A SMARCA4-Deficient Uterine Sarcoma Arising in a Uterine Adenosarcoma: Expanding the Spectrum of SMARCA4-Deficient Uterine Neoplasms With Hybrid Morphologic Features

Background SMARCA4 genetic alterations have been associated with aggressive neoplasms in various organs. In the uterus, SMARCA4-deficiency has been reported rarely, typically presenting as undifferentiated uterine sarcoma with a poor prognosis and younger age onset. The spectrum of SMARCA4-driven uterine tumors has recently expanded reporting hybrid features to include adenosarcoma components. Clinical Presentation We report a 27-year-old woman who presented with abnormal uterine bleeding. The endometrial curettage revealed a high-grade adenosarcoma. One month later, the patient underwent tumor debulking surgery. The histologic examination showed a tumor with leaf-like architecture and marked stromal atypia. The stromal component exhibited epithelioid and rhabdoid features, with cells arranged in nests. Extensive lymphovascular invasion and infiltration of surrounding tissues were noted. SMARCA4 mutation was confirmed by next-generation sequencing, with no other mutations detected. Despite prompt initiation of aggressive chemotherapy, the cancer continued to spread to the lungs and peritoneum. The patient died 19 months after the initial presentation. Conclusion This case report reinforces the emerging pattern of SMARCA4-deficient tumors presenting aggressively in premenopausal women with hybrid morphologic features. It highlights the importance of molecular testing in patients of all ages and the need for early recognition and prompt treatment of tumors harboring mutations associated with rapid progression.