsiveness: concentration of the sex arising from sciatic nerve endometriosis.
endometriosis. Our case is unique, however, steroid receptor, and relative expression of the Obstet Gynecol 2004;104:1147-9.
because it was a low-grade tumor positive for progesterone receptor (PR) isoforms (PR-A 3. Kaseki H, Mizuno K, Inoue T, et al. Post-
both estrogen and progesterone receptors; yet and PR-B). It is conceivable that receptor con- hysterectomy extra-uterine endometrial
the tumor progressed on progestin therapy. In centration and the predominant isoform may stromal sarcoma: A case report. Jpn J Clin
our review of the literature, we found two vary in ESS originating in the uterus versus Oncol 1990;20:413-9.
other reports (Kusaka et al.,1 Lacroix-Triki et extrauterine sites, such as to make the latter 4. Baiocchi G, Kavanagh JJ, Wharton JT.
al.2) describing patients with primary less hormone responsive. Endometroid stromal sarcomas arising
extrauterine, extraovarian ESS in whom hor- In summary, we report a trend favoring poor from ovarian and extraovarian
mone therapy alone was administered. The responsiveness of extrauterine, extraovarian endometriosis: Report of two cases and
treatment used and the clinical response rela- ESS to hormone therapy. This is significant review of literature. Gynecol Oncol 1990;
tive to estrogen and progesterone receptor sta- given the predilection to extrapolate from the 36:147-51.
tus is summarized in Table 1. treatment responses observed in uterine ESS.
Interestingly, all three patients (including Although our conclusion is based on a limited
our case) shown in Table 1 did not respond to number of cases, our report raises an important
hormone therapy. All reported associated question that needs to be investigated further.

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The managament of rare nasal line deformities, recurrent infections, airway

obstruction and intracranial complications can Correspondence: Ömer Tarik Selçuk, Refik
mass-nasal dermoid sinus occur when the diagnosis has been prolonged.6 Belendir sk. 67A/3 Ayranc›, 06410, Ankara, Turkey
cysts: open rhinoplasty The oldest case in the literature was a 56-year E-mail: omertarikselcuk@yahoo.com
old patient with intracranial extension.9 We
Emel Cadalli Tatar, Ömer Tarik Selçuk, are presenting an 18-year old adult and a two Key words: congenital, dermoid cyst, adult, nasal
and a half-year old child with a rare congeni- mass.
Güleser Saylam, Ali Özdek,
Hakan Korkmaz tal nasal midline lesion and their surgical
Received for publication: 2 July 2009.
treatment with a review of the literature. Accepted for publication: 13 September 2009.
Ministry of Health, Dișkapi Research and
Educational Hospital 2.ENT Clinic, This work is licensed under a Creative Commons
Ankara Turkey Case Report Attribution 3.0 License (by-nc 3.0).
©Copyright E.C. Tatar et al., 2009

Case #1 Rare Tumors 2009; 1:e40
Abstract An 18-year old patient with chronically doi:10.4081/rt.2009.e40
draining sinus opening after his birth and
recurrent nasal midline infection history has
The differential diagnosis of midline nasal
been seen in our clinic. He had no other comas a flap, we entrenched a catheter to the open-
masses includes inflammatory lesions, post-
plaints. He had no specific history within his
traumatic deformities, benign neoplasms, ing of the fistula which was located above the
family and no maxillofacial trauma. In his
malignant neoplasms, congenital and vascular septum and between the two alar cartilages
examination there was widening at nasal dor-
masses. Midline congenital lesions of the nose (Figure 1). Elevation was performed around
sum and draining sinus opening on the skin of
are rare congenital anomalies. Their incidence the catheter and tract of the fistula. The fistu-
the nasal tip (Figure 1). In anterior rhinoscopy
is estimated at 1 per 20,000 to 40,000 births la tract was extended to the nasion. The tract
nasal mucous membrane was normal. In the
consisting of gliomas, encephaloceles, and was continuing with a cyst. The skin of the
cranial computed tomography (CCT) scan
nasal dermoid sinus cysts. Nasal dermoid opening of fistula, the tract of the fistula and
there was no intracranial extension. We per-
sinus cysts account for 1-3% of dermoid cysts
formed an open technique rhinoplasty in local the cyst were excised without rupturing.
overall and 11-12% of head and neck dermoids.
anesthesia. During elevation of the skin of the Specimen was sent for pathological examina-
Most lesions are diagnosed within the first
columella, the infratip, the tip and the supratip tion (Figure 1). There was no problem in the
three years of life but in some cases the diag-
nosis can be prolonged. We present an 18-year
old and a two and a half-year old male patients
who are concerned about drainage from the tip
of the nose with recurrent infection and oper-
ated with a diagnosis of nasal dermoid sinus
cyst.
Introduction
Midline congenital lesions of the nose are a
rare congenital anomaly. Their incidence is
estimated at 1 per 20,000 to 40,000 births.1-3
The differential diagnosis of midline nasal
masses includes inflammatory lesions, post-
traumatic deformities, benign neoplasms,
malignant neoplasms, and vascular masses.3,4
Gliomas, encephaloceles and nasal dermoid
sinus cysts are the main part of the congenital
midline lesions of the nose.4,5
The central nervous system's (CNS)
involvement in gliomas and encephaloceles is
well known. Nasal dermoid sinus cyst (NDSC)
has a potential for intracranial involvement.
NDSC originates from ectoderm that forms Figure 1. Draining sinus
from neuroectodermal and ectodermal insepa- opening on the skin of
ration.1 Nasal dermoid sinus cysts account for nasal tip. The catheter
1-3% of dermoid cysts overall and 11-12% of entrenched to the opening
of the fistula, which was
head and neck dermoids.6,7 NDSCs account for located above the septum
61% of all midline nasal lesions in children.4,7 and between the two alar
Early diagnosis is made in the first three years cartilages. Specimen was
after birth in most cases. But in some cases sent for pathological exam-
the diagnosis may be prolonged.4,5,8 Nasal mid- ination.

Case Report
post-operative period and the patient was dis-

charged after one day. The post-operative
pathology report was epidermal inclusion cyst.
The patient had no complaints in the one year
follow-up and the esthetic result was satisfy-
ing.
Case #2
A two and a half-year old child with chroni-
cally draining sinus opening after his birth and
recurrent nasal midline infection history was
seen in our clinic. He also had no specific his-
tory within the family and no maxillofacial
trauma. In his examination there was a 1x1 cm
immobile subcutaneous mass with opening of
the fistula at rhinion of the nasal dorsum. The
mass was unable to be compressed and did not Figure 2. A paranasal sinus computed tomography and magnetic resonance imagining
increase with crying. The anterior rhinoscopy showed a cyst with no intracranial extension.
was normal. A paranasal sinus computed
tomography (CT) and magnetic resonance
imaging (MRI) showed a cyst with no intracra-
nial extension (Figure 2).
We performed an open technique rhinoplas-
ty in general anesthesia (Figure 3). The tract
was continuing with a cyst, which elongated
cephalically between separated nasal bones
and eroded bony septum. The fistula tract and
the cyst were excised without rupturing. After
cyst removal, the defect was filled with surgi-
cell. Specimen was sent for pathological exam-
ination (Figure 3).
There was no problem in the post-operative
period and the patient was discharged after
three days. The post-operative pathology report
was epidermal inclusion cyst. The patient had
no complaints in the 6-month follow-up and
the esthetic result was satisfying. Figure 3. The tract that was continuing
with a cyst. The fistula tract and the cyst
were excised without rupturing.
Discussion
NDSCs are the most frequent congenital
midline lesions.6,8,10 The first report about ature is a 56-year old patient with intracranial ature.4 There is no proved described genetic
NDSC was published by Bramann in 1890.4,7 extension.9 There are some reports about male transmission. There is some familial transmis-
There are lots of theories like sequestration, predominance.10 sion reported in the literature. NDSCs make up
trilaminary and prenasal, about NDSCs. The NDSCs are typically seen as midline masses. 11-12% of all head and neck dermoids.5 They
most accepted theory is Pratt’s prenasal theory. They usually have a sinus opening in the nasal can be seen between glabella and columella.
Pratt descibed the common embriologic path- dorsum.1,2 Intermittent secretion of sebaceous The ratio of the intracranial extension is con-
way of gliomas, encephaloceles and naso- material and recurrent infections are seen fre- troversial. Suspicion of intracranial extension
frontal dermoid sinus tract.4,5 During the quently. The hair outgoing from the opening is is important for every patient with NDSC.
extension of dura between the unconnected pathognomonic for the NDSC but is found in Cranial CT and/or MRI are essential to deter-
bones in the skullbase to nasal region the dura less than half of the patients.2,7 NDSC is seen mine the extension.1,5,6 Cranial CT is valuable
is related with dermis in the nasal tip. If the sporadically but familial cases have been to show the bone alterations and help diagno-
bone tissue could not separate the dura from reported in the literature.1,6 sis. Disadvantages of CCT are expectation of
dermis during the ossification, anomalies There is no association of a syndrome with ionized radiation and interpretation problems
occur. the formation of the NDSC. There are other because of the unseparated crista galli and
For the congenital nasal masses, which orig- congenital anomalies that have been reported. perpendicular plate of the ethmoid bone in
inate from ectoderm and mesoderm, the term These include craniofacial anomalies, hyper- infants under one year old.4 MRI has high res-
NDSC was first used in 1982.1,5 The diagnosis telorizm, cleft palate, hemifacial microsomia, olution in soft tissue so it clearly exhibits the
for most of the NDSCs is made in the first aural atresia, pinna deformities, branchial intracranial extension.1,4,5
three years of childhood. But in some cases, sinus anomalies, cardiac, genital and gastroin- The treatment of the NDSC is surgical exci-
like our first case, the diagnosis can be delayed testinal anomalies. These associations have sion.1,5-7 The most favorable technique is the
until a later age. The oldest patient in the liter- been reported with different ratios in the liter- open rhinoplasty like in our two cases.7 The

Case Report
Article
-
reasons for choosing this technique are expo- 2005;26:403-5.
sure, good esthetic results and allowing the References 6. Rahbar R, Shah P, Mulliken JB, et al. The
reconstruction of the nasal dorsum. The for- presentation and management of nasal der-
mation of the surgery depends on the lesions' 1. Bilkay U, Gundogan H, Ozek C, et al. Nasal moid: a 30-year experience. Arch
localization and extension. dermoid sinus cysts and the role of open Otolaryngol Head Neck Surg 2003;129: 464-
With the clinical findings and imaging rhinoplasty. Ann Plast Surg 2001;478-14. 71.
modalities, we can estimate the intracranial 2. Sreetharan V, Kangesu L, Sommerlad BC. 7. Rohrich RJ, Lowe JB, Schwartz MR. The
extension and plan appropriate surgical treat- Atypical congenital dermoids of the face: a role of open rhinoplasty in the management
ment.10 In most of the cases an early diagnosis 25-year experience. J Plast Reconstr of nasal dermoid cysts. Plast Reconstr Surg
is made in the first three years after birth. In Aesthet Surg 2007;60:1025-9. 1999;104:2163-70
some cases, however, the diagnosis may be 3. Zapata S, Kearns DB. Nasal dermoids. Curr 8. Yavuzer R, Bier U, Jackson IT. Be careful: it
prolonged.4,5,8 This must be kept in mind for dif- Opin Otolaryngol Head Neck Surg. might be a nasal dermoid cyst. Plast
ferential diagnosis. The treatment is surgical. 2006;14:406-11. Reconstr Surg 1999;103:2082-3.
The investigation for the intracranial exten- 4. Hanikeri M, Waterhouse N, Kirkpatrick N, 9. Hacker DC, Freeman JL. Intracranial exten-
sion must be performed before the surgery. et al. The management of midline transcra- sion of a nasal dermoid sinus cyst in a 56-
With the open septorinoplasty technique we nial nasal dermoid sinus cysts. Br J Plast year-old man. Head Neck 1994;16:366-71.
can achieve good esthetic and functional Surg 2005;58:1043-50. 10. Denoyelle F, Ducroz V, Roger G, Gara-bedian
results. 5. Post G, McMains KC, Kountakis SE. Adult EN. Nasal dermoid sinus cysts in children.
nasal dermoid sinus cyst. Am J Otolaryngol Laryngoscope 1997;107:795-800.

Lipid-rich histology in a tumor types and staging respond differently to

treatment and do not share the same prognosis. Correspondence: Serena Russo, Via Epomeo 72,
basal-type immuno-profile Lipid-rich invasive breast cancer is a rare enig- 80126 Napoli, Italy. E-mail: qubmur@tin.it
breast carcinoma: matic entity among special types of infiltrating
Key words: breast carcinoma, basal type, EGFR,
a clinicopathological duct carcinoma, with difficult diagnosis.1
c-kit, lipid-rich.
Only a few cases are reported in the litera-
histochemical and ture.2 Tumor cells contain abundant intracyto-
immunohistochemical plasmatic lipids.3 Contributions: SR has contributed to data acqui-
sition and interpretation; AS and FB collected the
analysis of a case Lipid-rich carcinoma was first described in
references and reviewed the literature; FMM,
women by Aboumrad et al.4 These authors Pathology Department Director, gave final
Serena Russo,1 Diana Coppola,2 thought that the lipid droplets were produced approval of the manuscript to be published; DC
Paola Vinaccia,2 Antonella Siciliano,2 and secreted by the tumor cells instead of and GB contributed to the technical histochemi-
being the result of regressive degeneration cal studies; PV carried out the immunohisto-
Francesca Baldassarre,2
because lipid droplets existed uniformly in chemical staining and participated in the design
Giovanni Battista,2 Giuseppe Pisani,3
metastasized lymph nodes and in tumor cells of the study; GP is the surgeon who performed
Joseph Sepe,4 Francesco M. Maiello2 undergoing mitosis.5 the operation; JS edited the English version of
1
ASL NA3 Sud, Maresca Hospital, Torre Since there was great heterogeneity in clin- the manuscript.
del Greco, Naples, Italy; 2ASL NA1, ical outcome for estrogen positive tumors com-
pared to the uniform behavior of hormone neg- Conflict of interest: the authors report no con-
Pellegrini Hospital, Division of Pathology,
flicts of interest.
Naples, Italy; 3ASLNA1, Pellegrini ative tumors,6 researchers have invested in
Hospital, Breast Unit, Naples, Italy. molecular aspects of breast cancer by investi-
Received for publication: 1 September 2009.
4
gating biological markers.7 Revision received: 1 October 2009.
University of Maryland University Recent literature8 suggests a new classifica-
College, USA Accepted for publication: 5 October 2009.
tion of breast cancer, based on its biological
features and categorizes tumors according This work is licensed under a Creative Commons
their immunophenotype in a luminal and a Attribution 3.0 License (by-nc 3.0).
basal-type,9 corresponding to two distinct types
Abstract of epithelial cells found in the normal mamma-
©Copyright S. Russo et al., 2009
ry gland. doi:10.4081/rt.2009.e41
We describe the clinicopathological and Basal-type breast tumors show no hormonal
morphological features of an unusual breast receptor expression, rarely over-express HER-2
carcinoma classifiable as a lipid-rich variant of (triple negative) but show high-molecular
ductal invasive carcinoma, with a basal-type weight cytokeratins, EGFR and c-kit positivity. geneous disease shifts to the new one that
immunohistochemical profile. Basal-type It was suggested10 that the heterogeneity of breast cancer is at least two different diseases
breast cancers show no hormonal receptor breast cancer may be derived from the diversi- with age-specific incidence. Estrogen-negative
expression, rarely over-express HER-2 but ty of the original cells for neoplastic transfor- tumors usually consist of high-grade, aggres-
exhibit molecular high weight cytokeratins, mation, which is thought to exist in the termi- sive tumors or rare histoypes (adenoid cystic,
EGFR and c-kit positivity. Special stains and nal duct lobular unit of the mammary gland. metaplastic). The basal-like subtype has an
histochemistry tests were used to elucidate the The cells in the terminal duct lobular unit interval presentation and it is not usually
nature of vescicles in the neoplastic cells. consist of glandular, basal and myoepithelial detected during a mammographic screening.11
Sudan IV was performed on formalin-fixed tis- cells. This heterogeneous population of epithe- We describe the clinicopathological and
sue. Commercially available antibodies tested lial cells arises from a common progenitor but morphological features of an unusual breast
were: ER, PgR, EGFR, HER2, c-kit, high molec- they each express unique markers and per- carcinoma classifiable as a “lipid-rich” variant
ular weight cytokeratins. Cytoplasmic lipids form unique functions. of ductal invasive carcinoma and correlate it
were highlighted as red-orange droplets on The paradigm that breast cancer is a hetero- with a basal immunohistochemical profile.
Sudan IV staining. As for immunohistochem-
istry, the tumor showed no reactivity to ER,
PgR and HER2 (triple negative), and diffuse
and strong positivity to high weight cytoker-
atins, EGFR and c-kit, such as a basal-type
breast carcinoma. A basaloid phenotype in a
lipid-rich carcinoma has not been previously
reported.
Introduction
Breast cancer represents a heterogeneous
group of tumoral entities, associated with spe-
cific morphological changes and immunohisto- Figure 1. Fine nee-
chemical features: the clinical presentation and dle aspiration cytol-
molecular alterations make it a highly diverse ogy: Large, vac-
uolized cells. 400X.
disease. That is why patients with the same

Article
Materials and Methods Figure 2. Fine nee-

dle aspiration cytol-
ogy. E.E. 400X.
A 73-year old woman, previously in good
health, in menopause since she was 38 years
old, presented with a sudden breast mass.
Mammography performed 10 months earlier
was negative.
Imaging studies further evaluated the
extent of the disease: CT scan revealed no evi-
dence of metastatic disease.
The patient was treated at the Breast Unit of
Pellegrini Hospital (Naples, Italy). She under-
went a modified radical mastectomy with axil-
lary lymphadenectomy after a fine needle aspi-
ration cytologic diagnosis of carcinoma
(Figures 1 and 2).
All available paraffin blocks or unstained Figure 3. Sudan IV.
sections were retrieved and the original hema- 250X.
toxylin and eosin-stained sections were
reviewed. After gross examination, the speci-
men was serially sectioned into 3 mm thick
slices and formalin-fixed.
In addition, 9 invasive ductal carcinomas,
not otherwise specified were used as a control
group for histological and immunohistochemi-
cal correlations. Whole tissue sections (5 μm)
were cut and used for histochemistry and
immunohistochemistry.
The immunohistochemical stains were per-
formed using Ventana® Benchmark™
Automated Immunostainer on formalin-fixed
paraffin-embedded specimens. Commercially
available antibodies tested were: ER, PgR, Figure 4.
EGFR, HER2, c-kit (Ventana, Tucson, AZ, USA), Hematoxylin-Eosin.
high molecular weight cytokeratins (clone 250X.
34βE12-ORG-8735, Novocastra) all prediluted
according to the manufacturers’ instructions.
Peroxidase activity was visualized with
diaminobenzidine chromogen as per routine
protocol to obtain a brown-black end product.
Appropriate internal and external positive con-
trols were used. In an effort to elucidate the
nature of the vescicles, special stains and his-
tochemistry tests were performed. Sudan IV
(modified by Coppola) method for fat: after fix-
ation in 10% buffered neutral formalin, the
specimen was rinsed in water for 24 hours to
remove the excess. Then 10 micron frozen sec-
tions were cut, collected in distilled water and
stained in a Sudan IV solution (Sudan was dis-
solved in 70% alcohol). After that we mounted
slides with glycerin jelly (Figure 3). We chose measured 2.2 cm in diameter. On morphologi- (CAPSS) in uninvolved parenchima.
alcohol instead of Herxheimer solution, made cal grounds it was a high-grade invasive ductal All the axillary lymphnodes (fourteen) were
of alcohol and acetone, to avoid an excessive carcinoma with an 80% histiocyte-like neo- negative. We also observed some calcifications
extraction since we dealed with previous for- plastic component and a 15% in situ ductal car- and a mild chronic intra and peritumoral
malin that is a fat solvent. cinoma component . inflammation. No reaction with Periodic
The neoplastic cells, arranged in nests and Acid–Schiff, Alcian and PAS-D histochemical
cords were medium-sized, with a small round, technique was observed within tumor cells.
dark, nucleolatus nucleus and a large foamy Cytoplasmic lipids were highlighted as red-
Results clear cytoplasm (Figure 4). There were per- orange droplets at the Sudan IV staining. In
ineural invasion, peritumoral neoplastic agreement with the current morphological
On gross examination the tumor was firm embolization and columnar alteration with description of human and canine tumors, the
and whitish with ill defined margins and prominent apical snouts and secretion cells we examined with large vacuoles of neu-

Article
tral lipids were consistent with lipid-rich carci-

Figure 5. EGFR.
noma, a rare and distinct variant of infiltrative 250X.
ductal breast carcinoma (lipid-rich invasive
ductal carcinoma according to WHO classifica-
tion, 2003). As for immunohistochemistry, the
tumor showed no reactivity to ER, PgR and
HER2 (triple negative), and diffuse and strong
positivity to high weight cytokeratins,12 EGFR
(Figures 5 and 6) and c-kit (Figure 7), such as
a basal-type breast carcinoma.
Discussion
The foregoing data suggest that breast can-
cers show great diversity in their morpholo-
gies, clinical histories and responsiveness to Figure 6. High mole-
chemiotherapy. This wide diversity poses a cu-lar weight cytok-
eratins. 250X.
challenge to provide accurate diagnostic, prog-
nostic and predictive information and effective
treatment. Traditional therapies targeting the
estrogen-receptors or HER2 oncogene would
not be expected to be effective on basal-like
breast cancers because this subtype expresses
neither of these proteins.
“Breast cancer can no longer be viewed as
one biologic entity. If breast cancer overall con-
sists of at least two main types, we need a
stratified rather than a unified approach to
breast cancer research, prevention and treat-
ment”.13 Some investigators have previously
suggested that basal-like carcinoma may con-
sist of components of invasive ductal carcino- Figure 7. c-kit. 250X.
ma, not otherwise specified, metaplastic carci-
noma, and medullary carcinoma.14
This is the first report of a lipid-rich breast
carcinoma with a basaloid phenotype.
Even if, based on one case, definitive con-
clusions about pathogenic implications cannot
be reached, it is peculiar that we observed car-
cinoma secreting cells showing a basaloid
immunoprofile, since the secretory function
usually belongs to luminal cells.
It is reasonable to conclude that this paper
may raise new questions, but it cannot give
ultimate results.
References
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1. Espinosa de los Monteros A, Hellmén E, of 13 examples. Cancer 1974;33:812-9. EGFR basal cytokeratins expression. Appl
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of the Mammary Gland in Seven Dogs: secreting mammary carcinoma. Report of 7. Perou CM, Sorlie T, Eisen MB, et al.
Clinicopathologic and Immunohi- a case associated with Paget’s disease of Molecular portraits of human breast
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2. Wrba F, Ellinger A, Reiner G, et al. Schmitt FC. Pathologic quiz case: a 62- Tissue microarray study for classification
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the breast. Virchows Arch A Pathol Anat ma. Arch Pathol Lab Med. 2003;127:396-8. 9. Rakha EA, El-Sayed ME, Green AR, et al.
Histopathol 1988; 413:381-5. 6. Paredes J, Albergaria A, Carvalho S, Prognostic markers in triple negative
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Article
10. Anderson WF, Matsuno R. Breast cancer Epidemiol Biomark Prev 2005;14:1108-12. eratins in human breast cancer. J Pathol
heterogeneity: a mixture of at least two 12. Matos I, Dufloth R, Alvarenga M, et al. P63, 2004;203:661-71.
main types. J Natl Cancer Inst 2006; cytokeratin 5, and P-cadherin: three 14. Kuroda N, Fujishima N, Inoue K, et al.
98:1011-4. molecular markers to distinguish basal Basal-like carcinoma of the breast: further
11. Collett K, Stefansson IM, Eide J, et al. A phenotype in breast carcinomas. Virchows evidence of the possibility that most meta-
basal epithelial phenotype is more fre- Arch 2005; 447:688-94. plastic carcinomas may be actually basal-
quent in interval breast cancers compared 13. Abd El-Rehim DM, Pinder SE, Paish CE, et like carcinomas. Med Mol Morphol 2008;
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Synchronous malignant B-cell revealed leukocytoclastic vasculitis with severe

perivascular infiltration of eosinophils. The Correspondence: Kazuhisa Nozawa, Department
lymphoma and gastric tubular cutaneous vasuculitis was considered to be a of Rheumatology, Juntendo University Urayasu
adenocarcinoma associated manifestation of HES with MC, although there Hospital and Institute for Environment and
Gender Specific Medicine, Juntendo University
with paraneoplastic cutaneous were no etiological factors of HES and MC.
Graduate School of Medicine, 2-1-1 Tomioka,
Therefore, the vasculitis seems to be a symp-
vasculitis: hypereosinophilic tom of paraneoplastic syndrome in this case. Urayasu, Chiba, 279-0021, Japan.
syndrome with mixed Our finding suggests that the potential pres- E-mail: kazunozawa@juntendo-urayasu.jp
cryoglobulinemia is an ence of malignancies should be kept in mind

Key words: cryoglobulinemia, malignant lym-
as a possible underlying disorder especially in
important sign of the presence of HES with MC; this possibility
phoma, paraneoplastic vasculitis, tubular adeno-
carcinoma.
paraneoplastic syndrome is interesting also as regards at least part of
the pathogenesis for paraneplastic syndrome. Contributions: KN was the main contributor for
Kazuhisa Nozawa,1,6 Hiroshi Kaneko,1 this manuscript.
Tomoyasu Itoh,3 Yoko Katsura,3 Masaaki
Noguchi,5 Fujihiko Suzuki,4 Conflict of interest: the authors report no con-
Yoshinari Takasaki,2 Hideoki Ogawa,6 Introduction flicts of interest.
Kenji Takamori,6 Iwao Sekigawa1,6
Acknowledgments: this work was supported by
1
Department of Internal Medicine and Hypereosinophilic syndrome (HES) is a
the grants from The Institute for Environment
Rheumatology, Juntendo University clinical disorder characterized by persistent
and Gender-specific Medicine, Juntendo
eosinophilia and systemic signs, and the cuta- University Graduate School of Medicine.
Urayasu Hospital, Chiba, Japan;
2
neous lesions are one of the common manifes-
Department of Rheumatology, School of
tations derived from HES, including vasculitis.1 Received for publication: 5 August 2009.
Medicine, Juntendo University, Tokyo,
Although malignant T-cell lymphoma and other Revision received: 26 September 2009.
Japan; 3Department of Internal Medicine, malignant tumors associated with eosinophilia Accepted for publication: 1 October 2009.
Juntendo University Urayasu Hospital, have been reported sporadically,1-3 B-cell lym-
Chiba, Japan; 4Department of Pathology, phoma, originating from lymph nodes, with This work is licensed under a Creative Commons
Juntendo University Urayasu Hospital, Attribution 3.0 License (by-nc 3.0).
eosinophilia is extremely rare.4,5 On the other
Chiba, Japan; 5Department of hand, cryoglobulinemia is defined as the pres- ©Copyright K. Nozawa et al., 2009
Hematology, Juntendo University ence of circulating immunoglobulins that pre- Rare Tumors 2009; 1:e42
Urayasu Hospital, Chiba, Japan; 6Institute cipitate with cold temperature. After immuno- doi:10.4081/rt.2009.e42
for Environment and Gender Specific chemical typing, cryoglobulinemia is classified
Medicine, Juntendo University Graduate as type I, II, and III cryoglobulinemia.
School of Medicine, Chiba, Japan Furthermore, type II and III are defined as
mixed cryoglobulinemia (MC), with a mono- ing lymphomas. Furthermore, the association
clonal component in type II and only polyclonal between vasculitis and malignancy has been
immunoglobulins in type III. Since the discov- widely reviewed, and recently neoplasms have
Abstract ery of hepatitis-C virus (HCV) infection, it has been suggested to be a causative factor of the
become clear that HCV is associated with most vasculitis.7,8 Many reports regarding neoplastic
Gastric adenocarcinoma developing con- cases of MC. In addition, MC is known to cause vasculitis have been published since, thus sug-
comitantly with a lymphoma is rare. a systemic vasculitis and, interestingly, it has gesting that cutaneous vasculitis especially
Furthermore, B-cell lymphoma, originating been reported that patients with non-HCV may appear as an initiating sign of paraneo-
from lymph nodes, with eosinophilia is related MC vasculitis have a four-fold plastic syndrome.9-12 We report here a female
extremely rare. We report here a case with a increased risk of developing B-cell lym- patient with cutaneous vasculitis caused by
synchronous diffuse large B-cell lymphoma phomas.6 These data suggest the presence of HES and MC, subsequently diagnosed as syn-
(DLBCL) and an early adenocarcinoma of the MC itself is one of the risk factors for develop- chronous diffuse large B-cell lymphoma
stomach. In addition, this case seemed to be
associated with paraneoplastic cutaneous vas-
culitis caused by hypereosinophilic syndrome
(HES) with mixed cryoglobulinemia (MC).
Many neoplastic diseases that affect internal
organs display cutaneous manifestations,
which may be the presenting signs and symp-
toms of the underlying malignancy. In particu-
lar, the association between cutaneous vas-
culitis and malignancy has been widely
A B C
reviewed, and recently neoplasms have been
suggested to produce antigens and the result-
Figure 1. Skin lesions. (A) The gross appearance of purpura on the lower legs; (B, C) the
ant immune complex formations, activating histological findings of the purpura, showing massive infiltration of neutrophils and lym-
the serum complement, thus cause paraneo- phocytes with deposits of fibrin on the vessel wall. Marked eosinophil and red blood cell
plastic vasculitis. In this case, severe infiltration is observed in the perivascular region. The cutaneous lesion was diagnosed as
eosinophilia and cryoglobulinemia with low leukocytoclastic vasculitis with severe perivascular eosinophil infiltration. (Hematoxylin-
eosin stain; magnification: B, 100X and C, 400X.)
complements were observed in a laboratory
test. A biopsy specimen from a skin lesion

