Pediatric high-grade gliomas (HGGs) arising in the cerebellum remain rare, and detailed accounts in the literature are limited. Medulloblastoma constitutes a major differential diagnosis when encountering poorly differentiated tumors in the pediatric cerebellum. The present study delineates the histological and molecular attributes of five cerebellar high-grade gliomas in children. These neoplasms exhibited considerable histological and immunohistochemical overlap with medulloblastomas and registered high scores on a NanoString-based diagnostic assay for medulloblastoma. Epigenetic analysis via methylation profiling revealed heterogeneity, with tumors clustering into the GBM_MID, DMG_K27, and GBM_RTKIII methylation classes. One case harbored MYCN amplification, and two others showed PDGFRA amplification. Targeted sequencing revealed TP53 mutations in all tumors. These observations emphasize that pediatric cerebellar high-grade gliomas can imitate medulloblastomas both morphologically and at the transcriptomic level. This report contributes additional cases to the sparse literature concerning cerebellar HGGs in children. Combined use of methylation array profiling and TP53 screening is recommended when evaluating poorly differentiated cerebellar embryonal-like tumors.
