Classification of diffuse gliomas in adults

ATRX: ATRX chromatin remodeler; CDKN2A/B: cyclin-dependent kinase inhibitor 2A/B; CNS: central nervous system; EGFR: epidermal growth factor receptor; H3: histone 3; IDH: isocitrate dehydrogenase; NEC: not elsewhere classified; TERT: telomerase reverse transcriptase; TP53: tumor protein p53; WHO: World Health Organization.

* Immunohistochemical staining for the most common mutant form of IDH1 (R132) should be performed on all diffuse glioma specimens for diagnostic purposes. Less common mutations in IDH1 and all IDH2 mutations will not be identified using this antibody but can be detected using DNA sequencing approaches. If immunohistochemistry for mutant IDH1 R132H is negative, sequencing of IDH1 (codon 132) and IDH2 (codon 172) should be performed in patients with grade 2 and grade 3 diffuse gliomas and in younger patients (<55 years) with glioblastomas, as the distinction between IDH-mutant and IDH-wildtype is central to an integrated diagnosis.

¶ For tumors in midline location and in younger patients, assumes testing for H3 K27M and H3 G34 (respectively) has been performed and is negative.

Δ Tumors with none of these alterations receive a provisional diagnosis of astrocytoma, IDH-wildtype, NEC. The biologic behavior of such tumors is uncertain. Further molecular testing may lead to a more definitive diagnosis.