Carmen Tornos

Memorial Sloan-Kettering Cancer Center, New York City, NY, USA

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Publications (22)84.49 Total impact

  • Article: Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms.
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    ABSTRACT: Carcinomas of the endometrium and ovary with undifferentiated components are uncommon neoplasms that are likely underdiagnosed. They are important to recognize as they have been shown to be clinically aggressive. We identified 32 carcinomas with undifferentiated components as defined by Silva and co-workers, 26 endometrial and 6 of ovarian origin. The patient age ranged from 21 to 76 years (median 55); 40% of patients were <or=50 years of age. Most patients (58% of endometrial and 83% of ovarian carcinomas with undifferentiated components) presented at advanced stages (FIGO III-IV). Pelvic and para-aortic lymph nodes were the most frequent sites of metastases. Twenty tumors, entirely undifferentiated, consisted of sheets of dyshesive, ovoid cells with uniform, large vesicular nuclei, whereas 12 tumors contained combinations of differentiated endometrioid adenocarcinoma with undifferentiated components. Although most undifferentiated tumors had a monotonous cytologic appearance without prominent stroma, six showed focal nuclear pleomorphism and eight cases had variably sized zones of rhabdoid cells in a background of myxoid stroma. The tumors were frequently misdiagnosed; they received a wide range of diagnoses, including FIGO grade 2 or 3 endometrioid carcinoma, carcinosarcoma, high-grade sarcoma including endometrial stromal sarcoma, neuroendocrine carcinoma, lymphoma, granulosa cell tumor and epithelioid sarcoma. Up to 86% of the cases showed focal, but strong keratin and/or epithelial membrane antigen staining, with CK18 being the most frequently positive keratin stain. They were predominantly negative for neuroendocrine markers, smooth muscle markers and estrogen receptor/progesterone receptor. Mismatch repair protein expression by immunohistochemistry was evaluated in 17 cases, and 8 (47%) were abnormal (7 with loss of MLH1/PMS2 and 1 with MSH6 loss). Follow-up was available for 27 patients, although it was very short in many cases, ranging from 0.5 to 89 months (median 9 months). Eleven patients (41%) died of the disease in 0.5-20 months, four are alive with disease and twelve patients have no evidence of disease. Endometrial and ovarian carcinomas with undifferentiated components have a broad histologic differential diagnosis, but they show specific histologic features that should enable accurate diagnosis. These tumors can occur in young women, may be associated with microsatellite instability and behave in a clinically aggressive manner.
    Modern Pathology 03/2010; 23(6):781-9. · 4.79 Impact Factor
  • Article: "Malignant" uterine perivascular epithelioid cell tumor, pelvic lymph node lymphangioleiomyomatosis, and gynecological pecomatosis in a patient with tuberous sclerosis: a case report and review of the literature.
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    ABSTRACT: We report a case of uterine perivascular epithelioid cell tumor (PEComa) with malignant histological features in a 59-year-old woman with tuberous sclerosis (TBS). The patient also had extrapulmonary lymphangioleiomyomatosis involving pelvic lymph nodes, myometrium, cervix, and ovary ("pecomatosis"). The uterine tumor measured 2.6 cm and had marked nuclear pleomorphism, necrosis, and 2 mitoses per 50 high-powered field, with an occasional atypical mitosis and infiltrative borders. The nonneoplastic myometrium, the cervical wall, and the hilum of the ovary had multiple clusters of bland-looking epithelioid clear cells that ranged from 1 to 5 mm (pecomatosis). The uterine tumor cells were positive for HMB-45 (90%), Melan-A (70%), smooth muscle actin (50%), and estrogen receptor (30%). Of the 16 pelvic lymph nodes excised, 3 were involved with lymphangioleiomyomatosis that was positive for HMB-45 and estrogen receptor. This is only the second reported PEComa associated with pecomatosis and the fourth PEComa described in a patient with TBS. The clinical significance of pecomatosis is still uncertain but seems to be seen only in patients with TBS.
    International Journal of Gynecological Pathology 02/2008; 27(1):86-90. · 1.45 Impact Factor
  • Article: Prognostic features of surgical stage I uterine carcinosarcoma.
