A global clinicopathologic and molecular portrait of spindle cell/sclerosing rhabdomyosarcoma with emphasis on retroperitoneal cases

Introduction: Spindle cell and sclerosing rhabdomyosarcoma (Sc/SRMS) are rare histologic subtypes of rhabdomyosarcoma, increasingly recognized for their distinct molecular profiles and aggressive clinical behavior. Retroperitoneal involvement is exceptionally uncommon and poorly characterized. To characterize the clinical, pathological, and molecular features of retroperitoneal Sc/SRMS through a combined institutional case series and individual patient data (IPD) meta-analysis. Methods: We retrospectively analyzed 12 adult patients with retroperitoneal Sc/SRMS treated at Peking University International Hospital between 2014 and 2023. Clinical data, imaging, histopathology, immunohistochemistry, and MYOD1 mutation status were evaluated. In parallel, we conducted a systematic review and IPD meta-analysis of 136 publications, yielding 403 unique Sc/SRMS cases. Data were extracted on demographics, tumor characteristics, treatment, molecular alterations, and outcomes. Results: All institutional cases presented with large, high-grade retroperitoneal tumors, frequently invading adjacent organs. MYOD1 mutations were detected in 33.3% of patients, and MyoD1 immunopositivity exceeded myogenin (92% vs. 42%, P