Head and neck rhabdomyosarcoma in pediatric patients : an international collaborative study

Abstract

BACKGROUND : Rhabdomyosarcoma (RMS), a rare malignant tumor, frequently affects pediatric patients, with 35%–40% occurring in the head and neck. This study analyzes the clinicopathologic profile of pediatric head and neck rhabdomyosarcomas from Brazil, Guatemala, Mexico, and South Africa. METHODS : We reviewed 44 cases from 10 Oral and Maxillofacial Pathology services, conducting immunohistochemical analyses of desmin, myogenin, Myo-D1, and Ki67, with quantification via QuPath software. Cases with ≥ 50% myogenin expression were tested for fusion status using AP2β, NOS-1, and HMGA2. Statistical analyses included the Kruskal–Wallis test for age and marker expression comparisons, Fisher's exact test for categorical variables, Spearman's rank correlation for marker relationships, and multinomial logistic regression to assess fusion status likelihood. RESULTS : Cases were predominantly from Brazil (40.9%), followed by South Africa (27.3%), Guatemala (22.7%), and Mexico (9.1%). Two-thirds of patients were diagnosed in their first decade with no gender predilection. Nonparameningeal sites (45.5%) were more affected than parameningeal (40.9%) and orbital sites. Microscopically, embryonal RMS (77.3%) was most common, followed by alveolar (18.2%) and spindle cell (2.3%) tumors. Immunohistochemistry revealed positivity for myogenic markers, with significant differences in myogenin expression between embryonal and alveolar RMS variants (p < 0.05). Fusion status prediction identified two potential fusion-positive alveolar RMS cases, while all embryonal RMS and one alveolar RMS case appeared fusion-negative. Significant correlation with positive fusion status was found only between AP2β and NOS1 (p < 0.05). CONCLUSION : Although there are slight clinical-demographic variations among pediatric head and neck rhabdomyosarcomas in these regions, identifying fusion status through immunohistochemistry remains a diagnostic challenge.