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    ABSTRACT: Uterine carcinosarcomas (CSs) are aggressive neoplasms, with 5-year overall survival (OS) rates of less than 35%. They are customarily separated into types harboring either heterologous or homologous mesenchymal elements, but the prognostic significance of this finding is controversial. Our goal was to study clinicopathologic features of possible prognostic relevance in surgical stage I uterine CS. A retrospective clinical and histopathologic review was performed for all women diagnosed with surgical stage I uterine CS. These tumors were compared with stage I high-grade endometrial (HGEm) carcinomas for clinical outcomes. There were 42 cases of surgical stage I uterine CS identified between January 1990 and January 2004. The disease-free survival and OS rates for patients with stage I CS were significantly worse compared with stage I HGEm (P=0.001; P=0.01). The median disease-free survival for patients with heterologous CS was 15 months and had not been reached for women with homologous CS (P=0.001). The 3-year OS rates were 45% versus 93% in women with heterologous compared with homologous stage I CS (P<0.001). The 3-year OS rates for homologous CS and HGEm were both >90%. Homologous stage I CSs have survival outcomes that are similar to HGEm. This further supports the concept that homologous stage I CSs are carcinomas with sarcomatoid features, not sarcomas. More importantly, the presence of heterologous sarcomatous elements is a powerful negative prognostic factor in surgical stage I uterine CS.
    American Journal of Surgical Pathology 11/2007; 31(11):1653-61. · 4.35 Impact Factor
  • Article: Interobserver and intraobserver variability of a two-tier system for grading ovarian serous carcinoma.
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    ABSTRACT: Although grading has been demonstrated to be an important prognostic factor in ovarian serous carcinoma, there is no system universally used to perform this task. A few years ago, we proposed a two-tier system for grading ovarian serous carcinoma that is based primarily on the assessment of nuclear atypia (uniformity vs. pleomorphism) in the worst area of the tumor. Tumor grade in this two-tier system is correlated with survival. After being used by numerous pathologists and trainees at The University of Texas M.D. Anderson Cancer Center (MDACC) for 15 years, we have observed that this system is user-friendly and reproducible. We undertook this study to evaluate the interobserver and intraobserver variability among a group of 7 gynecologic pathologists and 2 general surgical pathologists using this grading system. A total of 80 cases of ovarian serous carcinoma, 40 low-grade and 40 high-grade, were circulated twice among these pathologists. Slides with examples of low-grade and high-grade serous carcinoma were sent with the unknowns. A website was used to provide diagnostic criteria, images of examples of ovarian low-grade and high-grade carcinoma, and a log form to facilitate data entry. Statistical analysis demonstrated an overall kappa statistic among the different observers of 0.909. The intergrader kappa's ranged from 0.717 to 1.000 in the first round of the review and from 0.701 to 1.000 in the second round. Eight of the participants had an intragrader kappa ranging from 0.775 to 1.000 (excellent agreement), whereas a single participant had an intragrader kappa of 0.725 (good agreement). This study demonstrates that the two-tier grading system (the MDACC grading system) for ovarian serous carcinoma on the basis of the assessment of nuclear atypia is easy to learn and is highly reproducible. These findings would support its universal use, which would be beneficial for the standardization of clinical trials and protocols, thus facilitating the understanding of this disease and investigation into the treatment of patients affected by these tumors.
    American Journal of Surgical Pathology 09/2007; 31(8):1168-74. · 4.35 Impact Factor
  • Article: p53 aerosol formulation with low toxicity and high efficiency for early lung cancer treatment.
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    ABSTRACT: To develop an optimal nonviral aerosol formulation for locoregional treatment of early lung cancer. The formulation was made of polylysine/protamine combination (AND) as the carrier and p53 gene (p53sm) as therapeutic agent. To estimate the aerosol deposition, the aerodynamic size of the AND-p53sm was measured with extrusion-precipitation method. To accurately determine the dose, the aerosol efficiency in mice was measured with a fluorescent dye. The transfection efficiency and DNA protection function of the aerosolized formulation in cultured cells and mouse lungs were detected with reporter gene assays and/or reverse transcription-PCR. The preclinical safety and efficacy of AND-p53sm were studied in healthy mice and mice bearing orthotopic human non-small-cell lung cancer (NSCLC) xenograft. After aerosolization, AND is 3- to 17-fold more effective than commonly used PEI or cationic lipid formulations in transfecting the NSCLC cells (relative light units, 1,494 versus 534 and 86; P < 0.003). Aerodynamic size of AND-p53sm ranged 0.2 to 3 mum is the optimal aerosol droplets for deposition in the entire human respiratory tract. Significant gene expression was detected in the lungs of mice given aerosolized AND-p53sm and AND-luciferase. Aerosolized AND-p53sm significantly prolonged the life of mice bearing orthotopic human NSCLC xenografts, and it was more effective than an optimal i.v. cisplatin chemotherapy (increased life span, 93% versus 25%; P = 0.014). Inhalation of AND produced low and reversible pulmonary toxicity and no systemic toxicity. This optimal formulation is suitable for delivering biological materials to human lung with aerosol administration. This therapeutic strategy is an option for patients with early lung cancer and bronchoalveolar carcinoma.
