Epithelioid sarcoma in patients with rhabdoid tumor predisposition syndrome (RTPS): A novel cancer in the RTPS spectrum

Abstract Background Rhabdoid tumor predisposition syndrome (RTPS) is characterized by germline biallelic loss of SMARCB1 (RTPS1) or SMARCA4 genes, leading to early-onset tumors primarily in the brain and kidneys. Epithelioid sarcoma (EpS) is a rare malignant soft tissue sarcoma in children and young adults, characterized by loss of nuclear SMARCB1 expression. Here, we describe survivors of atypical teratoid rhabdoid tumors (ATRT) with RTPS1 who developed EpS during follow-up. Methods Data were collected through a retrospective chart review of 4 patients with RTPS and ATRT diagnosed with EpS during routine follow-up. A literature review on RTPS and EpS was also conducted. Results All 4 patients were diagnosed with ATRT and RTPS1 in infancy and treated with surgery, high-dose chemotherapy, and autologous stem cell transplantation. Relapse occurred in 3 of the 4 patients, with 2 patients undergoing surgery followed by focal radiation. EpS was diagnosed at regular follow-up, with patients presenting with multiple skin lesions in their extremities (hands, fingers). Histopathological analysis confirmed EpS with characteristic loss of SMARCB1 expression. Staging scans showed no evidence of disseminated disease. All 4 patients underwent surgical excision with negative margins, and 2 patients experienced multiple local recurrences managed with wide surgical excision. A literature review identified 1 additional case of RTPS1 with metachronous ATRT and late-onset EpS. Conclusions Our findings, supported by literature review, suggest that EpS is a primary malignancy within the RTPS1 cancer spectrum. Recognizing this predisposition is critical for implementing appropriate long-term surveillance and early intervention strategies in patients with RTPS1.