Genomic Profiling Aids Classification of Diagnostically Challenging Uterine Mesenchymal Tumors With Myomelanocytic Differentiation.

Although diagnosis of high-grade uterine mesenchymal tumors (UMTs) exhibiting classic morphologic features is straightforward, diagnosis is more challenging in tumors in which prototypical features are poorly developed, focal, and/or coexist with features seen in other neoplasms. Here, we sought to define the repertoire of somatic genetic alterations in diagnostically challenging UMTs with myomelanocytic differentiation, including some reported as perivascular epithelioid cell tumors (PEComas). In 17 samples from 15 women, the tumors were histologically heterogenous. Immunohistochemical expression of at least 1 melanocytic marker (HMB45, Melan-A, or MiTF) was identified in all tumors, and of myogenic markers (desmin or smooth muscle actin) in most tumors. Targeted massively parallel sequencing revealed several genetic alterations, most commonly in TP53 (41% mutation, 12% deletion), TSC2 (29% mutation, 6% deletion), RB1 (18% deletion), ATRX (24% mutation), MED12 (12% mutation), BRCA2 (12% deletion), CDKN2A (6% deletion) as well as FGFR3, NTRK1, and ERBB3 amplification (each 6%). Gene rearrangements (JAZF1-SUZ12; DNAJB6-PLAG1; and SFPQ-TFE3) were identified in 3 tumors. Integrating histopathologic, immunohistochemical, and genetic findings, tumors from 4 patients were consistent with malignant PEComa (1 TFE3-rearranged); 6 were classified as leiomyosarcomas; 3 showed overlapping features of PEComa and other sarcoma types (leiomyosarcoma or low-grade endometrial stromal sarcoma); and 2 were classified as sarcoma, not otherwise specified. Our findings suggest that diagnostically challenging UMTs with myomelanocytic differentiation represent a heterogenous group of neoplasms which harbor a diverse repertoire of somatic genetic alterations; these genetic alterations can aid classification.

Cytologic features of upper gynecologic tract adenocarcinomas exhibiting mesonephric-like differentiation.

BACKGROUND: Mesonephric adenocarcinomas are rare neoplasms which most commonly arise in the lateral cervix and vagina. Tumors with similar morphologic, immunophenotypic, and molecular characteristics recently have been described in the uterine corpus and ovary. Herein, the authors sought to characterize the cytomorphologic features of adenocarcinomas exhibiting mesonephric-like differentiation arising in the upper gynecologic tract. METHODS: Institutional databases were queried retrospectively for tumors of the upper gynecologic tract described as a "tumor of Wolffian origin" or "with mesonephric features" between 2007 and 2017. All available cytologic material was reviewed. Cytomorphologic characteristics were evaluated by 3 pathologists. RESULTS: The current study cohort consisted of 8 cases taken from 7 patients. Primary sites included the ovary (3 cases); endometrium (4 cases); and pelvis, not otherwise specified (1 case). All cases demonstrated tight 3-dimensional clusters of overlapping cells. Additional architectural features included tubular (5 of 8 cases; 63%) and papillary (3 of 8 cases; 38%) formations. Cells were small with scant (7 of 8 cases; 88%) to moderate (1 of 8 cases; 12%) cytoplasm. Three of the 8 cases (38%) demonstrated extracellular hyaline globules. Nuclei were uniform in size (6 of 8 cases; 75%) or showed mild anisonucleosis (2 of 8 cases; 25%). Nuclear grooves and indentations were observed in all cases. Mitoses (5 of 8 cases; 63%) and apoptotic bodies (4 of 8 cases; 50%), when present, were rare. No necrosis was noted. CONCLUSIONS: Adenocarcinomas exhibiting mesonephric-like differentiation show a monotonous population of small cells with scant to moderate cytoplasm and abundant nuclear grooves arranged in tight, overlapping, 3-dimensional clusters. Occasionally, papillary or tubular architecture, as well as extracellular hyaline globules, may be seen. These features should prompt further testing (eg, immunohistochemistry) to confirm the diagnosis and to exclude potential mimics.

Molecular Classification of Grade 3 Endometrioid Endometrial Cancers Identifies Distinct Prognostic Subgroups.

Our aim was to investigate whether molecular classification can be used to refine prognosis in grade 3 endometrial endometrioid carcinomas (EECs). Grade 3 EECs were classified into 4 subgroups: p53 abnormal, based on mutant-like immunostaining (p53abn); MMR deficient, based on loss of mismatch repair protein expression (MMRd); presence of POLE exonuclease domain hotspot mutation (POLE); no specific molecular profile (NSMP), in which none of these aberrations were present. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method (Log-rank test) and univariable and multivariable Cox proportional hazard models. In total, 381 patients were included. The median age was 66 years (range, 33 to 96 y). Federation Internationale de Gynecologie et d'Obstetrique stages (2009) were as follows: IA, 171 (44.9%); IB, 120 (31.5%); II, 24 (6.3%); III, 50 (13.1%); IV, 11 (2.9%). There were 49 (12.9%) POLE, 79 (20.7%) p53abn, 115 (30.2%) NSMP, and 138 (36.2%) MMRd tumors. Median follow-up of patients was 6.1 years (range, 0.2 to 17.0 y). Compared to patients with NSMP, patients with POLE mutant grade 3 EEC (OS: hazard ratio [HR], 0.36 [95% confidence interval, 0.18-0.70]; P=0.003; RFS: HR, 0.17 [0.05-0.54]; P=0.003) had a significantly better prognosis; patients with p53abn tumors had a significantly worse RFS (HR, 1.73 [1.09-2.74]; P=0.021); patients with MMRd tumors showed a trend toward better RFS. Estimated 5-year OS rates were as follows: POLE 89%, MMRd 75%, NSMP 69%, p53abn 55% (Log rank P=0.001). Five-year RFS rates were as follows: POLE 96%, MMRd 77%, NSMP 64%, p53abn 47% (P=0.000001), respectively. In a multivariable Cox model that included age and Federation Internationale de Gynecologie et d'Obstetrique stage, POLE and MMRd status remained independent prognostic factors for better RFS; p53 status was an independent prognostic factor for worse RFS. Molecular classification of grade 3 EECs reveals that these tumors are a mixture of molecular subtypes of endometrial carcinoma, rather than a homogeneous group. The addition of molecular markers identifies prognostic subgroups, with potential therapeutic implications.

Perceptions of successful aging among older Latinos, in cross-cultural context.

Latinos are the largest and fastest growing minority group in the U.S. but they have been overlooked in studies of successful aging. This study used a multi-method approach with an open-ended question and Phelan et al.'s (Journal of American Geriatrics Society 52:211-216, 2004) Successful Aging Measure to determine whether the quantitative measure fully captured perceptions of successful aging of 60 older Latinos living in three Western states. Then, the findings were compared with other studies that had used the measure with Anglo, Japanese, Japanese-American, and Latin American samples. The results revealed that Latinos and Latin Americans responses are very similar to each other, and somewhat different from other cultural groups. Latinos focus on maintaining a positive outlook, living in the present, enjoying a sense of community, and relying on spirituality and family for comfort and meaning as they age, but they also worry about finances. There are several components of this study that professionals can use to guide their practice, including a summary of methodological challenges and ongoing conceptual debates in the successful aging literature.