    Clinical Cancer Research 08/2007; 13(16):4900-8. · 7.74 Impact Factor
  • Article: Sertoliform endometrioid carcinoma of the endometrium with dual immunophenotypes for epithelial membrane antigen and inhibin alpha: case report and literature review.
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    ABSTRACT: We report a rare case of sertoliform endometrioid carcinoma of the endometrium in a 71-year-old African American woman who presented with postmenopausal bleeding. Her medical condition was remarkable for hypertension, diabetes, and obesity. She underwent total hysterectomy, right salpingo-oophorectomy and lymph node sampling. The endometrium was occupied by a 4.5-cm solid polypoid tumor, which grossly invaded into the myometrium. Microscopically, the tumor consisted of small hollow tubules, anastomosing cords and trabeculae, and tightly packed nests. Microglandular areas mimicking adult granulosa cell tumors were also present. But true Call-Exner bodies were absent. Component of typical endometrioid carcinoma was noted only focally. The uninvolved endometrium demonstrated atypical complex hyperplasia. The tumor cells were diffusely immunoreactive for epithelial membrane antigen, estrogen receptor, and progesterone receptor (PR), and focally for vimentin. The tumor cells were also diffusely positive for inhibin alpha and CD99. Immunostains for other sex cord markers (calretinin, WT-1, and Melan-A) were also positive in approximately 30% to 40% of the tumor cells. Immunostains for CD10, smooth muscle actin, desmin, or HHF35 were negative. Two ovarian sertoliform endometrioid carcinomas from our archived tissue were, however, immunoreactive for epithelial membrane antigen but negative for inhibin alpha. Despite the prominent sertoliform features, both histologically and immunohistochemically, the tumor was of a high-grade endometrial carcinoma and will likely behave as such. As of today, dual differentiation of epithelium and sex cord by immunohistochemical staining has not been demonstrated in sertoliform endometrioid carcinomas of either endometrial or ovarian origin. Our case is the first documentation of such example and suggests that endometrial carcinoma can undergo true sex cord differentiation.
    International Journal of Gynecological Pathology 08/2007; 26(3):291-7. · 1.45 Impact Factor
  • Article: Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma.
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    ABSTRACT: Identification of the microsatellite instability (MSI) phenotype in endometrial carcinoma is important given that such tumors are the most common noncolorectal tumors to occur in hereditary nonpolyposis colorectal cancer syndrome, and may bear prognostic relevance. The objective of this study was to assess the utility of immunohistochemistry (IHC), a simple and fast technique, in detecting MSI in endometrial carcinoma. The study subjects consisted of 90 endometrial carcinoma patients with equal representation of MSI-high (MSI-H) and non-MSI-H tumors. MSI was tested using the standard polymerase chain reaction-based method and the 5 NCI-recommended markers. Overall, IHC with MLH1 and MSH2 antibodies detected 69% of MSI-H tumors with a specificity of 100%. Adding PMS2 and MSH6 to the antibody panel increased the sensitivity to 91% but decreased the specificity to 83%. The most common IHC abnormality in MSI tumors was concurrent loss of MLH1/PMS2. Assessment of staining was straightforward in most cases but not in all. Staining inadequacies existed. Five stains (4 MLH1 and 1 MSH6) were not interpretable because of the lack of any internal positive control. Two percent to 10% of the cases (depending on the antibody assessed) had only focal weak staining; the highest frequency (10%) occurred with MLH1 antibody. PMS2 staining detected 7 MLH1-staining present MSI-H cases, thus partly accounting for the increased sensitivity with the 4-antibody panel. MSH6 staining identified 9 cases with loss of MSH6 alone, 6 of 9 were non-MSI-H, thus partly accounting for the decreased specificity with the 4-antibody panel. In conclusion, our results suggest that IHC is useful in detecting MSI in endometrial carcinoma. Although IHC has a lower sensitivity with more apparent staining inadequacies in detecting MSI in endometrial carcinoma than it does in colorectal carcinoma, its use in endometrial carcinoma may be an important adjunct when screening for hereditary cases. In the future, as prognostic and therapeutic implications of MSI phenotype become better defined, it may be reasonable to perform IHC for mismatch repair proteins in large numbers of endometrial carcinomas.
    American Journal of Surgical Pathology 06/2007; 31(5):744-51. · 4.35 Impact Factor
  • Article: Carcinomas of ovary and lung with clear cell features: can immunohistochemistry help in differential diagnosis?
