Endometrial carcinoma represents the most common gynecological cancer in Europe and the USA. Histopathological classification based on tumor morphology and tumor grade has played a crucial role in the management of endometrial carcinoma, allowing a prognostic stratification into distinct risk categories, and guiding surgical and adjuvant therapy. In 2013, The Cancer Genome Atlas (TCGA) Research Network reported a large scale molecular analysis of 373 endometrial carcinomas which demonstrated four categories with distinct clinical, pathologic, and molecular features: POLE/ultramutated (7% of cases) microsatellite instability (MSI)/hypermutated (28%), copy-number low/endometrioid (39%), and copy-number high/serous-like (26%). In the present article, we report a detailed histological and molecular review of all endometrial carcinoma histotypes in light of the current ESGO/ESTRO/ESP guidelines. In particular, we focus on the distribution and prognostic value of the TCGA groups in each histotype.

An increased prevalence of malignant lymphoma and of gastric cancer has been observed in large cohorts of patients with common variable immunodeficiency (CVID), the most frequently symptomatic primary immunodeficiency. Surveillance strategies for cancers in CVID should be defined based on epidemiological data. Risks and mortality for cancers among 455 Italian patients with CVID were compared to cancer incidence data from the Italian Cancer Registry database. CVID patients showed an increased cancer incidence for all sites combined (Obs = 133, SIR = 2.4; 95%CI = 1.7–3.5), due to an excess of non-Hodgkin lymphoma (Obs = 33, SIR = 14.3; 95%CI = 8.4–22.6) and of gastric cancer (Obs = 25; SIR = 6.4; 95%CI = 3.2–12.5). CVID patients with gastric cancer and lymphoma had a worse survival in comparison to cancer-free CVID (HR: 4.8, 95%CI: 4.2–44.4 and HR: 4.2, 95%CI: 2.8–44.4). Similar to what observed in other series, CVID-associated lymphomas were more likely to be of B cell origin and often occurred at extra-nodal sites. We collected the largest case-series of gastric cancers in CVID subjects. In contrast to other reports, gastric cancer was the leading cause of death in CVID. Standardized mortality ratio indicated a 10.1-fold excess mortality among CVID patients with gastric cancer. CVID developed gastric cancer 15 years earlier than the normative population, but they had a similar overall survival. Only CVID diagnosed at early stage gastric cancer survived >24 months. Stomach histology from upper endoscopy performed before cancer onset showed areas of atrophic gastritis, intestinal metaplasia or dysplasia. CVID patients might progress rapidly to an advanced cancer stage as shown by patients developing a III-IV stage gastric cancer within 1 year from an endoscopy without signs of dysplasia. Based on high rate of mortality due to gastric cancer in Italian CVID patients, we hereby suggest a strategy aimed at early diagnosis, based on regular upper endoscopy and on Helicobacter pylori infection treatment, recommending an implementation of national guidelines.

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Background: The chemotherapy response score (CRS) has emerged as a simple and reproducible histopathological grading system for assessing chemotherapy response in patients affected by ovarian high-grade serous carcinoma. Objective: To evaluate the prognostic impact of histological tumor response in ovarian and omental surgical specimens from patients with advanced stage ovarian high-grade serous carcinoma. Study Design: A cohort of 161 women were identified from the database of Department of Gynecology, “Fondazione Policlinico Universitario Agostino Gemelli IRCCS” of Rome, Italy between January 2014 and December 2017 with a follow-up of 65 months. All the omentum, the ovarian tissue and peritoneal samples, defined as “other sites,” were reviewed by gynecological pathologists to assign a CRS of 1–3 to the omentum and ovarian sites and a score of 0–1 to the peritoneal tissue. The Cox proportional hazards regression and the log-rank test were used to assess the survival pattern and the prognostic value of the CRS adjusting for age and stage. The Kaplan-Meier method was applied to estimate the progression free and overall survival. Results: The evaluation of adnexal disease showed significant differences in PFS, both in univariate and in multivariate analyses. On PFS univariate analysis, ovCRS1 vs. ovCRS3: HR, 2.27; 95% CI, 1.37–3.77; p = 0.001; ovCRS2 vs. ovCRS3: HR, 1.83; 95% CI, 1.03–3.23; p = 0.04, and on PFS multivariate model ovCRS1 vs. ovCRS3; HR, 2.53; 95% CI, 1.5–4.24; p = 0.001 and ovCRS2 vs. ovCRS3; HR, 1.90; 95% CI, 1.08–3.37; p = 0.03. Regarding the omental residual disease, as expected, CRS showed a significant prognostic value for OS and PFS; in detail the median PFS of patients with CRS1, 2 and 3 was 15, 15, and 22 months, respectively, the median OS was 41 and >50 months, respectively. Moreover, the univariate analysis for OS suggested that in our cohort the “other sites” score of 0 was significantly associated with an improvement in overall survival compared to score 1. Conclusions: We demonstrated for the first time the prognostic significance of adnexal CRS confirming also the prognostic role of omental CRS.