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• WHO has updated NET classifications in order to simplify terminology across NETs. • Treatment recommendations for cervical NEC have been updated and outlined. • Hypercalcemic type ovarian NECs are no longer considered true NENs. • Treatment for most gynecologic NECs/NENs is derived from experience with other NETs. • Clinical trials are needed to improve outcomes in patients with NETs. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Uterine serous carcinoma (USC) constitutes 10% of uterine cancers but ~40% of deaths. Tumor size is a known prognostic factor in other solid tumors. In endometriod cancers it is one element used to identify the need for complete staging, while its significance in USC is debated. Therefore tumor size was examined as an independent prognostic factor. Methods: Clinical and pathologic variables were recorded for 236 institutional patients, and those patients in the SEER database with USC. Chi-square and Fisher exact t-tests were utilized and survival data generated via Kaplan–Meier method; multivariate analysis was performed via cox-regression. Results: The patients'' mean age was 67.2years (range 40–91). Survival ranged from 0 to 184months (mean 42.8). We used a tumor size cut-off of 1cm and noted significant associations with myometrial invasion (p <0.0001), angiolymphatic invasion (p <0.0001), peritoneal washings (p =0.03), stage (p =0.015) and positive lymph nodes (p =0.05). Furthermore, recurrence was associated with larger tumors (p =0.03). In multivariate analysis, extra-uterine disease was the only factor associated with both recurrence and survival. Review of the SEER database noted association of larger tumors with lymph node involvement and a significant survival advantage with tumors <1cm in both univariate and multivariate analysis. Conclusions: Treatment options for USC are often predicated on the surgical stage and therefore components of the staging are vitally important. The 1cm tumor-size cut-off should be studied prospectively as a prognostic indicator of survival and recurrence in USC and considered for inclusion in USC staging. [Copyright &y& Elsevier]

Immuno-oncology (IO) has rapidly evolved, with many IO therapies either approved or under investigation for multiple malignancies. Biomarkers exist that can predict response to IO therapies including PD-L1 expression, microsatellite instability (MSI), and total mutation burden (TMB). This paper serves to analyze the presence of these biomarkers across gynecologic cancers. A total of 16,300 gynecologic cancer specimens submitted for molecular profiling to Caris Life Sciences were reviewed. Immunohistochemistry was performed using the SP142 anti-PD-L1 clone and assessed for intensity. Next-generation sequencing, immunohistochemistry, and fragment analysis were used to determine MSI status. TMB was measured by counting all non-synonymous missense mutations found per tumor not previously described as germline alterations. Chi-Square, Fisher Exact, and the Kruskal-Wallis test were used to compare cohorts. Of 16,300 specimens, 54.1% were ovarian, 37.2% uterine, 7.2% cervical, 0.3% vulvar, 1.2% vaginal, with 0.1% unspecified. MSI-H was most frequent in uterine cancer (17.7%) and only 1% of ovarian cancers. PD-L1 expression was present in 38.3% of cervical and 62.5% of vulvar cancers, but less than 8% of ovarian and uterine cancers. TMB-H was present in 21.1% cervical, 19.7% uterine, and 5% ovarian cancers. Few specimens exhibited a "triple positive" phenotype - 0.3% ovarian, 1.5% uterine, and 1.5% cervical. Associations were seen between MSI, TMB, and PD-L1 across all cancer types. The frequency of individual biomarkers pertinent to IO therapy varies by cancer type. HPV-driven genital tract cancers have higher frequencies of PD-L1 expression, MSI-H, and TMB H. Endometrial cancers are characterized by MSI-H and TMB, whereas ovarian cancers have a low frequency of MSI-H and modest PD-L1 or TMB H. The incidence of 'triple positive" cases was less than 2%. • This study analyzes PD-L1, MSI, and TMB in 16,300 gynecologic cancer specimens. • Gynecologic cancers have markedly variable response to immunotherapy. • Gynecologic cancers with one immune biomarker are more likely to be positive for others. [ABSTRACT FROM AUTHOR]