Genomic Determinants of Early Recurrences in Low-Stage, Low-Grade Endometrioid Endometrial Carcinoma.

Low-stage, low-grade endometrioid endometrial carcinoma (EEC), the most common histologic type of endometrial cancer, typically has a favorable prognosis. A subset of these cancers, however, displays an aggressive clinical course with early recurrences, including distant relapses. All statistical tests were 2-sided. Using a combination of whole-exome and targeted capture sequencing of 65 FIGO stage IA and IB grade 1 EECs treated with surgery alone, we demonstrate that chromosome 1q gain (odds ratio [OR] = 8.09, 95% confidence interval [CI] = 1.59 to 54.6; P = .02), PIK3CA mutation (OR = 9.16, 95% CI = 1.95 to 61.8; P = .01), and DNA mismatch repair-deficient molecular subtype (OR = 7.92, 95% CI = 1.44 to 87.6; P = .02) are independent predictors of early recurrences within 3 years in this patient population. Chromosome 1q gain was validated in an independent dataset of stage I grade 1 EECs subjected to whole-exome sequencing. Our findings expand on the repertoire of genomic parameters that should be considered in the evaluation of patients with low-stage, low-grade EEC.

Corded and Hyalinized and Spindled Endometrioid Endometrial Carcinoma: A Clinicopathologic and Molecular Analysis of 9 Tumors Based on the TCGA Classifier.

Corded and hyalinized and spindled carcinomas are rare variants of endometrioid carcinoma (EC) characterized by cords of low-grade epithelial cells (±spindle cells) within a hyalinized stroma or spindled epithelial cells, respectively, that merge with conventional low-grade EC. Due to their "biphasic" morphology, these tumors are often misdiagnosed as carcinosarcoma. The clinicopathologic features including mismatch repair protein (PMS2 and MSH6) and p53 immunohistochemical expression and POLE mutational status of 9 corded and hyalinized and spindled endometrial ECs were evaluated and classified into The Cancer Genome Atlas (TCGA) based molecular subgroups. Beta-catenin immunohistochemistry was performed as a surrogate for CTNNB1 mutational status. The mean age at diagnosis was 49 years (range: 34 to 68 y) with staging information available for 6 patients: stage IA (n=1), stage IB (n=1), stage II (n=2), stage IIIA (n=1), stage IIIC1 (n=1). A prominent corded and hyalinized component was present in 7 ECs comprising 15% to 80% of the tumor with a minor (5% to 15%) spindled morphology in 5. Two additional tumors were composed of a low-grade spindled component comprising 25% to 30% of the neoplasm. Tumors were grade 1 (n=3), grade 2 (n=5), and grade 2 to 3 (n=1) and squamous differentiation was identified in 8/9. All tumors had preserved expression of mismatch repair proteins with 8 showing a p53 wild-type phenotype including the grade 2 to 3 EC; 1 grade 2, stage IB tumor exhibited a mutant pattern of expression. All (n=7) but 1 tumor demonstrated nuclear beta-catenin expression in the glandular, squamous, and corded or spindled components. POLE exonuclease domain mutations were absent in all tumors. Based on our findings, corded and hyalinized EC and EC with spindle cells are usually low grade, low stage, and present at a younger age and exhibit squamous differentiation at an increased frequency compared to typical EC. Unlike carcinosarcomas, which frequently harbor TP53 mutations, these tumors usually exhibit wild-type p53 and nuclear beta-catenin expression, indicative of underlying CTNNB1 mutations. According to the TCGA subgroups of endometrial carcinoma, the majority of corded and hyalinized and spindled EC appear to fall into the copy number low ("no specific molecular profile") subgroup.

Malignant Mixed Germ Cell Tumors of the Ovary: An Analysis of 100 Cases Emphasizing the Frequency and Interrelationships of Their Tumor Types.

