Supplementary Material for: Primary Embryonal Rhabdomyosarcoma of the Breast: a case report and literature review

Background: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and adolescents, but primary RMS of the breast is exceptionally rare and diagnostically challenging. Imaging findings are nonspecific and can mimic benign adolescent lesions (e.g., fibroadenoma), making timely histopathologic confirmation crucial. Immunohistochemistry for muscle markers—particularly Desmin and Myogenin—supports definitive diagnosis of embryonal RMS (ERMS). Case Presentation: A 14-year-old Arab female presented with a rapidly enlarging left-breast mass and ipsilateral axillary lymphadenopathy. Core biopsy showed small round blue cells with rhabdomyoblastic differentiation; tumor cells were Desmin- and Myogenin-positive, consistent with ERMS. She received six cycles of MAID chemotherapy, followed by local recurrence; one cycle of ICE achieved ~50% partial response but was complicated by cystitis and rapid radiologic progression. After three cycles of VAC, she underwent total mastectomy with lymph-node dissection. Restaging FDG-PET/CT demonstrated local recurrence and nodal metastases (bilateral axillary, subpectoral, internal mammary) with pulmonary nodules. Despite multimodal therapy, the disease remained refractory and the patient ultimately died of complications from metastatic RMS. Case Discussion: This case highlights the aggressive biology of primary breast ERMS in adolescents and the risk of early recurrence and dissemination despite intensive therapy. While standard management of RMS is multimodal—systemic chemotherapy with surgical resection and/or radiotherapy—responses can be transient, and treatment interruptions (e.g., toxicity-related delays) may jeopardize disease control. The diagnostic value of Myogenin (highly specific for rhabdomyoblastic differentiation) and Desmin was pivotal here, while the clinical course underscores the limitations of currently available regimens (MAID, ICE, VAC) for refractory disease at this uncommon site. Conclusion: Primary embryonal RMS of the breast is rare and highly aggressive, with a strong propensity for local recurrence and metastatic spread. Even with aggressive multimodal therapy, outcomes can be poor. Earlier recognition, rigorous treatment delivery, and development of novel strategies are urgently needed to improve survival in this devastating presentation.