Case Report
(DLBCL) and early gastric cancer. Our present A B C

case is extremely rare and it suggests the
requirement of surveillance of the cutaneous
vasculitis for the underlying malignancies
especially in the presence of HES with MC.
Case Report D E
A 63-year-old female visited our outpatient

department because of continuous fever, pur-
pura with pitting edema, and dysethesia in her
lower legs (Figure 1A) for a month. She was
admitted to our hospital for further examina-
tion. A biopsy specimen from a skin lesion
Figure 2. Biopsy specimens from lymph node (A-C) and stomach (D-E), showing anti-
revealed leukocytoclastic vasculitis with severe CD20 antibody immunohistochemical staining (A) and anti-BCL2 antibody immunohis-
perivascular infiltration of eosinophils (Figure tochemical staining of the lymph node specimen (B), magnification: 40X; hematoxylin-
1B). Her laboratory findings on admission are eosin staining of the lymph node specimen (C), magnification: 12.5X; and (D) the
summarized in Table 1. These data revealed macroscopic finding of a biopsy specimen from the gastric lesion (indicated by arrow),
significant hypereosinophilia (white blood cell and (E) hematoxylin-eosin staining, magnification: 10X. The specimen from the lymph
node was strongly positive for CD20 and BCL2. Hematoxylin-eosin and BCL-2 staining
count [WBC], 7200 mm3 with 52% eosinophils; showed some follicular formations and diffuse proliferation of the cells concomitantly.
normal range: 1-5%), and elevated serum lev- The patient was diagnosed with DLBCL transformed from follicular B-cell lymphoma.
els of interleukin (IL)-4 (7.4 pg/mL; normal The gastroscopy specimen revealed irregular atypical cell proliferation in the mucosa, and
range: <6 pg/mL) and IL-5 (59.3 pg/mL; normal the patient was diagnosed with early gastric cancer (tubular adenocarcinoma).
range: <10 pg/mL), which are known to be
growth factors for eosinophils. Neither atypical
lymphocytes nor lymphoblastic cells were rec-
ognized. The C-reactive protein (CRP) level
was 0.8 mg/dL (normal range: <0.3 mg/dL),
thus indicating a weak inflammatory reaction.
Both titers of myeloperoxidase anti-neutrophil
cytoplasmic antibody (MPO-ANCA) and pro-
teinase-3 (PR3)-ANCA were negative. The
serum level of rheumatoid factor (RF) was
strongly positive (751 IU/mL; normal range:
<20 IU/mL) although no clinical symptoms of
rheumatoid arthritis (such as tenderness or
swollen joints) were observed, and antinu-
clear-antibody (ANA) titers and disease-specif-
ic antinuclear antibodies were negative (40X;
normal range: <80X). She also demonstrated
some abnormal findings such as cryoglobu-
linemia or decreased serum complement lev-
els, especially the C4 component (<3 mg/dL;
normal range: 13-35 mg/dL). Several days
before admission, she progressively developed
systemic peripheral lymphadenopathy (medi-
astinal, axillar, and inguinal), and her labora-
tory tests revealed an elevated serum level of Figure 3. A schematic figure illustrating the hypothesis for paraneoplastic vasculitis with
hypereosinophilic syndrome and mixed cryoglobulinemia. IC: immune complexes, APC:
soluble IL-2 receptor (sIL-2R). FIP1L1-PDGFRA antigen-presenting cells, T: T-lymphocytes, B: B-lymphocytes, Eo: eosinophilia, MC:
mutation was not observed. MC is known to mixed cryoglobulinemia, HES: hypereosinophilic syndrome.
cause leukocytoclastic vasculitis owing to the
deposition of immune complexes on the vessel
wall and the activation of complements result-
ing in vascular damage. Therefore, we consid- inguinal lymph node. The lymph node speci- proliferation of the cells was recognized con-
ered the cutaneous vasculitis to be a manifes- men showed an accumulation of CD20-positive comitantly. Subsequent CD10 staining was
tation of HES with MC because of the presence B-cells on immunohistochemical staining negative and genetic transformation t(14;18)
of severe eosinophila and perivascular infiltra- (Figure 2A). Initially the patient was diag- was not observed (data not shown). CD10 and
tion by eosinophils. Regarding the lym- nosed with follicular lymphoma because BCL2 t(14;18) are generally highly positive in follic-
phadenopathy and elevated serum level of sIL- staining was positive (Figure 2B); however, ular lymphoma; therefore, the patient was
2R, we suspected the presence of malignant hematoxylin and eosin (HE) staining (Figure diagnosed ultimately with DLBCL transformed
lymphoma or other hematological malignan- 2C) and BCL2 staining revealed that the follic- from follicular B-cell lymphoma. To exclude the
cies; thus, a biopsy was performed on the ular formation was not so obvious and diffuse possibility of other types of B-cell lymphomas

Case Report
such as mucosa-associated lymphoid tissue

Table 1. Laboratory findings on admission.
(MALT) lymphoma, mantle cell lymphoma,
Burkitt lymphoma, and small lymphocytic lym-
phoma, a gastroscopy was performed and it WBC 7900/mL AST 15 IU/L RF 751 IU/mL
revealed a protruding lesion with ulceration at Neutro 27.0% ALT 6 IU/L ANA 40X
the lesser curvature in the corpus ventriculi Lympho 13.0% ALP 362 IU/L αDNA Ab (-)
(Figure 2D, left). Unexpectedly, the histologi- Mono 5.0% LDH 271 IU/L αRNP Ab (-)
cal findings indicated an early stage of gastric
cancer (Figure 2D, right) and the histological Eosino 52.0% CPK 61 IU/lL αSm Ab (-)
diagnosis was a gastric cancer, IIc, tubular ade- AtyLy (-) BUN 11 mg/dL αSS-A Ab (-)
nocarcinoma (tub1), m, ly0, v0, cut margin(-), Blast (-) Crea 0.6 mg/dL αSS-B Ab (-)
although there was no evidence of lymphoma. RBC 382x104/mL UA 3.1 mg/dL αCL‚2GP1 Ab (-)
As a result, the patient was diagnosed with Hb 12.4 g/dL TP 5.9 g/dL PR3-ANCA (-)
cutaneous leukocytoclastic vasculitis with syn-
Ht 35.7% ALB 3.8 g/dL MPO-ANCA (-)
chronized occurrence consisting of DLBCL and
early gastric adenocarcinoma. An endoscopic Plt 16.1 x IgG 874 mg/dL Cryogloblin (+)
mucosal resection was performed as a treat- CRP 104/mL IgA 178 mg/dL MMP-3 41.7 ng/mL
ment for her gastric cancer, and thereafter she ESR 0.8 mg/dL IgM 170 mg/dL HCV (-)
underwent chemotherapy for the lymphoma in PT-INR 5 mm/h IgE 43.0 mg/dL HBV (-)
the hematological department of our hospital. APTT 1.18 CH50 <5 U/mL sIL-2R 2610 U/mL
The treatment for DLBCL was successfully
Ferritin 33.4 sec C3 70 U/mL IL-4 7.3 pg/mL
accomplished using chemotherapy with a THP-
COP regimen comprising cyclophosphamide, 191.4 ng/mL C4 <3 U/mL IL-5 59.3 pg/mL
pirarubicin (tetrahydropyranyl adriamycin Urinalysis CEA 0.9 U/mL ECP 2.7 μg/lL
[THP]), vincristine, and prednisolone. The Blood (-) CA19-9 1.9 U/mL
symptoms related to the cutaneous leukocyto- Protein (-) FIP1L1- mutation (-)
clastic vasculitis disappeared totally.
Glucose (-) PDGFRA
Discussion
cific antigens or endothelial antigens, and the or dysfunction, and exclusion of secondary
deposition of circulating immune complexes, causes of eosinophilia such as parasite infec-
It is extremely rare that HES occurs not in B-
resulting in tissue damage because of completion or allergic reaction. HES is classified fur-
cell but in T-cell lymphomas, and that lym-
phoma and gastric adenocarcinoma occur ment-mediated cell destruction. The presence ther as myeloproliferative HES, lymphocytic
simultaneously. In a MEDLINE literature of cryoglobulin and low plasma C4 levels in our HES, familial HES, associated HES, overlap
search (keywords: gastric cancer, B-cell lym- patient also indicate that circulating immune HES, and undefined HES.18 Identification of the
phoma, and vasculitis), no item was found. We complexes may play an important role in the lymphocytic HES rests on recognition of the
believe that this is the first report of synchro- induction of the vasculitis. Interestingly, it has helper T-cell subset (especially TH2) and clon-
nous malignant B-cell lymphoma and early been reported that MC itself is a risk factor for al overgrowth of specific cytokine (especially
gastric cancer associated with paraneoplastic lymphoma development.16 Although MC is IL-5) producing cells. Although we did not con-
vasculitis caused by HES with MC. In addition, known to be observed frequently in patients firm the T-cell clonality producing IL-5, B-cell
it appears clinically important for us to recog- with HCV infections, our patient did not abnormality derived from DLBCL may stimu-
nize cutaneous vasculitis as paraneoplastic demonstrate any antibodies or antigens for late the T-cell clones resulting in HES.
syndrome. In this report, we discuss the etiolo- HCVs. In a case of non-HCV related MC, we Literature analyses indicate that character-
gy of paraneoplastic vasculitis. should pay more attention to lymphocytic dis- istics of representative paraneoplastic vasculi-
The relative risk of the occurrence of solid orders or malignant tumors, which are under- tis show cutaneous leukocytoclastic vasculitis
tumors and hematological malignancies is lying MC as reported previously.6 Furthermore, or cryoglobulinemic vasculitis. Recently,
known to be higher in autoimmune patients it has been reported that hypocomple- Solans-Laque et al. reported that the most com-
than in the normal population, and some mentemia is associated with lymphoma devel- mon vasculitis in solid tumors was leukocyto-
autoimmune disorders can appear to be para- opment in primary Sjogren’s syndrome.17 Our clastic vasculitis and the most common malig-
neoplastic syndrome before a malignant tumor case is able to support these notions. nancies were in urinary organs, gastrointesti-
is identified.13 Several reports have indicated Regarding another etiology of paraneoplastic nal tract, and lung.19 Furthermore, they men-
that vasculitis can be a paraneoplastic symp- vasculitis, tumor antigens may activate lym- tioned that 13 of 15 patients demonstrated con-
tom in either hematological malignancies or phocytes, thus resulting in an over-production cordance of disease activity and treatment
solid tumors.14-16 Vasculitis is an inflammatory of T-helper (TH)-2 type cytokines, such as IL-4 response for cancer and vasculitis, apart from
condition that can affect any type of blood ves- or IL-5, and subsequently recruiting 46.6% cases of the vasculitis that flared up,
sel owing to several immunologic mecha- eosinophils to the vessels; these phenomena heralding tumor recurrence or progression.
nisms. The possible mechanisms of paraneo- seem to have contributed to the development They suggested that resolution of vasculitis
plastic vasculitis include invasion of circulat- of HES. In fact, higher expressions of these following effective treatment of the putatively
ing tumor cells toward the vessel wall, damage cytokine proteins in certain lymphoma cells linked malignancy, and recurrence of vasculi-
to the endothelium by cytokines released from have been reported.16 HES is defined by three tis heralding tumor recurrence or progression,
circulating tumor cells, the cross-reaction with diagnostic criteria: eosinophils, >1.5x109/L, provide strong evidence for vasculitis being a
autoantibodies that can bind either tumor-spe- persistent eosinophilia and/or organ damage true paraneoplastic syndrome, not occurring

Case Report
by chance.19 Skin purpura or papules appear to ent case, the latter appeared to be the main extravascular necrotizing granuloma
be the most common skin manifestations, factor of the vasculitis rather than the former, (Churg Strauss) as a paraneoplastic man-
while hematological malignancies such as because the gastric cancer is at the early stage, ifestation of non-Hodgkin’s B-cell lym-
lymphoma are the most common malignancies and it is difficult to think that small early gas- phoma. J R Soc Med 1993;86:549-50.
presenting as underlying diseases.9-12 Our case tric cancers cause the paraneoplastic phenom- 10. Sanchez NB, Canedo IF, Garcia-Patos PE,
supports these notions and reminds us that we enon. et al. Paraneoplastic vasculitis associated
should pay attention to the importance of per- with multiple myeloma. J Eur Acad
forming careful examinations in order to Dermatol Venereol 2004;18:731-5.
exclude other diseases, especially malignan- 11. Simon Z, Tarr T, Toth L, et al. Cutaneous
cies that may exist as underlying causes of References vasculitis as initiating paraneoplastic
HES and MC, with skin involvement as an symptom in Hodgkin lymphoma.
important sign of paraneoplastic syndrome. 1. Gleich GJ, Leiferman KM. The hypere- Rheumatol Int 2008;28:719-23.
Finally, our hypothesis regarding the patho- osinophilic syndromes: current concepts 12. Ydav BS, Sharma SC, Kapoor RK. Para -
genesis of the paraneoplastic vasculitis in the and treatments. Br J Haematol 2009;145: neoplastic leukocytoclastic vasculitis in
present case is shown in Figure 3. We think 271-85. chronic lymphoid leukemia. J Cancer Res
two possible mechanisms for the paraneoplas- 2. Choi W, Park YH, Paik KH, et al. Peripheral Ther 2006;2:206-8.
tic vasculitis derived from gastric cancer and T-cell lymphoma-unspecified (PTCL-U) 13. Ponyi A, Constantin T, Garami M, et al.
lymphoma are considerable. In gastric carcino- presenting with hypereosinophilic syn- Cancer-associated myositis. Ann NY Acad
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released into the extracellular region and rec- Intern Med 2006;21:57-61. 14. Farrell AM, Stern SC, El-Ghariani K, et al.
ognized by the immune system as autoanti- 3. Gutierrez A, Solano C, Ferrandez A, et al. Splenic lymphoma with villous lympho-
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immune activation against the tumor anti- consecutively with hemophagocytic lym-
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2008;112:3818-26.
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es on the vessel wall. Then, complement is 5. Krunic AL, Medenica MM, Laumann AE, et Mixed cryoglobulinemia syndrome as an
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Hemangiopericytomas of the HPC with cervical spinal metastasis that

occurred six years after the primary lesion was Correspondence: Meic H. Schmidt, Department of
spine: case report and review detected. We also reviewed the literature to Neurosurgery, University of Utah, 175 N. Medical
of the literature identify HPCs affecting the spine and to identi- Drive, Salt Lake City, UT 84132, USA
fy recognized treatment options. E-mail: meic.schmidt@hsc.utah.edu
Chad D. Cole1 Meic H. Schmidt1,2
Key words: hemangiopericytoma; neoplasm;
1
Department of Neurological Surgery, spinal.
University of Utah, Salt Lake City, Utah;
2
Case Report Acknowledgments: we thank Kristin Kraus,
Spinal Oncology Service, Huntsman
Cancer Institute, University of Utah, Salt M.Sc., for editorial assistance in preparing this
A 36-year-old woman visited the emergency paper for publication.
Lake City, Utah room after experiencing several years of visu-
al disturbances of increasing severity and fre- Contributions: Dr. Cole prepared the manuscript
quency, nausea, dizziness, imbalance, hyper- under supervision of Dr. Schmidt, who also criti-
ventilation, and numbness and upper extremi- cally reviewed and contributed to the content.
Abstract ty tingling. Imaging indicated that she had a
left occipital lesion that enhanced on adminis- Conflict of interest: the authors report no con-
We describe a rare case of a primary tration of a contrast agent. A complete resec- flicts of interest.
intracranial meningeal hemangiopericytoma tion was performed, and her symptoms
(HPC) with late metastasis to the cervical Received for publication: 7 August 2009.
improved. Pathological analysis of the resec-
spine. A 36-year-old woman had a left occipital Revision received: 17 September 2009.
tion was consistent with a meningioma. Accepted for publication: 17 September 2009
lesion that was histopathologically identified The patient did well for fourteen years but
as HPC. Fourteen years after resection, the redeveloped visual and neurological symptoms This work is licensed under a Creative Commons
tumor recurred and was treated with radio- and was found to have local recurrence of the Attribution 3.0 License (by-nc 3.0).
therapy. Three years later, CT imaging showed lesion. At this time, histopathological analysis
a large mass in the liver consistent with ©Copyright C.D. Cole and M.H. Schmidt, 2009
showed the lesion to be HPC. Re-review of the
metastatic HPC, and MRI of the cervical spine pathological analysis done of the original doi:10.4081/rt.2009.e43
showed an extensive lesion of the C3 vertebral lesion demonstrated that the tumor was a HPC
body. The patient underwent C3 corpectomy that had been misdiagnosed as a meningioma.
with en-bloc tumor removal and follow-up radi- The patient underwent a course of radiothera-
ation with no local recurrence or other spinal py to the left tentorium cerebellar region at a tectomy, and the tissue was found to be consis-
metastasis for the following 4 years. dose of 5400 cGy. Three years later, she devel- tent with metastatic HPC. Along with the
Regardless of the subtype of spinal HPC, com- oped right upper abdominal pain syndrome, metastasis in the liver, a lesion at the C3 ver-
plete surgical removal and radiotherapy appear and a computed tomography (CT) scan showed tebral body was found (Figure 1). On follow-up
to be treatment of choice. a large mass that filled the right lobe of the clinical evaluation, the patient had mild neck
liver. She underwent a biopsy and a right hepa- pain, with no motor deficits or sensory deficits.
Introduction A
The term “hemangiopericytoma” (HPC) is

used to describe a wide variety of lesions shar-
ing certain morphological characteristics: a
monotonous appearance at low-power examina-
tion, moderate to high cellularity, and numer-
ous, variably thick-walled, branching ‘staghorn’
vessels.1 HPCs demonstrating obvious malig-
nant features generally behave aggressively;
however, a small proportion of benign-looking
lesions can recur and even metastasize.1
Meningeal HPCs (M-HPCs) have different
light microscopic, ultrastructural, and immuno-
histochemical features than meningiomas and B
are not considered variants of meningiomas.
Their clinical behavior is more aggressive than
that of benign meningiomas, and they have a
strong tendency for local recurrence and
extracranial metastasis.2-4 Figure 2. Preoperative T2-weighted axial
Spinal HPCs are significantly less common MR image of C3. The hyperintense lesion
than intracranial M-HPCs. Despite the well- is noted anterior to the spinal canal within
Figure 1. A. Preoperative axial CT scan of the vertebral body of C3 adjacent to the
known but rare occurrence of HPC within the C3. Note the destructive process involving left vertebral artery.
vertebral column, its natural history and man- the vertebral body. B. Preoperative coronal
agement remain somewhat elusive. We CT scan of C3.
describe a patient with primary intracranial M-

Case Report
Table 1. Reported cases of spinal HPC.
Study Age Level Treatment Follow-up Outcome

(yrs)/Sex period
Extradural
Schirger et al. 33/F T2 Surgery 1 yr Recurrence
195843
Kriss et al. 16/M C6-C7 Surgery, RT 9 No symptoms of
196820 months recurrence
Fathie 21/M T6 Surgery – –
197019
Pitkethly et al. 6 spinal tumors reported, no additional information
Figure 3. Postoperative sagittal CT of the
cervical spine. A corpectomy of the verte- 197036
bral body has been performed with the McMaster et al. – T1,T2 Surgery – –
placement of a titanium mesh cage, 197544 – T6,T7 Surgery – –
PMMA, and an anterior cervical plate.
– T10 Surgery – –
– T11 Surgery – –
– S1 Surgery – –
Stern et al. 31/F C6 Surgery 1 yr Tumor free
198045
Muraszko et al. 41/F L2 Surgery – –
198221 15/M T12 RT then surgery – –
11/F T11 Surgery, RT 6 yrs Recurrence at 3
yrs, surgery/RT
recurrence at 6 yrs
Bridges et al. 25/M S1 Surgery, RT 9 Tumor free
198846 months
Cappabianca et al. 52/F C6 Surgery 1 Died (unknown

198117 36/F C5 Surgery month cause)
2 yrs Died (unknown
cause)
Ciappetta et al. 48/M C4 Surgery 7 yrs Recurrence at 6 yrs
Figure 4. Postoperative T2-weighted sagit- 198518
tal MR image of the cervical spine. A cor-
pectomy of the vertebral body has been Ijiri et al. 39/F L1-L2 Surgery 2 yrs Tumor free
performed, and the C3 vertebral body is 200247
distorted by the placement of a titanium Akhaddar et al. 39/M Thoracic Surgery, RT – Tumor-free
mesh cage, PMMA, and an anterior cervi-
cal plate. 200248
Mohammadianpanah 21/M T2 Surgery, RT – –
et al. 200449
Primary osseous
Magnetic resonance imaging (MRI) of the
cervical spine showed an extensive lesion of Gerner et al. 62/M L5 Surgery, RT – –
the C3 vertebral body that occupied approxi- 197450
mately 90% of that vertebral body. It was direct- Wold et al. 47/F Sacrum Surgery, RT 1.5 yrs Died (unknown
198251 62/F Sacrum – – cause)
ly adjacent to both vertebral arteries, and there
33/F Vertebra Surgery 31 yrs Died (unknown
was no evidence of epidural extension (Figure
37/F Sacrum Surgery, RT 5 yrs cause)
2). An attempt was made to embolize the
Died (unknown
tumor, which had high vascularity, but the pro- cause)
cedure was unsuccessful because there was Died (unknown
significant arterial supply to the anterior cause)
spinal artery. None of the branches were large
Tang et al. 19/M L2 Chemotherapy, 4 yrs Local recurrence
enough to be accessed safely for embolization.
198824 RT, surgery after 3 years,
Two months later, the patient underwent a C3
treated with
corpectomy with removal of the tumor en bloc.
chemotherapy,
To reconstruct the vertebral body, a titanium persistent growth
mesh cage, polymethylmethacrylate (PMMA), 1 yr later
and an anterior cervical plate were used
(Figure 3).7 Follow-up radiation treatment of RT, radiation therapy; –, not available.

Case Report
the cervical spine was administered with a

total dose of 3750 cGy in 15 fractionated doses Table 2. Reported cases of metastatic HPC to the spine.
over 21 days. Clinical and imaging monitoring
during the past four years has demonstrated Study Age Time until Location of Location Treatment Outcome
no local recurrence or other spinal metastasis (yrs) metastasis primary of
(Figure 4). /Sex (yrs) tumor metastasis
Cranial meningeal
Discussion Kruse 22/F 8 Frontoparietal Lumbar Surgery –
196152 vertebra
HPCs are soft tissue tumors composed of Scott et al. 38/M 16 Posterior T12/L1 Surgery, RT Improvement
capillary blood vessels with one or more layers 197453 cranial fossa but death
of rounded cells showing features of pericytic after
differentiation. The thick-walled, branching complication
‘staghorn’ vessels are easily identified. Nonaka et al. 40/F 9.5 Tentorium T8 Surgery, RT Good
Pericytic differentiation, which is more diffi- 199826 recovery
cult to diagnose, has been based historically on Woitzik et al. 40/F 8 Frontal C6-T2 Surgery, RT Good
the presence of elongated cell processes, peri- 200316 recovery
cellular basal lamina, plasmalemmal pinocyto- 9 L2 RT Not stated
sis, and variable numbers of microfilaments.8 Lee et al. 48/F 6.5 Middle cranial C6-C7 Surgery, RT Improvement
Immunohistochemical analysis has shown that 200625 fossa
these tumors usually express muscle-specific Taniura et al. 30/F 4 Posterior L4-S1 Surgery, RT Improvement
actin, smooth muscle actin, and tropomyosin 200754 cranial fossa
but are mostly negative for desmin and h- Present 36/F 17 Posterior C3 Surgery, RT Good
caldesmon.9,10 case cranial fossa recovery
The clinical behavior of HPCs, especially
extrapleural HPCs, is unpredictable.
Extracranial locations
Approximately 10% to 15% of these tumors
demonstrate malignant behavior in the form of Mao and 56/M – Heart; – Surgery, RT Death due to
recurrent or metastatic disease.11,12 Systemic Angrist spine: L3 cardiac arrest
metastases from intracranial HPCs have been 196755
reported. The specific criteria that define Herrmann 68/F 2 Right arm T8 Surgery Gradual
malignancy for HPCs include large tumor size et al. (subtotal), RT improvement
(>50 mm), disseminated disease at presenta- 196856 of paraparesis
tion, infiltrative margins, high cellularity, Harris et al. 46/M 4 Groin; lung 3 C5 Surgery, RT, Neurological
nuclear pleomorphism, areas of tumor necro- 197857 years later chemotherapy deterioration
sis, and an increased mitotic index (>4 Hansen et al. 50/M 17 months Lung L3 RT ‘Relief of
mitoses per 10x high-powered field).11-14 199058 symptoms,’
Nevertheless, the correlation between mor- patient
phology and outcome is poor: some histologi- refused
cally malignant-looking lesions may behave further
benignly, and some morphologically innocuous treatment
lesions behave aggressively.1,11,13,15 Brass et al. 48/M 5 Lower T2-3 Partial 1 yr
Cases of spinal HPC are much less common 200459 cervical and resection, RT recurrence, at
than cases involving other anatomical loca- upper 2 yrs
tions. Intraspinal extradural M-HPCs and pri- thoracic complete
mary osseous HPCs are difficult to differenti- musculature sensory-motor
paralysis at
ate but are more frequent than intradural
T4 level
HPCs and secondary osseous HPCs. Thirty-one
cases of extradural and primary osseous spinal RT, radiation therapy; –, not available.
HPC have been reported within the English lit-
erature (Table 1). HPCs of intracranial or
extracranial primary sites that metastasize to the cervical spine. Often, but not always, these neck pain or pain accompanied by weakness.25
the spine (Table 2) are much rarer.5,6,16 tumors demonstrate a dural attachment.17-21 Once symptomatic spinal metastasis is diag-
Intradural spinal HPCs (Table 3) are as rare as Because of the involvement of the epidural nosed, there is no satisfactory treatment
these latter two spinal HPC subtypes. space, radiculomyelopathy is a common find- modality to stop the fast and fatal progres-
We have separated extradural (intraspinal) ing.22,23 In contrast, primary osseous HPCs of sion.25 Bone scintigraphy may be a useful
from primary osseous HPCs according to their the spine mostly affect the lumbosacral spine screening tool to detect osseous metastasis
original case reports, although delineating and have paravertebral extension 24 but do not early; however, a single negative scan may not
them is often difficult. In reviewing the litera- result in neurological deficit. The most com- be sufficient to confirm that there has been no
ture, we found that different clinical features mon complaints are pain and mass effect.24 bony metastasis.26 In addition, gadolinium-
have been observed in extradural M-HPC and Spinal metastasis should be considered a enhanced MRI provides a very sensitive
primary osseous HPC. Extradural HPCs gener- possibility when a patient who has been treat- method of detecting spinal metastasis. For
ally involve the middle and lower portions of ed previously for HPC presents with back or those patients who survive more than several

Case Report
years after the diagnosis of their primary HPC,

Table 3. Reported cases of spinal HPC.
aggressive spinal surveillance should be advo-
cated.25
Several long-term studies have documented Study Age Level Treatment Follow-up Outcome
the propensity of M-HPCs to recur locally or (yrs)/Sex period
regionally within the cranial or spinal Kruse 196152 53/M C3 Surgery, 4 yrs Recurrence at 3
meninges.2,27-36 Results from the literature sug- RT yrs
gest that complete excision is more successful
Pitlyk et al. 60/M C4 Surgery – –
in preventing or delaying recurrence than is 196560 49/F C3 Surgery 10 yrs Tumor free
incomplete excision.2,27,31,34,37,38 Complete exci- 39M T8 Surgery 18 yrs Recurrence at 9,
sion at the first operation significantly extend- 17, and 18 yrs
ed the average time before first recurrence
Muraszko et al. 30/M L3 Surgery, 12 yrs Recurrence at 11
from 43 months to 111 months. The five-year 198221 RT yrs
recurrence-free rate for those patients treated
Betchen et al. 31/M L4 Surgery 6 months Tumor free
with complete excision was 72.7%, whereas
20025
that for those patients treated with incomplete
excision was just 20.8%. RT, radiation therapy; –, not available.
The surgeon should be prepared for a sub-
stantial amount of bleeding during tumor exci-
sion because of the high vascularity of HPCs.16 can be considered in the setting of prior radia- study. Clin Neuropathol 1988;7:93-9.
tion, although the role of radiosurgery for 5. Betchen S, Schwartz A, Black C, Post K.
This bleeding can lead to high surgery-related
metastatic spine disease is evolving because Intradural hemangiopericytoma of the
morbidity and mortality and can be the great-
new technologies that deliver higher, more lumbar spine: case report. Neurosurgery
est hindrance to gross total resection.
conformal doses of radiation could result in 2002; 50:654-7.
Preoperative embolization can be used to
better local control.42 The use of chemotherapy 6. Lin YJ, Tu YK, Lin SM, Shun CT. Primary
reduce blood loss. Thus, en bloc resection with
remains controversial, as most attempts have hemangiopericytoma in the axis bone:
extratumoral devascularization is the option
been disappointing. case report and review of literature.
most likely to reduce operative blood loss and
Neurosurgery 1996;39:397-9.
possibly decrease the risk of recurrence; how-
7. Liu JK, Rosenberg WS, Schmidt MH.
ever, this may not be possible for those tumors
Titanium cage-assisted polymethylme-
with extensive premedullary portions.16 When
considering resection options, the surgeon
Conclusions thacrylate reconstruction for cervical
spinal metastasis: technical note. Neuro-
should also be mindful that a piecemeal
Intradural, intraspinal extradural menin- surgery 2005;56:E207.
removal is associated with an earlier recur-
geal/primary osseous, and secondary metastat- 8. Dardick I, Hammar SP, Scheithauer BW.
rence rate.5
ic osseous HPCs in the spine are rare and have Ultrastructural spectrum of hemangioperi-
Even after en bloc resection, the possibility
only been infrequently reported. Regardless of cytoma: a comparative study of fetal, adult,
of recurrence necessitates close monitoring of
the subtype, complete surgical removal and RT and neoplastic pericytes. Ultrastruct
the patient and consideration of adjuvant ther-
appear to be treatment of choice for HPC in the Pathol 1989;13:111-54.
apy. The length of survival for each patient also
spine. Overall and progression-free survival 9. Skalli O, Pelte MF, Peclet MC, et al. Alpha-
depends on the site and size of the primary
times of patients with HPCs have continuously smooth muscle actin, a differentiation
tumor.39 Tumors larger than 6 cm are associat- marker of smooth muscle cells, is present
improved; however, the treatment of HPC is
ed with much poorer prognosis than are small- in microfilamentous bundles of pericytes.
still unsatisfactory and remains a great chal-
er tumors.14 Outcomes for patients with J Histochem Cytochem 1989;37:315-21.
lenge.
intradural and extradural HPCs have been 10. Schurch W, Skalli O, Lagace R, et al. Inter-
found to be similar. Even with the similar mediate filament proteins and actin iso-
recurrence rates, however, disease-free sur- forms as markers for soft-tissue tumor dif-
vival was longer for those patients with an
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Recent experience in the management of 43. Schirger A, Uihlein A, Parker HL, Ker- Primary hemangiopericytoma of the lung.
meningeal hemangiopericytomas. Tumori nohan JW. Hemangiopericytoma recurring Case report. Scand J Thorac Cardiovasc
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29. Coffey RJ, Cascino TL, Shaw EG. Proc 1958;33:347-52. 59. Brass SD, Guiot MC, Albrecht S, et al.
Radiosurgical treatment of recurrent 44. McMaster MJ, Soule EH, Ivins JC. Hem- Metastatic hemangiopericytoma present-
hemangiopericytomas of the meninges: angiopericytoma. A clinicopathologic study ing as an epidural spinal cord lesion. Can
preliminary results. J Neurosurg 1993;78: and long-term followup of 60 patients. J Neurol Sci 2004;31:550-3.
903-8. Cancer 1975;36:2232-44. 60. Pitlyk PJ, Dockery MB, Miller RH. Hem -
30. Craven JP, Quigley TM, Bolen JW, Raker 45. Stern MB, Grode ML, Goodman MD. angiopericytoma of the spinal cord: report
EJ. Current management and clinical out- Hemangiopericytoma of the cervical spine: of three cases. Neurology 1965; 15:649-53.

