RESUMO
OBJECTIVE: To describe the clinical characteristics and outcome of patients with Li-Fraumeni-associated rhabdomyosarcoma (RMS). METHOD: Retrospective analysis of data from 31 French patients with RMS diagnosed before the age of 20 years associated with a TP53 pathogenic germline variant. Cases were identified through the French Li-Fraumeni database. Central histologic review was performed in 16 cases. RESULTS: The median age at diagnosis was 2.3 years, and the median follow-up was 9.1 years (0.3-34.8). The main tumor sites were head and neck (n = 13), extremities (n = 8), and trunk (n = 8). The local pathology report classified the 31 tumors in embryonal (n = 26), alveolar (n = 1), pleomorphic (n = 1), and spindle-cell (n = 1) RMS (missing = 2). After histological review, anaplasia (diffuse or focal) was reported in 12/16 patients. Twenty-five patients had localized disease, three had lymph node involvement, and three distant metastases. First-line therapy combined surgery (n = 27), chemotherapy (n = 30), and radiotherapy (n = 14) and led to RMS control in all, but one patient. Eleven patients relapsed, and 18 patients had second malignancies. The 10-year event-free, progression-free, and overall survival rates were 36% (95% CI: 20-56), 62% (95% CI: 43-77) and 76% (95% CI: 56-88), respectively. The 10-year cumulative risk of second malignancies was 40% (95% CI: 22-60). CONCLUSION: The high incidence of multiple primary tumors strongly influences the long-term prognosis of RMS associated with TP53 pathogenic germline variants. Anaplastic RMS in childhood, independently of the familial history, should lead to TP53 analysis at treatment initiation to reduce, whenever possible, the burden of genotoxic drugs and radiotherapy in carriers and to ensure the early detection of second malignancies.