Papers by Michael Deavers
The American Journal of Surgical Pathology, Feb 1, 2004
In this study, we investigated HMB-45 expression in epithelioid uterine leiomyosarcomas with clea... more In this study, we investigated HMB-45 expression in epithelioid uterine leiomyosarcomas with clear cell areas. From 12 epithelioid leiomyosarcomas, we selected 5 that had: 1) clear cell areas and 2) spindle cell areas that were at least focally positive for desmin and caldesmon. The patients' ages ranged from 47 to 82 years (mean 64 years). Presenting symptoms were uterine bleeding (three), abdominal pain (one), and a pelvic mass (one). There was no history of tuberous sclerosis or lymphangioleiomyomatosis. One patient had stage II disease, one stage III, and three stage IV. All were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Two received radiotherapy, and three were also treated with chemotherapy. The tumors ranged in size from 4 x 3 x 3 cm to 10 x 7 x 6 cm; all had significant cellular atypia, areas of coagulative necrosis, and between 10 and 90 mitoses per 10 high power fields. Vascular invasion was seen in three cases. The epithelioid component varied from 50% to 90% in each case; and the percentage of clear cells was < 1% in one case, 5% in one case, and 10% to 80% in three cases. Smooth muscle actin and desmin were positive in all cases. Four cases were positive for HMB-45 only in the clear cell areas. The tumor with < 1% of clear cells was negative for HMB-45. All were negative for S-100 and c-kit. Three patients died of disease at 9, 30, and 32 months; one patient is alive with progressive disease at 6 months, and one patient (stage II disease) is alive with no evidence of disease at 8 months. Unequivocal uterine epithelioid leiomyosarcomas may have clear cells positive for HMB-45. These tumors might belong to the group of lesion designated as PEComas; however, it is advisable to designate them as uterine leiomyosarcomas. In uterine smooth muscle tumors, some epithelioid cells most likely undergo clear cell changes and become positive for HMB-45. It would be advisable to perform this stain in all epithelioid smooth muscle tumors of the uterus.
International Journal of Clinical and Experimental Pathology, 2011
TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulat... more TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening.
Gynecologic Oncology, May 31, 2007
Primary non-diethylstilbestrol (DES)-associated adenocarcinoma of the vagina (NDAV) is a rare ent... more Primary non-diethylstilbestrol (DES)-associated adenocarcinoma of the vagina (NDAV) is a rare entity that has not been well described. The purpose of this study was to define the pathologic characteristics of verified NDAV and characterize the outcomes of patients who present with this rare malignancy. The tumors of all patients treated with definitive radiation therapy for NDAV between 1970 and 2000 were centrally reviewed. Data regarding patient, tumor, and treatment characteristics were abstracted from the hospital records of each patient. Survival rates were calculated and outcomes of patients with NDAV were compared with those of patients with squamous cell carcinoma (SCC) of the vagina treated similarly over the same period. Twenty-six patients with a median age of 54 years had primary NDAV confirmed by central pathologic review. Twenty patients (77%) were treated with external-beam radiation therapy (EBRT) followed by brachytherapy, and six patients (23%) were treated with EBRT alone. At 5 years, the overall survival rates of patients with NDAV and SCC were 34% and 58%, respectively (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). Patients with NDAV had a significantly worse pelvic disease control rate than patients with SCC (31% vs. 81%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). At 5 years, 39% of patients with NDAV and 15% with SCC had developed distant metastasis (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). Primary NDAV is a rare disease with a poor prognosis. Patients with this disease have significantly worse outcomes than do patients with SCC, and chemotherapy or novel systemic biologic agents may be needed to achieve higher cure rates.