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    ABSTRACT: Metastatic lung carcinomas with clear cell morphology can be confused with primary ovarian clear cell carcinomas. We performed immunohistochemical stains in 14 cases of non-small cell lung carcinomas with clear cell features and 14 cases of ovarian clear cell carcinomas using a panel of markers, including thyroid transcription factor 1 (TTF-1), carcinoembryonic antigen (CEA), Wilms tumor gene 1, octamer-binding transcription factor 4 (OCT-4), cancer antigen 125 (CA-125), estrogen receptor, and progesterone receptor. Among non-small cell lung carcinomas with clear cell features, 87.5% of adenocarcinomas (or 50% overall frequency in lung carcinomas) were positive for TTF-1, whereas none of the ovarian clear cell carcinomas were positive (P = 0.002). All 14 ovarian clear cell carcinomas stained for CA-125 as compared with 1 non-small cell lung carcinoma (P < 0.001). On the other hand, 85% of non-small cell lung carcinomas stained for CEA, whereas none of the ovarian clear cell carcinomas did (P < 0.001). Interestingly, 4 ovarian clear cell carcinomas (28%) showed positive staining for the germ cell marker OCT-4. Either lung or ovarian carcinomas stained for Wilms tumor gene 1, estrogen receptor, or progesterone receptor very infrequently; and the difference between the 2 groups was not statistically significant. Our results suggest that an immunohistochemical panel consisting of TTF-1, CEA, CA-125, and OCT-4 is helpful in distinguishing most pulmonary and ovarian carcinomas with clear cell features.
    International Journal of Gynecological Pathology 04/2007; 26(2):134-40. · 1.45 Impact Factor
  • Article: The outcomes of patients with positive margins after excision for intraepithelial Paget's disease of the vulva.
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    ABSTRACT: Vulvar Paget's disease is a rare neoplasm that usually occurs in postmenopausal women. Treatment with surgical excision can be complicated by extension of microscopic disease in an irregular manner well beyond the visible margins of the lesion. The objective or our study was to analyze the outcomes of patients with primary vulvar intraepithelial Paget's disease who had positive microscopic margins after primary excision. We reviewed the records of all patients with Paget's disease of the vulva treated at our institution from 1/80 to 9/02. Patients whose sample showed stromal invasion or an underlying carcinoma were excluded. Data were collected regarding patient demographics, disease location, treatment, surgical margin status, additional treatment, and clinical outcome. The medical records and histopathologic specimens of 28 women with intraepithelial Paget's disease of the vulva were evaluated. Surgical treatment consisted of radical vulvectomy in 3 patients (11%), simple vulvectomy in 18 patients (64%), and wide local excision in the other 7 patients (25%). Of the 20 patients with microscopically positive margins, 14 (70%) developed recurrent disease and the remaining 6 (30%) are disease free. Of the 8 patients with negative margins, 3 (38%) developed disease recurrence and the remaining 5 (63%) are disease free. With a median follow-up of 49 months (range, 3-186 months), there was no correlation between disease recurrence and margin status (P=0.20). Of the 17 patients who recurred, 14 (82%) underwent additional surgical excision and 1 patient was treated with Retin-A. The remaining 2 patients refused further treatment and were lost to follow-up. In those patients who underwent surgery for recurrence, between 1 and 3 re-excisions were performed. Of the 15 evaluable patients who were treated for recurrent disease, 12 (80%) had no evidence of persistent disease and 3 (20%) had persistent disease at a median follow-up of 63.7 months (range, 18.5-186 months). Microscopically positive margins following surgical excision of vulvar intraepithelial Paget's disease is a frequent finding, and disease recurrence is common regardless of surgical margin status. Long-term monitoring of patients is recommended, and repeat surgical excision is often necessary.
    Gynecologic Oncology 04/2007; 104(3):547-50. · 3.89 Impact Factor
  • Article: Vulvar varices: an uncommon entity in surgical pathology.
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    ABSTRACT: Varicose veins in the vulvar and perivulvar area are seen in 4% of women. Most of them are secondary to pregnancy and usually regress spontaneously. Vulvar varicose veins are rare in nonpregnant women. When present, they can be seen alone, associated with leg varices or associated with venous malformations of the labia, clitoral area, or vagina with or without arteriovenous malformations on the limbs or trunk (Klippel-Trenaunay-Weber syndrome and Parkes-Weber syndrome). In some cases, vulvar varices are seen as part of the so-called "pelvic congestion syndrome." Clinically, vulvar varices may present as small isolated protrusions, mainly in the labia majora, or as large masses, involving the vulva and even the perivulvar area. The treatment of choice of vulvar varices seen during pregnancy is conservative and symptomatic. Surgical pathologists need to be aware of the existence of vulvar varicose veins and its possible presence in biopsy specimens. Vulvar varicose veins can be misdiagnosed clinically as cysts or masses mainly in the Bartholin gland area. Correct diagnosis of the lesion is important to determine appropriate therapy and to recognize the possibility of associated anatomical or pathological problems.
