Clinicopathological and molecular features of breast metastases in alveolar rhabdomyosarcoma: A series of 3 cases

Breast metastases are exceedingly uncommon in pediatric and adolescent populations; however, rhabdomyosarcoma (RMS) is the predominant histological subtype in such cases. Metastatic RMS and primary breast tumors may exhibit overlapping histological features, potentially leading to misclassification. In a cohort of 318 RMS patients treated at our institution between 2011 and 2025, we identified three female patients aged 16, 17, and 31 years who showed breast metastases. All three patients had alveolar RMS (ARMS), with their primary tumors located in the sinonasal region (two patients) and buttocks (one patient). The detection of breast metastases occurred within 0–9 months of the initial diagnosis. Histopathological examination revealed tumors composed of small, round cells organized in alveolar or solid nests, demonstrating infiltrative growth and significant cytologic atypia. Immunohistochemical analyses showed the tumor cells to display strong diffuse positivity for desmin, MyoD1, and myogenin, with Ki-67 proliferation indices that ranged from 70% to 85%. All tumors exhibited FOXO1 rearrangements, as determined by fluorescence in situ hybridization, with two tumors demonstrating 3′ signal amplification. The tumor for patient 3 displayed a PAX3::FOXO1 fusion by next generation sequencing. After 12-months follow-up, patient 3 remained alive with disease, whereas patients 1 and 2 were lost to follow-up. In summary, breast masses in adolescent and middle-aged women comprised of small round cell tumor cells with an invasive growth pattern should prompt consideration of metastatic ARMS as a diagnostic possibility. Accurate diagnosis requires a careful integration of medical history, morphologic and immunophenotypic tumoral features, and confirmation through the detection of specific alterations in the FOXO1 gene.