Cervical intramedullary tetraparesis and sphincterian disturbances.

The symptoms had developed progressively Correspondence: Igor Vilela Faquini, Rua Dr
schwannoma: a case report with onset two years before admission. Diogo de Farias, 1201, apt. 148, Vila Clementino,
and review of the literature Initially the patient complained of left infe- São Paulo, 04037004, Brazil.
rior limb weakness that affected the right infe- E-mail: ifaquini@yahoo.com.br
Jardel Mendonça Nicácio,1 José Carlos rior limb after five months together with uri-
nary urgency , high thoracic column pain with- Key words: intramedullary schwannomas, spinal
Rodrigues Jr,2 Marcos Henrique Lima
cord tumors, neurofibromatosis.
Galles,2 Igor Vilela Faquini,1 Clemente out irradiation and arms and shoulders muscu-
Augusto de Brito Pereira,3 Mario Ganau4 lar fasciculations. After ten months the pares-
Contributions: CABP conceived and supervised
1
thesia and motor weakness achieved the supe- the paper, and approved the final version; JMN
Pediatric Neurosurgery Fellow of the rior limbs. The neurologic examination and IVF wrote and translated the article; MHL and
Federal University of São Paulo, Brazil; showed an asymmetric progressive spastic
2
JCJ gathered the data; MG helped in the transla-
Neurosurgeon of the Heliopolis Hospital, tetraparesia especially in the left side whith tion and critical analysis of the paper.
Brazil; 3Chairman of Neurosurgery of the impaired deambulation. Diffuse pyramidal
Heliopolis Hospital, Brazil; 4Resident in signs and normal deep sensitivity were also Conflict of interest: the authors report no con-
Neurosurgery of the University of described. The first diagnostic hypothesis was flicts of interest.
Verona, Italy amyotrophic lateral sclerosis and the patient
was treated with rilusole for 14 months. After Received for publication: 7 July 2009.
this, and given his physical weakness and Accepted for publication: 14 July 2009.
sphincterian dysfunction progression, he This work is licensed under a Creative Commons
sought assistance from another medical center Attribution 3.0 License (by-nc 3.0).
Abstract where a cervical spinal magnetic resonance
(MRI) was performed. This demonstrated a ©Copyright J. M. Nicácio et al., 2009
Intramedullary schwannomas unrelated C4-C6 intramedullary lesion (hypointense in Rare Tumors 2009; 1:e44
with neurofibromatosis are uncommon T1-weighted, hyperintense in T2-weighted, doi:10.4081/rt.2009.e44
tumors, but if correctly diagnosed and properly
treated they may have a good prognosis.
They have a wide range of clinical presenta-
tions, commonly presenting as a slowly pro-
gressive motor or sensory syndrome. We pres-
ent a case report of a patient without neurofi-
bromatosis with a surgically treated cervical
intramedullary schwannoma.
Introduction
Spinal schwannomas are tumors originating
from the Schwann cells1 and correspond to Figure 1. Pre-
30% of spinal tumors, most of which have an operative cervi-
cal spine mag-
intradural extramedullary location.2 netic resonance
They are generally associated with neurofi- (Sagittal T1- and
bromatosis types 1 and 2.3 T2-weighted
Intraparenchimal schwannomas of the cen- images).
tral nervous system (CNS) are extremely rare
when no relationship with neurofibromatosis
is present and several parts of CNS can be
affected, such as the spinal cord, cerebellum
and brain stem.4-6
Intramedullary lesions represent 0.3% of all
medullary tumors and 1.1% of spinal schwan-
nomas.7 This article reports a case of
intramedullary schwannoma and presents a
review of literature.
Case Report
Our patient is a 40-year old Caucasian male. Figure 2. Post-
He was admitted to the department of operative magnetic
Neurology and Neurosurgery of the Heliopolis resonance. Gross
Hospital, São Paulo, Brazil, presenting spastic total ressection.

Case Report
heterogeneous contrast impregnation and

syrin-gomyelia) (Figure 1). Intravenous Figure 3. Electronic microscopy of a
schwannoma with palisade cells and
steroids were started in the pre-operative peri- Verocay bodies.
od (30 mg/kg in bolus) followed by a mainte-
nance 5.4 mg/kg dosage over the following 23
hours. Surgical treatment was made through a
C3-C5 laminotomy with a careful duramater
microscopic opening, one centimeter mieloto-
my and tumor subtotal resection (Figure 2).
The intraoperative aspect of the lesion was
of a grayish and infiltrative mass making total
resection impossible. The nerve roots were not
involved by the tumor.
Microscopically examination demonstrated
compact palisade cells with lined nucleus
mixed with some enucleated areas called Table 1. Intramedullary schwannoma cases without Von Recklinghausen disease.
Verocay bodies (Figure 3).
During the immediate post-operative period
Author/year Sex Topography Duration of symptoms Treatment
a worsening of tetraparesis was noted with
recovery in the first 48 hours. After 24 months, Penfield, 19329 M C5 8 years Subtotal resection -
a significant regression of the motor and
Rasmussen, 194019 M C4 – C7 4 years Subtotal resection PR
sphincterian dysfunction was observed and
this allowed the patient to hold objects with his Roka, 195120 M Cervical 3 years Subtotal resection Worsening
hands and walk with help again. Riggs & Clary,195716 M C4 – C5 3 years Autopsy finding -
Ramamurthi, 1958 8
M T2 9 months Total resection PR
Lang & Bridge, 195921 M Cervical 1 year Total resection PR
Discussion M Thoracic 3 years Total resection Worsening
Scott & Bentz, 196222 F T3 – T4 12 years Subtotal resection Stable
The first surgical description of a spinal Lu, et al., 1963 23
M C4 – C5 3 months Total resection + RDT PR
tumor was made in 1888 by Sir Victor Horsley8 M C2 – C5 18 months Subtotal resection PR
who reported an extramedullary intradural McCormick, 196417 M L2 6 weeks Autopsy finding -
meningioma resection. However, it was just in
1907 that Von Eiselberg published the success- Slooff, et al., 1964 24
M C4 – C7 4 years - -
ful resection of an intramedullary neurofi- Guidetti, 196725 - Connus - Total resection TR
brosarcoma. Though Kernohan has been Mason & Keigher, 1968 26
M T8 – T10 3 months Total resection PR
recognised as the first neurosurgeon to report
Chigasaki, 196827 F T3 - Subtotal resection -
an intramedullary schwannoma case in 1952,
Penfield had already described an Van Duinen, 1971 28
M C3 - Total resection -
intramedullary lesion with schwannoma char- Cambier, et al., 197429 M C2 – C4 16 months Total resection Worsening
acteristics in 1932.9 Wood, et al., 19752 M C1 – C3 3 months RDT Death -PE
Up until today, approximately 50 cases of
intramedullary schwannomas not related to Schmitt, 197530 M Connus 6 months Autopsy finding -
neurofibromatosis have been described, some Isu, et al., 197631 F C1 6 months Subtotal resection -
of them are shown in Table 1. The melanotic Pardatscher, et al., 197932 M C4 – T9 9 months Decompressive Death
schwannomas, although not the scope of this
Vailati, et al., 197933 F T8 – T9 1 year Total resection PR
discussion, are even rare; from 39 cases
reported, just 5 were intramedullary lesions Shalit & Sandbank, 198134 F C2 – T2 6 months Total resection + RDT TR
and 10% of those malignized,10 as shown in Cantore, et al., 198235 M T12 – L1 - Total resection TR
Table 2. F C3 – C5 2 years Total resection PR
The male:female ratio for intramedullary Lesoin, et al., 198336 F C3 – C7 6 months Total resection TR
schwannomas is 3:1 with a mean age of 40- M Conus 5 years Total resection TR
years old. They are usually single lesions
affecting the cervical spinal cord (63%), the Rout, et al., 198337 F C2 – C6 5 years Total resection TR
thoracic spinal cord (26%) and the lumbar F C2 – C5 5 years Subtotal resection PR
spinal cord (11%). They have a slow growth Sharma, et al., 19843 M C2 – C6 18 months Total resection TR
pattern and because of this the average inter- Ross, et al., 1986 7
M C4 – C5 4 months Total resection TR
val between first symptoms and diagnosis is F C2 – T1 4 years Subtotal resection PR
28.2 months (from six months to 20 years).11
Gorman, et al., 198938 F C2 – C5 8 months Total resection PR
The most described clinical manifestation is
the pyramidal syndrome followed by sensitivity Herregodts, et al., 1991 1
F T3 – T4 5 years Total resection PR
complaints and sphincterian dysfunction. Nicácio, et al., 2007 M C4 – C6 2 years Subtotal resection PR
There are reports of muscular fasciculations as
the first symptom. Another complaint is the RDT, radiotherapy; PR, partial recovery; TR, total recovery; PE, pulmonary embolism.

Case Report
Table 2. Intramedullary melanotic schwannoma cases in literature. of the literature. Neurosurgery 1984;15:
Author/year Age Signs and Duration of Location Treatment Results 546-8.
/Sex symptoms symptoms 4. Prakash B, Roy S, Tandon PN. Schwan-
noma of the brain stem: case report. J
Solomon, et al.39 69/M Brown-Séquard 4y C3 Total resection Neurosurg 1980;53:121-3.
Marchese &McDonald40 72/F Tetraparesis 20 y C4-C6 Total resection PR 5. New PF. Intracerebral schwannoma. Case
Sola-Perez, et al.41 63/F Radicular pain C7 - T1 Partial resection PR report. J Neurosurg 1972;36:795-7.
Acciarri, et al.,42 44/F Tetraparesis 10 y T2 - T3 Total resection PR 6. Beskonakli E, Cayli S, Turgut M, et al.
Santaguida, et al.10 35/M 39 M Hemip./Parap. 10 m C4-C5/C4-C6 Total resection Intraparenchymal schwannomas of the
+ CMT+RDT central nervous system: an additional case
report and review. Neurosurg Rev 1997;
RDT, radiotherapy; CMT, chemotherapy; PR, partial recovery . 20:139-44.
7. Ross DA, Edwards MS, Wilson CB. Intra-
medullary neurilemomas of the spinal
motor-sensitive alternal deficit associated with liferation derived from nerve fibers of the
cord: report of two cases and review of the
amiotrophy in patients with predominantly spinal arteries.16
literature. Neurosurgery 1986; 19:458-64.
one-sized located medullary tumors.12 The X- Ramamurthi et al. suggested that a few
8. Ramamurthi B, Anguli VC, Iyer CG. A case
ray findings are correlated to tumoral growth ectopic Schwann cells of the embrionary neu-
of intramedullary neurinoma. J Neurol
characteristics. ral tube (during the fourth gestational week)
Neurosurg Psychiatry 1958;21:92-4.
Mielography denotes precisely the tumor could be the origin of these schwannomas.8
9. Penfield W. Notes on operative technic in
location and the relationship with dura mater In 1964, MacCormick and Wood stated that
neurosurgery. Ann Surg 1946;124:383-5.
and the spinal cord. However, MRI is the gold intramedullary schwannomas came from some
10. Santaguida C, Sabbagh AJ, Guiot MC, Del
standard to study intramedullary tumors. Schwann cells found in aberrant intra -
Maestro RF. Aggressive intramedullary
In 1988, Takemoto stated that MRI allows medullary nervous fibers arising through the
melanotic schwannoma: case report. Neu-
pre-operative diagnosis of schwannomas, neu- posterior roots.17 But the most acceptable theo-
rosurgery 2004;55:1430.
rofibromas, meningiomas and hemangioblas- ry was reported by Rusell and Rubenstein in
11. López J, Diaz DR, Medina YC, et al.
tomas.13 On the other hand, according to 1971. According to them, these tumors emerge
Schwanoma intramedular cervical. Arch
Nicoletti in 1994, neither the MRI nor CT scan from the transformation of neuroectodermal
Neurocien 2004;9:55-8.
can differentiate the intramedullary tumor his- pial cells into Schwann cells, leading to a pos-
sible fast neoplastic growth of Schwann cells 12. Carrillo-Esper R, Solís-Maldonado G,
tological type.14 Sagittal and axial images Trujillo V, Téllez-Morales MA. Schwanoma
demonstrate a widening of the spinal cord. located in a “critical area” in the dorsal roots.18
intra-medular cervical. Cir Ciruj 2001:5-7.
Perilesional edema and cystic cavities can 13. Takemoto K, Matsumura Y, Hashimoto H,
be observed. These tumors are hypointense or et al. MR imaging of intraspinal tumors -
isointense on T1-weighted sequences and gen- capability in histological differentiation
erally hyperintense on T2-weighted sequences.
Conclusions
and compartmentalization of extramedul-
When gadolinium is injected there is a hetero- lary tumors. Neuroradiology 1988;30:303-
geneous enhancement. Although rare, the intramedullary schwan-
9.
According to Demachi, there is no correla- nomas should be considered as a possible diag-
14. Nicoletti GF, Passanisi M, Castana L,
tion between the classification of Antoni and nosis for young adults presenting with an
Albanese V. Intramedullary spinal neurino-
the MRI findings.15 The Antoni A-type is char- intramedullary lesion. Once suspected, surgi-
cal treatment is recommended. Gross total ma: case report and review of 46 cases. J
acterized by the presence of compact wave- Neurosurg Sci 1994;38:187-91.
resection is the goal but sometimes this can-
shaped cells rounded by a reticular net. The 15. Demachi H, Takashima T, Kadoya M, et al.
not be accomplished due to the infiltrative
Antoni B-type has large and loose cells sur- MR imaging of spinal neurinomas with
characteristic of the tumor. Finally, a better
rounded by a collagenous web.12 pathological correlation. J Comput Assist
understanding of the etiology and phys-
The infiltrative pattern of some intra- Tomogr 1990;14:250-4.
iopathology will certainly contribute to the
medullary schwannomas make total gross 16. Riggs HE, Clary WU. A case of intra-
treatment of these patients.
resection impossible and some authors sug- medullary sheath cell tumor of the spinal
gest in these cases the use of radiotherapy for cord; consideration of vascular nerves as a
residual lesions.2 According to the new WHO source of origin. J Neuropathol Exp Neurol
classification of tumors there are three types References 1957;16:332-6.
of schwannomas: cellular, plexiform and 17. McCormick WF. Intramedullary spinal cord
melanotic. schwannoma. A unique case. Arch Pathol
1. Herregodts P, Vloeberghs M, Schmedding
However, the controversial question about 1964;77:378-82.
E, et al. Solitary dorsal intramedullary
this pathology emerges from the unknown 18. Russel D, Rubinstein LJ, eds. Pathology of
schwannoma. Case report. J Neurosurg
pathogenesis. Previous studies have claimed tumors of the nervous system. 3rd ed.
1991;74:816-20.
that the central nervous system cells have no 2. Wood WG, Rothman LM, Nussbaum BE. London: Edward Arnold; 1971.
Schwann cells, thus making the presence of Intramedullary neurilemoma of the cervi- 19. Rasmussen TB, Kernohan JW, Adson AW.
intramedullary schwannomas a paradox. cal spinal cord. Case report. J Neurosurg Pathologic classification, with surgical
In the pursuit of an answer to that question, 1975;42:465-8. consideration, of intraspinal tumors. Ann
several theories have been suggested over the 3. Sharma R, Tandon SC, Mohanty S, Gupta Surg 1940;111:513-30.
last fifty years. In 1957, Kernohan, McCarty, S. Intramedullary neurofibroma of the cer- 20. Roka L. Clinical aspects and pathologic
Riggs and Clary proposed that the origin of vical spinal cord: case report with review anatomy of tumors of the oblongata and
such lesions could be from Schwann cells' pro- cord in the region of the foramen magna.

Case Report
Arch Psychiatr Nervenkr Z Gesamte ma. Ned Tijdschr Geneeskd 1971;115: Solitary intramedullary schwannomas.
Neurol Psychiatr 1951;186:413-36. 1070-4. Surg Neurol 1983;19:51-6.
21. Lang EF Jr., Bridge C. Intramedullary 29. Cambier J, Masson M, Hurth M, et al. 37. Rout D, Pillai SM, Radhakrishnan VV.
spinal cord tumors. Surg Clin North Am Unilateral posterior-column syndrome due Cervical intramedullary schwannoma.
1959;39:831-9. to intramedullary neurinoma. Imitative Case report. J Neurosurg 1983;58:962-4.
22. Scott M, Bentz R. Intramedullary neuri- homolateral synkinesias. Rev Neurol 38. Gorman PH, Rigamonti D, Joslyn JN.
lemmoma (neurinoma) of the thoracic (Paris) 1974;130:189-99.
Intramedullary and extramedullary
cord. A case report. J Neuropathol Exp 30. Schmitt HP. "Epi-" and intramedullary
schwannoma of the cervical spinal cord-
Neurol 1962;21:194-200. neurilemmoma of the spinal cord with
23. Lu AT, Eisenstein BE. Papillary subependy- denervation atrophy in the related skeletal case report. Surg Neurol 1989;32:459-62.
mal gliosis (gliomatosis) associated with muscles. J Neurol 1975;209:271-8. 39. Solomon RA, Handler MS, Sedelli RV, Stein
Von Recklinghausen's disease and sub- 31. Isu T, Tashiro K, Mitsumori K, et al. A case BM. Intramedullary melanotic schwanno-
ependymal glioma. Bull Los Angel Neuro of intramedullary spinal schwanoma ma of the cervicomedullary junction.
Soc 1963;28:151-6. (author's transl). No Shinkei Geka 1976; Neurosurgery 1987;20:36-8.
24. Slooff JL. Primary tumors of the cerebel- 4:897-901. 40. Marchese MJ, McDonald JV. Intra-
lum. A clinicopathological study. Jaarb 32. Pardatscher K, Iraci G, Cappellotto P, et al. medullary melanotic schwannoma of the
Kankeronderz Kankerbestrijd Ned 1964; Multiple intramedullary neurinomas of the cervical spinal cord: report of a case. Surg
14:309-11. spinal cord. Case report. J Neurosurg Neurol 1990;33:353-5.
25. Guidetti B. Intramedullary tumours of the 1979;50:817-22. 41. Sola-Perez J, Perez-Guillermo M, Bas-
spinal cord. Acta Neurochir (Wien). 33. Vailati G, Occhiogrosso M, Troccoli V. Bernal A, et al. Melanocytic schwannoma:
1967;17:7-23. Intramedullary thoracic schwannoma.
the cytologic aspect in fine-needle aspira-
26. Mason TH, Keigher HA. Intramedullary Surg Neurol 1979;11:60-2.
tion cytology (FNAC): report of a case
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Neurosurg 1968;29:414-6. medullary schwannoma. Surg Neurol located in the spinal cord. Diagn
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low-up study of 128 cases of intra- 35. Cantore G, Ciappetta P, Delfini R, et al. 42. Acciarri N, Padovani R, Riccioni L.
medullary spinal cord tumours. Neurol Intramedullary spinal neurinomas. Report Intramedullary melanotic schwannoma.
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Primary mediastinal giant cell the mass to be composed of a mixture of round

and oval mononuclear and multinucleated Correspondence: Judd Goldberg, Long Island
tumor osteoclast-like giant cells with a background of Jewish Medical Center, 270-05 76th Ave,
rich vascular stroma (Figures 4 and 5). The New Hyde Park, NY 11040, USA.
Judd Goldberg, Shameen Azizad, Jela tumor also showed areas of cystic degenera- E-mail:juddgoldberg@gmail.com
Bandovic, Arfa Khan tion and hemorrhage. There was no increase
Key words: primary mediastinal giant cell tumor.
Long Island Jewish Medical Center, New in the mitotic index. Immunohistochemically,
Hyde Park, NY, USA the mass was positive for CD68 and CD34, and Received for publication: 30 July 2009.
was diagnosed as a giant cell tumor of soft tis- Revision received: 13 October 2009.
sue. Five mediastinal lymph nodes were Accepted for publication: 16 October 2009.
resected without evidence of malignancy. The
patient had an uneventful postoperative This work is licensed under a Creative Commons
Abstract Attribution 3.0 License (by-nc 3.0).
course and received postoperative radiation
Giant cell tumor of soft tissue is a rare treatment to the left chest wall. A follow-up ©Copyright J. Goldberg et al., 2009
tumor first described by Salm and Sissons in non-contrast chest CT scan did not show evi- Rare Tumors 2009; 1:e45
1972 as being a distinct entity.1 Histologically, dence of recurrent disease or metastases. doi:10.4081/rt.2009.e45
it is composed of multinucleated giant cells
dispersed among mononuclear cells, and is A
indistinguishable from its bone equivalent.2
The majority of these tumors have been report- Discussion
ed to occur in the lower extremity.2,3 We
describe a case of giant cell tumor of soft tis- Giant cell tumor of soft tissue is a rare
sue within the posterior mediastinum. The tumor, which demonstrates a spectrum of
only other report of a primary mediastinal benign to malignant characteristics. Microsco-
giant cell tumor of soft tissue in the English lit- pically, these tumors are composed of multinu-
erature was published by Fu et al. in 2002, in cleated giant cells evenly dispersed among
which they described two patients with poste- mononuclear cells, and are histologically indis-
rior mediastinal masses.4 tinguishable from their bone equivalent.2 In
1972, Salm and Sissons were the first to B
describe a series of 10 patients with giant cell
tumors of soft tissue.1 In their study, the
Case Report tumors demonstrated benign features without
metastases. However, there was local recur-
A 53-year-old man with a history of hyper- rence in two patients. In the same year,
tension presented with increasing left anterior Guccion and Enzinger reported a series of 32
chest pain. He was seen by a cardiologist and patients with soft tissue tumors similar to
had a treadmill stress test, which was normal. those studied by Salm and Sissons, but with
A chest radiograph revealed a large left medi- malignant features and widespread metas-
astinal mass (Figure 1). A follow-up non-con- tases.3 These tumors were called “malignant C
trast chest CT scan showed a large left posteri- giant cell tumors of soft parts.” In 2000,
or mediastinal mass with compression of the O’Connell et al. described a series of 18
adjacent lung (Figure 2). There was pressure patients with giant cell tumors of soft tissue
erosion and sclerosis of the left posterior fifth that demonstrated a spectrum from benign to
rib, suggestive of a slowly growing mass. The malignant behavior determined by the cytolog-
mass contained areas of low density suggest-
ing necrosis. It was unclear on the CT scan if
the mass was arising from the rib, pleura, or D
soft tissue. One week later, the patient had a
bronchoscopy, which was negative for malig-
nant cells. A PET-CT scan showed patchy
hypermetabolic uptake within the mass con-
sistent with malignancy without evidence of
metastatic disease. A CT-guided core biopsy of
the mass was performed, which revealed a
giant cell tumor.
A left lateral thoracotomy was performed
with gross resection of the tumor via a left Figure 2. Non-contrast axial computed
lower lobectomy and partial left chest wall tomography scan showing A: soft tissue,
and B: lung windows; C: coronal, and D:
resection. Gross examination revealed a 13 cm sagittal reformations. There is a large het-
mass within the extra-pleural left chest wall erogeneous left posterior mediastinal mass
with compression of the adjacent lung and ribs with sharp lateral margins causing com-
(Figure 3). Fragments of the fourth, fifth, pressive atelectasis of the left lower lobe.
sixth, and eighth ribs showed no evidence of Figure 1. Frontal chest radiograph demon- There is pressure erosion of the adjacent
strating a large left mediastinal mass. posterior rib (A: arrow).
tumor. Microscopic examination demonstrated

Case Report
ical appearance of the mononuclear cells and

mitotic activity.5 References
Giant cell tumors of soft tissue can be seen
at any age, but usually affect middle-aged 1. Salm R, Sissons HA. Giant-cell tumors of
adults of both sexes. These tumors can occur soft tissues. J Pathol 1972;107;27-39.
in both the superficial and deep soft tissues. 2. Oliveira AM, Dei Tos AP, Fletcher CDM, et
The majority of these tumors reported in the al. Primary giant cell tumor of soft tissues.
literature have been located in the lower Am J Surg Pathol 2000;24:248-56.
extremity, particularly in the thigh.2,3 Other 3. Guccion JG, Enzinger FM. Malignant giant
sites of involvement include the upper extrem- cell tumor of soft parts. An analysis of 32
ities, trunk, and rarely the skin.6 The most cases. Cancer 1972;29:1518-29.
common clinical presentation is a painless soft 4. Fu K, Moran CA, Suster S. Primary medi-
Figure 3. Gross specimen of the giant cell tissue mass.5 astinal giant cell tumors: A clinicopatho-
tumor of soft tissue. In a series of 22 patients with giant cell logic and immunohistochemical study of
tumor of soft tissue, Oliveira et al.2 described two cases. Ann Diagn Pathol 2002;6:100-5.
the recurrence rate to be 6.2%, which was less 5. O’Connell JX, Wehrli BM, Nielsen GP, et al.
than the 25% reported recurrence rate of giant Giant cell tumors of soft tissue: A clinico-
cell tumors of bone.1 However, the metastatic pathologic study of 18 benign and malig-
and death rates were determined to be higher nant tumors. Am J Surg Pathol 2000;
in giant cell tumors of soft tissue.1 24:386-95.
Immunohistochemically, the giant cell tumor 6. Holst VA, Elenitsas R. Primary giant cell
of soft tissue in this case report expressed tumor of soft tissue. J Cutan Pathol 2001;
CD68 and CD34. Conversely, the giant cell 28:492-5.
tumors of soft tissue reported in the literature
expressed only CD68.
This case report illustrates a primary giant
cell tumor of soft tissue located within the pos-
terior mediastinum. The only other report of a
Figure 4. Low-power microscopic examina- primary mediastinal giant cell tumor of soft
tion demonstrating the tumor, tumor cap- tissue in the English literature was published
sule, and uninvolved lung. by Fu et al. in 2002, in which they described
two patients with posterior mediastinal mass-
es.4 Our case is very similar to those described
by Fu et al., as the cells all had low mitotic
activity and the patients had a favorable clini-
cal course without metastases or recurrence of
the tumor.
In conclusion, giant cell tumors of soft tis-
sue are rare tumors that demonstrate a spec-
trum of benign to malignant potential.
Although the majority of these tumors are
located in the lower extremity, they may occur
rarely in the posterior mediastinum and pres-
ent as a posterior mediastinal mass.
Figure 5. Microscopic examination at 600X

magnification demonstrating the mass to
be composed of a mixture of round and
oval mononuclear and multinucleated
osteoclast-like giant cells.

Benign multicystic lar menses, use of oral contraceptive pills for 5

years, and normal pap smears in her lifetime. Correspondence: Eve M. Bernstein, Department
mesothelioma: The patient had three normal spontaneous of Obstetrics and Gynecology, Yale University,
a case report vaginal deliveries. Her medical history was sig- New Haven, CT, USA
E-mail: eve.bernstein@yale.edu
of three sisters nificant for hypothyroidism, which was well
controlled on levo-thyroxine. Her past surger-
ies included a benign breast biopsy, wisdom Key words: gynecology, oncology, tumors, benign
Eve M. Bernstein,1 Alison Tate,1 multicystic mesothelioma, peritoneal mesothe-
Dan Arin Silasi,2 Thomas Rutherford2 teeth extraction, and removal of her tonsils
lioma, genetic or familial association, peritoneal
1
and adenoids. Her family history was signifi- inclusion cyst, multilocular inclusion cyst.
Department of Obstetrics and cant for a maternal grandfather who died of
Gynecology, Yale University, New Haven, breast cancer in his 80’s and an aunt with Received for publication: 8 July 2009.
Connecticut; 2Division of Gynecologic colon cancer. Revision received: 1 October 2009.
Oncology, Department of Obstetrics and On physical exam the patient was a thin, Accepted for publication: 5 October 2009.
Gynecology, Yale University, New Haven, healthy-appearing woman. She was normoten-
CT, USA This work is licensed under a Creative Commons
sive, with a blood pressure of 144/78 mmHg,
and a body mass index of 22.8 kg/m2. Her
abdomen was soft with no masses appreciated. ©Copyright E.M. Bernstein et al., 2009
Her pelvic exam was notable for a 7 cm irregu- Rare Tumors 2009; 1:e46
Introduction lar mass in the cul-de-sac, which was non-ten- doi:10.4081/rt.2009.e46
der and immobile.
Benign multicystic mesothelioma (BMCM) A transvaginal ultrasound was performed
is a rare tumor of the abdomen-peritoneum of that revealed bilateral ovarian masses. For fur-
unknown etiology.1 This benign tumor was ini- ther evaluation, an MRI was obtained, which
tially described by Plaut in 1928 when he revealed a multilobulated cystic structure with Case #2
observed loose cysts in the pelvis during a sur- septations present in the cul-de-sac. CA-125
gery for a uterine leiomyoma.2 The mesothelial level was normal (12 U/mL). M.S., the younger sister of K.S., was 35-
origin was later confirmed by electron micro- The patient underwent a total abdominal hys- years old when a pelvic mass was discovered
scopy by Mennemeyer and Smith in 1979.3 To terectomy, bilateral salpingo-oophorectomy, and on routine gynecologic exam. She is a G3P3003
date, there are approximately 140 cases of tumor debulking to no visible residual disease. with normal spontaneous vaginal deliveries
BMCM reported in the literature.4 This disease Intra-operative findings included a 14–week and a surgical history significant only for wis-
primarily occurs in pre-menopausal women sized uterus with a globular contour and numer- dom teeth removal. She is a non-smoker, takes
and is associated with a history of pelvic ous cystic, mucoid lesions on the uterine no medications, and is allergic to trimetho-
inflammatory disease, prior abdominal sur- serosa. The right ovary had mucinous, grape- prim-sulfamethoxazole.
gery, and endometriosis.4,5 The pathogenesis of like cystic structures attached. The pelvic peri- After the incidental finding of a pelvic mass,
this disease remains controversial, with possi- toneum had mucin-like cystic masses scattered she underwent a CT scan of the abdomen and
ble etiologies including a neoplastic versus a along the pelvic sidewalls as well as in the cul- pelvis that confirmed a pelvic mass measuring
reactive process.5 de-sac. Numerous similar cystic lesions were 8.6x5.3x4.9 cm. It was located posterior to the
In the literature, a few case reports discuss present on the omentum at the level of the uterus, extending to the cul-de-sac, and
a possible genetic or familial association with hepatic flexure, along the right lateral margin of described as multicystic-appearing in nature;
BMCM.6 Specifically, one report describes a the infracolic omentum and on the mesentery of no free fluid or ascites were noted. The patient
man with familial Mediterranean fever who the terminal ileum. The fallopian tubes and the complained of occasional left lower quadrant
developed BMCM. Although familial Mediter- left ovary appeared to be within normal limits. discomfort. Serum tumor markers were within
ranean fever is associated with malignant Intra-operative examination revealed bilat- normal limits.
mesothelioma, he had only BMCM, and did not eral ovaries and fallopian tubes to have multi- She underwent a supracervical abdominal
suffer from malignant mesothelioma.6 A genet- ple cystic structures on their serosal surfaces. hysterectomy with bilateral salpingo-oophorec-
ic evaluation and chromosomal analysis were The cysts ranged in size from 2 mm to 4.5 cm, tomy and lysis of adhesions. Intraoperatively,
not able to identify a specific genetic cause of and were clear-walled structures containing multiple cystic grape-like structures along the
the family’s pattern of disease. thin, clear fluid. The cyst walls contained no pelvic sidewall, cul-de-sac peritoneum, and
This case report describes two female sib- papillary projections and were smooth. Many of bladder were described. Intra-operative frozen
lings diagnosed with BMCM. In addition, a the pelvic sidewall cystic masses that were section returned with findings of a benign
third sister also had findings consistent with resected were macroscopically tan-red in multicystic mesothelioma.
BMCM, however, the discrete histological diag- appearance with irregular membranous tissue. The masses were tan-pink in color, polycys-
nosis was never confirmed. The largest of these cystic masses measured tic, and semi-translucent on macroscopic
9.0x5.0x0.2 cm. On microscopic evaluation, inspection. There were multiple varied sizes of
these cysts were lined with benign appearing translucent “grape-like” cysts present along
mesothelial cells that were flat to cuboidal. the ovaries and fallopian tubes bilaterally.
Case #1 They stained positive for calretinin immunos- Microscopic evaluation revealed the cystic
tain further supporting the diagnosis of benign structures to be of varying size, and lined with
K.S. is a 53-year-old G3P3003 menstruating multicystic mesothelioma. flat or low cuboidal mesothelial cells contain-
female who presented to her gynecologist with The final diagnosis was benign multicystic ing serous fluid. Multicystic nodules contained
a complaint of intermittent urinary urgency. mesothelioma, endometriosis, and focal endo- marked congested fibrovascular tissue, some
She denied symptoms of bloating, fullness, and salpingiosis. The patient had an uneventful with inflammatory cells with varying degrees
constipation. Her gynecological history was recovery and has had no recurrences one year of severity. Several of the nodules contained
significant for menarche at age 13 with regu- after surgery. adenomatoid tumors.

