As such, the 2021 classification no longer allows the use of not otherwise specified (NOS) when reporting GBM, as well as introducing a new entry-astrocytoma, WHO CNS grade 4, consisting of the IDH mutant forms of tumors with identical morphology and diffuse hemispheric glioma, WHO CNS grade 4 for tumors with H3 G34 mutation [1-4]. This evidence concerns the gene IDH2 and glioblastoma.