A case of ATLL (adult T-cell leukemia/lymphoma) mimicking

odontogenic infection
Tomohiro Yamada, DDS, PhD,a Katsuaki Mishima, DDS, PhD,b Akiko Ota, DDS, PhD,b
Norifumi Moritani, DDS, PhD,b Tatsushi Matsumura, DDS, PhD,b Naoki Katase, DDS, PhD,c
and Tetsuya Yamamoto, DDS, PhD,a Kochi and Okayama, Japan
KOCHI UNIVERSITY AND OKAYAMA UNIVERSITY

A case of adult T-cell leukemia/lymphoma (ATLL) in which cheek swelling was the initial symptom is
presented. A 44-year-old man referred to our hospital with swelling in his right cheek, and a dental infection was
suspected by a previous physician. Computerized tomographic scans and magnetic resonance imaging revealed
tumorous lesions from the right alveolus of the maxilla to the anterior and posterior walls of the maxillary sinus. Anti–
HTLV-1 antibodies were positive, and the level of sIL-2R was high; other laboratory test results were normal., based on
immunohistochemical results on a specimen biopsy, the patient was diagnosed with a lymphoma-type ATLL.
Immediately, the patient was treated in the department of hematologic medicine. After several courses of multiagent
chemotherapy, 27 Gy radiation therapy was directed to the maxilla. However, remission was not achieved. Cord
blood transplantation was subsequently performed, but his general condition gradually worsened until he died 7
months after his initial visit. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:e51-e55)

Adult T-cell leukemia/lymphoma (ATLL) is a malig- pected a dental infection. The patient was born in Nagasaki in
nant tumor caused by the human T-cell lymphotropic the southeastern part of Japan. His medical history revealed
virus (HTLV-1).1 ATLL shows various signs and no other past disease. He had not seen a dentist for many
symptoms, such as fever, general fatigue, lymphade- years. Physical examination showed no lymphadenopathy or
skin lesions, but he had paresthesia in the right infraorbital
nopathy, and atypical lymphocytes in the peripheral
region. An intraoral examination revealed diffuse swelling
blood.1,2 Extranodal lesions occasionally occur in the
with tenderness in the right maxillary buccal molar region,
skin, liver, spleen, and bone marrow and less com- and his right canine had not erupted. His oral hygiene was
monly in the head and neck.3,4 Extranodal ATLLs in relatively poor. He had a history of alcohol use and smoking
the sinonasal tract have also been reported in the liter- tobacco daily. Routine blood tests and biochemical examina-
ature.4-8 However, there are few reports of tumors in tions were performed and revealed no alterations in blood
the maxillofacial region.9,10 The present article reports count, lactate dehydrogenase (LDH), and calcium. However,
a case of ATLL presenting as a maxillary tumor which a serum antibody titer for HTLV-1 was extremely high, and
mimicked a dental infection around an impacted max- his serum soluble interleukin-2 receptor (sIL-2R) was signif-
illary canine. icantly elevated (4,326 U/mL).
Panoramic radiography showed a diffuse radiolucent lesion
CASE REPORT in the right maxilla, and it contained the root of an impacted
A 44-year-old man was referred to our department (Oral canine (Fig. 1). Maxillofacial computerized tomography (CT)
and Maxillofacial Reconstructive Surgery, Okayama Univer- showed a diffuse bone-destructive mass in the anterior max-
sity Hospital) for a right cheek swelling of 1 month’s dura- illa that infiltrated beyond the bony wall (Fig. 2). Magnetic
tion. An otorhinolaryngologist from another hospital sus- resonance imaging showed a similar mass with muscle-like
density in the T1-weighted image and a mass slightly denser
than muscle in the T2-weighted image. Abdominal CT re-
a
Department of Oral and Maxillofacial Surgery, Kochi Medical vealed several liver lesions, osteolytic changes in the verte-
School, Kochi University. brae (L2 and L3), and lymphadenopathy around the jejunum.
b
Department of Oral and Maxillofacial Reconstructive Surgery, Positron emission tomography with 2-deoxy-2-[18F]fluoro-
Okayama University Graduate School of Medicine, Dentistry, and D-glucose (FDG) revealed multiple uptakes of FDG in the
Pharmaceutical Sciences. right maxilla, right lung, liver, vertebrae, and intra-abdominal
c
Department of Oral Pathology and Medicine, Okayama University lymph nodes (Fig. 3).
Graduate School of Medicine, Dentistry, and Pharmaceutical Sci-
An incisional biopsy was performed from the subcutaneous
ences.
Received for publication Dec 16, 2009; returned for revision Feb 3,
granulation-like tissue on the buccal side of the maxilla under
2010; accepted for publication Feb 7, 2010. local anesthesia, and the specimen was submitted for histo-
1079-2104/$ - see front matter logic and immunohistochemical examination. The hematox-
© 2010 Mosby, Inc. All rights reserved. ylin-eosin–stained sections revealed diffuse proliferation of
doi:10.1016/j.tripleo.2010.02.021 small and medium atypical lymphocytes. These tumor cells