The American Journal of Surgical Pathology, Sep 1, 2005
Ovarian serous carcinoma (OSC) is the most common ovarian epithelial malignancy. Recently, a dual... more Ovarian serous carcinoma (OSC) is the most common ovarian epithelial malignancy. Recently, a dualistic pathway of ovarian serous carcinogenesis has been proposed based on morphologic observations and molecular genetic analysis. In this scheme, low-grade OSC arises in a stepwise fashion from a benign serous cystadenoma through a usual serous borderline tumor through a micropapillary variant of serous borderline tumor. In contrast, the more common high-grade OSC arises de novo from the ovarian surface epithelium or the epithelium of cortical inclusion cysts with an as yet unrecognized precursor lesion. Although the division of OSC into low- and high-grade variants is gaining greater acceptance, and although there is accumulating molecular genetic evidence for this, there is little published information regarding a comparison of protein expression between these two types of OSC. In this study, we have investigated the immunohistochemical expression of a wide range of proteins in cases of low-grade (n = 22) and high-grade (n = 47) OSC. Antibodies used were p53, MIB1, BCL2, WT1, HER-2/neu, C-KIT, osteopontin, and survivin. For all antibodies, except MIB1, cases were scored as 0 (negative or occasional positive cells), 1+ (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10% cells positive), 2+ (10%-25% cells positive), 3+ (26%-50% cells positive), 4+ (51%-75% cells positive) or 5+ (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;75% cells positive). For MIB1, the percentage of positive nuclei was calculated. There was a statistically significant higher expression of p53, MIB1, BCL2, HER-2/neu, and C-KIT in high-grade compared with low-grade OSC (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Thirty of 47 (64%) cases of high-grade OSC exhibited 5+ staining with p53 compared with 4 of 22 (18%) low-grade neoplasms. Twelve of 47 (26%) high-grade OSCs exhibited 5+ staining with BCL2 compared with 1 of 22 (5%) low-grade OSCs. The mean MIB1 proliferative index in high-grade OSCs was 55.4% compared with 23.0% in low-grade OSCs. Virtually all cases of both low-grade and high-grade OSCs exhibited diffuse nuclear positivity with WT1 and diffuse cytoplasmic positivity with survivin. Osteopontin expression was variable with no significant difference in expression between low-grade and high-grade OSC. Although expression of both HER-2/neu and C-KIT was significantly higher in high-grade compared with low-grade OSC, only rare cases exhibited strong positivity with these antibodies, which could be of therapeutic value in individual cases, although this would require additional molecular investigations. The significant differences in protein expression between low-grade and high-grade OSC provides further support for a different underlying pathogenesis. In particular, the differences in p53 immunoreactivity are in keeping with the observation that p53 gene mutation is more common in high-grade than low-grade OSC.
Clinical Cancer Research, Jun 1, 2002
Purpose: The purpose of this study was to examine ovarian cancer cells for the expression of deco... more Purpose: The purpose of this study was to examine ovarian cancer cells for the expression of decorin, a proteoglycan component of the cell matrix that can inhibit cancer cell growth.
Skeletal Radiology, Apr 18, 2011
Parachordoma is a rare tumor, with fewer than 100 cases reported. We present an unusual presentat... more Parachordoma is a rare tumor, with fewer than 100 cases reported. We present an unusual presentation of a long tumor tracking along the median nerve, with regional metastasis to the axillary nodes in a 67-year-old woman. The tumor extended from the wrist proximally along the forearm to the elbow, coursing intraneurally along the median nerve. We present this case due its rarity, interesting radiographic appearance, and atypical presentation.
The American Journal of Surgical Pathology, Dec 1, 2006
Ovarian serous borderline neoplasm with noninvasive implants traditionally have been considered t... more Ovarian serous borderline neoplasm with noninvasive implants traditionally have been considered to be nonaggressive tumors associated with an excellent prognosis. However, in our experience, recurrences commonly develop as patients are followed over many years. Eighty cases of advanced-stage ovarian serous borderline tumor with noninvasive implants were identified; the minimum follow-up period for these cases was 5 years or until the death of the patient. The following cases were excluded: patients treated by cystectomy, patients who died of other causes, patients who developed other tumors, and patients who had as the only positive material after resection of the primary borderline neoplasm a tumor detected on a second look or third look operation. Hematoxylin and eosin-stained slides from the original ovarian tumor and the staging biopsies were reviewed in all cases. Slides of the recurrent tumor were available in all cases except for 2 in which the diagnosis was established clinically. The presence or absence of a micropapillary/cribriform pattern and microinvasion in the ovarian tumor was recorded. Follow-up was obtained