    International Journal of Gynecological Pathology 02/2007; 26(1):99-101. · 1.45 Impact Factor
  • Article: Is surgical excision warranted after benign, concordant diagnosis of papilloma at percutaneous breast biopsy?
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    ABSTRACT: The study objective was to determine the cancer frequency in lesions yielding a benign, concordant diagnosis of papilloma at percutaneous breast biopsy. Retrospective review was performed of 3,864 lesions that had percutaneous imaging-guided biopsy. In 50 lesions (1.3%), percutaneous biopsy yielded a benign, concordant diagnosis of papilloma. Surgical pathology (n = 25) or minimum 2 years' mammographic follow-up (n = 10) was available for 35 lesions that had biopsy with 11-gauge vacuum-assisted (n = 20) or 14-gauge automated (n = 15) needles. Medical records, imaging studies, and histologic results were reviewed. Cancer was found in five (14%) of the 35 lesions yielding a benign, concordant diagnosis of papilloma at percutaneous biopsy. Cancer histology was ductal carcinoma in situ in four (80%) and node-negative invasive cancer in one. Four (80%) of five cancers were identified due to interval change at follow-up (median, 22 months; range, 7-25 months). In six (17%) of 35 lesions, surgery revealed high-risk lesions including atypical ductal hyperplasia (n = 3), radial scar (n = 2), and lobular carcinoma in situ (n = 1). There was a significantly (p = 0.02) higher frequency of cancer or high-risk lesion in women with multiple versus solitary papillomas and a trend (p = 0.09) toward a higher cancer rate in women with versus without a family history of breast cancer. Breast cancer history, menopausal status, mammographic pattern, biopsy method, and removal of imaging target had no significant impact on cancer rate. In our study of percutaneously diagnosed papillomas, surgery revealed cancer in 14% and high-risk lesions in 17%. Lesions yielding a benign, concordant diagnosis of papilloma at percutaneous biopsy may warrant surgical excision.
    American Journal of Roentgenology 06/2006; 186(5):1328-34. · 2.78 Impact Factor
  • Article: Clinicopathologic significance of defective DNA mismatch repair in endometrial carcinoma.
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    ABSTRACT: Defective DNA mismatch repair is commonly present in sporadic manifestations of gastrointestinal, endometrial, and other cancers. The pathognomonic molecular manifestation of this repair defect is microsatellite instability (MSI). Here, we test the hypothesis that MSI predicts the clinicopathologic features of endometrial carcinoma. A retrospective cohort of 473 patients treated for endometrial carcinoma at this institution was identified. All cases were reviewed by a gynecologic pathologist, and clinical information was abstracted from medical records. Using consensus criteria, DNA samples from nontumor and tumor tissue pairs were genotyped for MSI. Associations between MSI status and pathologic and clinical variables were assessed. Ninety-three (20%) of 473 tumors were MSI+. In the MSI+ tumor group compared with the MSI- tumor group, the proportion of advanced compared with early-stage tumors was higher (92% v 81%; P = .01), as was the proportion of tumors of endometrioid compared with nonendometrioid histologic subtype (94% v 23%; P = .001), and the proportion of tumors with myometrial invasion compared with those with none (92% v 78%; P = .01). By multivariate analyses, disease-free survival (hazard ratio, 0.3; 95% CI, 0.2 to 0.7) and disease-specific survival (hazard ratio, 0.3; 95% CI, 0.1 to 0.8) were significantly improved in patients with MSI+ tumors. In endometrial carcinoma, the presence of MSI was independently associated with a more favorable clinical outcome.
    Journal of Clinical Oncology 05/2006; 24(11):1745-53. · 18.37 Impact Factor
  • Article: Expression of WT1, CA 125, and GCDFP-15 as useful markers in the differential diagnosis of primary ovarian carcinomas versus metastatic breast cancer to the ovary.
