The distinction of ovarian clear cell carcinomas (CCCs) from high-grade serous carcinomas (HG-SCs) is sometimes a diagnostic challenge. With the recognition that CCCs respond poorly to conventional chemotherapy there are efforts to initiate clinical trials for CCC, making accurate diagnosis critical. The purpose of this study was to test and validate a set of antibodies that could aid in the diagnosis of CCC, using a series of cases from different centers in North America. Using a test set of 133 CCCs, we identified the following markers: Cyclin E, estrogen receptor, hepatocyte nuclear factor (HNF)-1beta, Ki-67, p21, p53, and Wilms tumor (WT)1 that show significant discrimination from 200 HG-SCs. For validation, these markers were characterized on an independent set of 104 CCCs from 3 other centers. There were no significant differences in expression of these 7 markers between the independent test and validation sets of CCC. Combining all CCC cases (N=237), HNF-1beta showed the highest sensitivity (82.5%) and specificity (95.2%) for CCC, and WT1 for HG-SC (sensitivity: 79.9%, specificity: 97.4%). A diagnostic panel consisting of WT1, ER, and HNF-1beta demonstrated nearly identical performance as a panel using all 7 markers in distinguishing CCCs from HG-SCs, correctly classifying 84% of cases. Three percent of cases were misclassified and 13% carried an uninformative triple negative immunophenotype. CCCs show a distinct, reproducible immunophenotype, compared with HG-SCs, and a panel of 3 immunomarkers can serve as a diagnostic aid in problematic cases.

Uterine leiomyosarcomas (Ut-LMSs) are aggressive tumors with an overall poor prognosis (15% to 25% 5-year survival rate). However, patients with stage I Ut-LMSs are reported to have a relatively better outcome when compared with the overall group with a 5-year survival rate ranging from 25% to 75%. The purpose of this study was to evaluate the histopathologic parameters that may impact outcome in stage I Ut-LMSs. Twenty-seven patients with stage I Ut-LMSs were identified from the files of 5 tertiary care hospitals between 1974 and 2006. Tumors were primarily staged based on pathologic information, supplemented with radiologic findings (10 cases) and clinical records (1 case). Patients with stage I tumors with no additional clinical or radiologic staging information were included in the study if no recurrence was documented after 6 months from the initial staging operation (16 cases). Clinicopathologic parameters that were statistically evaluated included age [mean, 54 y (37 to 73)], tumor size [mean, 9.5 cm (5.5 to 16)], cell type (17 spindled, 5 epithelioid, 2 myxoid, and 3 mixed), mitotic activity [mean count, 24 (4 to 69)/10 high-power fields], marked cytologic atypia (26 of 27 cases), tumor cell necrosis (12 of 27 cases), and lymphovascular invasion (6 of 27 cases). Follow-up was available for all the patients. Poor outcome was defined when patients either died of disease or were alive with disease. Overall, accounting for any length of follow-up, 16 of 27 (59%) patients with stage I Ut-LMSs had poor outcome; 7 died of disease (mean follow-up, 13 mo) and 9 were alive with disease (mean follow-up, 31 mo). The remaining 11 patients were alive and well with a mean follow-up of 48 months. However, at 2 years of follow-up by univariate analysis, only nonspindle morphology (P<0.0183) and diffuse high-grade cytologic atypia (P<0.02) were statistically associated with poor outcome. No statistically significant association with survival was identified by univariate analysis when evaluating mean age, mean tumor size, presence of tumor cell necrosis, mean mitotic count, or lymphovascular invasion. In conclusion, stage I leiomyosarcoma is associated with poor prognosis. No conclusive differences were observed among different clinicopathologic parameters and prognosis, although it seemed that spindle cell morphology and diffuse high-grade cytologic atypia were associated with longer overall survival and higher death rates, respectively.