from the patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; charts. Fischer exact test was used for statistical analysis. The patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; ages ranged from 17 to 67 years (median 36 y). Seventy-three patients were treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy. Seven patients were treated by total abdominal hysterectomy and unilateral salpingo-oophorectomy. The International Federation of Gynecology and Obstetrics stage was as follows: stage II (29 cases), stage III (50 cases), and stage IV (1 case). After surgery, 58 patients were treated with chemotherapy, 7 with radiotherapy, and 1 with hormonal therapy. The follow-up ranged from 5 to 31 years (median 15.7 y). Thirty-five patients (44%) developed recurrences. Only 10% of the patients had a recurrence in less than 5 years, 19% had their recurrences between 5 and 10 years, 10% between 10 and 15 years, and 5% more than 15 years after resection of the primary neoplasm. The only statistically significant feature associated with recurrence was the presence of a micropapillary/cribriform pattern, although this pattern was present in only 26% of the cases that recurred. Of the 35 patients who had a recurrence, 2 were diagnosed clinically, both are alive with progressive disease at 1 and 5 years after the diagnosis of the recurrence; 6 had recurrent serous borderline tumors, all are without evidence of disease with a follow-up ranging from 7 to 18 years after resection of the ovarian borderline tumor (median 14 y); and 27 patients subsequently developed low-grade serous carcinoma, 7 are alive with progressive disease with a follow-up ranging from 10 to 29 years (median 15 y) and 20 died of disease between 3 to 25 years after resection of the ovarian borderline tumor (median 16 y). In summary, the true recurrence rate of ovarian serous borderline tumors with noninvasive implants can only be obtained through a long follow-up. In this group of patients, 77% and 34% of the subsequent tumors developed 5 years and 10 years after diagnosis of the ovarian tumor, respectively. Histologic examination of the recurrent tumor is important in determining further therapy and prognosis for these patients; all patients who recurred with borderline tumor are without evidence of disease, whereas 74% of the patients who recurred with low-grade serous carcinoma died of disease. We propose that patients be followed for a minimum of 10 years to evaluate for recurrences and for 20 years to evaluate for survival.
Obstetrics and Gynecology, Feb 1, 2010
Women with Lynch syndrome or hereditary nonpolyposis colorectal carcinoma (HNPCC) have a 40-60% l... more Women with Lynch syndrome or hereditary nonpolyposis colorectal carcinoma (HNPCC) have a 40-60% lifetime risk of endometrial cancer and a 7-12% lifetime risk of ovarian cancer. Risk-reducing surgery, including hysterectomy and bilateral salpingo-oophorectomy (BSO), is currently recommended once child bearing is complete. We describe two cases of primary peritoneal cancer after BSO in women with Lynch syndrome or HNPCC. The first patient was a 44-year-old woman who underwent hysterectomy with BSO for benign disease. She presented 12 years later with a pelvic mass and was diagnosed with a high-grade serous primary peritoneal cancer. Genetic testing showed a mutation in the MSH2 DNA mismatch repair gene. The second case was a 58-year-old woman who had a hysterectomy and BSO for endometrial cancer. She developed a high-grade serous primary peritoneal cancer 8 years later and was found to have a mutation in the PMS2 DNA mismatch repair gene. Women with Lynch syndrome or HNPCC should be counseled that they may be at risk for developing primary peritoneal cancer despite undergoing gynecologic cancer risk-reducing surgery. The magnitude of this risk remains to be determined.
International Journal of Gynecological Pathology, Sep 30, 2001
Primary ovarian carcinomas with unusual histologic patterns can be difficult to differentiate fro... more Primary ovarian carcinomas with unusual histologic patterns can be difficult to differentiate from metastases. In this study, we reviewed 15 cases of mixed-epithelial carcinoma (12 serous, 1 serous and endometrioid, 1 endometrioid, 1 undifferentiated) with a predominant microcystic pattern and signet-ring cells. The patients&#39; ages ranged from 31 to 78 (mean 58) years. The microcystic component in 11 patients had features of high-grade carcinoma and in 4 patients had features of low-grade carcinoma associated with areas of borderline tumor. The tumors in all 15 patients showed a predominant microcystic growth pattern composed of small cysts that were variable in size and shape. Signet-ring cells were also present in all cases (diffusely in nine cases, focally in six cases) within the neoplastic epithelial proliferation. Mucin was present in the lumina of some of the microcysts and in the cytoplasm of most of the signet-ring cells. A microcystic pattern and mucin-containing signet-ring cells can be seen as small foci or as a predominant component in primary epithelial nonmucinous ovarian carcinomas. It is important for pathologists to recognize these unusual findings in ovarian neoplasms, because they may produce a confusing apperance, even potentially suggesting a metastasis.
