The World Health Organization (WHO) central nervous system tumor classification represents the primary source of updates on diagnostic classes, grades and criteria [17]. However, recent and ongoing advances in our understanding of brain tumor molecular pathogenesis warrant more rapid integration of this information into clinical practice between WHO updates. To accomplish this, cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established in 2016 [15, 16]. Since then, cIMPACT-NOW has convened three separate working committees to address classification and grading questions and challenges. Working Committee 1 focused on a concern that the classification and grading of Isocitrate Dehydrogenase (IDH)-wildtype diffuse astrocytic gliomas do not reflect our current understanding of the molecular pathogenesis and clinical outcomes associated with these tumors.

Numerous high-profile publications have documented the distinct genetic alterations and clinical behavior of IDH-mutant and IDH-wildtype diffuse astrocytic gliomas in the adult population [4, 6, 8]. Based on this, the WHO has designated IDH-mutant and IDH-wildtype diffuse astrocytic gliomas as distinct diagnostic categories within the 2016 update of the fourth edition [17, 19]. The WHO also recognizes H3 K27-mutant diffuse midline glioma as a tumor with aggressive clinical behavior corresponding to WHO grade IV [19]. Similarly, detection of an H3 G34 mutation in a diffuse glioma, irrespective of histological grade, indicates high-grade biology with only modestly longer survivals than other IDH-wildtype glioblastomas [13, 28]. The WHO 2016