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    ABSTRACT: Metastatic breast carcinoma to the ovary is sometimes difficult to differentiate from primary ovarian carcinoma. This problem is often encountered in breast carcinoma patients who develop adnexal masses. ER and PR can be positive in a high percentage of breast and ovarian carcinomas, and therefore cannot be used in the differential diagnosis of these entities. WT1 and CA125 have been identified as possible markers for ovarian cancer. However, no studies have been done that specifically compare the immunophenotype of breast carcinoma metastatic to ovary with that of primary ovarian cancer. Thirty-nine cases of metastatic breast carcinoma to the ovary, 36 primary breast carcinomas, and 42 primary ovarian carcinomas were examined immunohistochemically for the expression of WT1, CA125, carcinoembryonic antigen, MUC2, MUC1, and GCDFP. The percentage of cells stained and the intensity of staining were recorded. Thirty-two ovarian carcinomas (76%) were positive for WT1, including 31 of 33 (94%) serous carcinomas. Most of them had strong and diffuse staining. None of the breast cancers either primary or metastatic to the ovary expressed WT1. Thirty-eight (90%) ovarian carcinomas were positive for CA125, most of them with strong and diffuse staining. Most breast carcinomas were negative for CA125, with only 6 (16%) of the primary ones and 5 (12%) of the metastatic showing weak and focal positivity. All ovarian carcinomas were negative for GCDFP. Five primary breast cancers (14%) and 17 (43%) metastatic to the ovary were positive for GCDFP. Nine (21%) ovarian carcinomas, 8 (22%) primary breast carcinomas, and 13 (33%) metastatic to the ovary were positive for carcinoembryonic antigen. Almost all tumors examined were positive for MUC1 (100% ovarian carcinomas, 100% primary breast carcinomas, and 95% metastatic breast carcinomas to ovary). MUC2 was positive in 10 (24%) ovarian carcinomas, 3 (8%) primary breast cancers, and 12 (30%) metastases to the ovary. The presence of immunoreactivity for WT1 and CA125 in a carcinoma involving ovary strongly favors a primary lesion. Most ovarian carcinomas are positive for both markers, whereas the majority of metastatic breast carcinomas to the ovary are negative. GCDFP can be complementary in this differential diagnosis.
    American Journal of Surgical Pathology 12/2005; 29(11):1482-9. · 4.35 Impact Factor
  • Article: Invasion patterns in stage I endometrioid and mucinous ovarian carcinomas: a clinicopathologic analysis emphasizing favorable outcomes in carcinomas without destructive stromal invasion and the occasional malignant course of carcinomas with limited destructive stromal invasion.
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    ABSTRACT: Stage I, low-grade endometrioid and mucinous ovarian carcinomas have an excellent prognosis. Published data have suggested that destructive stromal invasion, a relatively uncommon finding in these tumors, is a poor prognostic factor. We investigated this by studying all FIGO stage I, grades 1 and 2 (of 3) endometrioid and mucinous ovarian carcinomas that were surgically staged at the Memorial Sloan-Kettering Cancer Center from 1980 to 2000. We undertook a careful review of all available slides using current diagnostic criteria and correlated histopathologic indices with clinical outcome data. Cases studied included 13 endometrioid ovarian carcinomas (stage IA, eight; stage IC, five) and six intestinal mucinous ovarian carcinomas (stage IA, three; stage IC, three). All of the tumors contained areas of expansile invasion, greater than that acceptable for microinvasion, and were thus diagnosed as carcinomas instead of borderline tumors. Nevertheless, nearly all demonstrated borderline tumor (noninvasive) components. Six tumors contained at least one focus of destructive stromal invasion (two endometrioid and four mucinous ovarian carcinomas). Four additional cases showed a focus suspicious for but not diagnostic of destructive invasion ('indeterminate for destructive invasion') (two endometrioid and two mucinous ovarian carcinomas). Follow-up data were available for 17 patients. The median follow-up was 81 months (range, 9-161 months). In all, 14 patients were alive with no evidence of disease (expansile invasion alone, eight; destructive stromal invasion, four; and indeterminate for destructive invasion, two). Three patients died of their disease (destructive stromal invasion, two; and indeterminate for destructive invasion, one). The size, number, and nuclear grade of destructive stromal invasion foci did not appear to have an impact on survival in this relatively limited number of patients. Outcome data in patients with stage I, low-grade endometrioid and mucinous ovarian carcinomas without destructive stromal invasion indicate that these tumors have a very limited malignant potential. The literature has not documented recurrences in this setting when the staging has been complete, the sampling adequate, and the cytologic features no more than grade 2, and metastasis to the ovary has been excluded. In contrast, carcinomas harboring even limited foci of destructive stromal invasion, although frequently cured surgically, can pursue a malignant clinical course.
    Modern Pathology 08/2005; 18(7):903-11. · 4.79 Impact Factor
  • Article: Borderline endometrioid tumor arising in a paratubal cyst: a case report.
    Charbel Salamon, Carmen Tornos, Dennis S Chi
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    ABSTRACT: Paratubal cysts, generally known as hydatid cysts of Morgagni, are small round cysts attached by a pedicle to the fimbriated end of the tube. The following represents the first reported case of an endometrioid tumor of low malignant potential arising in a paratubal cyst. A 45-year-old nulliparous female was referred with a complex right adnexal mass on pelvic sonogram. She underwent laparoscopic bilateral ovarian cystectomy and partial right salpingectomy (for a 3-cm torsed paratubal cyst). All frozen-section diagnoses were benign; however, final pathology revealed a borderline tumor of low malignant potential of endometrioid type in the right paratubal cyst. The patient underwent extensive counseling regarding management options and decided to have a laparoscopic right salpingo-oophorectomy. Final pathologic analysis revealed no evidence of persistent borderline tumor. Paratubal cysts are very difficult to diagnose with sonography; therefore, their management should be approached as any other adnexal mass. Laparoscopic surgery is an option in the management of adnexal masses; however, rupture or puncture of masses should be avoided when possible to prevent potential tumor dissemination in the event of a malignancy.