e51
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e52 Yamada et al. June 2010

eral blood (Fig. 6). Furthermore, the right maxillary abscess

recurred and was treated conservatively with local irrigation
and periodontal currettage. Additionally, vindesine 4 mg,
etoposide 160 mg ⫻ 3, carboplatin 400 mg, and prednisolone
60 mg (VECP) and mensa 1,200 mg ⫻ 3, ifosfamide 2 g ⫻
3, mitoxantrone hydrochloride 12 mg, and etoposide 100 mg ⫻ 3
(MINE) chemotherapy was undertaken, plus local radiother-
apy on the right maxilla (27 Gy). Subsequently, an umbilical
cord blood transplant was performed with the previous treat-
ment (etoposide 2.7 g ⫻ 2, cytarabine 8.2 g ⫻ 2, and total
body irradiation 12 Gy). The transplant succeeded, but he
developed an acute lung injury and acute respiratory distress
syndrome. Despite steroid pulse therapy and cyclophospha-
Fig. 1. Panoramic radiograph. The right maxillary canine is mide pulse therapy, his general condition gradually worsened,
impacted, and an ill-defined osteolytic lesion is observed in and he died 7 months after his initial visit.
the right infraorbital region.

DISCUSSION
Adult T-cell leukemia/lymphoma is caused by an
HTLV-1 infection and has a very poor prognosis.2,3
The infection routes are mainly through breast-feeding,
blood transfusion, and sexual contact. The most impor-
tant route is vertical transmission by breast-feeding.11
In the present patient, we could not confirm whether his
mother was an HTLV-1 carrier or not. The distribution
of HTLV-1 carriers is heterogeneous in that area, and
the same is true for the patient distribution.12 The
common regions for this disease are southeastern Ja-
pan, central Africa, the Caribbean area, and Central and
South America.2 In Japan, ⬎1,200,000 carriers exist,
and ⬎700 people develop ATLL annually. Approxi-
mately 2%-3% of these carriers develop ATLL a few
decades after infection.13 The present patient was from
Nagasaki, a common region for ATLL in Japan.
ATLL is classified by 4 types: 1) a smoldering vari-
ant; 2) a chronic variant; 3) an acute variant; and 4) a
lymphomatous variant.3 The survival periods has been
reported to be 5 years, 2 years, 6 months, and 10
Fig. 2. Computerized tomography images of the maxilla. A months, respectively.14 Symptoms include general fa-
diffuse destructive mass is shown in the anterior maxilla that tigue, fever, lymphadenitis, hepatosplenomegaly, and
infiltrates beyond the bony wall. skin eruptions. Disturbances in consciousness occur,
accompanied by hypercalcemia, thirst, constipation,
muscle weakness, and nephropathy. Abdominal pain
and refractory diarrhea occur with digestive tract infil-
infiltrated into the fatty tissues and destroyed and replaced the tration, and headaches occur with central nervous sys-
existing tissue. There were some cells with large and very tem infiltration.1,3,12,14 These symptoms were not rec-
atypical nuclei (Fig. 4). Immunohistologically, CD3 (Fig. 5, ognized in the present patient, because the disease was
a), CD4, CD43, and CD45R0 were positive, but CD8, CD20, in its early stage. Demanding treatment precaution,
CD56, CD79a, TdT, and TIA-1 were negative. Ki-67 was ATLL is accompanied by severe immunodeficiency,
strongly immunopositive (Fig. 5, b).
and infection control is very important. The present
The patient was diagnosed with ATLL and referred to the
Department of Hematology and Oncology of Okayama Uni-
patient had a tumor in an impacted canine and devel-
versity Hospital. The patient was treated with 3 courses of oped a concurrent dental infection that required oral
cyclophosphamide 1,200 mg, adriamycin 80 mg, vincristine 2 health care by professionals knowledgeable of this dis-
mg, and prednisolone 100 mg (CHOP) chemotherapy. Al- ease.
though the abdominal lymphomas were reduced, the cheek The head and neck region is a common site for
tumor did not shrink, and flower cells appeared in the periph- malignant lymphomas, and 3%-5% of head and neck
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Volume 109, Number 6 Yamada et al. e53