The American Journal of Surgical Pathology, Dec 1, 2004
Metastasis of ovarian or peritoneal serous carcinoma to the breast and/or axillary lymph nodes is... more Metastasis of ovarian or peritoneal serous carcinoma to the breast and/or axillary lymph nodes is a rare event. Nevertheless, its recognition and distinction from mammary carcinoma are of great clinical importance because the treatment and prognosis differ significantly. Eighteen cases of ovarian or peritoneal serous carcinoma metastatic to the breast and/or axillary LNs from a 14-year period (1990-2003) were retrieved from our files. Clinical information was obtained from the patients' charts. The age of the patients ranged from 21 to 67 years (median, 55 years). The primary tumors included 14 ovarian serous carcinomas (11 high grade and 3 low grade; 2 of the low-grade tumors presented as serous tumors of low malignant potential and recurred as low-grade serous carcinoma) and 4 peritoneal serous carcinomas (3 high grade and 1 low grade). Of the ovarian neoplasms, 1 was stage I and 10 were stage III tumors; the breast and/or axillary lymph node metastases were discovered on average 30 months after presentation (range, 7-135 months). Three of the ovarian serous carcinomas were stage IV tumors; in 1 case, there were axillary lymph node metastases at initial presentation; and in 2 cases, breast and/or axillary lymph node metastases developed at 18 and 102 months. Two of the 4 patients with peritoneal serous carcinoma presented with stage IV disease, having synchronous breast and axillary lymph node metastases; the other 2 patients developed them at 11 and 16 months after presentation. Four patients had multiple breast lesions and 8 patients had a single metastasis. In 4 cases, the breast metastases were initially interpreted as infiltrating ductal carcinoma. The remaining 6 patients had axillary lymph node involvement only. The metastases in 17 of the cases had papillary features, with psammoma bodies present in 4. Immunoperoxidase studies for GCDFP-15 and WT-1 were performed in 4 cases; all 4 were positive for WT-1 and negative for GCDFP-15. Follow-up was available for 17 patients, with 7 patients known to be dead from disease (survival range, 2-31 months) after the development of metastatic disease to the breast or axillary lymph nodes. Ten patients were alive with disease at their last follow-up, which ranged from 1 to 30 months after the breast or axillary LN metastasis developed. Metastases to the breast or axillary lymph nodes from ovarian and/or peritoneal serous carcinomas are uncommon. Most of the patients in whom metastatic disease develops have a known history of advanced stage ovarian or peritoneal carcinoma. Breast and/or axillary LN involvement at initial presentation can occur but is rare. Differentiation between metastatic and primary tumors of the breast is of great importance because treatment and prognosis differ significantly. Clinical history, the presence of papillary architecture, and WT-1 expression are useful in establishing the correct diagnosis.
The American Journal of Surgical Pathology, Aug 1, 2005
Although differential WT-1 expression between ovarian and uterine serous carcinoma has been discu... more Although differential WT-1 expression between ovarian and uterine serous carcinoma has been discussed in the literature, there have been no studies of WT-1 expression in serous carcinomas in the peritoneum with or without concurrent serous carcinoma in an endometrial polyp. This study addresses this issue and includes a small series of uterine and ovarian serous carcinomas for comparison. Nine peritoneal serous carcinomas with coexistent serous carcinoma in an endometrial polyp, 10 peritoneal serous carcinomas without serous carcinoma in an endometrial polyp, 9 uterine serous carcinomas, and 12 ovarian serous carcinomas were stained with antibody to WT-1. Ninety-two percent of ovarian serous carcinomas and 80% of peritoneal serous carcinomas without serous carcinoma involving an endometrial polyp expressed WT-1. In contrast, 12% of peritoneal serous carcinomas with serous carcinoma in an endometrial polyp expressed WT-1 with the serous carcinoma in the endometrial polyp staining concordantly. For uterine serous carcinoma without an endometrial polyp, only 11% expressed WT-1. Peritoneal serous carcinomas without coexistent serous carcinoma in an endometrial polyp have a WT-1 expression pattern similar to ovarian serous carcinoma while peritoneal serous carcinomas with coexistent serous carcinoma in an endometrial polyp have a staining pattern similar to uterine serous carcinoma. The difference in WT-1 expression among serous carcinomas suggests a difference in biology based on the site of origin. Additionally, the difference in WT-1 expression between peritoneal serous carcinomas with and without coexistent serous carcinoma in endometrial polyps suggests that peritoneal serous carcinoma may have different pathogenetic pathways.