    Gynecologic Oncology 05/2005; 97(1):263-5. · 3.89 Impact Factor
  • Article: Distinction of endometrial stromal sarcomas from 'hemangiopericytomatous' tumors using a panel of immunohistochemical stains.
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    ABSTRACT: Endometrial stromal sarcomas are low-grade malignant tumors that may pose a diagnostic challenge, especially when they are present in an extrauterine site. Owing to the presence of an arborizing vasculature and cells with an undifferentiated appearance, endometrial stromal sarcomas can be confused with several soft-tissue neoplasms. We studied 17 endometrial stromal sarcomas, eight hemangiopericytomas, 14 solitary fibrous tumors, and 16 synovial sarcomas immunohistochemically, detecting the following antigens: CD10, estrogen receptor, progesterone receptor, bcl-2, CD34, smooth muscle antigen, epithelial membrane antigen and cytokeratin (AE1/AE3). Most endometrial stromal sarcomas stained positively for CD10 (16/17), estrogen receptor (17/17), progesterone receptor (15/17), and bcl-2 (17/17). Staining with antismooth muscle antigen was seen in 11 of 17 cases of endometrial stromal sarcoma, with more intense staining seen in areas showing smooth muscle differentiation. Staining with AE1/3 was seen in four of 17 endometrial stromal sarcomas, with two of the positive cases containing epithelioid cells. None of the endometrial stromal sarcomas expressed epithelial membrane antigen or CD34. More than half of the hemangiopericytomas (4/8) and solitary fibrous tumors (9/14) cases demonstrated CD10 expression either focally or in a patchy cytoplasmic and membranous pattern. Hemangiopericytomas, solitary fibrous tumors, and synovial sarcomas did not express estrogen receptor. Four of eight hemangiopericytomas and seven of 14 solitary fibrous tumors also showed patchy progesterone receptor expression. CD34 expression was identified in six of eight hemangiopericytomas and 13 of 14 solitary fibrous tumors, but we did not find expression of CD34 in synovial sarcoma. Differences between endometrial stromal sarcoma and other soft-tissue tumors were detected for all of the immunohistochemical markers (P<0.05), except anti-bcl-2 and AE1/3. Antibodies against CD10 mark a substantial number of hemangiopericytomas and solitary fibrous tumors (albeit not diffusely) and should always be combined with antiestrogen receptor and CD34 when the differential diagnosis includes endometrial stromal sarcoma. Unlike estrogen receptor antibodies, progesterone receptor antibodies show at least focal nuclear staining in most hemangiopericytomas, solitary fibrous tumors and rare synovial sarcomas, and are not useful for this differential diagnosis. All endometrial stromal sarcomas expressed bcl-2, mostly in a diffuse pattern, but this did not distinguish between endometrial stromal sarcoma and mimics. We therefore recommend the use of a small antibody panel comprising anti-CD10, anti-estrogen receptor, and anti-CD34 to distinguish endometrial stromal sarcomas from tumors with a predominant hemangiopericytomatous growth pattern.
    Modern Pathology 02/2005; 18(1):40-7. · 4.79 Impact Factor
  • Article: The association of benign and malignant ovarian adenofibromas with breast cancer and thyroid disorders.
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    ABSTRACT: An unexpected association with breast cancer and thyroid disorders was found during a review of 91 cases of benign and malignant ovarian adenofibromas. Sixty-three tumors were benign, 11 had areas of borderline neoplasms, and 17 had a component of carcinoma. Such tumors were divided into glandular/cystic (61 cases) and papillary (30 cases) according to their gross and microscopic appearance. Among the 61 patients with glandular/cystic adenofibromas, 13 (21%) had breast cancer and 19 (31%) also had thyroid disorders. Among the 30 patients with papillary adenofibromas there were no cases of breast cancer and only 2 patients had thyroid disorders. The average age of the patients with ovarian adenofibroma and breast cancer or thyroid disorders was higher (66 years) than that of patients without breast cancer or thyroid disorders (55 years). More patients with breast cancer and thyroid disorders had bilateral adenofibromas than patients without breast cancer or thyroid disorders. We also reviewed the medical records of 100 patients with ovarian cancer without adenofibroma component, 100 patients with breast cancer, and 100 patients with ovarian and breast cancer. Six percent of patients with ovarian cancer had breast cancer and 16% of each one of these groups had thyroid disorders. This unexpected association found between glandular/cystic adenofibromas, breast cancer, and thyroid disorders might be explained by defects common to these organs. Disorders of some of these organs have been linked by common genetic changes and it is known that these organs are under the influence of similar hormones. Mutations of PTEN have been found in breast and thyroid cancer. The thyroid and ovaries are controlled by glycoprotein hormones of the pituitary gland, which have common alpha subunits.