One hundred malignant mixed germ cell tumors of the ovary that occurred in patients 3 to 55 years (mean: 20 y) of age are described. The clinical presentation was usually that of any highly malignant tumor of the ovary (abdominal pain and distension), but rarely (3 cases) endocrine manifestations were present. The tumors were usually unilateral (96%), ranged from 4 to 38 cm (mean: 16 cm), and were uniformly solid or, more often, solid and cystic; occasionally the typical appearance of dysgerminoma could be appreciated. The most common tumor type was yolk sac tumor (91%), followed by dysgerminoma (61%), immature teratoma (58%), embryonal carcinoma (38%), and choriocarcinoma (11%). A variety of admixtures were encountered; dysgerminoma and yolk sac tumor was the most common combination (25% of the tumors) with the 2 components often being sharply demarcated. Immature teratoma and yolk sac tumor was the next most common pairing (20%) followed by yolk sac tumor and embryonal carcinoma, with or without immature teratoma (16%). Tumors with a choriocarcinoma component had the most varied combinations of tumor types. Embryoid bodies were seen in 21% of the tumors, most often as fragmented forms arranged in a nodular manner with yolk sac tumor and/or embryonal carcinoma; uncommonly they occurred singly or in clusters. Numerous confluent well-formed embryoid bodies (polyembryoma) were prominent in 2 tumors. Three tumors had a focal diffuse embryoma pattern. The specific tumor types showed the known diverse spectrum of microscopic appearances, but the frequent haphazard arrangement of 2 or more subtypes often resulted in complex morphology. Overgrowth of another neoplastic component, most often primitive neuroectodermal tumor, occurred in 10% of the tumors further complicating the histologic picture. This is the largest series of ovarian malignant mixed germ cell tumors reported and details their characteristics including associations of their subtypes and the frequent apparent role of embryoid bodies in giving rise to yolk sac tumor and embryonal carcinoma components.

Outcomes Following Complete Surgical Metastasectomy for Patients with Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

PURPOSE: The benefit of complete surgical metastasectomy for patients with metastatic renal cell carcinoma remains controversial due to limited outcome data. We performed a systematic review and meta-analysis to determine whether complete surgical metastasectomy confers a survival benefit compared to incomplete or no metastasectomy for patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: Ovid Embase®, MEDLINE®, Cochrane and Scopus® databases were searched for studies evaluating complete surgical metastasectomy for metastatic renal cell carcinoma through January 19, 2016. Only comparative studies reporting adjusted hazard ratios (aHRs) for all cause mortality of incomplete surgical metastasectomy vs complete surgical metastasectomy were included in the analysis. Generic inverse variance with random effects models was used to determine the pooled aHR. Risk of bias was assessed with the Newcastle-Ottawa Scale. RESULTS: Eight published cohort studies with a low or moderate potential for bias were included in the final analysis. The studies reported on a total of 2,267 patients (958 undergoing complete surgical metastasectomy and 1,309 incomplete surgical metastasectomy). Median overall survival ranged between 36.5 and 142 months for those undergoing complete surgical metastasectomy, compared to 8.4 to 27 months for incomplete surgical metastasectomy. Complete surgical metastasectomy was associated with a reduced risk of all cause mortality compared with incomplete surgical metastasectomy (pooled aHR 2.37, 95% CI 2.03-2.87, p <0.001), with low heterogeneity (I2 = 0%). Complete surgical metastasectomy remained independently associated with a reduction in mortality across a priori subgroup and sensitivity analyses, and regardless of whether we adjusted for performance status. CONCLUSIONS: Complete surgical metastasectomy for metastatic renal cell carcinoma is associated with improved survival compared with incomplete surgical metastasectomy based on meta-analysis of observational data. Consideration should be given to performing complete surgical metastasectomy, when technically feasible, in patients with metastatic renal cell carcinoma who are surgical candidates.

Utility of a standardized protocol for submitting clinically suspected endometrial polyps to the pathology laboratory.

The purpose of the study is to assess whether a protocol for submitting clinically suspected endometrial polyps will improve the detection rate of polyps and evaluation of the background endometrium. A retrospective review from 1999 to 2015 was performed. Cases were divided into (1) polyps and curettings placed in 2 containers (separate, n=61) and (2) polyps and curettings placed in 1 container (combined, n=80). Polyps were identified in 100% of cases in the separate compared with 95% in the combined group (P=.62). The background endometrium was evaluable in 79% of cases in the combined compared to 90% in the separate group (P=.07). The frequency of hyperplasia without atypia, atypical hyperplasia, and carcinoma was 4.4%, 3.6%, and 1.5%, respectively. In conclusion, the enhanced rate of polyp detection and evaluation of the background endometrium in the separate group is minimal. This supports the recommendation of submitting endometrial polyps and curettings combined in 1 container.