Rare Pediatric Cerebellar High-Grade Gliomas Mimic Medulloblastomas Histologically and Transcriptomically and Show p53 Mutations.

Simple Summary: High-grade gliomas (HGGs) in the cerebellum of children have been rarely described. We studied the histological and molecular features of a series of five pediatric high-grade gliomas in the cerebellum. These unique cases showed histological and immunohistochemical similarities to medulloblastoma, which is a main differential diagnosis of poorly differentiated tumors in the cerebellum in children. Furthermore, these tumors showed high scores by NanoString-based transcriptomic assay for medulloblastoma. Genomic methylation profiling, however, revealed that they clustered to the glioblastoma subclasses. TP53 mutations were found in all cases by panel sequencing. This study adds to the rare pathological and molecular characterization of pediatric cerebellar high-grade gliomas and shows that their histological, immunohistochemical, and transcriptomical characteristics overlap with those of medulloblastoma. We recommend the use of both methylation array and TP53 screening in the differential diagnoses of poorly differentiated embryonal-like tumors of the cerebellum. Pediatric high-grade gliomas (HGG) of the cerebellum are rare, and only a few cases have been documented in detail in the literature. A major differential diagnosis for poorly differentiated tumors in the cerebellum in children is medulloblastoma. In this study, we described the histological and molecular features of a series of five pediatric high-grade gliomas of the cerebellum. They actually showed histological and immunohistochemical features that overlapped with those of medulloblastomas and achieved high scores in NanoString-based medulloblastoma diagnostic assay. Methylation profiling demonstrated these tumors were heterogeneous epigenetically, clustering to GBM_MID, DMG_K27, and GBM_RTKIII methylation classes. MYCN amplification was present in one case, and PDGFRA amplification in another two cases. Interestingly, target sequencing showed that all tumors carried TP53 mutations. Our results highlight that pediatric high-grade gliomas of the cerebellum can mimic medulloblastomas at histological and transcriptomic levels. Our report adds to the rare number of cases in the literature of cerebellar HGGs in children. We recommend the use of both methylation array and TP53 screening in the differential diagnoses of poorly differentiated embryonal-like tumors of the cerebellum. [ABSTRACT FROM AUTHOR]