    International Journal of Surgical Pathology 02/2002; 10(1):33-9. · 1.00 Impact Factor
  • Article: Ovarian Mixed-Epithelial Carcinomas With a Microcystic Pattern and Signet-Ring Cells
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    ABSTRACT: 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' 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 appearance, even potentially suggesting a metastasis.
    International Journal of Gynecological Pathology 09/2001; 20(4):323-328. · 1.45 Impact Factor
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    Article: Staging Laparotomy for Endometrial Carcinoma: Assessment of Retroperitoneal Lymph Nodes
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    ABSTRACT: The surgical staging scheme for uterine corpus cancer adopted in 1988 by the International Federation of Gynecology and Obstetrics assigns patients with tumor spread to retroperitoneal lymph nodes to stage IIIC. However, a recommended approach to the detection of lymph node metastasis is not delineated. As part of an ongoing project to assess the value of surgical staging procedures, we reviewed the techniques of lymph node evaluation in 295 at-risk patients. Cases included clinical stage I patients whose preoperative biopsies demonstrated grade 2 or 3 adenocarcinoma or papillary serous, clear cell, or mixed carcinoma. We arbitrarily divided the retroperitoneal space into 10 lymphatic zones: left and right para-aortic, common iliac, external iliac, hypogastric, and obturator. Eighty-two percent of patients had some type of node sampling that involved a mean of three zones. Thirty-three of 244 sampled cases (13.5%) had nodal metastases: 20 had gross involvement and 13 had microscopic. We stratified patients into three groups: (1) those who had no node sampling (n = 51), (2) those with some nodes biopsied (n = 193), and (3) those whose node sampling included a minimum of one para-aortic plus at least one right and left pelvic specimen (n = 51). Retroperitoneal recurrences thought to originate from lymph node sites were identified for the "node-negative" patients in each group: Group 1, 4/51 (8%); Group 2, 9/173 (5%); and Group 3, 0/38 (0%). Lymphatic site failures were seen in 8 of 33 (24%) patients with biopsy-proven metastases. We found that failure to systematically sample pelvic and para-aortic nodes results in a small, but real, risk of undetected extrauterine metastasis. A selective approach to sampling that includes biopsy from both para-aortic and bilateral pelvic lymphatic zones appears to provide an accurate estimate of true node negativity. Further evaluation of this approach is warranted.
    Gynecologic Oncology 09/1995; · 3.89 Impact Factor
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    Article: Staging Laparotomy for Endometrial Carcinoma: Assessment of Peritoneal Spread
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    ABSTRACT: To evaluate surgical staging procedures in women with endometrial carcinoma, we examined the techniques used to assess the peritoneal cavity in 295 clinical stage I patients treated between 1985 and 1993. These patients were felt to be at increased risk for extrauterine disease because of significant myometrial invasion, high-grade (2 or 3), or variant histology (papillary serous, clear cell, or mixed). Patients had a mean of two intraperitoneal samples taken: 224 patients (76%) had at least an omental biopsy and peritoneal cytology. Additional peritoneal biopsy sites included pericolic gutters (50), pelvic peritoneum (45), bowel serosa/mesentery (24), diaphragm (22), appendix (11), and adhesions (7). At the time of staging laparotomy, 22 patients (7.5%) had gross evidence of peritoneal spread, which was readily confirmed by directed biopsy. In the 273 women without gross peritoneal disease, 3 (1%) had occult metastases detected by routine biopsy, 3 (1%) had microscopic metastases in palpably abnormal biopsies, and 22 bad positive cytology as the only evidence of peritoneal disease. Only three operative complications were potentially attributable to peritoneal assessment: cystotomy (1), partial small bowel obstruction (1), and ileus (1). Peritoneal failures have been noted in 12 patients over a mean follow-up interval of 39 months. Seven of these patients had obvious peritoneal disease at laparotomy. Two of the remaining 5 had optimal peritoneal sampling and represent false-negative cases. A staging laparotomy that included total abdominal hysterectomy with adnexal resection, cytology, omental biopsy, and biopsy of grossly abnormal sites would have potentially identified all patients with known peritoneal disease. Routine biopsy of other grossly normal peritoneal sites is associated with extremely low yield and is not recommended.
    Gynecologic Oncology 02/1995; · 3.89 Impact Factor