Case Report
After her surgery, the patient was started on difficult as there are no reliable clinical find- recurrence is common, several investigators
continuous estrogen replacement therapy due ings, features on imaging, or tumor markers have proposed alternative and more conserva-
to her desire to prevent estrogen withdrawal that are pathogonomic for this tumor.12 tive treatments with hormonal therapy.
symptoms. She was then followed closely with Ultrasound and CT scan reveal cystic masses Hormonal regulation of BMCM has been
ultrasounds and CT scans of the abdomen and that cannot be differentiated from other pelvic suggested by several authors who point to the
pelvis. Two years after her surgery, the BMCM pathology. characteristically pre-menopausal state of
recurred with multiple cysts throughout her Differential diagnosis includes both benign patients with this disease.16-18 Additionally, this
pelvis, which has been managed conservative- and malignant abdominal lesions including disease rarely occurs in post-menopausal
ly without further surgery. The patient remains cystic lymphangioma, endosalpingiosis, ade- women or after bilateral salpingoophorectomy.
asymptomatic, and her lesions remain stable. nomatoid tumors, mesonephric duct remnants, At present, scant literature exists regarding
malignant mesothelioma, sarcoma, and non- estrogen receptor (ER) or progesterone recep-
Hodgkin’s lymphoma.8,11 Clinically, the differ- tor (PR) expression in BMCM. A case series by
ential diagnosis of BMCM from other ovarian Sawh et al.16 found that some BMCM tumors
Case #3 tumors is important, since BMCM can be treat- stain positive for either estrogen or proges-
ed with ovarian preservation techniques.11 terone receptors, or both. They identified 17
The two sisters presented above have a third The pathogenesis of BMCM remains contro- cases of BMCM at their institution spanning
sister, who, at age 46, presented to her gyne- versial. Some believe it is a reactive process over a 20 year period with sufficient clinical
cologist with a persistent left ovarian cyst. She while others believe it is a neoplastic process. and pathological tissue for evaluation.
underwent a laparoscopic bilateral salpingec- There is an association between prior surger- Immunohistochemical staining for ER and PR
tomy. Intraoperatively, multiple small “blister- ies, endometriosis, pelvic inflammatory dis- were performed on all samples and among
like” excrescences in the cul-de-sac and on the ease, intra-peritoneal inflammation and these three were identified with ER and or PR
surface of the right ovary were noted. The peri- BMCM, which suggests a possible reactive expression. One case revealed the mesothelial
toneal surfaces and omentum were found to process. The hypothesis behind the reactive lining to be diffusely positive for ER only. A sec-
have multiple “blister-like” excrescences. In process pathogenesis says that chronic peri- ond case was focally positive for PR and a third
addition, the distal right fallopian tube con- toneal irritation may react with mesothelial case revealed the mesothelial lining to be focal-
tained a “simple” cystic structure and the dis- cell entrapment, and cause reactive prolifera- ly positive for both ER and PR. These authors
tal left fallopian tube had a multiloculated cys- tion and cyst formation.5,11 On the other hand, speculate that the finding of hormone receptor
tic structure. Intra-operative frozen section others believe that a neoplastic process is the expression in only 3 of their 17 patients may be
described these specimens to be benign in cause, with a slow progressive nature and the result of metaplastic changes in the cells
nature. The final pathology returned with marked tendency to recur after multiple surgi- lining the cyst walls. Alternatively, immunohis-
benign mesothelial and serous cysts, hydros- cal resections.5 tochemical studies may not be sensitive
alpinges, and Walthard cysts. No further stain- The tumor is usually found on the surfaces enough to detect clinically relevant levels of
ing was performed to suggest or exclude the of the pelvic viscera, especially on the peri- hormone receptor expression.
diagnosis of BMCM. This sister remains toneum of the cul-de-sac, rectum, and bladder.8 Experimental treatment with anti-estrogen
asymptomatic and has had no further surger- Macroscopically, BMCM appears as solitary or therapy (e.g., tamoxifen), GnRH agonists (e.g.,
ies. multi-septated, translucent, grape-like cysts leuprolide acetate), and intraperitoneal
with thin walls that are separated by fibrous chemotherapy have been attempted with vary-
tissue.6,8 Cyst size can vary from 1-2 mm to ing degrees of success.11 Letterie et al.17,18
greater than 30 cm, and are usually multilocu- reported on two women with BMCM who
Discussion lar.6,8 The cysts are either empty or filled with declined surgical management in favor of med-
serous, bloody or mucinous fluid. At the time of ical management. The first case report
Benign multicystic mesothelioma is a rare diagnosis, the mean cyst diameter is 13 cm.7 In describes a 17-year old woman who recurred
lesion that most commonly arises from the women it usually arises along the peritoneal twice after surgical intervention and was treat-
surfaces of the pelvic peritoneum. It has had surfaces of the uterus and rectum. In men it ed medically. She was started on a GnRH ago-
several different names used in the literature arises along the peritoneal surfaces of the nist (leuprolide), which initially caused an
due to an ongoing debate regarding its origin. bladder and rectum.7 increase in the size of her pelvic mass as
Alternate nomenclature for this disease Microscopic examination reveals cysts lined measured on ultrasound. After one month of
includes: peritoneal inclusion cyst, multilocu- by a single layer of flattened or cuboidal treatment a decrease in the pelvic mass size
lar inclusion cyst, and multicystic mesothe- mesothelial cells without atypia or mitosis.6,8,10 was observed. After 6 months of treatment she
lioma.7 It most commonly occurs in pre- Focal reactive mesothelial changes such as began supplemental estrogen and proges-
menopausal women with a mean age of onset hobnail-shaped cells and foci of mesothelial terone to counteract the side effects of the
of 37 years.8 It has been described in post- hyperplasia can be present.7 With immunohis- GnRH agonist. Within 4 weeks an increase in
menopausal women, and 16-17% of cases have tochemical analysis, these cells stain positive mass size was appreciated and the patient
been reported in men with a mean age of onset for calretinin and cytokeratins, a reflection of once again became symptomatic. No immuno-
of 47 years.7,9 There is no association with their mesothelial origin.7 histochemical staining for estrogen or proges-
asbestos exposure.8,10 Treatment of BMCM primarily involves sur- terone receptors were performed on the surgi-
Most patients are diagnosed incidentally gery, as complete resection has been shown to cal specimens from her initial surgeries.
either on physical exam or as a finding on be the only effective treatment.6 Some authors A second case described by Letterie et al.18
imaging, or during laparotomy for other indi- have used more aggressive methods with some describes a pre-menopausal woman who was
cations.11 A small number of patients present success such as laparoscopic laser ablation treated with tamoxifen. Within 4 weeks she
with abdominal pain, distention, ascites, dys- with potassium titanyl phosphate,13 sclerosing reported a significant reduction in pelvic pain.
functional uterine bleeding, referred shoulder therapy with tetracycline, hyperthermic peri- Imaging with ultrasound confirmed a decrease
pain, dysuria, or dyspareunia.9,11 Rarely, BMCM toneal infusion with cisplatin, and peritonecto- in pelvic mass size. However, no tissue was
presents as an acute abdomen.8 Diagnosis is my with intraperitoneal chemotherapy.14,15 As obtained for histopathologic evaluation.

Case Report
True prognosis of BMCM is unclear. The dis- In conclusion, BMCM is a rare disease with 9. Bansal A, Zakhour HD. Benign mesothe-
ease has a high recurrence rate of up to 50%.19 an uncertain prognosis. It has a high recur- lioma of the appendix: an incidental find-
Time to recurrence varies from a few months rence rate with a high likelihood for multiple ing in a case of sigmoid diverticular dis-
to years, with an average of 32 months.10 In medical and surgical treatments over a life- ease. J Clin Pathol 2006;59:108-10.
addition, size of lesions, site of disease, extent time. The purported benign nature of this dis- 10. Saad S, Brockmann M, Maegele M. Benign
of disease burden and previous recurrence ease also remains in question. Therefore, a peritoneal multicystic mesothelioma diag-
have not been found to be helpful in predicting high level of suspicion with a lifetime of close nosied and treated by laparoscopic sur-
future recurrences.16 It is recommended that follow-up are required for these patients. At gery. J Laparoendosc Adv Surg Tech A.
patients be followed throughout their lifetime present, our case report is one of few illustrat- 2007;17:649-52.
for recurrences. ing a possible genetic association with BMCM. 11. Safioleas MC, Constantinos K, Michael S,
Additionally, due to high recurrence rates,
et al. Benign multicystic peritoneal
some authors regard BMCM as a borderline
mesothelioma: a case report and review of
tumor, possibly between the realm of an adeno-
References the literature. World J Gastroenterol 2006;
matoid tumor and malignant mesothelioma.6
12: 5739-42.
There are only two case reports to date in the
current literature that describe the malignant 12. Varma R, Wallace R. Multicystic benign
1. Curgunlu A, Karter Y, Tufekci IB, et al.
transformation of BMCM to malignant meso- mesothelioma of the peritoneum present-
Benign cystic mesothelioma: a rare cause
thelioma.5 One of these cases presented as of ascites in a case with familial Medit- ing as postmenopausal bleeding and a soli-
both benign and malignant disease simultane- erranean fever. Clin Exp Rheu 2003;21 tary pelvic cyst – a case report. Gynecol
ously, which makes it impossible to ascertain (suppl.30):S41-S3. Oncol 2004;92:334-6.
which came first. The second case, however, 2. Plaut A. Multiple peritoneal cysts and their 13. Rosen DM, Sutton CJ. Use of the potassi-
reports of a young woman who was being fol- histogenesis. Arch Pathol 1928;754-6. um titanyl phosphate (KTP) laser in the
lowed for benign disease, and after 10 years of 3. Mennemeyer R, Smith M. Multicystic, treatment of benign multicystic peritoneal
conservative management with biopsy-proven peritoneal mesothelioma: a case report mesothelioma. Br J Obstet Gynaecol 1999;
benign disease, malignant transformation with electron microscopy of a case mim- 106:505-6.
occurred.5 icking intra-abdominal cystic hygroma 14. Sethna K, Mohamed F, Marchettini P, et al.
A familial or genetic association with BMCM (lymphangioma). Cancer 1979;44:692-8. Peritoneal cystic mesothelioma: a case
has been rarely reported in the literature.6 As 4. Usha Kiran TS, Agboola A, Davies R, Stout series. Tumori 2003;89:31-5.
stated in the introduction, there are a few case TV. Benign cystic mesothelioma: a diag- 15. Cuartas JE, Maheshwari AV, Qadir R, et al.
reports describing the already well-known nostic dilemma. Aust N Z J Obstet Benign multicystic peritoneal mesothe-
association between malignant mesothelioma Gynaecol 2002;42:552-4. lioma in a cesarean-section scar present-
and familial Mediterranean fever. However, 5. Gonzalez-Moreno S, Yan H, Alcorn KW, ing as a fungating mass. Int J Clin Oncol
there is another case report of a patient with Sugarbaker PH. Malignant transformation 2008;13:275-8.
familial Mediterranean fever who subsequent- of “benign” cystic mesothelioma of the 16. Sawh RN, Malpica A, Deavers MT, et al.
ly developed BMCM.1 A different case report peritoneum. J Surg Oncol 2002;79:243-51. Benign cystic mesothelioma of the peri-
discusses two sisters both with a history of 6. Tangjitgamol S, Erlichman J, Northrup H, toneum: a clinicopathologic study of 17
diverticulosis and cataracts who later devel- et al. Benign multicystic peritoneal
cases and immunohistochemical analysis
oped BMCM. In addition to diverticulosis and mesothelioma: cases reports in the family
of estrogen and progesterone receptor sta-
early onset cataracts with retinal detachments, with diverticulosis and literature review.
tus. Hum Pathol 2003;34:369-74.
their family history was also significant for Int J Gynecol Cancer 2005;15:1101-7.
ovarian cancer, colon cancer, and congenital 7. Levy AD, Arnaiz J, Shaw JC, Sobin LH. 17. Letterie GS, Yon JL. Use of a long-acting
defects including renal agenesis, diaphragmat- From the archives of the AFIP: primary GnRH agonist for benign cystic mesothe-
ic hernia, and anencephaly. peritoneal tumors: imaging features with lioma. Obstet Gynecol 1995;85:901-3.
In our case report of three sisters, there are pathological correlation. Radiographics 18. Letterie GS, Yon JL. The antiestrogen
no obvious or grossly unusual familial diseases 2008;28:583-607. tamoxifen in the treatment of recurrent
or anomalies in their family history. 8. Van Ruth S, Bronkhorst MW, Van Coevor benign cystic mesothelioma. Gynecol
Additionally, none of the sisters reported histo- den F, Zoermulder FA. Peritoneal benign Oncol 1998;70:131-3.
ries of the risk factors often associated with cystic mesothelioma: a case report and 19. Soreide JA, Soreide K, Korner H, et al.
BMCM such as prior surgery, pelvic inflamma- review of the literature. Eur J Surg Oncol Benign peritoneal cystic mesothelioma.
tory disease or endometriosis. 2002;28:192-5. World J Surg 2006;30:560-6.

Congenital infantile digital of IDF, the tendency to spontaneous regression,

and the frequent recurrences after surgery.6,8 Correspondence: Arjen F. Nikkels, Department of
fibromatosis: a case report Dermatology, CHU of Sart Tilman, University of
and review of the literature Liège, B-4000 Liège, Belgium.
Case Report E-mail: af.nikkels@chu.ulg.ac.be
Valérie Failla,1 Odile Wauters,1
Key words: fibromatosis, imiquimod, surgery,
Nazli Nikkels-Tassoudji,1 Alain Carlier,2 A six-month-old Caucasian girl presented
childhood.
Josette André,3 Arjen F. Nikkels1 after birth with three reddish, confluent, small,
Departments of 1Dermatology and painless, indurated, ill-circumscribed nodules Contributions: all authors provided substantial
2 on the fourth digit of the left hand, which pro- contributions to the conception and design,
Surgery, University Hospital of Liège,
gressively increased in size (Figure 1). acquisition or analysis and interpretation of data,
Liège; 3Deparment of Dermatology, CHU
Previous medical history was unremarkable drafting of the article or revising it critically for
Brugman, Brussels, Belgium and there was no history of trauma or inflam- intellectual content. All authors provided final
mation. No allergic history was reported. The approval of the manuscript.
other hand and both feet were unremarkable.
None of the family members had experienced Conflict of interest: the authors report no con-
Abstract similar lesions. There was no functional flicts of interest.
impairment and the size of the lesion did not
Infantile digital fibromatosis (IDF) is a rare Received for publication: 21 August 2009.
appear to bother the child in daily life. No signs
benign fibroproliferative tumor of early child- Revision received: 20 October 2009.
of scratching were present. Further clinical Accepted for publication: 21 October 2009.
hood. IDF preferentially affects the fingers and examination was normal and Rontgen exami-
the toes. Malignant transformation or metas- nation revealed the cutaneous and subcuta- This work is licensed under a Creative Commons
tases have never been reported. Surgical treat- neous location of the lesion without further Attribution 3.0 License (by-nc 3.0).
ment has been advocated previously but local bone or joint involvement. Six months later a
recurrences were observed frequently. Recent ©Copyright V. Failla et al., 2009
second examination showed no differences
literature supports clinical surveillance with- Licensee PAGEPress, Italy
and the developmental stage of the child was Rare Tumors 2009; 1:e47
out any medical or surgical intervention as normal according to age. doi:10.4081/rt.2009.e47
spontaneous regression usually occurs after A 3-mm punch biopsy was performed under
two to three years. A six-month-old Caucasian local anesthesia, and the histopathology
girl with IDF on the left fourth digit is present- revealed a fibromatosis affecting the reticular
ed here. The tumor progressively increased in and adventitial dermis, arranged as sheets and
size after birth. Topical imiquimod cream and interlacing bundles of eosinophilic myofibrob-
diflucortolone valerate cream, both displaying lasts set in a collagenous background. Some
antifibrotic properties, had no effect on tumor cells demonstrated eosinophilic cytoplasmic
growth. Currently the lesion size remains sta- inclusions (Figure 2). No mitotic figures and
ble without any treatment. Early recognition of no atypical cells were observed. The overlying
IDF is important in order to avoid unnecessary epidermis was unremarkable. A final diagnosis
surgical intervention that may prove to be of congenital IDF was suggested.
potentially aggravating, unless serious func- As the data in the current literature recom-
tional or cosmetic concerns intervene. Parents mend avoiding surgical intervention, non-
should be reassured concerning the benign invasive treatments exhibiting anti-fibrotic
nature of IDF and be informed that sponta- properties were sought. A topical treatment
neous involution of IDF might be expected. with imiquimod cream (Aldara cream), applied
Figure 1. Infantile digital fibromatosis
three times a week during four weeks, failed to affecting the fourth digit.
reduce the tumor size and was associated with
significant skin irritation, forcing the inter-
Introduction ruption of the treatment. Subsequently topical
applications of diflucortolone valerate signifi-
Infantile digital fibromatosis (IDF) is a rare cantly reduced the inflammation although no
benign tumor of fibromatous origin. IDF pref- effect on the lesion size was observed. Eight
erentially occurs during early childhood and is months later the tumor size remained identi-
present at birth in about 30% of the cases.1 cal. As no functional concerns were revealed,
Predilection sites include the distal phalanx of conservative management is being followed.
the fingers and the toes. Initially IDF was con-
sidered as a potentially malignant tumor, lead-
ing to the amputation of the affected digits.1-3
More recently several case reports of sponta- Discussion
neous regression suggest a benign biological
behavior.3-5 Malignant transformation and IDF is a rare tumor usually affecting one or
metastases have never been reported.1-6 more digits.1 Numerous synonyms describe Figure 2. High-power histological presen-
Histopathology often reveals paranuclear IDF, including Reye’s tumor,9 multiple hyaline tation of the characteristic perinuclear
inclusion bodies within proliferating spindle- fibromatosis, infantile dermal fibromatosis, cytoplasmic cellular inclusions found in
form cells.7 Currently conservative treatment is subdermal fibromatosis tumor of infancy, infantile digital fibromatosis.
(Hematoxylin and eosin stain).
recommended according to the benign nature fibroma durum multiplex, recurrent digital

Case Report
fibroma, and juvenile dermatofibroma. IDF typ- The differential diagnosis of IDF includes hood: case report with long-term follow-up
ically develops during the first year of life and keloids, hypertrophic scar tissue, terminal and review of the literature. J Pediatr
the majority of cases are sporadic. Congenital osseous dysplasia and pigmentary defects, and Orthop 1986;6:612-7.
onset, although rare, is described also,7,10 as juvenile aponeurotic fibroma.6 The diagnosis 3. Azam SH, Nicholas JL. Recurring infantile
observed in our patient. Occurrence of IDF in is clinical essentially but histological confir- digital fibromatosis: report of two cases. J
adulthood has been reported only once in a 52- mation confirms the diagnosis and prognosis. Pediatr Surg 1995;30:89-90.
year-old woman with a tumor on the dorsum of The current management of IDF recommends 4. Ishii N, Matsui K, Ichiyama S, et al. A case
the proximal nail fold of the right second toe.11 avoiding surgical intervention, as spontaneous of infantile digital fibromatosis showing
Clinically IDF presents as smooth, round, involution of IDF is the rule.6 In fact, wide local
spontaneous regression. Br J Dermatol
indurate, confluent nodules up to 2 cm in surgical excision has been associated with a
1989;121:129-33.
diameter. The lesions are single or multiple.7,8 recurrence rate of up to 60%.1-3 If required by
5. Kawaguchi M, Mitsuhashi Y, Hozumi Y, et
The color is pink to reddish. Initially IDF functional impairment, Mohs micrographic
surgery is recommended.11 An patient with IDF al. A case of infantile digital fibromatosis
exhibits an indolent progression followed by a
rapid growth phase during several months. was treated effectively by Mohs surgery with- with spontaneous regression. J Dermatol
Subsequently the tumor size remains stable out any residual functional impairment or 1998;25:523-6.
until spontaneous regression without scarring recurrence of the tumor.15 However even Mohs 6. Niamba P, Léauté-Labrèze C, Boralevi F, et
occurs.8 IDF is painless and not pruritic. It is surgery is regularly associated with recur- al. Further documentation of spontaneous
localized usually on the lateral and dorsal rences.12 Consequently surgical treatment regression of infantile digital fibromato-
aspects of the fingers and/or toes sparing the should be avoided unless severe dysfunction is sis. Pediatr Dermatol 2007;24:280-4.
thumb and the great toe. Ulceration may occur. observed. Several medical approaches have 7. Kanwar AJ, Kaur S, Thami GP, et al.
Functional impairments or deformities are been evaluated. A 7-year-old boy was treated Congenital infantile digital fibromatosis.
rare. successfully with five monthly injections of flu- Pediatr Dermatol 2002;19:370-1.
Histopathology reveals a proliferation of orouracil.16 Topical imiquimod, an imidazo- 8. Heymann WR. Infantile digital fibromato-
myofibroblasts often displaying characteristic quinoline amine, acts as a toll-like receptor sis. J Am Acad Dermatol 2008;59:122-3.
paranuclear eosinophilic inclusion bodies.1 (TLR) 7 and 8 agonist and stimulates the 9. Reye RD. Recurring digital fibrous tumors
They are juxtanuclear typically and sometimes innate and cell-mediated immune system of childhood. Arch Pathol 1965;80:228-31.
indent the nucleus.6,7 Mitotic figures are rare. through induction of interferon-α (IFN-α), 10. Kang SK, Chang SE, Choi JH, et al. A case
Usually the tumor cells immunohistochemical- IFN-γ, and interleukin-1, 6, 8, and 12 produc-
of congenital infantile digital fibromato-
ly express vimentin, calponin, desmin, and α- tion. Beside the antiviral and antitumor prop-
sis. Pediatr Dermatol 2002;19:462-3.
smooth muscle actin, whereas results for ker- erties, imiquimod also inhibits human fibro-
11. Plusjé LG, Bastiaens M, Chang A, et al.
atin and muscle actin are negative.1 The posi- blast collagen production by INF-α and INF-γ.17
Infantile-type digital fibromatosis tumour
tive actin staining suggests the presence of Topical and intralesional corticosteroids also
display anti-fibrotic properties, and are used in an adult. Br J Dermatol 2000;143:1107-
contractile filaments. Masson trichrome histo-
chemical staining reveals a red staining and a for treating keloids and hypertrophic scars.17 8.
purple coloration with phosphotungstic acid- Despite these anti-fibrotic properties, our case 12. Hinz B. Formation and function of the
hematoxylin. failed to respond to topical imiquimod therapy myofibroblast during tissue repair. J Invest
The etiology of IDF remains uncertain but and was associated with significant adverse Dermatol 2007;127:526-37.
the following hypothesis is proposed currently. events. Topical corticosteroid applications 13. Zhu WY, Xia MY, Huang YF, et al. Infantile
The differentiation from fibroblasts to myofi- reduced only the inflammatory aspect of IDF digital fibromatosis: ultrastructural
broblasts is a cornerstone process in wound without reducing the lesion size. human papillomavirus and herpes simplex
healing and tissue repair. Myofibroblasts may In conclusion, IDF is a rare benign child- virus DNA observation. Pediatr Dermatol
create high contractile forces that are benefi- hood tumor, which is important to recognize to 1991;8:137-9.
cial for physiological tissue remodeling but avoid unnecessary surgery unless serious 14. Albertini JG, Welsch MJ, Conger LA, et al.
harmful for tissue function, especially when it functional concerns intervene. Parents should Infantile digital fibroma treated with Mohs
becomes excessive such as in hypertrophic be informed of the benign nature of IDF. This micrographic surgery. Dermatol Surg
scars, in nearly all fibrotic diseases, and during represents a strong argument for a conserva- 2002;28:959-61.
stroma reactions to tumors.12 The intracellular tive approach until spontaneous involution 15. Campbell LB, Petrick MG. Mohs micro-
inclusions suggest a viral origin. However, this occurs.
graphic surgery for a problematic infantile
etiopathogenic hypothesis was invalidated as digital fibroma. Dermatol Surg 2007;33:
human papillomavirus HPV DNA types 6, 11,
385-7.
16, and 18, and herpes simplex virus DNA type
References 16. Oh CK, Son HS, Kwon YW, et al. Intra-
I and II could not be demonstrated in IDF.13 IDF
lesional fluorouracil injection in infantile
may be associated with articular alterations
and dysfunction.6,8,14 The etiopathogenesis of 1. Laskin WB, Miettinen M, Fetsch JF. digital fibromatosis. Arch Dermatol
IDF joint deformities is not clear. Given the Infantile digital fibroma/ fibromatosis: a 2005;141:549-50.
presence of contractile proteins within the clinicopathologic and immunohistochemi- 17. Berman B, Harrison-Balestra C, Perez OA,
pathological cells, as suggested by histochemical study of 69 tumors from 57 patients et al. Treatment of keloid scars post-shave
cal, immunohistochemical, and ultrastructural with long-term follow-up. Am J Surg Pathol excision with imiquimod 5% cream: A
studies, they may intervene in the progressive 2009;33:1-13. prospective, double-blind, placebo-con-
contracture, especially when the tumor occurs 2. Dabney KW, MacEwen GD, Davis NE. trolled pilot study. J Drugs Dermatol 2009;
adjacent to a joint.8 Recurring digital fibrous tumor of child- 8:455-8.

