Extraskeletal Ewing sarcoma with uterine cornua attachment mimicking high grade endometrial stromal sarcoma: A case report and brief literature review

• Ewing sarcoma involving the uterus morphologically overlaps with high-grade endometrial stromal sarcoma. • The chemotherapy regimen for Ewing sarcoma is typically vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VDC-IE), while for high-grade endometrial stromal sarcoma, doxorubicin is typically combined with ifosfamide or dacarbazine. • Molecular evaluation, with detection of EWSR1 rearrangement in Ewing and YWHAE, BCOR or other characteristic rearrangements in high-grade endometrial stromal sarcoma, is critical for definite diagnosis and management. Ewing sarcoma is an EWSR1-rearranged aggressive malignancy that occurs commonly in bone and has small round blue cell morphology. A diagnostic challenge is presented in the cases of extraskeletal Ewing sarcoma involving solid organs, such as the uterus. We present the case of a 54-year-old female with a large pelvic mass connected to the uterine cornua and retroperitoneal soft tissue. Upon surgical debulking, the mass was characterized by infiltrative tumor cells with high nuclei-to-cytoplasmic ratio invading from the serosal surface into the myometrium. The initial diagnostic work-up was muddied by radiographic suggestion of uterine origin, histologic identification of uterine involvement and diffuse positivity for Cyclin D1, KIT and CD99, which raised the diagnostic possibility of high-grade endometrial stromal sarcoma. However, molecular testing that revealed EWSR1::FLI fusion, indicative of Ewing sarcoma. She was thus referred from the gynecologic oncology service to the soft tissue sarcoma service for adjuvant chemotherapy of vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide (VDC/IE). We performed a literature review highlighting immunohistochemical and molecular features along with treatment and outcomes in case series of YWHAE-rearranged high-grade endometrial stromal sarcomas and Ewing sarcoma with uterine and/or retroperitoneal involvement. This case and accompanying literature review highlight the benefit of molecular testing in the context of round cell tumors involving the uterus and the importance of distinguishing high-grade uterine stromal sarcomas from sarcomas of soft tissue origin, as they have different treatment strategies.