Opinion & Special Article: Glioma Classification

Diffuse infiltrating gliomas are the most common malignant brain tumors in adults. The 2021 World Health Organization classification for CNS tumors (CNS5 WHO) has significantly altered the rules for classification and grading of diffuse gliomas. Clinicians, including neurology residents and neurologists, will have to consider the changes that include the introduction of new tumor types, allotting established tumor types to other groups and substituting previously essential morphological features for additional molecular markers. For example, in the current classification, glioblastoma is defined as isocitrate dehydrogenase (IDH)-wildtype, grade 4. Whereas, a grade 4 IDH-mutated astrocytic glioma is referred to as astrocytoma, IDH-mutated, grade 4. In addition, potential targeted treatments, based on the underlying molecular alterations, have become therapeutic options for diffuse gliomas. For clinicians, it is important to know the rationale for why these options are only available for specific tumors. Owing to the emphasis of molecular markers in the CNS5 WHO classification, interpretation of a pathology report and understanding of its clinical implications can be challenging. This review describes the most important molecular alterations in glioma, summarizes the recent changes in the CNS5 WHO classification for glioma, and presents a stepwise approach for trainees and neurologists to decipher a glioma pathology report. Additional information is summarized in eTable 1 (links.lww.com/WNL/C324).