Giant mesenteric cystic retroperitoneum, which was suspected to be of

ovarian origin. Magnetic resonance imaging Correspondence: John Maa, 521 Parnassus
lymphangioma presenting (MRI) again demonstrated a multicystic lesion Avenue, San Francisco, CA 94131-0790, USA.
with abdominal pain and that appeared intense on a T2-weighted image E-mail: maaj@surgery.ucsf.edu
masquerading as a (Figure 1). The mass extended superiorly to
Key words: cystic lymphangioma, mesenteric
the base of the mesentery, abutting the superi-
gynecologic malignancy or mesenteric vessels and occupying the entire lymphangioma, retroperitoneal lymphangioma.
pelvis inferiorly. Although the ovaries and
John Maa,1 Christianne Wa,2 Acknowledgments: the authors thank Pamela
uterus appeared to be distinct from this mass, Derish, UCSF Department of Surgery, for editori-
Adnan Jaigirdir,1 Soo-Jin Cho,3 a gyneocologic etiology could not be excluded. al assistance and Dr. Annemieke van Zante,
Carlos U. Corvera1 Given the concerns of either a gynecologic UCSF Department of Anatomic Pathology, for
malignancy, pseudomyxoma peritonei, or a review of the pathologic findings.
1
Department of Surgery, University of peritoneal mesothelioma, a curative resection
California; 2University of Southern was planned. During the operation, a multicys- Contributions: JM, AJ, and CC were involved in the
California; 3Department of Anatomic tic mass that appeared to engulf the entire sig- design of the study, perioperative care of the patient,
Pathology, University of California, San moid colon was noted. It was well encapsulated and obtaining operative photographs of the tumor.
Francisco, CA, USA and was contained within the leaflets of the CW, JM, and CC drafted and revised the manuscript,
grossly distorted sigmoid mesentery. The tran- and approved the final version. SC was involved in
the pathologic examination of the resected speci-
sition to normal colon mesentery proximally,
men and critical revision of the manuscript.
and mesorectum distally, was clear, sharp, and
Abstract abrupt, suggesting a benign etiology. There Conflict of interest: the authors report no con-
was no evidence of either carcinomatosis or flicts of interest.
Lymphangiomas are congenital malforma- suspicious metastatic tumor deposits. The
tions of the lymphatic system that account for fluctuant mass was exteriorized and resected Received for publication: 15 October 2009.
about 5% of all benign tumors in infants and with a wide mesenteric and colon margin. A Accepted for publication: 21 October 2009.
children.1 The most common sites are the neck primary hand-sewn anastomosis was utilized
and axilla, which account for 95% of cases.2 for bowel reconstruction. After an uneventful
Abdominal cystic lymphangiomas are quite recovery, the patient was discharged on post-
rare, and can arise from either the retroperi- operative day five. ©Copyright J. Maa et al., 2009
toneum, gastrointestinal tract, or the mesen- Gross pathologic evaluation revealed an Rare Tumors 2009; 1:e48
tery of the abdominal viscera.3 The presenting unremarkable segment of colon with an asso- doi:10.4081/rt.2009.e48
symptoms are painless abdominal distension, ciated large cystic mass (Figure 2). Permanent
a palpable mass, or secondary complications in sections revealed a benign cystic lymphan-
the abdomen such as intestinal obstruction, gioma, composed of innumerable thin-walled
volvulus, intestinal infarction, or bleeding.4 channels, the walls of which focally contained
Typically diagnosed during childhood, these aggregates of bland lymphocytes. A few clus-
tumors prompt surgical intervention. We ters of macrophages with moderate amounts of
describe an atypical case of an abdominal cys- eosinophilic cytoplasm were present in the
tic lymphangioma, which did not manifest lumina of the cystic spaces, as is seen com-
until adulthood, with atypical symptoms of a monly in cystic vascular spaces with sluggish
rapidly expanding and symptomatic mass. flow. Immunohistochemical staining for D2-40
(a marker of lymphatic endothelium) showed
positive staining in the attenuated cyst lining
cells, supporting the impression of lymphan-
Case Report gioma (Figure 3). In addition, immunohisto-
chemical staining for calretinin (a mesothelial
A 36-year old gravida 4 para 2 woman came marker) was performed and the cyst lining
to the emergency department with vague cells were negative, arguing against a cystic
abdominal discomfort, abdominal distension, mesothelial proliferation. The left ovary,
and decreased energy. She had noted an although cystic, was uninvolved by the lym-
abdominal mass while on vacation approxi- phangioma.
mately one month before presentation, which
had expanded rapidly over the following 10
days. She was healthy otherwise but had
undergone dilatation and curettage for a molar Discussion
pregnancy three years previously. Though she
had immigrated to the United States, she did Cystic lymphangiomas are rare congenital
not report previous exposure to toxic chemical benign malformations of the lymphatic system
Figure 1. Magnetic resonance image
agents. A palpable fullness in the left lower and account for about 5-6% of all benign demonstrating the mesenteric cystic lym-
quadrant was noted during her physical exam- tumors in infants and children.1 Abdominal phangioma. (A) Axial T2-weighted image.
ination. A CA-125 blood test for ovarian cancer cystic lymphangiomas are more frequent in White arrow points to the sigmoid colon
and serum laboratory studies were normal. A boys than girls (5:2), and approximately 80- engulfed by the tumor mass. (B) Sagittal
computed tomography (CT) scan revealed a 90% are diagnosed within the first few years of view. White arrow points to the engulfed
sigmoid colon.
14.0x5.4x16.2 cm cystic lesion in her pelvis and life. Approximately 50% of cases involve the

Article
painful abdominal symptoms.5 When a cystic lymphangiomas are rare tumors that can pres-
lymphangioma is suspected, either an abdomi- ent in adult life occasionally, and masquerade
nal ultrasound examination, CT scan, or MRI as a malignant gynecologic lesion. Continued
can be used for diagnosis.6 Percutaneous biop- advances in cross-sectional imaging undoubt-
sy is not recommended because the diagnostic edly will help further distinguish benign cystic
value is likely to be low owing to the low cellu- lesions from malignant ones. In the meantime,
larity index of these tumors. Moreover if the we think these cystic tumors should be man-
tumor is demonstrated to be malignant, the aged as malignant until proven otherwise.
risk of needle tract metastasis or peritoneal
dissemination of the fluid is unacceptably
high. In our patient, the preoperative imaging
studies suggested the mass to be technically References
resectable even if malignancy would have been
encountered, thus obviating the need for pre- 1. Méndez-Gallart R, Solar-Boga A, Gómez-
operative tissue biopsy. Although laparoscopic Tellado M, et al. Giant mesenteric cystic
approaches utilizing partial aspiration intraop- lymphangioma in an infant presenting
Figure 2. Gross specimen of resected lym- eratively have been described,7 we selected the
phangioma and adjacent sigmoid colon en with acute bowel obstruction. J Can Chir
bloc. open approach via laparotomy given the large
2009;5:E42-3.
size of the lesion and the concerns of a possi-
2. Jang JH, Lee SL, Ku YM, et al. Small bowel
ble malignancy.
volvulus induced by mesenteric lymphan-
Our patient is unusual because she was
gioma in an adult: a case report. Korean J
diagnosed as an adult and experienced the
Radiol 2009;10:319-22.
rapid onset of abdominal swelling and disten-
3. Prabhakaran K, Patankar JZ, Loh DLSK, et
sion as her presenting symptoms. Given her
al. Cystic lymphangioma of the mesentery
previous history of a molar pregnancy three
causing intestinal obstruction. Singapore
years before, a possible gynecologic origin of
Med J 2007;48:E265-7.
trophoblastic tissue accounting for the mass
was strongly considered. No abnormalities had 4. Wani I. Mesenteric lymphangioma in
been visualized on her previous abdominal adult: A case series with a review of the lit-
sonograms for a subsequent pregnancy. The erature. Dig Dis Sci 2009 Jan 14 [Epub
cause of the rapid expansion of the tumor ahead of print].
remains unknown. No free fluid was found at 5. de Perrot M, Rostan O, Morel P, et al.
Figure 3. Immunohistochemical staining of surgery to suggest perforation. Abdominal lymphangioma in adults and
a representative section of the resected children. Br J Surg 1998;85:395-7.
specimen using the D2-40 antibody (a Surgeons should be aware of this rare enti-
ty. In our case, the low Hounsfield units on CT 6. Weeda VB, Booij KA, Aronson DC.
marker of lymphatic endothelium).
scan raised suspicion of lymphangioma, a Mesenteric cystic lymphangioma: a con-
diagnosis supported by the MRI characteris- genital and an acquired anomaly? Two
tics, particularly on the T2-weighed images.8 cases and a review of the literature. J Ped
However although imaging studies favored a Surg 2008;43:1206-8.
head and neck, with only 10% occurring in benign cystic condition, it was important to 7. Ryu WS, Kwak JM, Seo UH, et al. Laparo-
internal organs.4 These tumors result from an consider that the patient might have a malig- scopic treatment of a huge cystic lymphan-
abnormal embryonic development of the lym- nant mucinous tumor. Accordingly she was gioma: partial aspiration technique with a
phatic system causing sequestration of lym- counseled preoperatively that if malignancy spinal needle. J Laparoendosc Adv Surg
phatic tissue and fluid, as in our patient. was found, an aggressive surgical approach Tech 2008;18:603-5.
Clinical manifestations are variable, with- would be warranted, potentially involving a 8. Su CM, Yu MC, Chen HY, et al. Single-cen-
out characteristic signs and symptoms that can multiorgan resection to achieve gross com- tre result of treatment of retroperitoneal
be attributed solely to the mesenteric lymphan- plete resection or a diverting colostomy. and mesenteric cystic lymphangiomas.
gioma. They may present as nonspecific but In conclusion, cystic abdominal mesenteric Dig Surg 2007;24:181-5.

Malignant peritoneal weeks after draining about 10 liters of ascitic

fluid. Although repeated CT scan showed some Correspondence: Kakil Ibrahim Rasul, CABM,
mesothelioma. resolution of the enlarged lymph nodes, omen- FRCP Edinburgh, ESMO, Senior Consultant
Is there a new treatment? tal and peritoneal nodes, the patient required Physician and Haem/Oncology, Assistant
aspiration of nearly 6-8 liters of ascitic fluid Professor of Clinical Medicine, Weill Cornell
Kakil Ibrahim Rasul,1 David J. Kerr2 with each cycle. With other chemotherapy reg- Medical College/ Qatar, Hamad Medical
imens including gemcitabine + pemetrexed Corporation, Al-Amal Hospital, P.O. Box 3050,
1
Al-Amal Hospital, Hamad Medical Doha, Qatar. E-mail: kakil954@yahoo.com
for 2 cycles and intraperitoneal cisplatin the
Corporation/Doha, Qatar; 2Al-Sidra
patient continued to have re-accumulation of Key words: mesothelioma, oncology, rare tumors.
Research Center Doha, Qatar
the ascitic fluid.
In January 2009 the patient started with Acknowledgement: Dr. Issam Bozm for preparing
combination of gemcitabine 1250 mg/m2 plus the histopathology pictures.
bevacizumab 5 mg/kg every 2 weeks. The
Abstract patient responded clinically with no require- Received for publication: 30 October 2009.
ment of aspiration from the very first cycle of Accepted for publication: 2 November 2009.
The authors report a novel, alternative treatment and received 6 cycles of treatment
approach to treat malignant peritoneal mesothe- This work is licensed under a Creative Commons
providing strong evidence of clinical response Attribution 3.0 License (by-nc 3.0).
lioma (MPeM) targeting, vascular endothelial and improvement in quality of life. Side effects
growth factor (VEGF) using anti-VEGF (beva- like epistaxis were observed which was mild ©Copyright K.I. Rasul et al., 2009
cizumab) chemotherapy combination. and managed by local pressure. Licensee PAGEPress, Italy
MPeM is a cancer of extremely rare occur- Rare Tumors 2009; 1:e49
rence and arises from the mesothelial cells of doi:10.4081/rt.2009.e49
the peritoneum. It accounts for only 10% of all
Case Report mesotheliomas with majority arising from
pleura and the role of asbestos exposure in the
In June 2008, a 60-year-old Jordanian man etiology compared to pleural mesothelioma is
presented with abdominal distension and para not well defined.1,2 The clinical manifestations
umbilical hernia. His medical history was sig- of this disease are usually abdominal pain,
nificant for hypertension, diabetes mellitus and increasing abdominal girth, weight loss and
hyperlipidemia and the patient was receiving abdominal masses with or without ascites.
regular treatment. The patient underwent her- Though it can occur in any age group, the most
nia repair and the hernia sac sent for histo- affected is the 50 to 69 year age group.2,3 The
pathologic examination. Histopathologic find- aggressive nature of the disease is evident
ings showed atypical mesothelial cells with with rapid spread within the confines of the
prominent nucleoli and occasional mieotic fig- abdominal cavity involving most accessible
ures as well as areas of focal necrosis, psammo- peritoneal and omental surfaces and requires
matous calcification and tumor cells showed aggressive treatment. Mortality and morbidity Figure 1. Micro-scopic appearance of the
encroachment on the adipose tissue illustrated are associated with the spread of the disease tumor showing papillary structures on one
by microscopic appearance (resolution 200X) rather than the metastasis and without aggres- side and sheets of mali-gnant tumor on the
other side.
of the tumor showing papillary structures on sive treatment the neoplasm is rapidly fatal.2,4,5
one side and sheets of malignant tumor on the Studies that have reported patients with
other side, as shown in Figure 1. Immuno- peritoneal mesothelioma are few and treat-
peroxidase stain for mesothelioma markers ment of MPeM have largely extrapolated from
was positive for calretinin, AE1, AE3, HBME-1, the treatment of pleural disease.6 Currently, no
cytokeratin 5/6 (CK 5/6), FMA, and negative for standard treatment for this disease has been
Vimentin, CEA, CD15 and Ber-FP4 providing a established and management involves an
conclusive diagnosis of MPeM. intensive loco-regional treatment strategy
Figure 2 shows microscopic appearance including cytoreductive surgery, intraoperative
(resolution 200X) of positive immunostaining and/or perioperative intraperitoneal chemo-
of neoplastic cells by HRP conjugated therapy using doxorubicin, cisplatin, and
Cytokeratin 5/6 antibody. Cytological examina- interferon gamma with or without abdominal
tion of ascitic fluid showed mesothelial cells radiation and cytoreductive surgery along with
with features of malignancy, CEA was 2.3 IU/L, hyperthermic intraperitoneal chemotherapy
AFP was 9.4 IU/L. Complete blood picture, renal using mitomycin and cisplatin followed by
and liver function tests were normal. CT scan whole body irradiation.1,5 Several studies
Figure 2. Positive immunostaining of neo-
of chest and abdomen showed gross ascites, demonstrated an improved overall survival plastic cells by HRP conjugated cytoker-
multiple mediastinal and abdominal lymph with these regimes as compared to historic atin 5/6 antibody (resolution 200X).
nodes enlargement, diffused nodular mass in controls, treated with systemic chemotherapy
the omentum and peritoneal lining central and and palliative surgery in which the median
right side of the abdomen, as revealed in survival was uniformly less than 1 year.4
Figure 3 CT scan image taken in October 2008 However, extensive intraperitoneal disease morbidity.1
showing peritoneum thickening and ascites. precludes the possibility of cytoreductive sur- A number of chemotherapeutic agents
The patient was treated with cisplatin 75 gery always and these multimodality therapeu- either single or in combination with other
mg/m2 + pemetrexed 500 mg/m2 i.v every three tic strategies are associated with significant drugs have shown promise in the treatment of

Case Report
MPeM. Nevertheless, the low incidence of the

disease and clinical heterogeneity precludes
Phase II efforts to define conclusively the ben-
efit of systemic chemotherapy and other treat-
ment options. The Expanded Access Program
(EAP) conducted both in the US and interna-
tionally provided access to 109 patients with
MPeM including chemo-naive or previously
treated patients with MPeM not amenable to
curative surgery. This study showed that medi-
an survival for pemetrexed (antifolates) was
10.3 months, and 1-year survival rates for
pemetrexed with cisplatin and pemetrexed
alone were 57.4% (95% CI: 10.3, 100) and
41.5% (95% CI 4.6, 78.4), respectively. The dis-
ease control rate was 71.2% in MPeM patients,
establishing the value of this treatment regime
in improving survival in patients with unre-
sectable MPeM.6-8
For patients who cannot tolerate a platinum-
based regimen a Phase II trial (20 patients)
provided an alternative regimen with gemc-
itabine and pemetrexed documenting a dis-
ease control rate (DCR) of 50%, median TTPD
(time to progressive disease) and OS of 10.4
months and 26.8 months, respectively.1
In addition, a Phase III trial where 456
patients was assigned randomly to cisplatin 75
mg/m2 alone or with pemetrexed 500 mg/m2
indicated that supplementation with folic acid
and vitamin B12 resulted in improved survival
time, TTPD, response rates and significantly Figure 3. CT scan in October 2008 showed peritoneal thickening and ascites.
reduced treatment related toxicity when com-
pared to non-supplemented patients.7
VEGF plays key role in MPeM biology and in
a Phase II trial anti VEGF antibody (beva-
cizumab 15 mg/kg) was added to gemcitabine
1250 mg/m2 plus cisplatin 75 mg/m2 regimen,
improvement in overall survival with beva-
cizumab combination was not demonstrated in
this study.9
This patient presented with abdominal dis-
tension, which is a presenting symptom in
majority of cases. CT scan findings of
mesothelioma are nonspecific but are useful
for detection, characterization and staging. It
is also useful for guiding biopsy of peritoneal
masses. Definitive diagnosis is based on histo-
logical and immunohistochemical examina-
tion.
Cytologic sampling of ascitic fluid and
Immunohistochemical expression of tumor
markers (calretinin and cytokeratin 5/6) pro-
vides a diagnosis of MPeM in approximately
80% of the cases. Since pemetrexed in combi-
nation with cisplatin showed survival improve-
ments, the patient started with this regime.
Failure to show clinical response as evidenced
by repeated aspirations of 6-8 liters, the treat-
ment was changed to gemcitabine plus peme-
trexed and cisplatin was not included in the
regime as the patient failed to respond to
intraperitoneal cisplatin. The constant non- Figure 4. CT scan in July 2009 showed resolution of the peritoneal thickening and
hydronephrosis of right kidney.
response of the patient to this regime, led to

Case Report
change in treatment and the patient was con- Options Oncol 2008;9:180-90.
tinued to be treated with bevacizumab and References 6. Janne PA, Wozniak AJ, Belani CP, et al.
gemcitabine due to a strong evidence of Open-label study of pemetrexed alone or in
improvement in clinical response and quality 1. Simon GR, Verschraegen CF, Janne PA, et combination with Cisplatin for the treat-
of life. This was observed by no requirement of al. Pemetrexed plus gemcitabine as first- ment of patients with peritoneal mesothe-
aspiration of ascitic fluid until August 2009 (7 line chemotherapy for patients with peri- lioma: outcomes of an expanded access
months post treatment) and the patient was toneal mesothelioma: final report of a program. Clin Lung Cancer 2005;7:40-6.
working and maintained his job during this phase II trial. J Clin Oncol 2008;26:3567- 7. Vogelzang NJ, Rusthoven JJ, Symanowski
period. Figure 4 showed CT scan image taken 72. J, et al. Phase III study of pemetrexed in
in July 2009 showed resolution of the peri- 2. Brigand C, Monneuse O, Mohamed F, et al. combination with cisplatin versus cis-
toneal thickening as depicted in the anterior Peritoneal mesothelioma treated by cyto- platin alone in patients with malignant
and hydronephrosis of the right kidney at the reductive surgery and intraperitoneal pleural mesothelioma. J Clin Oncol 2003;
posterior. This case demonstrates that beva- hyperthermic chemotherapy: results of a 21:2636-44.
cizumab in combination chemotherapy could prospective study. Ann Surg Oncol 2006;13: 8. Carteni G, Manegold C, Garcia GM, et al.
be an effective alternative treatment in 405-12. Malignant peritoneal mesothelioma -
patients who are non-responsive to other 3. Bridda A, Padoan I, Mencarelli R, et al. Results from the International Expanded
proven agents and highlights the need for fur- Peritoneal mesothelioma: a review. Med Access Program using pemetrexed alone
ther clinical studies to establish the role of Gen Med 2007;9:32. or in combination with a platinum agent.
bevacizumab in the treatment of MPeM to 4. Yan TD, Welch L, Black D, et al. A system- Lung Cancer 2009;64:211-8.
improve progression free survival and overall atic review on the efficacy of cytoreductive 9. Karrison T, Kindler HL, Gandara DR, et al.
survival. surgery combined with perioperative Final analysis of a multi-center, double-
intraperitoneal chemotherapy for diffuse blind, placebo-controlled, randomized
malignancy peritoneal mesothelioma. Ann phase II trial of gemcitabine/cisplatin
Oncol 2007;18:827-34. (GC) plus bevacizumab (B) or placebo (P)
5. Hesdorffer ME, Chabot J, DeRosa C, et al. in patients (pts) with malignant mesothe-
Peritoneal mesothelioma. Curr Treat lioma (MM). J Clin Oncol 2007;25:391.

Intracystic papillary carcinoma knowledge, there has been only one other case
report of this lesion occurring in pre- Correspondence: Ivy N. Umanah, Department of
of the breast in a 21-year old menopausal women in their second decade of Pathology, University of Uyo Teaching Hospital,
premenopausal Nigerian life.4 We recently encountered a case of low P.M.B. 1136, Uyo, AKS, Nigeria.
E-mail: innumah@gmail.com; nnekauma19dyvi
woman: a case report nuclear grade intracystic papillary carcinoma
@yahoo.com
of the right breast in a 21-year-old woman,
Ivy N. Umanah, 1 Akpan S. Okpongette2 which is probably the first report in our envi- Key words: intracystic papillary carcinoma,
1
ronment. breast, young women.
Departments of Pathology and 2 Surgery,
University of Uyo Teaching Hospital, Acknowledgments: the authors thank Dr.
Uyo, Nigeria Tuyethao Vinh and Gary Braithwaithe, both of the
Case Report GYN/Breast Department, Armed Forces Institute
of Pathology, Washington DC, for assistance with
immunohistochemistry. We also thank Professors
Abstract Clinical history E. Akang, E. Essien, and C. Adebamowo for their
A 21-year-old woman presented in our surgi- valuable contributions in reviewing the patholog-
cal out-patient department with a four-year ical materials and the manuscript.
We report the case of a 21-year-old Nigerian
history of a right breast mass and bloody nip-
woman who presented to us with features of Contributions: INU, writing of this paper, and
ple discharge. Her family history was negative
intracystic papillary carcinoma, a rare form of reviewing and reporting all pathological materials
for breast cancer and there was no history of of this patient in conjunction with Dr. T. Vinh
breast cancer usually seen in postmenopausal
exposure to anticancer drugs, radiation, or cig- (AFIP, Washington) and Prof. E. Akang (University
women in their sixth to eighth decades of life.
arette smoking. Clinical examination con- College Hospital, Ibadan, Nigeria); ASO, patient
To the best of our knowledge, there has been
firmed a well-defined 54-mm mass in the biopsies and surgical resections, contributions to
only one other case report of this lesion occur- the clinical history, and editing of the manuscript.
ring in women in their second decade of life. upper proximal quadrant of the right breast
Physical examination showed a well-defined close to the areola, with an ipsilateral bloody
Received for publication: 18 September 2009.
mass, 54 mm in diameter, in the upper proxi- nipple discharge (Figure 1). There was no Revision received: 3 November 2009.
mal quadrant of the right breast close to the associated axillary lymphadenopathy. Accepted for publication: 4 November 2009.
areola, histologically composed of monotypic Mammography was not performed as facili-
epithelial cells disposed in solid, cystic, and ties for this are unavailable in the state. Core This work is licensed under a Creative Commons
needle biopsy was performed using a 23-gauge Attribution 3.0 License (by-nc 3.0).
papillary patterns. A diagnosis of intracystic
papillary carcinoma was made because of the needle and showed a papillary tumor histolog-
ically composed of monotypic epithelial cells. ©Copyright I.N. Umanah, A.S. Okpongette, 2009
presence of intracystic arborization of the Rare Tumors 2009; 1:e50
fibrovascular stroma, a monotonous cell popu- The preliminary diagnosis was atypical ductal doi:10.4081/rt.2009.e50
lation, the presence of mitoses, and the lack of papilloma with a differential diagnosis of
myoepithelial cells determined by immunohis- intracystic papillary carcinoma. Four weeks
tochemistry using calponin and p63 stains. after the core biopsy, excision biopsy of the
Estrogen receptor status was positive while tumor was performed. this associated pathology and her age, we con-
progesterone status and HER-2-neu receptor sidered adjuvant radiotherapy appropriate for
status were negative. Pathological features her but opted for tamoxifen when her family
The patient has survived for 12 months Grossly the excised tissue showed a mass of expressed their inability to cope with the
without any sign of recurrence after the last fibro-fatty tissue weighing 101 g and measur- inconvenience and expense of radiotherapy in
surgical resection of the tumor. ing 80x60x12 mm. The cut surface of the tis- another center. Although she is yet to comply
sue showed a well-defined mass approximate- with hormonal therapy for poorly understood
ly 17 mm in diameter, with a cystic cavity filled reasons, she has been symptom-free for about
with pale, friable, papillary tissue. Histologic- a year.
Introduction ally the tumor was composed of closely packed
epithelial cells (nuclear Grade 2) with a papil-
Intracystic papillary carcinoma (IPC) is a lary architecture within a cyst (Figure 2).
variant of intraductal papillary carcinoma, a Biopsy site changes were apparent in the sur- Discussion
rare histological type of breast cancer occur- rounding tissue.
ring only in about 1-2% of women.1-3 Papillary Immunohistochemical (IHC) stains for Typically patients with IPC present with a
carcinomas can be divided into invasive and calponin, p63, and CK5/6 were performed on palpable mass (80% or more) and/or bloody
noninvasive forms. Intracystic (encysted) pap- the tumor and demonstrated the absence of a nipple discharge (up to 22%).6,7 Less frequent-
illary carcinoma is the localized, noninvasive myoepithelial cell border in the papillary cores ly they may present as a radiographic abnor-
form, occurring as a grossly evident tumor in a as well as at the periphery of the lesion. Based mality.8 Most patients are postmenopausal
cystic and dilated duct.2-4 The patterns seen on these findings, the diagnosis of intracystic women usually with median ages ranging from
include micropapillary, cribriform, trabecular, papillary carcinoma was made. Hormone 63-75 years.6,7,9 Its occurrence in this 21-year-
and solid. Occasionally they may be mistaken- receptor analysis showed mild estrogen recep- old was a novelty. The duration of symptoms in
ly diagnosed as papillomas.3,5 tor positivity (1+) while both progesterone patients with IPC varies but prolonged periods
Because of its rarity, there is a paucity of lit- and HER-2-neu were negative. of one year or more is not considered unusual.1
erature on IPC in women younger than thirty The patient had another excision 15 weeks Late presentation, as seen in our patient who
years old, as it predominantly affects elderly, later because of involved margins, which had a four-year history, is a typical feature of
postmenopausal women.1 It has been docu- revealed residual papillary lesions as well as a most patients with breast cancer in sub-
mented in males as well.1,6 To the best of our few foci of mucinous carcinoma. Based on Saharan Africa, in contrast to what occurs in

Case Report
increased breast density, except in high risk IPC had a survival rate of >90% of that of the
women or those with a prior diagnosis of general population.6 Factors such as age at
breast cancer.12 presentation, tumor diameter, and nuclear
Microscopically IPC is composed of an grade, necrosis, and the presence of associat-
encysted tumor within a dilated duct with ed lesions such as invasion and DCIS, all affect
arborization of the fibrovascular stroma, and patient survival.2,9,16-19
contains nodules of papillary carcinoma sur- In summary, intracystic papillary carcinoma
rounded by a thick fibrous capsule.1-2,6-7 is extremely rare in women in their second
Excision biopsy is recommended for pathologi- decade of life but it does occur. The diagnosis
cal diagnosis because of the frequently incon- depends on finding typical clinical features,
clusive findings associated with fine needle radiologic and pathologic investigations and,
aspiration or core needle biopsy alone.2 invariably, immunohistochemistry. The tumor
Figure 1. Breast lump showing a bloody nip- Immunohistochemistry with stains such as should be managed with or without adjuvant
ple discharge. Skin puncture wound indi- calponin, smooth-muscle myosin heavy chain therapy on the basis of any associated patholo-
cates the site of the needle biopsy.
(SMM-HC) cytoplasmic stains, and p63 gy, tumor size, and age of the patient. Although
nuclear stains have been invaluable in distin- our patient has been symptom-free for one
guishing IPC, which does not appear to have a year now, the prognosis in this age group is yet
myoepithelial cell layer around tumor nodules, to be evaluated.
from ductal carcinoma in situ (DCIS).2,14-15
Another differential diagnosis, papilloma, can
be distinguished from IPC using the criteria
proposed by Kraus and Neubecker.5 Usually IPC References
presents with low to intermediate grade, high
estrogen and progesterone receptor positivity, 1. Rosen PP. Papillary Carcinoma. In: Rosen’s
and negativity for c-erb-2.3,7 Breast Pathology, 2nd edn. Philadelphia:
There are no well-defined views on the man- Lippincotts-Raven, 2001, pp 381-404.
agement of IPC; however, surgical excision is 2. Collins LC, Schnitt SJ. Papillary lesions of
the mainstay of treatment.6-7,16 In selected stud- the breast: selected diagnostic and man-
ies, patients with IPC were divided into three agement issues. Histopathology 2008;52:
groups (IPC alone, IPC with associated ductal 20-9.
Figure 2. Intracystic papillary carcinoma carcinoma in situ, and IPC with associated
showing a monotonous population of 3. Ibarra JA. Papillary lesions of the breast.
epithelial cells in solid, cystic, and papillary invasion with or without ductal carcinoma in Breast J 2006;2:237-51.
patterns (hematoxylin and eosin stain, 10X situ), and the prognosis did not differ among 4. Jaffer S, Chen X, Lee L, et al. Pleomorphic
magnification). the three groups regardless of the type of sur- solid and cystic papillary carcinoma of the
gery performed (breast-conserving surgery or breast: two cases occurring in young
mastectomy) and whether adjuvant therapy women. Ann Diagn Pathol 2004;8:126-9.
the developed world where patients present was administered.7,16-18 Fayanju et al.18 observed 5. Kraus FT, Neubecker RD. The differential
with a median duration of symptoms of six that patients with IPC and associated DCIS or diagnosis of papillary tumors of the breast.
weeks before diagnosis.7,10 microinvasion were treated with adjuvant radi- Cancer 1962;15:444-55.
Mammography, ductography, galactography, ation and endocrine therapy on the basis of 6. Grabowski J, Salzstein LS, Sadler GB, et al.
ultrasonography, and magnetic resonance this associated pathology. Therefore sentinel Intracystic papillary carcinoma: a review of
imaging (MRI) are imaging techniques useful lymph node biopsy has been advocated for 917 cases. Cancer 2008;113:916-20.
in the diagnosis of breast cancer.8,11,12 On mam- these patients6,7,14 owing to the low rate of axil- 7. Solorzano CC, Middleton LP, Hunt KK, et
mography IPC often is seen as a round or oval lary lymph node metastases (8-11%) observed al. Treatment and outcome of patients with
circumscribed mass, frequently in the in those evaluated for regional disease.9,19 intracystic papillary carcinoma of the
retroareolar region. Spiculation is rare. Sentinel lymph node biopsy also seems justi- breast. Am J Surg 2002;184:364-8.
Ductography and galactography may be com- fied in large IPC tumors owing to the occasion- 8. Dogan BE, Whitman GJ, Middleton LP, et
bined with mammography in patients with nip- al axillary lymph node involvement observed in al. Intracystic papillary carcinoma of the
ple discharge to show filling defects, ductal a few cases of pure IPC7,20 characterized by breast. Am J Roentgenol 2003;181-6.
obstructions, and ductal wall irregularities, lesions measuring 4 cm or more. Pure IPC has 9. Lefkowitz M, Lefkowitz W, Wargotz ES.
while sonography usually reveals intracystic been reported to have an excellent prognosis Intraductal (intracystic) papillary carcino-
mural nodules, papillary projections, and even when treated with local excision only, but ma of the breast and its variants: a clinico-
septa.8,11-13 In resource-poor countries like the current clinical management remains vari- pathological study of 77 cases. Human
Nigeria, where mammographic facilities are able with a potential for overtreatment.7,16,17 Pathol 1994;25:802-9.
expensive and largely unavailable, interven- Only in a subset of younger patients (<50 10. Okobia MN, Osime U. Clinicopathologic
tional procedures like core needle biopsies years old) with pure IPC was adjuvant radio- study of carcinoma of the breast in Benin
often are performed blind, and surgeons have therapy and/or hormonal therapy administered City. Afr J Reprod Health 2001;5:56-62.
to depend on pathological evaluation of tumor and this is recommended.18 11. Liberman L, Feng TL, Susnik B. Case 35:
resection margins solely, as a means to ensure The prognosis of IPC, particularly in elderly intracystic papillary carcinoma with inva-
postoperative removal of all of the tumor. women, is excellent with few or no cancer- sion. Radiology 2001;219:781-4.
Accurate diagnosis in patients with multicen- related deaths in most study series.6,7 In con- 12. Samphao S, Wheeler A.J. Rafferty E, et al.
tric tumors is limited. Universally, young trast to the lower relative survival rate for Diagnosis of breast cancer in women aged
patients like ours usually are not subjected to patients with non-IPC cancers such as invasive 40 and younger: delays in diagnosis result
screening mammography because of their ductal carcinoma, even patients with invasive from underuse of genetic testing and breast

Case Report
imaging. Am J Surg 2009;198:538-43. breast: a reevaluation using a panel of of radiation and endocrine therapy. Am J
13. Adisa Y, Easson AM. Breast cancer - A myoepithelial cell markers. Am J Surg Surg 2007;194:497-500.
review for African surgeons. In: Surgery in Pathol 2006;30:1002-7. 19. Leal C, Costa I, Fonseca D, et al. Intracystic
Africa - Monthly Reviews, The Ptolemy 16. Harris KP, Faliakou EC, Exon DJ, et al. (encysted) papillary carcinoma of the
Project, Office of International Surgery. Treatment and outcome of intracystic pap- breast and its variants; a clinicopathologi-
Jani P, Ostrow B, editors. University of illary carcinoma of the breast. Br J Surg
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Pathol 1998;29:1097-104.
14. Hill CB, Yeh IT. Myoepithelial cell staining 17. Carter D, Orr SL, Merino MJ. Intracystic
20. Mulligan AM, O'Malley FP. Metastatic
patterns of papillary breast lesions: from papillary carcinoma of the breast. After
intraductal papillomas to invasive papil- mastectomy, radiotherapy or excisional potential of encapsulated (intracystic)
lary carcinomas. Am J Clin Pathol 2005; biopsy alone. Cancer 1983;52:14-9. papillary carcinoma of the breast: a report
123:36-4. 18. Fayanju OM, Ritter J, Gillanders WE, et al. of two cases with axillary lymph node
15. Collins LC, Carlo VP, Hwang H, et al. Therapeutic management of intracystic micrometastases. Int J Surg Pathol 2007;
Intracystic papillary carcinomas of the papillary carcinoma of the breast: the roles 15:143-7.

