SMARCA4-deficient primary bone sarcoma with "teratoid" features in a rhabdoid tumor predisposition syndrome patient.

SMARCA4 is a catalytic subunit of the SWItch/sucrose non-fermentable (SWI/SNF) complex. Truncating SMARCA4 germline pathogenic variants (PVs) lead to rhabdoid tumor predisposition syndrome type 2 (RTPS2), associated with small cell carcinoma of ovary hypercalcemic type (SCCOHT) and pediatric rhabdoid tumors. To our knowledge, no primary bone neoplasm with SMARCA4 loss is reported in the literature. We describe a primary high-grade sarcoma in the femur of a 13-year-old patient with undocumented germline history and without other lesions. The tumor showed morphologic features reminiscent of a "teratocarcinosarcoma," including high-grade primitive spindle and round cell morphology, low-grade fibroblastic proliferation, high-grade glandular epithelium, and low-grade squamous and mucinous epithelium. The tumor showed diffuse loss of SMARCA4 immunoexpression. We subsequently identified a heterozygous nonsense SMARCA4 PV in the patient's germline, with copy-neutral loss of heterozygosity in the tumor. Our report expands the spectrum of SMARCA4-deficient tumors, with implications for germline tumor predisposition and surveillance.