World Health Organization (WHO) grade 4
gliomas of the cerebellum are rare entities whose understanding trails that of their supratentorial counterparts. Like supratentorial high-grade
gliomas (sHGG), cerebellar high-grade
gliomas (cHGG) preferentially affect males and prognosis is bleak; however, they are more common in a younger population. While current
therapy for cerebellar and supratentorial HGG is the same, recent molecular analyses have identified features and subclasses of
cerebellar tumors that may merit individualized targeting. One recent series of cHGG included the subclasses of (1) high-grade
astrocytoma with piloid features (
HGAP, ~31% of
tumors); (2) H3K27M diffuse midline
glioma (~8%); and (3)
isocitrate dehydrogenase (IDH) wildtype
glioblastoma (~43%). The latter had an unusually low-frequency of
epidermal growth factor receptor (EGFR) and high-frequency of
platelet-derived growth factor receptor alpha (PDGFRA) amplification, reflecting a different composition of methylation classes compared to supratentorial IDH-wildtype
tumors. These new classifications have begun to reveal insights into the pathogenesis of HGG in the cerebellum and lead toward individualized treatment targeted toward the appropriate subclass of cHGG. Emerging therapeutic strategies include targeting the
mitogen-activated protein kinases (MAPK) pathway and PDGFRA,
oncolytic virotherapy, and
immunotherapy. HGGs of the cerebellum exhibit
biological differences compared to sHGG, and improved understanding of their molecular subclasses has the potential to advance treatment.