SMARCA4- deficient undifferentiated uterine sarcoma (SDUS) is a rare, highly aggressive SWI/SNF-deficient malignancy that can morphologically overlap with undifferentiated endometrial carcinoma (UDEC). Although prior targeted sequencing studies have suggested that SDUS often has a “quiet genome,” exome-wide corroboration remains limited. We report a 23-yr-old woman who presented with a >15 cm uterine mass and underwent hysterectomy with bilateral salpingo-oophorectomy, followed by rapid peritoneal dissemination and para-aortic metastases within 2 mo. The disease was refractory to gemcitabine/docetaxel and the patient died 6 mo postoperatively. Histologically, the tumor consisted of sheets of monomorphic undifferentiated epithelioid cells with rhabdoid features, focal phyllodes-like architecture entrapping benign endometrial glands and stromal hyalinization, and no identifiable carcinomatous component. Immunohistochemistry demonstrated complete loss of SMARCA4 (BRG1) and SMARCA2 (BRM) with retained SMARCB1 (INI1), a wild-type p53 pattern, intact mismatch repair protein expression, and negativity for claudin-4 and SOX2. Whole-exome sequencing with copy-number analysis of paired tumor and nontumor tissue identified biallelic SMARCA4 inactivation (somatic frameshift deletion c.3717del, p.W1239fs; VAF 0.89) with loss of heterozygosity at 19p13.2, microsatellite stability, and low tumor mutational burden (0.70 mut/Mb), without additional canonical driver mutations; notably, no TP53 mutation was detected despite hemizygous 17p loss. A focal copy-number gain involving the BRCA1 locus was also identified; however, its biological significance remains uncertain. This case provides exome-wide support for the “quiet genome” concept in SDUS and underscores its biological distinction from UDEC. Comprehensive genomic profiling may assist diagnosis in this aggressive malignancy.
Yoshida et al. (2026) studied this question.