Concerning the grading of IDH-mutant diffuse gliomas, morphological features play a critical role, but in the 2021 WHO classification, evaluation of CDKN2A/B status has been added as a grading criterion for IDH-mutant astrocytomas: in presence of homozygous CDKN2A/B deletion, grade 4 shall be assigned due to the association with an unfavorable outcome [48, 49]. The gene discussed is IDH2; the disease is astrocytoma (excluding glioblastoma).