1:exxxx
Diagnostic confusion resulting Case Report Correspondence: Sheeja Pullarkat, Department of

from CD56 expression by Pathology and Laboratory Medicine, David Geffen
cutaneous myeloid sarcoma A 61-year-old woman presented to her physi- School of Medicine at UCLA, 10833 Le Conte
cian with a left ear lobe skin nodule, left facial Avenue, A7-149 CHS, Los Angeles, CA 90095-
Thanh Ho,1 Franklin Sedarat,1 nerve palsy, and deafness. Biopsy of the ear 1732, USA. E-mail: spullarkat@mednet.ucla.edu
Nagesh Rao,2 Sheeja T. Pullarkat,1 lobe lesion was interpreted initially as Merkel
Key words: myeloid sarcoma, fluorescent in situ
1
Department of Pathology and cell carcinoma. She was referred to our institu-
hybridization, t(8;21) acute myelogenous
tion for further evaluation and treatment. Her
Laboratory Medicine and 2Department of leukemia.
past history was relevant for acute myeloge-
Cytogenetics, David Geffen School of
nous leukemia (AML) for which she had Contributions: TH, drafting the article; FS, acqui-
Medicine, University of California Los
received chemotherapy and was in remission. sition of photos, revision of article; NR, cytoge-
Angeles, Los Angeles, California, USA Imaging studies performed in our institution netics; STP, drafting, revision, and final approval
showed a soft tissue mass involving the left of article.
mastoid space and extending into the posteri-
or middle cranial fossa. In addition a paraver- Conflict of interest: the authors report no con-
Abstract tebral mass extending from the third to sixth flict of interests.
thoracic vertebra was noted.
Myeloid sarcomas are tumor masses com- The biopsy specimen from the ear lobe mass Received for publication: 23 September 2009.
posed of aggregates of malignant myeloid pre- Accepted for publication: 4 November 2009.
was received for consultation from the refer-
cursors in extramedullary sites including the ring hospital and revealed a diffuse prolifera- This work is licensed under a Creative Commons
skin. We report a case of myeloid sarcoma in a tion of atypical mononuclear cells within the Attribution 3.0 License (by-nc 3.0).
patient who presented with an ear lobe mass dermis with an intact epidermis (Figure 1A).
and facial nerve paralysis. Expression of CD56 These cells were medium to large and had ©Copyright T. Ho et al., 2009
by the malignant cells led to an initial misdiag- moderate amounts of cytoplasm, irregular Licensee PAGEPress, Italy
nosis as Merkel cell tumor. Comprehensive Rare Tumors 2009; 1:e51
nuclear contours, and finely dispersed chro-
doi:10.4081/rt.2009.e51
pathological evaluation confirmed the diagno- matin (Figure 1B). Immunohistochemical
sis of myeloid sarcoma with aberrant expres- stains showed the tumor cells to express
sion of CD56 and carrying the translocation myeloperoxidase (MPO) (Figure 1C). In addi-
t(8;21) (q22;q22). Aberrant antigen expression tion they were positive for CD45 (leukocyte monocytes.4,5 Hematopoietic and non-hema-
by cutaneous myeloid sarcomas can cause common antigen), CD43, CD117, CD34 topoetic neoplasms that express CD56 can
diagnostic confusion with other cutaneous (Figure 1D), and CD56 (Figure 1E). They were involve the skin. Cutaneous non-hematopoiet-
neoplasms. This is especially relevant when negative for CD20 and CD3. A diagnosis of ic tumors that are CD56 positive include
myeloid sarcoma is the sole manifestation of myeloid sarcoma was made. Fluorescent in situ Merkel cell carcinomas and metastases to the
acute myeloid leukemia. hybridization (FISH) studies were performed skin from other primary neuroendocrine carci-
on the skin lesion using dual-color DNA nomas. Merkel cell carcinomas present as der-
probes: Spectrum Orange-labeled LSI mal nodules mainly involving the head and
RUNX1T1 (8q22) probe and Spectrum Green- neck regions, with a characteristic salt-and-
Introduction labeled LSI RUNX1 (21q22) probe to identify pepper nuclear chromatin histologically.6-8 The
the t(8;21) fusion signals (Abbot Mol- tumors are CD45 negative and stain for cytok-
Certain hematopoietic neoplasms have a ecular/Vysis, Des Plaines, IL).3 The cells ana- eratin 20 (CK20), CAM 5.2, and CD56.
tendency to involve the skin. Of these the most lyzed were positive for the reciprocal transloca- Metastatic neuroendocrine tumors to the skin
common are CD4+/CD56+ hematodermic neo- tion t(8;21)(q22;q22) (Figure 1F). have an immunophenotype similar to the pri-
plasms (previously termed blastic natural A concurrent bone marrow biopsy showed a mary tumor and frequently express CD56.
killer (NK) cell lymphoma), myeloid sarcomas, hypercellular bone marrow involved by acute A review of CD56 positive hematological
nasal-type extranodal natural killer/T-cell lym- myelogenous leukemia with t(8;21)(q22;q22). neoplasms presenting in the skin, conducted
phoma, and cutaneous T-cell lymphomas.1 The She received myeloablative conditioning by the Cutaneous Lymphoma Task Force of the
term myeloid sarcoma refers to tumors com- chemotherapy and an allogeneic hematopoiet- European Organisation for Research and
posed of aggregates of immature leukemic ic stem cell transplant, following which she Treatment of Cancer,1 recognizes four different
myeloid precursors in extramedullary sites.2 developed persistent pancytopenia and died subtypes of proliferations with CD56 expres-
Myeloid sarcomas with the chromosomal from sepsis. sion: (i) CD4+/CD56+ hematodermic neo-
translocation t(8;21) frequently express non- plasms (previously designated as blastic NK-
myeloid antigens including CD2, CD19, and cell lymphomas); (ii) skin infiltration by CD56
CD56. Myeloid sarcomas involving the skin are positive acute myelogenous leukemia (myeloid
a frequent cause of misdiagnosis when they Discussion sarcoma); (iii) nasal-type extranodal NK/T cell
express aberrant non-myeloid antigens and lymphomas; and (iv) “classical” cases of cuta-
when the underlying leukemia is not overt. We Our case highlights a pitfall in the diagnosis neous T-cell lymphoma (CTCL) with coexpres-
report a case of CD56-expressing myeloid sar- of cutaneous myeloid sarcomas that express sion of the CD56 molecule.
coma that was misdiagnosed as Merkel cell CD56, a non-myeloid antigen. CD56 or neural CD4 and CD56 positive hematodermic neo-
carcinoma, and discuss the diagnostic cell adhesion molecule (NCAM) is a cell mem- plasm is a recently recognized entity that orig-
approach toward CD56 expressing cutaneous brane protein involved in adhesion of neural inates from plasmacytoid dendritic cells
tumors. cells. CD56 is expressed on NK cells, on a sub- (pDC), has a high incidence of skin involve-
set of peripheral CD8+ T-cells, on neural or ment and leukemic dissemination, an aggres-
neuroendocrine cells, and on peripheral blood sive clinical course, and a dismal prognosis.

Case Report
Article
CD43, CD4, CD31, and chloroacetate esterase.

The initial biopsy was reviewed and was found
to be a myeloid sarcoma and not a T-cell lym-
phoma.
A recent report by Pileri et al. reviewing 92
cases of myeloid sarcomas in adults has
heightened our knowledge on myeloid sarco-
mas. They have illustrated that the tumor cells
in myeloid sarcomas most commonly
expressed CD68/KP1 (100%), followed in
A D decreasing order by myeloperoxidase (83.6%),
CD117 (80.4%), CD99 (54.3%), CD68/PG-M1
(51%), CD34 (43.4%), CD56 (13%), CD61
(2.2%), CD30 (2.2%), and glycophorin A and
CD4 (1.1%).12 Chromosomal abberations were
detected in about 54% of cases and monosomy
7 (10.8%), trisomy 8 (10.4%), and mixed line-
age leukemia-splitting (8.5%) were the com-
monest abnormality.
Since detection of genetic lesions is critical
B E for classification, prognostic stratification, and
monitoring of AML, it is very important that
FISH studies on the paraffin-embedded tissue
for chromosomal abnormalities, namely mono-
somy 7, trisomy 8, 11q23 rearrangement, and
t(8;21), are performed to aid in further prog-
nostication when myeloid sarcoma is the sole
manifestation of acute myeloid leukemia. This
is mainly owing to the fact that since the diag-
nosis of myeloid sarcoma frequently is unex-
pected, fresh cells are not available usually for
cytogenetic and/or molecular studies.
C F In summary, myeloid sarcoma should be
considered in the differential diagnosis of
Figure 1. (A) Skin lesion from the left ear, showing intact epidermis with large mononu- cutaneous CD56 positive tumors that are CD45
clear cells within the dermis (hematoxylin and eosin stain, 40X). (B) Skin lesion from the positive and lack expression of cytokeratin and
left ear, showing large mononuclear cells with fine chromatin, and moderate amounts of other neural markers.
granular cytoplasm (hematoxylin and eosin stain, 400X). (C) Cytochemical staining for
myeloperoxidase shows cytoplasmic positivity in the malignant cells (400X). (D) CD34
immunohistochemical staining shows strong positivity in the malignant cells (400X). (E)
CD56 immunohistochemical staining identifies the neoplastic cells (100X). (F) FISH
studies of the skin lesion 8q22 (red); 21q22 (green); fusion (yellow) signals consistent References
with t(8;21)(q22;22).
1. Assaf C, Gellrich S, Whittaker S, et al. CD
56-positive haematological neoplasms of
Extranodal NK/T cell lymphoma most common- lymphoid antigens. Kurata et al.10 have the skin: a multicentre study of the
ly occurs in the nasopharngeal area and fre- described a case of a 39-year-old man who pre- Cutaneous Lymphoma Project Group of the
quently shows an angiocentric growth pattern sented with a forehead cutaneous nodule that European Organisation for Research and
with prominent necrosis, and once was was positive for CD45 and CD56, and negative Treatment of Cancer. J Clin Pathol 2007;
referred to as lethal midline granuloma. Most for CD3, CD20, CD34, TIA-1, and TdT. Only a 60:981-9.
cases are associated with Epstein Barr Virus limited panel of immunostains was performed, 2. Rappaport, H. Tumors of Hematopoetic
(EBV) and express cytotoxic molecules such as hence leading to a misdiagnosis of NK cell lym- System. Washington DC, Armed Forces
perforin, granzyme B, and TIA-1. Occasionally, phoma. The initial biopsy specimen when re- Institute of Pathology, 1966, Atlas of Tumor
CD56 may be expressed also by cutaneous T- evaluated showed expression of myeloid anti- Pathology, 1st series, fascicle 8.
cell lymphoma such as primary cutaneous gens, namely myeloperoxidase (MPO), and the 3. Mellinghoff IK, Wang MY, Vivanco I, et al.
CD30+ lymphoproliferations, anaplastic large diagnosis of myeloid sarcoma was made final- Molecular determinants of EGFR kinase
cell lymphomas (ALCL), and subcutaneous ly. Beswick et al.11 described a case of a 65- inhibitor response in glioblastoma. N Engl
panniculitis-like T-cell lymphomas. Results year-old man who presented with a nodule on J Med 2005;353:2012-24.
from this study showed that CD56+ cutaneous the back that was diagnosed as high-grade T- 4. Chan JK, Sin VC, Wong KF, et al. Nonnasal
lymphoproliferative disorders, with the excep- cell lymphoma by virtue of CD3 expression. He lymphoma expressing the natural killer
tion of CD56+ CTCL, have a very poor progno- received chemotherapy and three years later cell marker CD56: a clincopathologic study
sis. developed violaceous nodules over his trunk of 49 cases of an uncommon aggressive
Previous reports have highlighted the diffi- and limbs. Biopsy of this mass and a detailed neoplasm. Blood 1997;89:4501-13.
culty in the diagnosis of cutaneous myeloid immunohistochemistry panel revealed a 5. Suzuki R, Yamamoto K, Seto M, et al.
sarcomas owing to the aberrant expression of myeloid sarcoma that was positive for CD45, CD7+ and CD56+ myeloid/natural killer

ArticleReport
Case
cell precursor acute leukemia: a distinct sion in Merkel cell carcinoma: potential cases of CD 56 positivity to exclude granu-
hematolymphoid disease entity. Blood diagnostic pitfall with blastic hematologi- locytic sarcoma. Br J Dermatol 2002;147:
1997;90:2417-28. cal malignancies and expanded immuno- 609-11.
6. Skelton HG, Smith KJ, Hitchcock CL, et al. histochemical analysis. Mod Pathol 2007; 11. Beswick SJ, Jones EL, Mahendra P, et al.
Merkel cell carcinoma: analysis of clinical, 20:1113-20. Chloroma (aleukaemic leukaemia cutis)
histologic and immunohistologic features 9. Bekkenk MW, Jansen PM, Meijer CM, et al.
initially diagnosed as cutaneous lym-
of 132 cases with relation to survival. J Am CD56+ hematological neoplasms present-
Acad Dermatol 1997;37:734-9. ing in the skin: a retrospective analysis of phoma. Clin Exp Dermatol 2002;27:272-4.
7. Tai PT, Yu E, Tonita J, et al. Merkel cell car- 23 cases and 130 cases from the literature. 12. Pileri SA, Ascani S, Cox MC, et al. Myeloid
cinoma of the skin. J Cutan Med Surg Ann Oncol 2004;15:1097-108. sarcoma: clinico-pathologic, phenotypic
2000;4:186-95. 10. Kurata H, Okukubo M, Fukuda E, et al. and cytogenetic analysis of 92 adult
8. Sur M, Alardati H, Ross C, et al. Tdt expres- Myeloid markers should be undertaken in patients. Leukemia 2007;21:340-50.

The epidemiology of malignant firm its rare occurrence and suggest that age
and stage at diagnosis are strongly associated Correspondence: Jennifer L. Beebe-Dimmer,
giant cell tumors of bone: with long-term survival. Karmanos Cancer Institute, Prentis Center, 110
an analysis of data from the E. Warren Avenue #1115, Detroit, Michigan , USA
E-mail: dimmerj@karmanos.org
Surveillance, Epidemiology
and End Results Program Introduction
Key words: giant cell tumor of bone, surveil-
lance, epidemiology and end results, descriptive
(1975–2004) epidemiology, incidence, survival, osteosarcoma.
Giant cell tumors (GCTs) of bone occur
Jennifer L. Beebe-Dimmer,1 infrequently, comprising just 5% of all bone Acknowledgements: project funded by Amgen
Karynsa Cetin,2 Jon P. Fryzek,3 tumors, both benign and malignant.1 Inc, Thousands Oaks, CA.
Scott M. Schuetze,4 Kendra Schwartz5 However, the disease can be incapacitating, as
Received for publication: 12 October 2009.
1
Karmanos Cancer Institute and Wayne State patients with GCT of bone typically present
Revision received: 4 November 2009.
University Department of Internal Medicine, with mechanical difficulty and pain resulting Accepted for publication: 5 November 2009.
Detroit, MI; 2Amgen Inc., Department of from bone destruction and are at an increased
risk for fracture.1-3 GCTs are observed predom- This work is licensed under a Creative Commons
Global Epidemiology, Thousand Oaks, CA; Attribution 3.0 License (by-nc 3.0).
3
inantly at the ends of long bones, most com-
Medimmune Inc., One MedImmune Way,
monly located in and around the knee (distal
Gaithersburg, MD; 4University of Michigan ©Copyright J.L. Beebe-Dimmer et al., 2009
femur, proximal tibia) and wrist (distal
Department of Internal Medicine, Ann Arbor, Licensee PAGEPress, Italy
radius).1 They are categorized according to the Rare Tumors 2009; 1:e52
MI; 5Karmanos Cancer Institute and Wayne Enneking staging system, where the patholog- doi:10.4081/rt.2009.e52
State University Department of Family ic spectrum ranges from static and confined to
Medicine, Detroit, MI, USA the bone (Stage 1) to aggressive, extending
into the surrounding soft tissue (Stage 3).4 A tend to have poorest outcomes, suggesting that
radiographic grading system developed by rigorous follow-up of patients treated for
Campanacci et al. grades lesions from 1 to 3, benign tumors even decades after initial diag-
Abstract with Grade 1 lesions having well-defined mar- noses is crucial to insuring long-term survival.
gins and an intact cortex, and Grade 3 having Because of the rarity of the malignant vari-
Malignant giant cell tumor (GCT) of bone is irregular margins and cortical destruction.5
ety, there are limited sources which can be
a rare tumor with debilitating consequences. Metastases can develop from both benign and
used to characterize incidence and survival fol-
Patients with GCT of bone typically present malignant GCTs; and lung is the most frequent
lowing a diagnosis of malignancy in GCT of
with mechanical difficulty and pain as a result metastatic site.6
bone. Most published data on its epidemiology
of bone destruction and are at an increased Histologically, GCTs are a heterogeneous
have been generated from hospital-based
risk for fracture. Because of its unusual occur- mix of multinucleated giant cells resembling
patient series, which may not accurately trans-
rence, little is known about the epidemiology osteoclasts, spindle-shaped stromal cells
late to the larger population in terms of patient
of malignant GCT of bone. This report offers exhibiting features of osteoblast precursors
and tumor characteristics and frequency of
the first reliable population-based estimates of and CD-68 positive mononuclear cells.7,8 The
occurrence in the general population.
incidence, patient demographics, treatment neoplastic cell of origin has not been identified
To better understand the epidemiology of
course and survival for malignancy in GCT of conclusively. Recently, expression of the ligand
malignancy in GCT of bone, we consulted data
bone in the United States. Using data from the for receptor activator of nuclear factor κB
from the National Cancer Institute’s (NCI)
National Cancer Institute’s Surveillance, (RANKL), a factor critical in the development
Surveillance, Epidemiology and End Results
Epidemiology and End Results (SEER) pro- and activation of osteoclasts, was detected in
(SEER) Program, which represents the most
gram, we estimated the overall incidence and GCT, raising the possibility of controlling bone
comprehensive and complete source of infor-
determinants of survival among patients diag- lysis from GCT by inhibition of the RANKL-
mation available on the diagnosis, demograph-
nosed with malignant GCT of bone from 1975- RANK axis.9
ics, treatment and follow-up of cancer patients
2004. Cox proportional hazards regression was While GCTs account for approximately 20%
in the United States (U.S.).14 To our knowl-
used to evaluate demographic and clinical of all benign bone tumors,1 malignancies in
edge, this study represents the first systematic
determinants of survival among malignant GCT of bone are much rarer and are typically
U.S. investigation of the descriptive epidemiol-
GCT cases. Based on analyses of 117 malig- classified as primary or secondary according to
ogy of this rare tumor using a large, popula-
nant GCT cases, the estimated annual inci- specific criteria.10,11 A primary malignant GCT
tion-based dataset.
dence in the United States was 1.6 per of bone will most often arise concurrently and
10,000,000 persons per year. Incidence was closely with a benign tumor; however, sponta-
highest among adults aged 20 to 44 years (2.4 neous neoplasm may occur in the absence of
per 10,000,000 per year) and most patients benign growth. Secondary malignant GCTs are Materials and Methods
were diagnosed with localized (31.6%) or more common than primary malignant GCTs
regional (29.9%) disease compared to distant and arise after treatment of a previously
disease (16.2%). Approximately 85% of benign tumor and more often in patients Surveillance, Epidemiology and End
patients survived at least 5 years, with survival undergoing radiation therapy with or without Results registry and study population
poorest among older patients and those with curettage.6 While GCT is typically associated We used data gathered as part of the
evidence of distant metastases at time of diag- with a favorable prognosis, the long-term prog- National Cancer Institute’s SEER Program.
nosis. The current study represents the largest nosis for malignant transformation of a previ- SEER currently consists of 18 statewide and
systematic investigation examining the occur- ously benign-appearing tumor is poor. Further, regional tumor registries spread throughout
rence and distribution of malignancy in GCT of reports.3,11-13 indicate that those patients with a the U.S., covering approximately 26% of the
bone in the general U.S. population. We con- history of radiation treatment for benign GCT population (http://seer.cancer.gov/registries/

Article
data.html). The individual registries are geo- determine differences in incidence rates 10,000,000 persons (in 1975-1979 and 1985-
graphically located to over-sample minority across the study period by age at diagnosis, 1989). The average annual malignant GCT
populations, including African Americans, gender, race/ethnicity (white, black, other incidence across the entire study period did
Hispanics, Asian Pacific Islanders, and Native race) and SEER summary stage (localized, not differ significantly by gender or race/eth-
Americans. SEER routinely collects data on regional, distant). nicity. However, the annual incidence did dif-
patient demographics (age at diagnosis, gen- SEER*Stat was also used to calculate rela- fer depending upon age, with the highest inci-
der, race/ethnicity and geographic residence at tive survival rates for the entire study cohort. dence observed among those aged 20 to 44
the time of diagnosis), tumor characteristics SAS software version 9.1 (SAS Institute, Cary, years (2.4 per 10,000,000 persons), with esti-
(size, grade, stage), first course of treatment, N.C., USA) was used to build Cox proportional mates ranging from 1.6 in 2000-2004 to 3.2 in
as well as follow-up documentation of vital sta- hazards (PH) regression models to estimate 1975-1979 across the study period. Metastatic
tus (date and cause of death). Based on the the relation of select factors and survival fol- GCT of bone was exceedingly rare; its inci-
rare occurrence of malignancy in GCT of bone, lowing a diagnosis of malignant GCT of bone. dence was lower than that of either localized or
coupled with our initial goal of assessing epi- Individuals were censored at the date of death, regional disease (P=0.04).
demiologic time trends, we limited our analy- the date last known to be alive (if lost to follow- The mean survival time for patients diag-
ses to the longest running SEER registries up), or December 31, 2004, whichever came
nosed with malignant GCT of bone was 11
(Connecticut, Detroit, Hawaii, Iowa, New first. Variables included in the final Cox PH
years and 11 months, with a 5-year relative
Mexico, San Francisco-Oakland, Utah, Seattle- model were: age at diagnosis (in 5-year age
survival of 84.2%. As would be expected, Cox
Puget Sound, and Atlanta), all of which have groups), year of diagnosis, gender, race, stage
proportional hazards modeling indicated that
collected information on invasive cancers at diagnosis, and receipt of first-line treatment
diagnosed from 1975 through 2004 and repre- older age and more advanced stage at time of
(none, surgery, radiation, or a combination of
sent nearly 10% of the U.S. population. surgery and radiation). diagnosis were associated with an increased
Patients included in the current study were risk of death after controlling for other poten-
those diagnosed with malignant giant cell tial important determinants (Table 3). More
tumors of bone (ICD-O-3 codes, M-9250/1, M- specifically, for each 5-year increase in age at
9250/3, M-8003/3, and primary site codes Results diagnosis, the risk of death increased by 41%
C40.0-C41.9) between January 1, 1975 and (P<0.0001). Likewise, for patients with distant
December 31, 2004. Classification of tumors From 1975 through 2004, a total of 117 indi- metastases detected at the time of diagnosis,
was based upon SEER summary staging crite- viduals were identified as having been diag-
ria. SEER summary stage is produced using nosed with “primary” malignant GCT of bone
the extent of disease information from medical in the SEER 9 registry regions (Table 1). Table 1. Characteristics of patients diag-
records and pathology reports reviewed at the nosed with malignant giant cell tumors
“Primary” in this context means that the (GCT) of bone (SEER† 1975-2004)
time of diagnosis. A localized tumor is defined tumor is the first and/or only invasive cancer (N=117).
as an invasive neoplasm a.) confined to the diagnosed, not to be confused with the afore-
cortex of the bone; or b.) extends beyond the mentioned definitions of primary versus sec- Characteristic N (%)
cortex into the periosteum (with no break in ondary malignancy in GCT. Most patients diag- Age at diagnosis
the periosteum). Regional stage is defined as nosed were between the ages of 20 and 44 <20 years 12 (10.2)
a neoplasm that has a.) extended beyond the years (57.3%), female (53.9%), and white 20-44 years 67 (57.3)
periosteum into adjacent bone, cartilage or (74.4%). Of these patients, nearly one-third 45+ years 38 (32.5)
skeletal muscle; or b.) into regional lymph (31.6%) were diagnosed with disease confined Gender
nodes by way of the lymphatic system; or c.) a to the bone, 29.9% were diagnosed with cancer Female 63(53.9)
combination of extension and regional lymph with evidence of extension into the surround- Male 54(46.1)
node involvement. A distant classification ing soft tissue, 16% were diagnosed with dis- Race
would include a neoplasm that has spread to tant metastasis, and 22% were of unknown White 87 (74.4)
parts of the body remote from the primary stage. The primary treatment for most patients Black 14 (12.0)
tumor either by direct extension or by metasta- (69.3%) was surgical removal of the tumor Other 16 (13.6)
sis to distant organs, tissues or the distant either with (12.0%) or without (57.3%) radia- Stage at diagnosis
lymph nodes via the lymphatic system tion therapy. First-line treatment was associat- Localized 37(31.6)
(http://seer.cancer.gov/tools/ssm/muscu- ed with stage at diagnosis; as most patients Regional 35(29.9)
loskel.pdf). with localized disease received surgery where- Distant 19 (16.2)
as patients with more advanced disease Treatment
Statistical methods received radiation therapy (with or without Surgery only 67 (57.3)
Patient (age at diagnosis, gender, race/eth- surgery) as primary treatment (P<0.0001). Surgery + radiation 14 (12.0)
Radiation only 15 (12.8)
nicity), tumor (stage), and treatment (receipt The incidence of malignant GCT of bone
None 15 (12.8)
of surgery and/or radiation) characteristics was extremely low for the thirty-year study Unknown 6 (5.1)
were described for all individuals diagnosed period (1.6 per 10,000,000 persons per year)
SEER Region at diagnosis
with malignant GCT of bone across the study (Table 2). As one of the initial aims of the
Detroit, MI 24 (20.5)
period (1975-2004). Annual crude and age- investigation was to examine trends in occur-
Connecticut 23 (19.7)
adjusted incidence rates per 10,000,000 per- rence over time, incidence was estimated for San Francisco-Oakland, CA 21 (17.9)
sons were calculated using SEER*Stat v. 6.36 5-year time periods. However, because of the Seattle-Puget Sound, WA 15 (12.8)
and then averaged over the entire study period small number of cancers reported for each Hawaii 9 (7.6)
and for 5-year periods using U.S. county popu- time period, no formal tests of trend over time New Mexico 7 (6.0)
lation estimates. Estimates were age-adjusted were conducted. Annual incidence estimates Atlanta, GA 6 (5.2)
using the 2000 U.S. population as the standard varied from 1.0 per 10,000,000 in the most Iowa 5 (4.3)
population. Chi-square tests were conducted to recent time period (2000-2004) to 2.2 per Utah 7 (6.0)

Article
the risk of death was 5.2 times higher com- Table 2. Incidence of malignant GCTs of bone (in 5-year intervals), 1975-2004, accord-
pared to those diagnosed with tumor confined ing to age at diagnosis, gender, race and stage.
to the bone (P=0.007). However, there was no Incidence per 10,000,000 persons
significant difference in risk of death between 1975-2004 1975-79 1980-84 1985-89 1990-94 1995-99 2000-04
patients with regional and localized disease
(P=0.49). Year of diagnosis, gender and Overall 1.6 2.2 1.4 2.2 2.1 1.2 1.0
race/ethnicity were not significantly related to Age(years)
survival. <20 0.6 1.6 -- 1.0 0.3 0.3 0.3
20-44 2.4 3.2 2.3 2.9 2.2 2.2 1.6
45+ 1.7 1.7 1.2 2.4 3.6 0.5 1.0
p† <0.01
Discussion Gender
Male 1.5 2.0 1.1 2.1 1.8 1.1 1.3
To our knowledge, this represents the first Female 1.7 2.4 1.6 2.4 2.4 1.2 0.7
investigation of malignancy in GCT of bone p 0.53
conducted in the general U.S. population. Our Race
results confirm that malignant GCT of bone is White 1.5 2.4 1.4 2.1 1.9 0.9 0.9
a rare occurrence in the United States (less Black 1.8 - - 3.4 2.9 0.2 1.8
than one case per million persons per year). Other 2.5 3.2 2.6 2.6 3.5 2.2 1.3
While we observed a decrease in incidence p 0.17
over the decades from 2.2 cases per 10 million Stage
persons in the 1970’s to 1.0 case per 10 million Localized 0.5 0.8 0.3 0.9 0.5 0.5 0.3
persons in the 2000’s, the rarity of the tumor Regional 0.5 0.9 0.5 0.2 0.8 0.3 0.2
prevented any formal test of trend in incidence Distant 0.3 0.3 0.1 0.3 0.3 0.2 0.4
p 0.04
over time. Results reported in an analysis of 75
malignant GCT of bone cases from a Swedish †
Corresponding p of χ2 test to detect difference in incidence rates for period (1975-2004) between age, gender, race and stage groupings.
population-based national cancer registry
showed an average annual incidence of 0.63
Table 3. The association between patient, treatment and tumor characteristics and risk of
per million from 1958 to 1968, a somewhat death after diagnosis of malignant GCT of bone using Cox proportional hazards regres-
higher estimate than our own.15 However, sion.
based on the small number of cases identified
Characteristic Hazard ratio† p
in both the Swedish report and our current
‡
investigation, it is possible that the observed Age at diagnosis 1.41 <0.01
trends in incidence over time and/or difference Year of diagnosis 1.03 0.84
in incidence rates between these reports may
Gender
not be meaningful but merely a reflection of Female 1.00
chance variability in the populations studied. Male 0.73 0.46
The current investigation is also the first to
Race
examine racial/ethnic differences in the inci- White 1.00
dence and survival associated with this rare Black 0.45 0.17
disease. Our results suggest no significant Other 0.55 0.41
racial difference in the incidence of malignant Stage at diagnosis
GCT of bone. Survival estimates suggest a Localized 1.00
reduction in risk of death among non-white Regional spread 1.41 0.49
compared with white patients, but the results Distant metastases 5.20 <0.01
were not statistically significant. And although Stage unknown 0.20 0.14
a slightly greater proportion of cases diag- Treatment
nosed were females compared to males, there None 1.00
was no significant difference in the overall Surgery 0.99 0.15
incidence of malignant GCT by gender. We Radiation 0.76 0.69
found most malignant GCT cases are typically Surgery + radiation 1.04 0.94
diagnosed in the third and fourth decades of †
Estimate of relative risk adjusted for all other variables in the final multivariable model (age, year of diagnosis, gender, race, stage, treat-
life, a finding supported by most case- ‡
ment). Hazard Ratio represents an estimate of the increase in risk of death with each increase from one 5-year age group to the next
series.2,3,5,16-19 starting with and including the following age groupings (10-14 years, 15-19 years, …,>85 years)
The average 5-year relative survival rate for
patients with malignant GCT of the bone in our race, or treatment. Our survival rates are information on first line treatment, but no sub-
study was 84.2%. As seen with other cancer improved over hospital-based case-series in sequent treatment information is collected on
types, older age and metastatic disease at diag- malignant GCT, possibly reflecting advances in patients. Anract et al. observed a 5-year rela-
nosis were associated with poorer survival. treatment of these tumors over time and/or tive survival rate of 50% in a case-series of 29
However, we did not observe any significant geographic differences in referral patterns to malignant GCT patients diagnosed between
difference in risk of death among patients specific institutions as well as availability and 1954 and 1993.3 Case ascertainment in this
diagnosed with regionally advanced disease. access to medical care for these patients. study began approximately twenty years prior
No significant differences in risk of death However, these are difficult theories to prove to the establishment of the SEER registry and
were detected by year of diagnosis, gender, with existing data. The SEER registry records ended a decade prior to our patient follow-up.