Gynecologic Oncology, Apr 1, 2003
beta-Catenin has been previously associated with oncogenic activity in human cancers. We evaluate... more beta-Catenin has been previously associated with oncogenic activity in human cancers. We evaluated whether beta-catenin also plays a role in papillary serous ovarian neoplasms. Immunohistochemistry for beta-catenin was performed on the primary ovarian serous neoplasms of 105 women. Of these, 10 were low malignant potential (LMP) serous tumors, and 95 were serous cancers. Nuclear beta-catenin staining was correlated with grade of tumor and median survival. OVCAR-3, OVCA-420, OVCA-432, and MDAH-277-10c were evaluated for beta-catenin localization and transfected with a T-cell factor (TCF) responsive reporter to evaluate beta-catenin transcriptional activity. Of 105 serous tumors, 13 (12.3%) demonstrated beta-catenin nuclear staining. Eleven of 48 high-grade serous carcinomas (23.0%) demonstrated nuclear staining compared with 1 low-grade serous carcinoma (2.1%) (P = 0.006). One LMP tumor had nuclear staining. beta-Catenin nuclear localization was undetectable in the cell lines tested. Furthermore, transient transfection of the cell lines with a TCF-responsive reporter did not demonstrate significant constitutive transcriptional activation. We found a statistically significant correlation between beta-catenin nuclear localization and ovarian high-grade serous carcinomas. Thus, deregulation of beta-catenin may play a role in the pathogenesis of ovarian high-grade serous carcinomas in contrast to ovarian low-grade serous carcinomas and LMP serous tumors.
Cancer, Jan 15, 2007
BACKGROUND. EphA2 is overexpressed in the majority of ovarian cancers and predicts poor clinical ... more BACKGROUND. EphA2 is overexpressed in the majority of ovarian cancers and predicts poor clinical outcome. Based on EphA2's emerging role in angiogenesis, we hypothesized that tumors overexpressing EphA2 demonstrate greater microvessel density (MVD) and matrix metalloproteinase (MMP) expression.
The American Journal of Surgical Pathology, Feb 1, 2008
Uterine tumors with neuroectodermal differentiation, frequently referred to as primitive neuroect... more Uterine tumors with neuroectodermal differentiation, frequently referred to as primitive neuroectodermal tumors (PNETs), are uncommon. The clinicopathologic features of 17 such cases reviewed at the M.D. Anderson Cancer Center (MDACC) are presented along with a review of the literature. All of the pathology material was reviewed at MDACC, and in all cases, immunohistochemistry contributed to the diagnosis. In 12 cases, in situ hybridization techniques were used to determine whether a rearrangement of the EWSR1 gene, required for a diagnosis of peripheral PNET, was present. Clinical information was obtained from a patient chart review. Ages ranged from 31 to 81 years (median 58). Clinical presentations included vaginal bleeding (9), back pain (1), presumed fibroids (2), pelvic mass (1), incidental finding at hysterectomy (1), and unknown (3). Twelve patients had surgery or imaging to determine stage: I (2), II (0), III (6), and IV (4). Five patients had biopsy only. Ten tumors had only neuroectodermal components. In 7 tumors, the neuroectodermal component was admixed with an additional component including unclassified sarcoma (2 cases), rhabdomyosarcoma, endometrioid carcinoma, adenosarcoma and malignant mixed Mullerian tumor (2 cases). Follow-up, available for 13 patients, ranged from 2 to 41 months with 7 patients dead of disease 2 to 26 months after diagnosis. Six patients are alive with no evidence of disease after follow-up ranging from 6 to 41 months. Four patients were lost to follow-up. Results for the most commonly used immunohistochemistry studies include cytokeratin, 13/15 tumors negative (2 focally positive); synaptophysin, 15/16 tumors positive; neurofilament, 10/11 tumors positive; and CD99, 7/9 tumors positive (2 tumors had nonspecific cytoplasmic staining). None of the 12 tumors tested had a detectable rearrangement in the EWSR1 gene. Uterine tumors with neuroectodermal differentiation, similar to more common endometrial malignancies, tend to occur in postmenopausal women and frequently present with vaginal bleeding. An immunohistochemistry panel including cytokeratin, neurofilament, synaptophysin, and CD99 can highlight neuroectodermal differentiation and identify tumors for which molecular testing should be considered. Tumors without a rearrangement of the EWSR1 gene should be descriptively characterized as uterine tumors with neuroectodermal differentiation or alternatively central type PNETs rather than PNET, not otherwise specified to avoid confusion with peripheral PNET.
