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EWSR1/FUS-CREB-rearranged mesenchymal neoplasms are an emerging heterogeneous group of soft tissue tumors that encompasses low-grade lesions (angiomatoid fibrous histiocytoma/AFH) and a group of predominantly intra-abdominal aggressive sarcomas with epithelioid morphology and frequent keratin expression. Both entities occasionally harbor EWSR1::ATF1 fusions as alternate to the more frequent EWSR1/FUS::CREB1/CREM fusions. Although EWSR1/FUS-CREB-rearranged epithelioid malignant neoplasms have been described in diverse intra-abdominal sites, none involved the female adnexa. Herein, we describe three cases involving uterine adnexa in young females (41, 39, and 42-year-old); two associated with constitutional inflammatory symptoms. The tumors presented as a serosal surface mass of the ovary without parenchymal involvement (Case 1), as circumscribed nodule within ovarian parenchyma (Case 2), and as a periadnexal mass extending into the lateral uterine wall with lymph node metastasis (Case 3). They were composed of sheets and nests of large epithelioid cells with numerous stromal lymphocytes and plasma cells. The neoplastic cells expressed desmin and EMA, and variably WT1. One tumor expressed in addition AE1/AE3, MUC4, synaptophysin, chromogranin, and ALK. None expressed sex cord-associated markers. RNA sequencing identified EWSR1::ATF1 fusions in two cases and an EWSR1::CREM fusion in one. Exome-based RNA capture sequencing and clustering methods showed high transcriptomic proximity of tumor 1 with soft tissue AFH. This novel subset of female adnexal neoplasms should be included in the differential diagnosis of any epithelioid neoplasm involving female adnexa. Their aberrant immunophenotype can be misleading, underlining a wide spectrum of differential diagnosis.

The tumor microenvironment is crucial in tumourigenesis, response to therapy, and elimination of tumor cells. Tumor-infiltrating lymphocytes (TILs) promote the host immune response and are associated with a better prognosis in colorectal cancer (CRC). This multicentric retrospective study evaluated the relationship between the presence and intensity of TILs and survival outcomes. A total of 651 patients from four Portuguese oncological centers who underwent surgical resection for stages II or III colorectal adenocarcinoma between 2016 and 2019 were included in this study. The mean age of the study population was 70 years; 58.2% were males. The median overall survival was 58.03 ± 1.29 months (95% confidence interval (CI) 55.50 - 60.56), and the median disease-free survival (DFS) was 53.02 ± 1.39 months (95% CI 50.29 - 55.74). Patients with high infiltrate (including those with moderate, abundant, or Crohn-like infiltrate) had significantly longer DFS i.e., 58.48 ± 1.84 months (95% CI 54.87 - 62.09 months) vs 49.22 ± 1.75 months (95% CI 45.79 - 52.64 months) in the group with absent or minimal infiltrate; p = 0.003. Assessing the side of the tumor, high infiltrate was associated with higher DFS (59.86 ± 2.36 months (95% CI 55.23 - 64.50 months) vs 49.60 ± 2.40 months (95% CI 44.90 - 54.29 months), p = 0.011). This work reinforces the importance of research into possible prognostic and predictive factors in patients with CRC.