Fig. 3. Positron emission tomography images. Multiple uptakes of FDG are shown in the right maxilla, liver, vertebrae, ilium,
and intra-abdominal lymph nodes.

Fig. 4. Histology of the surgical specimen) obtained from the subcutaneous granulation-like tissue on the buccal side of the right
maxilla (hematoxylin-eosin stain; a, ⫻100; b, ⫻1,000. Diffuse proliferation of small and medium atypical lymphocytes is
observed. Tumor cells infiltrated into the fatty tissues and destroyed and replaced the existing tissue. Cells with large and very
atypical nuclei evident.

malignancies are malignant lymphomas.15-18 However, lesions are rare. The present case is the first that devel-
T-cell lymphoma is rare in the head and neck region, oped from periodontal infection of an impacted tooth.
and ⬎90% are B-cell lymphomas.17 ATLL in the max- Chronic inflammation is now accepted as a risk factor
illofacial region is rare, and only a few dozen cases for the development of malignancies. Rauch et al.20
have been reported,4,6-10,18,19 including our patient. reported that T cells activated by inflammation can
Most of the ATLLs in the maxillofacial region have promote lymphomagenesis. In the present patient, a
been in the paranasal sinus, and intraorally detectable similar mechanism may have occurred at the site of
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e54 Yamada et al. June 2010

Fig. 5. Immunohistochemistry of the surgical specimen. a, CD3 immunoreactivity was expressed on the cytomembrane (⫻100);
b, Ki-67 was extremely immunopositive in the nuclei (⫻1,000).

beyond the bony wall in lymphomas. For a definitive

diagnosis of ATLL, ATLL cells must be confirmed in
the peripheral blood or in the tumor. The origin of
ATLL is peripheral CD4-positive cells.3 The tumor
specimen from the present patient was CD4 positive on
immunohistochemical staining, and serum antibody to
HTLV-1 was also immunopositive. Furthermore, B-
cell markers CD20 and CD79a were both negative, and
the T-cell markers CD3, CD45RO, and CD43 were
immunopositive. The lymphoblast marker TdT and the
cytotoxic protein TIA-1 were negative, but the cell
growth marker Ki-67 was strongly immunopositive.
For all of these reasons, the tumor was diagnosed as a
peripheral T-cell lymphoma with high proliferative ca-
pacity.
The treatment for ATLL (acute and lymphoma vari-
Fig. 6. Histology of the peripheral blood (Giemsa stain,
ants) is aggressive multiple chemotherapy, with addi-
⫻500). A flower cell with a cleaved nucleus is seen in the tional supportive therapy for opportunistic infections
peripheral blood. and organ damage, and/or hematopoietic stem cell
transplantation. However, a standard treatment protocol
has not been established yet, and the prognosis is still
poor. The smoldering and chronic variants have mild
chronic odontogenic infection in the maxilla. Notably, courses, and they do not require immediate treatment,
the Japanese cases were all from southern Kyusyu or considering the side effects of chemotherapy.1,3,21
southeastern Shikoku, both in the southeastern region In dental and oral surgery practice, the differential
of Japan. diagnosis of ATLL is very important, especially distin-
In the maxillofacial region, a differential diagnosis of guishing it from infectious lesions. Helpful in the di-
lymphoma from infectious disease is sometimes diffi- agnosis is understanding its regional distribution, as
cult. As a characteristic of their CT images, bony de- well as examining for anti–HTLV-1 antibody and
struction is relatively slight and infiltration continues sIL-2R.
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Volume 109, Number 6 Yamada et al. e55

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13. Takatsuki K. Discovery of adult T-cell leukemia. Retrovirology
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