Are Dinucleotide Alterations Definitional for Myxoid Glioneuronal Tumor? Report of p. K385L Mutation in a Neonatal High-Grade Glioma.

Tumors are increasingly defined by molecular alterations but approach to cases with discordant histologic and molecular features is unclear. Myxoid glioneuronal tumor (MGNT), histologically similar to dysembryoplastic neuroepithelial tumor (DNET), is characterized by dinucleotide mutations in gene (K385L or K385I). Here, we report K385L mutation in a neonatal high-grade glioma. A male neonate presented at birth with hydrocephalus. Subsequent imaging showed a large, lobulated cerebral mass. He died at day 37 of life from intracranial hemorrhage. A brain-only autopsy was performed, which showed a diffusely infiltrative hemorrhagic glial tumor with variable histology. Regions with distinct mucin pools and monomorphic oligodendroglioma-like cells were present. Elsewhere, there was little mucin and markedly atypical nuclei. Increased mitotic rate and foci of microvascular proliferation were widely present. Targeted panel sequencing found K385L mutation. DNA methylation studies showed a match with diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype, RTK1 subtype with a high calibrated score. In summary, we report the occurrence of hotspot mutation in a neonatal high-grade glioma without distinct features of MGNT, demonstrating that this genetic alteration is not specific to MGNT. We recommend caution in classifying a tumor as MGNT solely by the presence of alteration.