High-grade endometrial carcinomas are a heterogeneous group of tumors and include grade 3 endometrioid (EC-3), serous (SC), and clear cell carcinomas (CCC). There are conflicting data about the prognosis of these subtypes of high-grade endometrial carcinoma; this may be a result of lack of reproducibility in classifying tumor cell type. The purpose of this study was to examine differences in immunophenotype and outcome in a series of high-grade endometrial carcinomas, focusing on the comparison of EC-3 versus SC. We selected 180 endometrial carcinomas of SC, EC, or CCC type. No mixed carcinomas were included in the study. We chose the following immunohistochemical markers, estrogen receptor (ER), insulin-like growth factor 2 mRNA-binding protein 3 (IMP3), p16, p53, progesterone receptor (PR), and phosphatase and tensin homolog (PTEN) as being significantly differentially expressed in endometrial carcinoma subtypes. The tumors were stratified into 4 groups on the basis of their cell type and grade: EC grade 1 or 2, EC-3, SC, and CCC. Univariate survival analysis revealed significant differences in outcome between the 4 groups (P<0.0001), with significantly longer disease-specific survival for grade 1 or 2 EC versus EC-3 (P=0.0001), and EC-3 versus SC (P=0.0003). p16, PTEN, and IMP3 expression was observed more frequently in SC compared with EC-3 (P<0.0001, P=0.021, and P=0.031, respectively). These 3 markers showed the highest sensitivity and specificity in distinguishing between EC-3 and SC, with receiver operating characteristics area under the curve of 0.85, 0.69, and 0.71, respectively. ER and p53 approached but did not reach significance for differential expression in EC-3 versus SC (P=0.055 and P=0.068, respectively). A combination of p16 and PTEN predicts EC-3 versus SC with a sensitivity of 90.0% and specificity of 96.8%. p16 and PTEN can aid in distinguishing between EC-3 and SC of the endometrium, and are superior to ER, PR, and p53 for this purpose. EC-3 carcinomas have a significantly better prognosis than SC carcinomas of the endometrium.

Cellular fibroblastic tumors of the ovary are currently classified as either cellular fibroma (CF) or fibrosarcoma. The former are characterized by bland nuclei, 3 or fewer mitotic figures per 10 high-power fields (MFs/10 HPFs), and a low malignant potential, whereas fibrosarcomas usually have severe nuclear atypia, > or = 4 MFs/10 HPFs, and an aggressive clinical course. The prognosis of cellular fibromatous tumors with > or = 4 MFs/10 HPFs and low-grade cytology is not established and it is the purpose of this study to investigate that aspect. It has been our anecdotal experience that otherwise typical CFs with > or = 4 MFs/10 HPFs usually have a benign clinical course, suggesting that such tumors should be regarded as "mitotically active cellular fibroma" (MACF) rather than fibrosarcoma. Seventy-five cellular fibromatous neoplasms were analyzed to determine their clinicopathologic features and the appropriateness of "MACF" as a designation for otherwise typical CFs with > or = 4 MFs/10 HPFs. The mean age of patients with CF (n = 35, 0 to 3 MFs/10 HPFs) and MACF (n = 40, > or = 4 MFs/10 HPFs) was 51 and 41 years, respectively. Patients most commonly presented with symptoms related to a pelvic mass. All tumors were unilateral. The mean tumor size of CFs was 8.0 cm and 9.4 cm for MACFs. The majority of the tumors were solid; approximately one-third of them had a cystic component. Ovarian surface adhesions, involvement of the ovarian surface, or both, was present in 6% of CFs and 10% of MACFs. Eleven percent of CFs and 13% of MACFs were associated with extraovarian involvement. All tumors consisted of cellular, intersecting bundles of spindle cells with bland nuclear features. The mean highest mitotic count for MACFs was 6.7 MFs/10 HPFs (range 4 to 19 MFs/10 HPFs). Follow-up of 3 months to 12 years (mean 4.75 y) was available in 18 of the 40 patients with MACFs and was uneventful in all cases. We conclude that cellular fibromatous neoplasms with bland cytology and elevated mitotic counts are associated with favorable patient outcome and should be diagnosed as MACF rather than fibrosarcoma, which usually have moderate to severe atypia and elevated mitotic rates. As prior observations have shown that even typical CFs can occasionally recur locally, particularly if they are associated with rupture or adherence, long-term follow-up for patients with CFs and MACFs is appropriate.