Article
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Italian study12 were diagnosed with primary survival must be interpreted with prudence, SA, Kansara M, Schlicht SL, et al.
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the French investigation were similarly diag- these subsets of the population are modest. bone and the osteoclastic localization of
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this investigation is the inability to classify gy of patients in this investigation was not pos- tor kappaB. Am J Pathol 2005;167:117-28.
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Temsirolimus in the treatment and comprise approximately one-third of pedi-

atric RCCs.3Fusion partners for the TFE3 gene Correspondence: Jigarkumar Parikh, 1120 15th
of renal cell carcinoma include the papillary renal cell carcinoma Street BAA-5407, Augusta, GA 30912, USA.
associated with Xp11.2 (PRCC) gene at 1q21, the splicing factor PSF E-mail: jparikh@mcg.edu
translocation/TFE gene gene at 1p34.1, the splicing factor NonO gene
Key words: renal cell carcinoma; Xp11.2 translo-
at Xp12, and the alveolar soft part sarcoma
fusion proteins: a case report (ASPL) gene at 17q25.3 cation, temsirolimus.
and review of literature Prognosis in children with TRCC is difficult
to ascertain from the literature, but would
1 2
Accepted for publication: 16 October 2009.
Jigarkumar Parikh, Teresa Coleman, appear to be favorable for patients with Stage
Nidia Messias,3 James Brown4 1-3 surgically resected disease and unfavor- This work is licensed under a Creative Commons
1 able for patients with stage 4 disease.3-9 The Attribution 3.0 License (by-nc 3.0).
Department of Medicine;
2 prognosis in adult onset translocation renal
Department of Medicine, Section of ©Copyright J. Parikh et al., 2009
cell carcinoma is especially poor. Argani et al.
Hematology/Oncology; 3Department of Licensee PAGEPress, Italy
analyzed 28 Xp11 translocation RCCs in Rare Tumors 2009; 1:e53
Pathology; 4Department of Surgery,
patients over the age of 20 years.8 All cases doi:10.4081/rt.2009.e53
Section of Urologic Surgery; Medical were confirmed by TFE3 immunohistochem-
College of Georgia, Augusta, GA, USA istry. Patients ranged in age from 22 to 78
years, with a strong female predominance
kidney prior to a left nephrectomy, periaortic
(female:male ratio 22:6). These cancers tend- lymphadenectomy, and caval thrombectomy. At
ed to present at advanced stage with 14 of the the time of nephrectomy, grossly, a 21x13x12.5 cm
Abstract 28 patients presenting with stage 4 disease. mass was noted extending from the hilum of
Lymph nodes were involved with metastatic the left kidney to the cortex. Pathological
Xp11.2 translocation renal cell carcinomas carcinoma in 11 of 13 cases in which they were examination of the tumor confirmed a
(TRCCs) are a rare family of tumors newly resected.8 Meyers et al. studied 5 cases of 21x13x12.5 cm mass which occupied the upper
recognized by the World Health Organization translocation carcinoma in adult patients, 18 pole and middle of kidney extending from the
(WHO) in 2004. These tumors result in the years or older (mean age 32.6 years). Patients cortex into the renal hilum. The mass grossly
fusion of partner genes to the TFE3 gene were again diagnosed with advanced disease, extended into the pelvic sinus, involved the
located on Xp11.2. They are most common in and most with distant metastases. Various renal vein and artery, and invaded into the per-
the pediatric population, but have been treatments met with minimal success. Unlike inephric fat and Gerota’s fascia. The tumor
recently implicated in adult renal cell carcino- pediatric patients, the adult patients followed a was a mostly solid red/brown to white/tan
ma (RCC) presenting at an early age. TFE3- rapidly terminal course, with a mean survival mass, with a variegated appearance, showing
mediated direct transcriptional upregulation of 18 months after diagnosis in the 3 patients areas of hemorrhage and necrosis, as well as
of the Met tyrosine kinase receptor triggers with follow-up data (range 10-24 months).9 multiple calcified areas. Periaortic lymph node
dramatic activation of downstream signaling Here we report the successful treatment of excision revealed that seven of thirty-seven
pathways including the protein kinase B adult onset TRCC with an inhibitor of the lymph nodes were involved with tumor. The
(Akt)/phosphatidylinositol-3 kinase (PI3K) mammalian target of rapamycin. liver lesions were not biopsied intraoperative-
and mammalian target of rapamycin (mTOR) ly due to the highly vascular nature of the
pathways. Temsirolimus is an inhibitor of Case Report tumor. Histopathological examination of the
mammalian target of rapamycin (mTOR) A 22-year old African American female pre- tumor revealed a renal cell carcinoma with a
kinase, a component of intracellular signaling sented to our institution with a two month his- heterogeneous appearance consisting of cells
pathways involved in the growth and prolifer- tory of hematuria, lower extremity swelling, with clear to eosinophilic cytoplasm, arranged
ation of malignant cells. Here we present a and a 25 lbs (11%) weight loss. On physical in nests and papillary cores, with extensive
case of a 22-year old female who has been examination she had tachycardia, pale oral associated necrosis and hemorrhage.
treated with temsirolimus for her Xp11.2/TFE3 mucosa, and a palpable mass in the left upper Extensive areas of ossification and focal calci-
gene fusion RCC. and lower quadrants of the abdomen. fication were also identified. Immunohisto-
A CT scan of the abdomen and pelvis chemical analysis of the primary tumor speci-
revealed a 14x14x20 cm necrotic mass in the men demonstrated the expression of the
left kidney with extension through the capsule, Xp11.2 translocation/TFE gene fusion product,
Introduction tumor invasion into the left renal vein, renal with intense and diffuse positivity. The pri-
hilar and celiac lymphadenopathy, and four ill mary tumor was also focally positive for pan-
Renal cell carcinoma predominantly mani- defined lesions in the right lobe of the liver cytokeratin, vimentin, CD-10 and negative for
fests after the age of 60 with most cases being measuring 3.3x3.2 cm, 2.4x2.5 cm, 1.6x2.6 cm, EMA. The final pathological staging reported a
sporadic. Most are clear cell carcinomas, with and 2.1x1.8 cm, respectively. A CT scan of the pT3bpN2pMX TRCC, Fuhrman grade G3, with
papillary subtypes representing a minority of chest revealed a 4 mm left lower lobe lung nod- lymphovascular invasion. Surgical margins
cases.1 Abnormalities of the Von Hipple Lindau ule and a small left pleural effusion. A bone were positive at the renal vein and artery, as
(VHL) gene are found in 40-50% of patients scan and brain MRI were negative for metasta- well as Gerota’s fascia. Unfortunately, the
with sporadic RCC, suggesting that the VHL sis. A subsequent ultrasound guided biopsy of patient’s post-operative course was complicat-
gene has a role in pathogenesis.2 The recently the kidney revealed scant fragments of an ed by a prolonged hospitalization due to a
recognized Xp11.2 translocation renal cell car- epithelioid tumor diagnosed as a renal cell car- wound infection.
cinomas are accepted as a distinctive entity in cinoma. Further classification and grading of Eight weeks post operatively the patient
the 2004 World Health Organization's renal the tumor were deferred to the permanent began chemotherapy with temsirolimus 25 mg
tumor classification.1 All bear gene fusions resection. The patient underwent an ultra- intravenously every week. Before starting
involving the TFE3 transcription factor gene sound guided alcohol embolization of the left chemotherapy the patient developed shortness

Case Report
of breath due to a worsening pleural effusion

demonstrated by chest X-ray. Her pleural effu-
sion was presumed to be malignant from
metastasis from her primary RCC. The patient
unfortunately declined a thoracentesis. The
patient responded exceptionally well to tem-
sirolimus clinically and her pleural effusion
completely resolved on chest X-ray after four
doses of temsirolimus. Significant clinical
improvement was also noted with an improve-
ment in appetite, weight gain, resolution of
her left flank pain, and a marked improvement
in her overall performance status.
Unfortunately after five months of tem-
sirolimus, the patient demonstrated disease
progression by CT scanning and recurrence of
her pleural effusion. A follow-up CT scan
revealed recurrence of her left pleural effu-
sion, a hilar mass, subcarinal lymphadenopa-
thy, and too numerous to count liver lesions.
She expired four weeks later after surviving 12 Figure 1. Pro-posed schema of ASPL-TF3-mediated MET activation and downstream effects
months from the time of diagnosis. in ASPL-TFE3-containing human cancers.
motility, and matrigel invasion 11 (Figure 1). some of their prooncogenic effects through the
Many recent publications have linked MET MET receptor tyrosine kinase signaling path-
Discussion activation to PI3K/Akt signaling.12-15 PI3K stim- way. In vitro data suggest that MEK inhibition
ulation leads to the activation of mTOR and enhances rapamycin inhibition of growth in
Translocation renal call carcinomas are usu- changes the translation rates of mRNA kidney cancer cell lines,16 and several trials of
ally considered pediatric carcinomas with a through the intermediates 4E-BP1 and p 70s6k MET inhibitors and mTor inhibitors are in
strong female predominance.1-7,10 The WHO ribosomal proteins.13 It has been shown in vitro phase I clinical trials.
describes these cancers as papillary renal cell that PI3K activation by growth factors leads to TRCCs are usually identified according to
carcinomas demonstrating translocations Akt dependant phosphorylation of the E3 ubiq- their distinct morphology, which is that of a
involving the TFE3 gene on chromosome uitin ligase Mdm2 and degradation of p53.14 In carcinoma organized in nests and papillae
Xp11.2. The histopathological appearance is vitro data also suggest that inhibition of either lined by clear cells, along with other features
usually that of a typical papillary carcinoma Mdm2 or mTOR is sufficient to block MET such as psammomatous type calcifications.1
with clear cells and cells with granular induced cell survival.13 Then, usually only in the setting of a pediatric
eosinophilic cytoplasm.1 Early adult onset Temsirolimus is an inhibitor of mammalian RCC or an adult who has disease onset at a
translocation RCC is associated with an target of rapamycin (mTOR) kinase, a compo- young age, are TRCCs suspected and immuno-
advanced stage at presentation and, most of nent of intracellular signaling pathways histochemical testing for TFE3 carried out. We
the time, with metastatic lesions.9 A mutated involved in the growth and proliferation of note with interest that several authors have
TFE3 gene leads to upregulation of the mes- cells and the response of such cells to hypoxic recently identified TRCCs by TFE3 testing on
enchymal-epithelial transition (MET) tyrosine stress. Temsirolimus binds to an abundant unusual clinical presentations of RCC that pre-
kinase receptor that triggers dramatic activa- intracellular protein, FKBP-12, and in this way sented with classical clear cell histology.3,5-7,9 If
tion of downstream signaling pathways lead- forms a complex that inhibits mTOR signal- mTOR/MEK inhibition is proven to be effective
ing to a neoplastic cascade in normal cells. ing. The disruption of mTOR signaling sup- in this subclass of renal cell carcinomas, we
Thus a therapy that blocks this pathway could presses the production of proteins that regu- would ask whether TFE3 testing would be war-
represent a reasonable approach to treatment late progression through the cell cycle and ranted in all cases of RCC in younger patients
based on biological rationale. angiogenesis.15 given the current poor prognosis of patients
The gene of interest, located at Xp11.2, is We believe that our patient’s improvement presenting with advanced stage disease.
TFE3, a member of the microphthalmia tran- with temsirolimus is due to its inhibitory
scription factor (MiTF) family. Members of this action on mTOR kinase leading to downregula-
family of genes code for basic-helix-loop-helix tion of cell proliferation and cell growth
leucine-zipper transcription factors that bind through two downstream pathways: p70S6K
DNA as homodimers or heterodimers. TFE3- and 4E-BP1.14 To date, and to our knowledge, References
mediated direct transcriptional upregulation of there has been no prior report of the use of
the Met receptor tyrosine kinase triggers dra- temsirolimus in Xp11.3/TFE3 fusion transloca- 1. Lopez-Beltran A, Scarpelli M, Montironi R,
matic activation of downstream signaling tion renal cell carcinomas. In our case report Kirkail Z. 2004 WHO Classification of the
pathways. The depletion of MET by RNA inter- we showed resolution of a presumed malig- renal tumors of adults. Eur Urol 2006;49:
ference or its functional inhibition by a selec- nant pleural effusion, weight gain, and a 798-805.
tive inhibitor abolishes hepatocyte growth fac- marked improvement in the performance sta- 2. Cohen H, McGovern F. Renal cell carcinoma.
tor (HGF) stimulated signaling pathways, lead- tus of the patient after four doses of tem- N Engl J Med 2005;353:2477-90.
ing to loss of various tumorigenic phenotypes sirolimus. We hypothesize that mTOR 3. Altinock G, Kattar M, Mohamed A, et al.
in TFE3-associated renal carcinoma cells, inhibitors interfere with effects of the TFE3 Pediatric renal carcinoma associated with
including cell proliferation, adhesion, cell gene fusion proteins leading to blockade of Xp11.2 translocations/TFE3 gene fusions

Case Report
and clinicopathologic associations. Pediatr Renal cell carcinoma in children: A different inhibition. Cancer Res 2007; 67:919-29.
Dev Pathol 2005;8:168-80. disorder from its adult counterpart? Med 12. Gentile A, Trusolino L, Comoglio P. The Met
4. Camparo P, Vasiliu V, Molinie V, et al. Renal Pediatr Oncol 1998;31:153-8. tyrosine kinase receptor in development
translocation carcinomas: clinicopathologic, 8. Argani P, Olgac S, Tickoo S, et al. Xp11 and cancer. Cancer Metastasis Rev 2008;
immunohistochemical, and gene expres- translocational renal cell carcinoma in 27:85-94.
sion profiling analysis of 31 cases with a adults: Expanded clinical, pathological and 13. Moumen A, Patane S, Porras A, et al. Met
review of the literature. Am J Surg Pathol genetic spectrum. Am J Surg Pathol acts on Mdm2 via mTOR to signal cell sur-
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5. Perot C, Boccon-Gibod L, Bouvier R, et al. 9. Meyer P, Clark J, Flanigan R, Picken M. 2007;134:1443-51.
Five new cases of juvenile renal cell carcino- Xp11.2 Translocation renal cell carcinoma 14. Adjei AA, Hidalgo M. Intracellular signal
ma with translocations involving Xp11.2: a with very aggressive course in five adults. transduction pathway proteins as targets for
cytogenic and morphologic study. Cancer Am J Clin Pathol 2007;128:70-9. cancer therapy. J Clin Oncol 2005; 23:5386-
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6. Ramphal R, Pappo A, Zielenska M, et al. carcinoma associated with MiTF/ TFE 15. Bjornsti MA, Houghton PJ. The TOR path-
Pediatric renal cell carcinoma: clinical, translocation: report of six cases in young way: a target for cancer therapy. Nat Rev
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associated with the members of the MiT 11. Tsuda M, Davis I, Argani P, et al. TFE fusions 16. Costa L, Gemmill R, Drabkin H. Upstream
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2006;126:349-64. up-regulation, defining another class of effect on growth of kidney cancer cells.
7. Carcao M, Taylor G, Greenberg M, et al. tumors as candidates for therapeutic MET Urology 2007;69:596-602.

Metastasizing pleomorphic the right side. The patient did not report any
symptoms that would point to a disease of the Correspondence: Jan Ebbing, Department of
adenoma presenting as an urogenital tract. The physical examination Urology, Campus Benjamin Franklin, Charité –
asymptomatic kidney tumor was without pathological findings. A comput- Universitätsmedizin Berlin, Hindenburgdamm
30, 12200 Berlin, Germany.
twenty-nine years after erized tomography (CT) scan of the abdomen
E-mail: jan.ebbing@charite.de
revealed the presence of two suspect cortical
parotidectomy – urological tumors (20 mm and 50 mm in diameter) in
viewpoint and overview of the right kidney. In addition, the CT scan was
Key words: carcinoma ex-mixed tumor, metasta-
sizing mixed tumor, metastasizing pleomorphic
the literature to date suspicious for pulmonary metastases and a CT
adenoma, kidney metastasis, kidney tumor.
scan of the chest confirmed the presence of
Jan Ebbing,1 Carolin Blind,2 Harald Stein,2 multiple pulmonary lesions in both lungs, with Contributions: JE was the main author and initia-
Kurt Miller,1 Christoph Loddenkemper2 a maximal diameter of 11 mm in the right tor of the case report; CB worked on the patholog-
1
lower lobe. The right kidney was removed by ical findings; HS approved the pathological find-
Department of Urology, and 2Institute of laparoscopic radical nephrectomy as clinically ings; KM was responsible for the patient´s urolog-
Pathology, Charité–Universitätsmedizin renal cell carcinoma was suspected, without ical treatment; CL was responsible for the patho-
Berlin, Campus Benjamin Franklin, Berlin, complications. logical findings and proofread the article.
Germany
Pathological Findings
Accepted for publication: 30 November 2009.
Gross findings This work is licensed under a Creative Commons
Abstract On sectioning the cut surface of the kidney Attribution 3.0 License (by-nc 3.0).
revealed a white, solid, lobulated, well-circum-
Pleomorphic adenomas (benign mixed scribed tumor in the middle third of the ©Copyright J. Ebbing et al., 2009
tumors) are the most common tumors of glan- parenchyma, which measured 55x55x50 mm Licensee PAGEPress, Italy
and penetrated the capsule (Figure 1A). Rare Tumors 2009; 1:e54
dular origin in the head and neck and are one
doi:10.4081/rt.2009.e54
of the few benign neoplasms that can undergo Another smaller, similar focus of 10 mm in
malignant transformation.1 Mixed tumors that diameter was found in the surrounding
are seemingly benign at the microscopic level parenchyma close to the hilus.
but metastasize have been termed metastasiz- ductal structures without atypia (Figure 1B).
ing mixed tumors (MZMTs). The entity of Histological findings Immunohistochemical studies showed that
metastasizing benign mixed tumors has been The microscopic features of both tumors the epithelial component stained positive for
reported since the early 1940s, with up to showed a mixed cell composition with mes- pan-cytokeratin AE1/AE3 with partial expres-
approximately 50 cases described in the liter- enchymal elements demonstrating chondroid sion of the myoepithelial markers p63
ature to date. Despite their bland morphologic differentiation embedded in a myxoid matrix, (Figure 1C) and a very low Ki-67 proliferation
appearance, MZMTs have been associated as well as epithelial components consisting of rate (Figure 1D).
with an overall mortality rate of about 20-40%.
We report the case of a MZMT of the kidney
almost 30 years after lateral parotidectomy
owing to the same tumor entity. For benign
Figure 1. (A) Gross appear-
mixed tumors, we are unaware of more than ance of the dissected
two other cases of metastasis to the kidney nephrectomy specimen
that have been published, whereas metastases showing a well-defined
to the bone, lung, and lymph nodes are more tumor with a homoge-
common. Parotidectomy is widely accepted as neous tan cut surface. (B)
Histology displays the typ-
the first choice of treatment,13 but once metas- ical features of a benign
tases have occurred the therapeutic strategy (metastasizing) pleomor-
is uncertain with surgery being the only cura- phic adenoma in the right
tive option in cases with resectable disease. kidney with a mesenchy-
This case report provides information about mal cartilaginous compo-
nent and an epithelial duc-
the rare event of metastatic disease to the kid- tal component within renal
ney and points out therapeutic strategies. tissue (left lower corner).
However, in view of the general lack of ade- (C) The myoepithelial cells
quate information in the literature, the best showing expression of p63.
therapy for systemic disease still remains (D) The Ki-67+ prolifera-
tive index is seen as
unresolved. extremely low (<1%). (E)
Macroscopy of the paraffin
block from 1978 showing
a small nodular tumor of
Case Report the parotid gland with a
white-to-tan cut surface.
(F) The identical morphol-
A 49-year-old woman suffered from a car ogy of a pleomorphic ade-
accident and was brought to our clinic. A rou- noma in the salivary gland
tine ultrasound scan of the abdomen in the tissue is demonstrated (left
lower corner).
emergency unit detected a kidney tumor on

Case Report
Statement of the pathologist which mixed tumor may have the potential to
The histopathological features of the tumors metastasize and which patient may die of References
disclosed a mixed tumor of salivary gland ori- metastatic disease.6 However, the probability
gin, in particular for a metastasizing pleomor- that a benign mixed tumor will become malig- 1. Klijanienko J, El-Naggar AK, Servois V, et al.
phic adenoma, but were not typical of a pri- nant depends on the period of time it has been Clinically aggressive metastasizing pleomor-
mary tumor of the kidney. allowed to develop without treatment. The risk phic adenoma: report of two cases. Head
The past history of the patient revealed that of malignant transformation – usually into a Neck 1997;19:629-33.
a lateral parotidectomy on the left side had carcinoma ex-pleomorphic tumor – ranges 2. Czader M, Eberhart CG, Bhatti N, et al.
been performed 29 years previously because of from 1.5% in the first five years to 9.5% after Metastasizing mixed tumor of the parotid:
a tumor mass of the parotid gland diagnosed as 15 years.7 It is estimated that approximately initial presentation as a solitary kidney
a pleomorphic adenoma. The pathological 20-40% of patients with MZMT will die from tumor and ultimate carcinomatous transfor-
report described a 45x35x28 mm gland with a the disease eventually.6 Surgical manipula- mation at the primary site. Am J Surg Pathol
tumor 22 mm in diameter. It was possible to tions are thought to create a metastatic poten- 2000;24:1159-64.
retrieve the old paraffin blocks from the tial but do not truly explain the occurrence of 3. Li X, Lu XY, Zhu XZ, et al. Metastasising pleo-
archives of the Institute of Pathology of the metastases.8 Metastases were discovered from morphic adenoma of the parotid presenting
Charité–Campus Benjamin Franklin, which 6 to 52 years after the primary tumor was as a solitary kidney mass. Pathology 2008;40:
showed a white cut surface of the tumor removed.9 About 40-50% of patients suffering 87-9.
(Figure 1E). On histology, even in retrospect, from carcinoma ex-pleomorphic adenoma 4. Fujimura M, Sugawara T, Seki H, et al.
no signs of malignancy were detected and the develop local recurrence and up to 70% develop Carcinomatous change in the cranial metas-
tumor was still classified as a pleomorphic ade- local or distant metastases.10 Systematic data tasis from a metastasizing mixed tumor of
noma with characteristic epithelial and mes- for MZMTs concerning recurrence and the salivary gland - case report. Neurol Med
enchymal composition (Figure 1F) and great metastatic rates are lacking. In contrast to our Chir (Tokyo) 1997;37:546-50.
morphological similarity to the kidney metas- case, the patients normally have at least one 5. Minic AJ. Unusual variant of a metastasizing
tasis 29 years later. episode of tumor recurrence at the primary malignant mixed tumor of the parotid gland.
site before the development of metastases, Oral Surg Oral Med Oral Pathol 1993;76:330-
which may occur many years after the presen- 2.
tation of the primary mixed tumor. The 6. Batsakis JG. Malignant mixed tumor. Ann
Discussion metastatic potential of mixed tumors is related Otol Rhinol Laryngol 1982;91:342-3.
to the accumulation of key genetic alterations. 7. Seifert G, Sobin LH. The World Health
We report the case of a metastasizing The development of a carcinoma ex-mixed Organization's Histological Classification of
“benign” pleomorphic adenoma of the kidney tumor apparently could be, in part, the conse- Salivary Gland Tumors. A commentary on the
almost 30 years after a lateral parotidectomy quence of the accumulative loss of chromoso- second edition. Cancer 1992;70: 379-85.
owing to the same tumor entity. A CT scan mal loci at 3p, 9p, and 17p.11 A number of case 8. Ellis G. Tumors of the Salivary Glands. In:
revealed suspect pulmonary masses in both reports describe the simultaneous appearance Tumors of the Salivary Glands. Ellis GL,
lungs that have remained stable over a period of benign and malignant components of mixed Auclair PL, eds. Washington, DC: 1996, pp
of three months. After discussion with an tumors in the same tumor manifestation.2,5,12 155-373.
oncologist a surveillance strategy of the The order of genetic alterations along tumor 9. Wenig BM, Hitchcock CL, Ellis GL, et al.
asymptomatic patient was agreed. progression seems to be variable and may dif- Metastasizing mixed tumor of salivary glands.
Mixed tumors of the salivary glands general- fer for each salivary tumor, but for MZMT no A clinicopathologic and flow cytometric analy-
ly are divided into benign mixed tumors and recurrent genetic defect has been reported. sis. Am J Surg Pathol 1992; 16:845-58.
malignant mixed tumors, represented by carci- Parotidectomy is widely accepted as the first 10. Bradley P. Metastasizing pleomorphic sali-
nosarcomas (true malignant mixed tumors) choice of treatment,13 but once metastases vary adenoma should now be considered a
and so-called carcinoma ex-mixed tumors, have occurred, the therapeutic strategy is low-grade malignancy with a lethal potential.
which can develop within a benign mixed uncertain with surgery being the only curative Curr Opin Otolaryngol Head Neck Surg
tumor over an extended period of time.1 Rarely option in cases with resectable disease. 2005;13:123-6.
will a mixed tumor that is seemingly benign at 11. Johns MM 3rd, Westra WH, Califano JA, et al.
the microscopic level metastasize. These Allelotype of salivary gland tumors. Cancer
tumors have been termed metastasizing mixed Res 1996;56:1151-4.
tumors (MZMTs) and have been classified as Conclusions 12. Hellquist H, Michaels L. Malignant mixed
metastasizing pleomorphic adenomas within tumour. A salivary gland tumour showing
the category of malignant epithelial tumors of Metastatic pleomorphic adenoma of the both carcinomatous and sarcomatous fea-
the salivary gland by the WHO. Some authors salivary gland to the kidney is a very rare neo- tures. Virchows Arch A Pathol Anat
suggest that a MZMT could be the intermediate plasm, which requires a careful patient histo- Histopathol 1986;409:93-103.
link in the transformation of a pleomorphic ry and knowledge of the lesion for patholo- 13. Paris J, Facon F, Chrestian MA, et al.
adenoma into a carcinoma ex-mixed tumor.2-5 A gists and clinicians to reach the correct diag- Recurrences of pleomorphic adenomas of
published case report from Czader et al. under- nosis. There is no approved hypothesis as to the parotid: changing attitudes. Rev Laryngol
lined the suggestion that MZMT and carcinoma how a morphologically benign tumor may Otol Rhinol (Bord) 2003;124:229-34.
ex-mixed tumor could represent different metastasize. Surgery of resectable disease
stages along a common biological pathway.2 with curative intent should be attempted
Histopathological and clinical criteria to dif- whenever possible. In view of the general lack
ferentiate metastatic mixed tumors from non- of adequate information in the literature, the
metastatic mixed tumors are lacking. There best therapy for systemic disease still
are no predictive factors available to determine remains unresolved.

