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The World Health Organization (WHO) central nervous system (CNS) tumor classification has represented the primary source of diagnosis and grading criteria of brain tumors. Nonetheless, recent advances of studies on their molecular alterations require more rapid update of recommendations for clinical practice. To accomplish this, cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established in 2016 and has published four updates. For adult gliomas, update 1 clarified the use of the term NOS (Not Otherwise Specified) and proposed a new term NEC (Not Elsewhere Classified); update 2 revised clarifications regarding diffuse astrocytoma/anaplastic astrocytoma, IDH-mutant; update 3 proposed molecular criteria for an IDH-wildtype diffuse or anaplastic astrocytic glioma without histological features of glioblastoma, which would behave similarly to a grade IV glioblastoma. Nonetheless, no consensus on pathologic or molecular markers that could be incorporated into a more clinically relevant grading scheme for IDH-mutant gliomas has been reached. The molecular alterations previously studied using relatively large cohorts include CDKN2A/B homozygous deletion, CDK4 amplification, RB1 mutation/homozygous deletion, PIK3CA or PIK3R1 mutations, PDGFRA amplification, NMYC amplification, global hypomethylation, genomic instability and chromosome 14 loss. The proliferative activity, based on the mitotic count or Ki67 indices, and other morphologic features typical of a high grade that might stratify the risk better than the current criteria have also been evaluated. Despite the discordance among the results of previous studies, CDKN2A/2B homozygous deletions have been shown prognostic significance in high-grade IDH-mutant astrocytomas and microvascular proliferation stratifies IDH-mutant gliomas lacking a CDKN2A homozygous deletion, suggesting that the integration of molecular information and traditional histological findings is still essential for achieving maximum risk stratification of adult cases of IDH-mutant diffuse gliomas. The grading scheme for adult IDH-mutant as well as wild-type gliomas should therefore be revised in the next WHO update.

S4-KL-1 UPDATE OF WHO2016 CLASSIFICATION OF ADULT DIFFUSE GLIOMAS