The American Journal of Surgical Pathology, Aug 1, 2007
International Journal of Gynecological Pathology Official Journal of the International Society of Gynecological Pathologists, 2009
Carcinomas with neuroendocrine (NE) differentiation have been associated with poor outcome in dif... more Carcinomas with neuroendocrine (NE) differentiation have been associated with poor outcome in different organs. The purpose of this study was to evaluate the presence and significance of NE expression in a series of 46 undifferentiated endometrial carcinomas diagnosed between 1988 and 2005. NE expression was studied by immunohistochemistry including synaptophysin, chromogranin, and/or CD56. The patients' age ranged from 30 to 84 years (mean 55). Staging information was available for 45 cases and according to the International Federation of Gynecology and Obstetrics system they were distributed as follows: stage I (9 cases), stage II (2 cases), stage III (9 cases), and stage IV (25 cases). NE expression was present in 19/46 (41%) cases; however, it was diffuse in only 9% of the tumors. The median survival for patients without NE expression was 7 months (95% confidence interval 4-10 mo) and for patients with NE expression was 12 months (95% confidence interval 6-27 mo). The survival curves do not differ significantly (P ¼ 0.49). NE expression is common in undifferentiated carcinoma of the endometrium, as it was found in 41% of our cases. In most cases, NE expression is only focally present (r10% of the cells). There is no difference in overall survival in patients with or without NE expression.
Asco Meeting Abstracts, May 20, 2010
10% of women with serous ovarian cancer have low-grade carcinomas. These patients are diagnosed a... more 10% of women with serous ovarian cancer have low-grade carcinomas. These patients are diagnosed at a younger age, have a longer overall survival and a lower response rate to platinum-based chemotherapy compared to women with high-grade serous ovarian carcinoma. It remains unclear if these features are similar in women with low-grade primary peritoneal cancer (PPC). To further explore this issue, a retrospective analysis of the clinical and pathologic characteristics of women with low-grade serous PPC was performed. A retrospective study of 53 patients with low-grade serous PPC evaluated at a single institution from 1986 to 2009 was performed. All cases were reviewed by a gynecologic pathologist to confirm low-grade serous PPC. Median age at diagnosis was 51.7 years (range 27.1-82.4). 46 patients (86.8%) underwent primary surgery, with optimal tumor reduction achieved in 30 patients (65.2%). 48 patients (90.6%) received chemotherapy as part of their initial treatment. At the completion of primary treatment, 66.7% of patients were noted to have persistent or progressive disease. With a median follow-up of 66.1 months, the 5-year PFS was 16%, yet the 5-year OS was 69%. To our knowledge, this is the first report of women with low-grade serous PPC. Similar to low-grade serous ovarian carcinoma, patients with low-grade serous PPC have high rates of persistent disease at the completion of primary treatment yet a long overall survival. Further study focusing specifically on low-grade serous ovarian and primary peritoneal carcinomas is needed to determine the optimal treatment of these diseases.