A case of primary mucosa- mild prostate enlargement and no lymph-

adenopathy or hepatosplenomegaly. Trans- Correspondence: Masanori Noguchi, Department
associated lymphoid tissue rectal ultrasonography showed a 4.3x3.2 cm of Urology, and Clinical Research Division of
lymphoma of the prostate prostate with high echoic spots in the transi- Research Center for Innovative Cancer Therapy,
tion zone. The laboratory data showed that the Kurume University School of Medicine, 67
Asahi-machi, Kurume 830-0011, Japan.
Noriko Koga,1 Masanori Noguchi,1,3 serum PSA level was 7.53 ng/mL (normal: <4.0
E-mail: noguchi@med.kurume-u.ac.jp
Fukuko Moriya,1,2 Kouichi Ohshima,2 ng/mL). A transrectal ultrasound-guided
Nobuyuki Yoshitake,4 Kei Matsuoka1 prostate needle biopsy was performed and the Key words: mucosa-associated lymphoid tissue
prostatic tissues of the biopsy demonstrated lymphoma, prostate, prostate-specific antigen,
Departments of 1Urology, 2Pathology, and radiation therapy.
3
diffuse lymphoid infiltrations extending in
Clinical Research Division of Research
most areas in 12 of 12 biopsy specimens. The Received for publication: 18 October 2009.
Center for Innovative Cancer Therapy, lymphoid cells invaded the prostate glandular Accepted for publication: 30 November 2009.
Kurume University School of Medicine, epithelium and the characteristic lympho-
Kurume, Japan; 4Yoshitake Urological This work is licensed under a Creative Commons
epithelial lesions were seen (Figure 1).
Clinic, Kurume, Japan Attribution 3.0 License (by-nc 3.0).
The lymphoid cells in these areas were uni-
form in size and shape. They were each char- ©Copyright N. Koga et al., 2009
acterized by a scanty, clear cytoplasm and a Licensee PAGEPress, Italy
round, slightly cleaved nucleus. The morpho-
Abstract doi:10.4081/rt.2009.e55
logic features were those of centrocyte-like
cells (Figure 2).
We report a case of primary mucosa-associat- In addition, cells with plasma cell differenti-
ed lymphoid tissue (MALT) lymphoma of the ation were seen. The immunohistochemical
prostate. A 67-year-old man presented with uri- analysis showed that the lymphoid cells were
nary obstruction and an elevated prostate-spe- positive for CD79a and partially positive for
cific antigen (PSA) level. A physical examina- CD20, and that a small number of cells were
tion revealed mild prostate enlargement and no positive for CD3. These histological results
lymphadenopathy. A needle biopsy and immu- confirmed a low-grade MALT lymphoma of the
nohistochemical studies of the prostate were prostate. A bone marrow aspiration and biopsy
performed, which revealed marginal zone B-cell did not show involvement by lymphoma.
MALT-type lymphoma. A bone marrow aspira- Magnetic resonance imaging (MRI) of the
tion and biopsy did not show involvement by abdomen and pelvis revealed no lym-
lymphoma. Magnetic resonance imaging (MRI) phadenopathy or ascites. Positron emission
Figure 1. Lymphoid cells invading the
of the abdomen and the pelvis revealed no lym- tomography (PET) images showed abnormal prostate gland-ular epithelium.
phadenopathy or ascites. There was no involve- uptake only in the prostate. There was no
ment of other sites by lymphoma. The patient involvement of other sites by lymphoma. The
was diagnosed and staged as extranodal mar- patient was diagnosed and staged as a margin-
ginal zone B-cell MALT-type lymphoma of the al zone B-cell MALT-type of non-Hodgkin’s lym-
prostate, low grade and stage I. The patient phoma of the prostate, low grade and stage I.
received external beam radiation therapy to the The patient received external beam radia-
prostate with a total dose of 3600cGy in 22 fraction therapy to the prostate with a total dose of
tions, and became free of disease within the fol- 3600cGy in 22 fractions. A follow-up biopsy of
lowing 15 months. the prostate was performed 12 months after
the radiation therapy. The immunohistochemi-
cal analysis showed that a small number of lym-
phocytes were more dominantly positive for CD3
Introduction than CD20 and CD79a, and negative for CD10,
Bcl2, and CD20. Light chain restriction staining Figure 2. Cells with scanty clear cytoplasm
Low-grade B-cell mucosa-associated lym- also showed no κ- and λ-reactivity. These find- and a round, slightly cleaved nucleus.
phoid tissue (MALT) lymphoma rarely presents ings confirmed no recurrence of MALT lym-
as a primary tumor in extranodal sites other phoma of the prostate. The patient was free of
than in the stomach, which is the most common disease within the following 15 months.
site.1 To date only seven cases of primary prosta- Primary prostatic MALT lymphoma is extreme-
tic MALT lymphoma have been reported in the ly rare and its clinicopathological features are
literature to our knowledge.2-8 We report here a not well clarified. To our knowledge only seven
new case that had an elevated prostate-specific Discussion cases have been reported previously. Clinical
antigen (PSA) level and was treated successful- features of these seven cases, as well as that
ly by external beam radiation therapy alone. The criteria for primary prostatic lymphoma of our case, are shown in Table 1. The patients
includes disease limited to the prostate and were elderly men with a mean age of 73 years
adjacent soft tissue, absence of lymph node (57-87 yr). The most frequent symptom was
involvement, and a systemic lymphoma-free urinary tract obstruction. Three patients had
Case Report interval of at least one month.9 Primary prosta- elevated PSA levels (>4.0 ng/mL). The diagno-
tic lymphoma is rare. It accounts for 0.1% of sis of prostatic MALT lymphoma was made by
A 67-year-old man presented with urinary newly diagnosed lymphomas and comprises transurethral resection (TUR) in seven
obstruction. A physical examination revealed less than 0.09% of all prostate neoplasms.10 patients and a trans-rectal needle biopsy in

Case Report
Table 1. Clinical features of eight primary prostatic MALT lymphoma.

Case Age Symptom Laboratory Clinical Treatment Response Outcome Follow-up Reference
(years) findings stage (months)
1 75 Hematuria, pyuria Normal II TUR, Cx CR AW 12 2
2 57 Urinary obstruction Normal I TUR, Cx CR AW 18 3
3 84 Urinary obstruction Elavated PSA I TUR CR DOC 24 4
4 67 Prostatism Normal I TUR, Rx CR AW 36 5
5 87 Urinary obstruction Normal I TUR NR NR NR 6
6 79 Urinary obstruction Normal I TUR CR AW 108* 7
7 70 Disuria Elevated PSA I TUR, Cx CR AW 5 8
8 67 Urinary obstruction Elevated PSA I Rx CR AW 15 Present case
*Relapse was noted 7 years after the initial treatment; AW, alive and well; CR, complete remission; Cx, chemotherapy; DOC, died of other causes; MALT, mucosa-associated lymphoid tissue; NR, not recorded; PSA,
prostate-specific antigen; Rx, radiotherapy; TUR, transurethral resection.
one patient. All patients had clinical stage I prostate. Leuk Lymphoma 2001;41:445-9.
disease except for one case with tumor References 6. Tissier F, Badoual C, Saporta F, et al.
involvement in the epididymis and spermatic Prostatic lymphoma of mucosa-associated
cord. Seven patients underwent TUR, three 1. The Non-Hodgkin’s Lymphoma Classifica- lymphoid tissue: an uncommon location.
had additional chemotherapy, and one had tion Project. A clinical evaluation of the Histopathology 2002;40:111-3.
additional radiotherapy. Our patient was treat- international lymphoma study group: clas- 7. Li C, Hibino M, Komatsu H, et al. Primary
ed by radiotherapy alone according to the non- sification of Non-Hodgkin’s lymphoma. mucosa-associated lymphoid tissue lym-
Hodgkin’s lymphoma (NHL) medical guide- Blood 1997;89:3909-18. phoma of the prostate: tumor relapse 7
line. The clinical course in each case was 2. FrancoV, Florena AM, Quinini G, et al. years after local therapy. Pathol Int 2008;
favorable, although one patient died of other Monocytoid B-cell lymphoma of the 58:191-5.
causes. Another site of marginal zone B-cell prostate. Pathologica 1992;84:411-7. 8. Kawamoto K, Takeshita T, Iwasaki H, et al.
lymphoma of the MALT type was characterized 3. Tomikawa S, Okumura H, Yoshida T, et al. Extranodal marginal zone B-cell lym-
by a high frequency of localized extranodal Primaly prostatic lymphoma of mucosa- phoma of mucosa-associated lymphoid tis-
disease and a prolonged survival, whereas associated lymphoid tissue. Intern Med sue (MALToma) of prostate; a case report.
nodal marginal zone (monocytoid) B-cell lym- 1998;37:628-30. J Diag Pathol 2008;25:43-6.
phoma more often occurred with advanced- 4. Tomaru U, Ishikura H, Kon S, et al. 9. Mermershtain W, Benharroch D,
stage disease and had a worse survival rate.1 Primary lymphoma of the prostate with Lavrenkov K, et al. Primary malignant lym-
However, in case 2, a tumor relapse was features of low grade B-cell lymphoma of phoma of the prostate: a report of three
detected seven years after the initial TUR. It mucosa-associated lymphoid tissue: a rare cases. Leuk Lymphoma 2001;42:809-11.
seems that long-term follow-ups and more cause of urinary obstruction. J Urol 1999; 10. Sarris A, Dimopoulos M, Pugh W, et al.
reports are needed to clarify the clinical char- 162:496-7. Primary lymphoma of the prostate: good
acteristics and pathogenesis of this disease. 5. Jhaver S, Agerwal JP, Naresh KN, et al. outcome with doxorubicin-based combi-
Primaly extranodal mucosa-associated nation chemotherapy. J Urol 1995;53:
lymphoid tissue (MALT) lymphoma of the 1852-4.

Re: Koga et al. A case of Moreover, the reported 1-year lymphoma spe-
cific survival in this series is in heavy contrast Correspondence: Damien C. Weber, Geneva
primary mucosa-associated of the favourable outcome of MALT prostate University Hospital, Radiation Oncology
lymphoid tissue lymphoma patient reported by Koga et al.1 Definitive con- Department, Geneva, Switzerland.
E-mail:damien.weber@hcuge.ch
of the prostate clusions about the importance of histology on
staging and prognosis cannot however be
inferred from these studies, because of the Received for publication: 22 December 2009.
Damien C. Weber Accepted for publication: 23 December 2009.
small sample size. Further research regarding
Geneva University Hospital, Radiation the outcome of these patients is justified in the This work is licensed under a Creative Commons
Oncology Department, Geneva, framework of future retrospective studies. As Attribution 3.0 License (by-nc 3.0).
Switzerland such, the Rare Cancer Network (http://www.
rarecancer.net) is currently undertaking a large ©Copyright D.C. Weber, 2009
study of primary low- and high-grade lymphoma Licensee PAGEPress, Italy
In the review of MALT of the prostate per-
formed in the case report published by Koga et of the prostate. Inclusion criteria are the follow-
doi:10.4081/rt.2009.e56
al1., the overall majority of these low-grade ing: i) biopsy-proven non-Hodgkin’s lymphoma
tumours seems to be of clinical stage IE. (NHL) extra nodal of the prostate gland; ii) neg-
Conversely, primary non-Hodgkin lymphomas ative work-up (abdominal-pelvic CT with or
of the prostate of non-MALT histology appear without bone marrow aspirate) and iii) mini-
to have a much higher rate of extraprostatic mal follow-up of 6 months. References
involvement. Botstwick et al. reported on 22 We invite all investigators to participate to
primary prostate NHL and observed a 50% and this study that aims to more comprehensively 1. Koga N, Noguchi M, Moriya F, et al. A case
19% of lymph node and spleen involvement, investigate and clarify the staging features and of primary mucosa-associated lymphoid
respectively.2 outcome of these exceptional patients. tissue lymphoma of the prostate. Rare
Tumors 2009;1e55.
2. Bostwick DG, Iczkowski KA, Amin MB, et
al. Malignant lymphoma involving the
prostate: report of 62 cases. Cancer 1998;
83:732-8.

A clinical and molecular project ent on the presence of part of the Y chromo-
some, known as the GBY region, tumor occur- Correspondence: Charles Sultan, Unité
on gonadoblastoma needs rence remains multi-factorial. The overall d’Endocrinologie-Gynécologie Pédiatriques,
international collaboration tumor risk is evaluated at 30% for complete Service de Pédiatrie 1 Hôpital Arnaud de
gonadal dysgenesis and is variable for other Villeneuve, CHU Montpellier, 34295 Montpellier,
Nicolas Kalfa,1,3 Olivier Maillet,1 cases of dysgenesis. Apart from the presence of France. E-mail: c-sultan@chu-montpellier.fr
Charles Sultan1,2 Y material, no other risk factor has been found.
Received for publication: 21 December 2009.
1 Moreover, GB can be a precursor of dysgermi-
Service d'Hormonologie, Hôpital Accepted for publication: 23 December 2009.
noma, but the predictive factor for the transfor-
Lapeyronie, CHU de Montpellier et UM1,
mation into an aggressive cancer is again This work is licensed under a Creative Commons
Montpellier, France; 2Unité
unknown.3,5 An early prophylactic gonadectomy Attribution 3.0 License (by-nc 3.0).
d’Endocrinologie et Gynécologie has thus been advocated for many patients
Pédiatriques, Service de Pédiatrie, with GD. In order to provide better guidelines ©Copyright N. Kalfa et al., 2009
Hôpital Arnaud de Villeneuve et UM1, for making therapeutic decisions about Licensee PAGEPress, Italy
CHU de Montpellier, France; 3Service de Rare Tumors 2009; 1:e57
patients with DSD and to prevent abusive
doi:10.4081/rt.2009.e57
Chirurgie et Urologie Pédiatrique, Hôpital gonadectomy, we plan to perform a clinical,
Lapeyronie, CHU de Montpellier et UM1, immunohistochemical and genetic study on
Montpellier, France gonadoblastoma. Hence, we here present an
international call to perform a multicenter
analysis of this rare tumor. The first objective References
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unusual tumor developed by patients present- factors, the diagnostic circumstances, and the 1. Scully RE. Gonadoblastoma; a gonadal
ing a disorder of sex development (DSD). The hormonal profiles of patients with GB. This tumor related to the dysgerminoma (semi-
term gonadoblastoma was first introduced in data collection will define the specific charac- noma) and capable of sex-hormone pro-
19531 to designate a steroid hormone-secret- teristics of these patients, guide subsequent duction. Cancer 1953;6:455-63.
ing gonadal tumor. This name was chosen research, and enable us to test the correlation 2. Scully RE. Gonadoblastoma. A review of 74
because the neoplasm appeared to recapitulate of these characteristics with histological crite- cases. Cancer 1970;25:1340-56.
gonadal development more completely than ria. Then, analysis of the molecular profile of 3. Hersmus R, de Leeuw BH, Wolffenbuttel
any other type of tumor. In 1970, Scully2 report- this tumor will focus on sexual determination KP, Drop SL, Oosterhuis JW, Cools M, et al.
ed 74 cases of GB and precisely defined it as factors (SOX9, FOXL2), pluripotency and dif- New insights into type II germ cell tumor
the association of embryonic germ cells and ferentiation factors (OCT3/4). Both expression pathogenesis based on studies of patients
supportive cells that resemble immature of candidate genes inside the tumor and their with various forms of disorders of sex
Sertoli/granulosa cells in a context of gonadal direct sequencing on tumor DNA (SOX9, development (DSD). Mol Cell Endocrinol
dysgenesis (GD). FOXL2, TSPY) could provide new pathophysio- 2008;291:1-10.
First, the natural history of GB remains logical insights into GB. 4. Page DC. Y chromosome sequences in
unclear. Patient phenotypes are often female For this purpose, we would appreciate Turner's syndrome and risk of gonadoblas-
but some degree of masculinization is possi- receiving the following: (i) a short report of toma or virilisation. Lancet 1994;343:240.
ble.3 Diagnosis is frequently made during con- the patient history recorded on a specific 5. Hersmus R, Kalfa N, de Leeuw B, Stoop H,
sultation for primary amenorrhea with the dis- patient form and (ii) ten uncolored slides of Oosterhuis JW, de Krijger R, et al. FOXL2
covery of Swyer syndrome. Tumor secretion the tumor, with if possible frozen tissue. and SOX9 as parameters of female and
may also induce the development of secondary Overall, the pathophysiology of GB develop- male gonadal differentiation in patients
sexual characteristics and diagnosis after sec- ment is unknown. A collaborative internation- with various forms of disorders of sex
ondary amenorrhea has been described. al study will bring much needed information development (DSD). J Pathol 2008;215:
Patients with true hermaphroditism can also on the connections between tumorogenesis 31-8.
present with GB. and developmental abnormalities, and could
Second, the predictive factors of GB develop- improve the follow-up of patients with DSD,
ment are largely unknown. Although Page4 while reducing the rate of prophylactic
hypothesized that GB development is depend- gonadectomy.

Primary NK/T cell lymphoma medium and large cells) is often found.6 This
type is known to be highly aggressive and asso- Correspondence: Sebastian Kobold,
nasal type of the stomach with ciated with a very poor prognosis in dissemi- Universitätsklinikum Hamburg Eppendorf,
skin involvement: a case report nated disease.7 Primary gastric lymphomas are Klinik für Hämatologie, Onkologie, Pneumologie
rare, especially of the NK/T cell nasal type.8 und Knochenmarkstransplantation,
Sebastian Kobold,1 Hartmut Merz,2 According to literature only 2 cases of primary Martinistrasse 52, 20246 Hamburg, Germany
gastric NK/T cell lymphoma nasal type have E-mail: sebastian.kobold@hotmail.de
Markus Tiemann,3 Carolina Mahuad,1
Carsten Bokemeyer,1 Irmtraut Koop,4* been reported.9,10 These patients did not show
Key words: NK/T cell lymphoma nasal type, pri-
Walter Fiedler1* involvement of other sites except stomach. mary intestinal lymphoma, skin involvement.
1
They died shortly after diagnosis.
Department of Oncology/Hematology/ Conflict of interest: the authors report no con-
Bone Marrow Transplantation/ flicts of interest.
Pneumology, University Medical Center
Eppendorf; 2Department of Pathology, Case Report Contributions: the original manuscript was writ-
University of Lübeck; 3Institute for ten by SK. All authors participated in drafting and
editing the manuscript. IK and WF share senior
Hematological Pathology, Hamburg; A 69-year old Caucasian man was first hos-
4
authorship. All authors read and approved the
Department of Internal Medicine, pitalized with hematemesis and melena. The final manuscript. The authors all provide special-
Amalie-Sieveking Hospital, Hamburg endoscopic examination revealed a bleeding ized multidisciplinary clinical care for cancer
*both authors share senior authorship, duodenal ulcer, Forrest 1a and a second ulcer patients in Hamburg, Germany.
Germany in the antrum of the stomach (Figure 1).
Biopsies were taken from the gastric ulcer. The Consent: the patient’s wife, as his legal supervi-
pathological examination revealed a high- sor, has provided informed consent for the publi-
grade lymphoma of the stomach. Roughly, the cation of this case report and accompanying
histo-morphology showed an angiocentric and images.
Abstract angiodestructive growth pattern with a mixed
cell population accompanied by a heavy admix-
Since nasal NK/T cell lymphoma and NK/T Revision received: 14 December 2009.
ture of inflammatory cells. Immunohisto- Accepted for publication: 14 December 2009
cell lymphoma nasal type are rare diseases, chemistry revealed positivity for CD2, CD56,
gastric involvement has seldom been seen. We and a weak expression of CD20, as well as a This work is licensed under a Creative Commons
report a unique case of a patient with a pri- negative stain for CD4, CD5, CD7, CD8, CD30, Attribution 3.0 License (by-nc 3.0).
mary NK/T cell lymphoma nasal type of the CD33, CD34, CD79a, CD103, CD117 and CD138
stomach with skin involvement. The patient ©Copyright S. Kobold et al., 2009
(Figure 2). A CD3ε, stain on a fresh tissue
had no history of malignant diseases and was Licensee PAGEPress, Italy
sample was also positive. The neoplastic cells Rare Tumors 2009; 1:e58
diagnosed with hematemesis and intense showed strong granular staining for the cyto- doi:10.4081/rt.2009.e58
bleeding from his gastric primary site. Shortly toxic molecules granzyme B, perforin and
after this event, exanthemic skin lesions TIA1. The immunostaining with a monoclonal
appeared with concordant histology to the pri- ry was insignificant apart from newly diag-
antibody for the anaplastic lymphoma kinase
mary site. Despite chemotherapy, the patient nosed diabetes and the loss of 10% body weight
(ALK) was negative. The molecular analysis of
died one month after the first symptomatic the TCR γ-chain-locus showed a germline con- in the previous four months rated as B-symp-
appearance of disease. figuration. By analyzing the samples for IgH toms. The patient met the Dawson criteria for
gene rearrangement by PCR analysis, no clon- primary intestinal lymphoma.12
al rearrangement could be found.11 Although In addition, shortly after the symptomatic
EBER (EBV encoded small nuclear RNAs) appearance of his disease, the patient devel-
Introduction expression was negative which is an unususal oped exanthemic non-pruriginous skin
finding for nasal NK-T-cell lymphoma; we per- lesions. A biopsy was performed and the
According to the WHO classification of lym- formed an LMP-1 stain, revealing strong cyto- immunohistochemical assessment showed the
phoma, the NK cell type can be classified into plasmatic and surface membrane expression same expression profile as described above
3 subgroups: NK/T cell lymphoma nasal/nasal in almost all lymphoma cells. Therefore, pres- (Figure 3). Dermal spread of the NK/T cell lym-
type, NK cell leukemia and chronic lymphopro- ence of an EBV-related lymphoma could be phoma nasal type was concluded. It can be
liferative disorders of NK cells.1,2 Among non- concluded. A NK/T cell lymphoma, nasal type deducted that the patient had a stage IVB dis-
Hodgkin’s lymphomas, NK/T cell lymphoma with partial aberrant expression of CD20 was ease before the start of the therapy.
nasal type is a very rare subtype, predominant- diagnosed. The patient underwent the usual Chemotherapy using the CHOP-protocol
ly found in East Asia. There it makes up 2-10% staging examinations with clinical exam, com-
(cyclophosphamid, hydroxydaunorubicin, onco-
of NHL (non-Hodgkin’s lymphoma).3 It is pri- putertomographic assessment of the chest, the
vin, prednison) was applied and well tolerated
marily located in the nasal/nasopharyngeal abdomen and the pelvis, a bone marrow biopsy
region (75%), the skin (4%), the gastrointesti- by the patient. About a week later, the patient
and a positron emission tomography. None of
nal tract (6%), the bone marrow and the these assessments uncovered another involved developed grade IV hematoxicity, becoming
spleen.4 NK/T cell lymphoma nasal type is diag- site. In particular, the nasal and nasopharyn- aplastic and septic. Supportive care was pro-
nosed by immunophenotyping. The typical geal regions as well as the bone marrow, were vided with antibiotic escalation and parenteral
phenotype has been described as CD2+, free of disease. No lymphadenopathy was support. Meanwhile skin infiltration increased
CD3/Leu4–, CD3ε+, CD3–, CD56+, TCR germline found. The patient had no history of celiac dis- with several new lesions. Despite all efforts,
and generally EBV+.5 Based on histological cri- ease and serological analysis was negative for the patient died of septic complications, most-
teria, angiocentric and/or angiodestructive specific antibodies. The LDH was 865U/L at ly due to a severe pneumonia. The patient’s
behavior with mixed in cell morphology (small, time of diagnosis. The patient’s medical histo- relatives declined autopsy.

Case Report
Discussion
The presence of this rare tumor lead us to
various differential diagnoses. First, an
anaplastic large cell lymphoma (ALCL) was dis-
cussed. According to the latest WHO classifica-
tion, these lymphomas are CD30 positive, and
are in 80% of all cases ALK positive. As the
present lymphoma completely lacked expres-
sion of these markers, an ALCL could be exclud-
ed. Enteropathy-associated T-cell lymphoma
(EATL) was then taken into consideration. The
WHO1 defines the polymorphic form (type I) of
EATL as CD3+, CD5–, CD7–, CD8+/-, CD4–,
CD103+, TCRβ+/- and cytotoxic proteins positive.
The monomorphic form (type II) is defined as Figure 1. Endoscopic appearances of primary gastric NK–/T−cell lymphoma: ulcerative
type.
CD3+, CD4–, CD8+, CD56+ and TCRβ+. The lym-
phoma cells were completely negative for these
markers except CD56 and the cytotoxic pro-
teins. These markers are insufficient for the
diagnosis of EATL.1 A primary cutaneous γ-d T-
cell lymphoma was excluded because of the
negativity for CD3 and the TCR germline con-
figuration, required for diagnosis by the WHO
classification.1 Finally, a peripheral T-cell lym-
phoma not otherwise specified was considered
due to the typical involvement of skin and stom-
ach.1 CD4+ and clonal TCR gene rearrangement
is most frequently seen, in contrast to the pres-
ent case, albeit a false negative TCR rearrange-
ment and a negative stain for CD4 have been
described before.1 In addition, a peripheral T-
cell lymphoma not otherwise specified could
only be diagnosed if other lymphoma types are Figure 2. Immunostain-ing with monoclonal antibody directed against CD56 (A) and
ruled out. As the morphology didn’t match the CD2 (B). Nearly all the stomach infiltrating cells were positive.
typical morphology of such a peripheral T-cell
lymphoma we didn’t favor this diagnosis.
Because of the CD20 positivity, a B-cell lym-
phoma was considered, but given the negativi-
ty for CD79a and a lack of clonal IgH gene
rearrangement associated with the above men-
tioned immunohistochemical profile, a B-NHL
seemed very unlikely. An aberrant expression
of CD20 was concluded.
We compared the findings in the present
patient with a recent analysis on the largest
series of NK/T-cell lymphoma.13 As was seen in
this collective, CD2, CD3ε, TIA-1, granzyme B
and CD56 stainings were positive. Although
CD30 was negative in our extranasal case, it
was negative in 37% of cases in this series and
it is not a prerequisite according to WHO clas-
Figure 3. Immunostain-ing with monoclonal antibody directed against CD56 (A) and
sification. The germline configuration of TCR CD2 (B). About 80% of the skin infiltrating cells were positive.
fits into the findings of this series, as most
extranasal cases were found negative for TCR
rearrangement. The EBER positivity was an ular tumor concurred only with an extranodal and LMP-1 analysis to assess EBV status of
obligatory inclusion criteria in this study. The NK/T-cell lymphoma nasal type. The EBER-neg- lymphomas, as is recommended in Hodgkin’s
strong LMP-1 expression of the present case, ativity could be explained by a low quality of lymphomas.16
which points towards an EBV-associated lym- preservation of the paraffin wax-embedded Several authors have advocated the estab-
phoma, can easily weigh out the EBER negativ- blocks14 or by a lack of expression of EBER-1, as lishment of a prognostic model for NK/T cell
ity for EBV diagnosis. has been reported in other tumors.14,15 Our find- lymphoma nasal type that is more reliable than
Finally the immunophenotype of this partic- ings argue in favor of the combination of EBER IPI1,7,17,18 (International Prognostic Index).

Case Report
Factors significantly associated with a worse ral killer/T-cell lymphoma and natural 14. Cabrera ME, Eizuru Y, Itoh T, et al. Nasal
prognosis are male gender, the presence of B- killer precursor lymphoma among natural killer/T-cell lymphoma and its
symptoms, high LDH, advanced stage and Koreans. Cancer 2000 Nov 15;89:2106-16. association with type "i"/XhoI loss strain
CD30 negativity. In our case, the patient pos- 5. Chan JK, Sin VC, Wong KF, Ng CS, Tsang Epstein-Barr virus in Chile. J Clin Pathol
sessed all negative prognostic factors and died WY, Chan CH, et al. Nonnasal lymphoma 2007;60:656-60.
shortly after diagnosis. expressing the natural killer cell marker 15. Jaffe ES, Chan JK, Su IJ, et al. Report of
Past experiences with the CHOP-regi- CD56: a clinicopathologic study of 49 cases the Workshop on Nasal and Related
menindicated that it might not be an adequate of an uncommon aggressive neoplasm. Extranodal Angiocentric T/Natural Killer
therapeutic approach for advanced stage dis- Blood 1997;89:4501-13. Cell Lymphomas. Definitions, differential
ease.19 Some authors have suggested high- 6. Ohshima K, Suzumiya J, Sugihara M, et al. diagnosis, and epidemiology. Am J Surg
dose chemotherapy associated with autologous Clinical, immunohistochemical and phe- Pathol 1996;20:103-11.
or allogeneic transplantation for patients with notypic features of aggressive nodal cyto-
16. Gulley ML, Glaser SL, Craig FE, et al.
NK/T cell lymphoma nasal type and poor prog- toxic lymphomas, including alpha/beta,
Guidelines for interpreting EBER in situ
nosis.20,21 In this case, the general condition of gamma/delta T-cell and natural killer cell
hybridization and LMP1 immunohisto-
the patient at the start of the therapy did not types. Virchows Arch 1999;435:92-100.
chemical tests for detecting Epstein-Barr
allow such an aggressive approach. Therefore, 7. Mraz-Gernhard S, Natkunam Y, Hoppe RT,
the standard CHOP therapy was chosen in virus in Hodgkin lymphoma. Am J Clin
LeBoit P, Kohler S, Kim YH. Natural
order to improve the overall condition of the killer/natural killer-like T-cell lymphoma, Pathol 2002;117:259-67.
patient.22 CD56+, presenting in the skin: an increas- 17. Assaf C, Gellrich S, Whittaker S, et al.
To our knowledge, this patient is a unique ingly recognized entity with an aggressive CD56-positive haematological neoplasms
case of a primary NK/T cell lymphoma of the course. J Clin Oncol 2001;19:2179-88. of the skin: a multicentre study of the
stomach with skin involvement. To date, no 8. Dargent JL, Roufosse C, Vanderschueren Cutaneous Lymphoma Project Group of the
conclusive theory has been described to B, Nouwynck C, Salhadin A, Jamsin S, et European Organisation for Research and
explain why this type of lymphoma remains al. Natural killer-like T-cell lymphoma of Treatment of Cancer. J Clin Pathol 2007;
confined to these unusual locations.22 We hope the stomach. Scand J Gastroenterol 1999; 60:981-9.
that our experience might help in the under- 34:445-8. 18. Lim ST, Hee SW, Quek R, et al.
standing of this very rare disease. 9. Ko YH, Cho EY, Kim JE, Lee SS, Huh JR, Comparative analysis of extra-nodal NK/T-
Chang HK, et al. NK and NK-like T-cell lym- cell lymphoma and peripheral T-cell lym-
phoma in extranasal sites: a comparative phoma: significant differences in clinical
clinicopathological study according to site characteristics and prognosis. Eur J
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