Ovarian Epithelioid Tumor With FUS::CREM Fusion in a 63-Year-Old Woman: A Case Report of an Emerging Entity Associated With Systemic Inflammation

Intra-abdominal epithelioid neoplasm with EWSR1/FUS::CREB fusions is an emerging entity characterized by a broad age distribution, epithelioid morphology, variable epithelial marker expression, prominent lymphoplasmacytic infiltration, and systemic inflammation. A few ovarian cases have been reported. We describe a 63-yr-old woman who presented with anemia and elevated C-reactive protein. She underwent surgery for a 14-cm right ovarian mass. Grossly, the tumor was solid with cystic change and hemorrhage, and had a light tan cut surface. Histologically, it consisted of uniform sheets of epithelioid cells with ample pale eosinophilic cytoplasm, divided by fibrotic septa with dense lymphoplasmacytic infiltration. Immunohistochemically, the tumor was positive for EMA, WT1, and vimentin; focally positive for CAM5.2; and negative for AE1/AE3, estrogen and progesterone receptors, PAX8, sex cord markers, desmin, HMB45, and Melan A. The Ki-67 labeling index was 20%. The differential diagnoses, including poorly differentiated carcinoma, sex cord-stromal tumors, perivascular epithelioid cell tumor, and inflammatory myofibroblastic tumor, were considered. Whole-genome sequencing revealed a FUS::CREM gene fusion. Based on clinicopathologic and genomic features, the tumor was classified as an ovarian example of EWSR1/FUS::CREB fusion-associated epithelioid neoplasm. Inflammation-related laboratory abnormalities resolved postoperatively. No adjuvant therapy was administered, and the patient remained disease-free at 12 mo. This represents the third reported ovarian tumor with FUS::CREM fusion and the seventh adnexal tumor with EWSR1/FUS::CREB family fusion. Prognostic information on these adnexal tumors is limited, but given the aggressive nature of analogous extra-adnexal and testicular tumors, cautious management and further studies are warranted.