International Journal of Gynecological Pathology, 2010
At a National Cancer Institute-sponsored workshop it was proposed that the borderline category of... more At a National Cancer Institute-sponsored workshop it was proposed that the borderline category of ovarian intestinal-type mucinous tumors (OInMTs) could be eliminated if the apparent benign behavior of these tumors could be confirmed. We reviewed 33 cases of borderline OInMT, with either optimal or adequate sampling and with at least 5 years of follow-up, to investigate their behavior. Optimal sampling and adequate sampling were defined as at least 1 section per centimeter of maximum tumor dimension and at least 1 section per 2 cm of maximum tumor dimension, respectively. The patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; age ranged from 16 to 89 years (mean 49 yr). Tumor size ranged from 8 to 39 cm (mean 20 cm). The sampling of the ovarian tumor was optimal in 28 cases and adequate in 5 cases. The patients were treated surgically as follows: cystectomy (1), unilateral oophorectomy or unilateral salpingo-oophorectomy with or without total abdominal hysterectomy (13), and bilateral salpingo-oophorectomy with or without total abdominal hysterectomy (19). Complete or partial staging was obtained in 26 patients. All of them had Federation of Gynecology and Obstetrics stage I disease. Thirty-one patients with a follow-up ranging from 5 to 18 years (mean 10 yr) had no recurrences. Two patients had recurrences 12 and 14 months after their initial surgery. The first patient underwent a left salpingo-oophorectomy and limited staging for a borderline OInMT adherent to the ileum and sigmoid. The tumor was incompletely removed and recurred in the pelvis 1 year later. It was again incompletely excised. Ten months later, the tumor re-recurred in the pelvis and could only be drained because of the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s advanced age and her poor medical status. She died of other causes 5 years later. The second patient with recurrent tumor had undergone a cystectomy and full staging for a borderline OInMT. Fourteen months later, she developed a recurrence in the residual ovary. She underwent a right salpingo-oophorectomy and total abdominal hysterectomy and has been without evidence of disease for 11 years. In this study of 33 Federation of Gynecology and Obstetrics stage I borderline OInMTs that were optimally or adequately sampled to exclude intraepithelial carcinoma, microinvasion, or invasive carcinoma, there were only 2 cases with recurrence, secondary to incomplete excision or cystectomy, and no deaths from disease. However, borderline OInMTs are usually large and heterogeneous, and the standard sampling protocol for them is not evidence based. As indicated by one of our consultation cases, there remains the potential for a sampling artifact in which a focus of carcinoma is missed. Caution dictates retaining the current nomenclature to ensure the follow-up of patients affected by this disease until uncertainty regarding the extent of sampling needed to exclude the presence of carcinoma is resolved.
The American Journal of Surgical Pathology, Sep 1, 2004
The clinicopathologic features of 35 cases of serous carcinoma of the ovary, fallopian tube, or p... more The clinicopathologic features of 35 cases of serous carcinoma of the ovary, fallopian tube, or peritoneum presenting as lymphadenopathy are described. The cases were retrieved from the files of the Department of Pathology at the University of Texas M. D. Anderson Cancer Center from a 20-year period (1982-2002). The following parameters were evaluated: patient age at diagnosis, lymph node involved, primary tumor site, tumor histology, peritoneal disease status, and survival. The patients ranged in age from 30 to 85 years (mean, 59 years). The lymph nodes involved were inguinal, 20 cases; supraclavicular, 11 cases; axillary, 2 cases; cervical, 1 case; and retroperitoneal, 1 case. Primary tumor sites included 20 ovarian, 10 peritoneal, and 2 fallopian tube. In 2 patients, total abdominal hysterectomy/bilateral salpingo-oophorectomy and complete staging showed no additional tumor, and in 1 patient with a previous history of total abdominal hysterectomy/bilateral salpingo-oophorectomy for a benign condition, imaging studies did not identify a primary site. The carcinoma was high grade in 30 cases and low grade in 4 cases. In one case, the diagnosis was made on cytology material and the tumor could not be graded. Peritoneal disease status was known in 33 patients and was as follows: omentum with gross disease, 16 cases; and omentum without gross disease, 17 cases. Follow-up was available in 33 patients and ranged from 4 to 204 months, with a median survival of 36 months for stage III patients and 29 months for stage IV patients. Patients with adenopathy and minimal peritoneal disease (grossly negative omentum) had a median survival of 120 months compared with 24 months for those with bulky peritoneal disease (grossly positive omentum). Serous carcinoma of the ovary, fallopian tube, or peritoneum presenting as a lymph node metastasis is uncommon. In rare cases, a primary site may not be found. The median survival of the patients for stage is not appreciably different from those patients presenting in the usual fashion, suggesting that this atypical presentation does not adversely affect survival. Patients with minimal peritoneal disease and extra-abdominal lymph node metastases survive longer than those with bulky peritoneal disease
Clinical Cancer Research, Feb 1, 2003
Experimental Design: Ninety specimens from 67 patients were plated in RPMI 1640 or inoculated in ... more Experimental Design: Ninety specimens from 67 patients were plated in RPMI 1640 or inoculated in nude mice. Growth characteristics of cell cultures and xenografts were determined. Expression of receptors for estrogen, progesterone, androgen, epithelial growth factor, fibroblast growth factor, HER-2/erbB-2/c-neu proto-oncogene, and the P53 expression were characterized by immunocytochemistry in 28 cell cultures.
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