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Aim: To study whether mismatch repair (MMR) status is related to the expression of programmed cell death-ligand 1 (PD-L1) and CD8 counts in a series of grade 3 endometrial carcinomas. Materials and Methods: The expression of MMR protein PD-L1 and CD8 + cell count were evaluated by immunohistochemistry and related to several clinicopathological parameters. Results: Among 105 endometrial carcinomas, 40% were of endometrioid and 60% of non-endometrioid histology. MMR deficiency was observed in 28.6% of cases and was related to endometrioid histology (p<0.001), positive PD-L1 expression (p=0.047) and high CD8 + cell count (p=0.022). When examined by histotype, endometrioid MMR-deficient tumors were related only to PD-L1 expression (p=0.032) but not to high CD8+ cell count (p=0.231), whereas nonendometrioid MMR-deficient carcinomas were not related to either of these markers. MMR deficiency was associated with PD-L1 + /CD8 high status (p=0.006), whilst MMR proficiency was associated with PD-L1 − /CD8 low status. In MMR-proficient tumors, high CD8 + cell infiltration alone and combined with PD-L1 − status was associated with better progression-free survival (p=0.013 and p=0.04, respectively). Conclusion: MMR-deficient high-grade endometrioid tumors might be more likely to benefit from immunotherapy compared to other grade 3 endometrial carcinomas.

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(1) Background: Highly differentiated follicular carcinoma of ovarian origin (HDFCO) is an extremely uncommon neoplasm, associated with struma ovarii. There are scarce cases reported in the literature and, subsequently, no reliable conclusions on its pathophysiology, treatment, and prognosis can be drawn. The goal of this study is to enrich the literature on the topic by adding our own experience with a case, and simultaneously accumulate all cases published up to date. (2) Methods: The present review was performed in accordance with the guidelines for systematic reviews and meta-analyses (PRISMA). PubMed (1966–2022), Scopus (2004–2022), and Clinicaltrials.gov databases were screened for relevant articles published up to July 2022. (3) Results: Twenty patients with HDFCO were identified. The included patients were aged 47.15 years (range 24–74). The predominant origin was ovarian (60%) and extraperitoneal spread was confirmed in 15% of the cases. Surgical treatment varied from conservative to radical (35.3% vs. 41.2%, respectively) and the administration of supplementary therapy and thyroidectomy was not universal. Combined thyroidectomy/radioactive iodine therapy was applied in just 62.5% of the reported cases. There was one patient who demonstrated disease recurrence and lives with the disease. No disease related morbidity was reported. (4) Conclusions: HDFCO represents a low-grade malignant tumor, whose rarity does not allow for reliable conclusions. Standard treatment including complete surgical excision and supplementary treatment seems to offer a favorable prognosis in selected cases.