Stage IA undifferentiated uterine sarcoma with SMARCA4 and SMARCA2 co-deficiency: a case report

Uterine sarcomas represent a rare and heterogeneous group of malignancies whose management remains clinically challenging. They account for approximately 3%-5% of all uterine malignancies. Undifferentiated uterine sarcoma (UUS) is a subtype of uterine sarcomas. SMARCA4 is a tumor suppressor gene that is aberrantly altered in approximately 5%-7% of human malignancies. SMARCA4-deficient UUS is a highly aggressive, undifferentiated mesenchymal neoplasm associated with a median overall survival (OS) of 7 months. During tumorigenesis, loss of function of either SMARCA4 or SMARCA2 is frequently observed; however, concurrent loss of both genes has been reported to be synthetically lethal and is therefore considered unexpected. In this case report, a 52-year-old Chinese woman with early-stage UUS and SMARCA4 and SMARCA2 co-deficiency underwent surgical resection followed by adjuvant chemotherapy and achieved a disease-free survival (DFS) of 32 months. This case suggests that patients with UUS harboring SMARCA4 and SMARCA2 co-deficiency may derive a survival benefit from early diagnosis and surgical resection. However, owing to the extreme rarity of UUS with co-deficiency of SMARCA4 and SMARCA2, conducting a high-level phase III randomized controlled trial to validate this observation remains impractical.