Clinicopathological and Molecular Characterization of Pediatric Breast Fibroepithelial Lesions: A Cohort Study

Objective The aim of this study is to characterize the clinicopathological and molecular features of pediatric breast fibroepithelial lesions (FELs) and evaluate the diagnostic and clinical relevance of distinguishing fibroadenomas (FAs) from phyllodes tumors (PTs).Methods We retrospectively analyzed 138 pediatric breast FELs. Pathologic evaluation, immunohistochemical staining, and Sanger sequencing of MED12 exon 2 and the TERT promoter were performed.Results Of the 138 cases, 133 were diagnosed as FAs (96.4%) and five as benign PTs (3.6%). CD34, Ki-67, and p16 expression were correlated with mitotic activity. CD34 also associated with atypia, and Ki-67 with stromal overgrowth. Larger sized tumors (≥4 cm) had mutant MED12 (30/45 cases). No TERT promoter mutations were detected. During follow-up (range 17–153 months), no true recurrences occurred; though, 13 patients developed new lesions in other quadrants or contralateral breast.Conclusions Pediatric FELs likely represent a diagnostic continuum. In this cohort, the distinction between FA and benign PT did not impact clinical outcome, suggesting limited prognostic significance.