Beyond the World Health Organization classification of central nervous system tumors 2016: what are the new developments for gliomas from a clinician's perspective?

PURPOSE OF REVIEW: The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 to include molecular biomarkers that are important for tumor classification and clinical decision making. Thereafter, the cIMPACT-NOW initiative further refined CNS tumor classification through a series of recommendations likely to shape the upcoming WHO classification 2021. RECENT FINDINGS: Mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes continue to play a major role in glioma classification. Among IDH-mutant gliomas, loss of ATRX expression identifies IDH-mutant astrocytomas without necessity for 1p/19q codeletion testing. The nomenclature for IDH-mutant glioblastoma has been changed to astrocytoma, IDH-mutant, WHO grade 4, with CDKN2A homozygous deletion representing a novel molecular marker for these tumors. IDH-wildtype astrocytomas that lack microvascular proliferation or necrosis but exhibit telomerase reverse transcriptase promoter mutation, epidermal growth factor receptor amplification, and/or a +7/-10 genotype are now classified as IDH-wildtype glioblastoma. H3.3 G34-mutant diffuse hemispheric gliomas have been proposed as a new entity separate from IDH-wildtype glioblastoma. SUMMARY: These changes increase diagnostic accuracy and refine clinical care by changing treatment recommendations, for example for patients with IDH-wildtype astrocytomas showing molecular features of glioblastoma. They also have major implications for clinical trial design.