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World Health Organization 2021 Classification of Central Nervous System Tumors and Implications for Therapy for Adult-Type GliomasA Review

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Importance  Previous histologic classifications of brain tumors have been limited by discrepancies in diagnoses reported by neuropathologists and variability in outcomes and response to therapies. Such diagnostic discrepancies have impaired clinicians’ ability to select the most appropriate therapies for patients and have allowed heterogeneous populations of patients to be enrolled in clinical trials, hindering the development of more effective therapies. In adult-type diffuse gliomas, histologic classification has a particularly important effect on clinical care.

Observations  In 2021, the World Health Organization published the fifth edition of the Classification of Tumors of the Central Nervous System. This classification incorporates advances in understanding the molecular pathogenesis of brain tumors with histopathology in order to group tumors into more biologically and molecularly defined entities. As such, tumor classification is significantly improved through better characterized natural histories. These changes have particularly important implications for gliomas. For the first time, adult- and pediatric-type gliomas are classified separately on the basis of differences in molecular pathogenesis and prognosis. Furthermore, the previous broad category of adult-type diffuse gliomas has been consolidated into 3 types: astrocytoma, isocitrate dehydrogenase (IDH) mutant; oligodendroglioma, IDH mutant and 1p/19q codeleted; and glioblastoma, IDH wild type. These major changes are driven by IDH mutation status and include the restriction of the diagnosis of glioblastoma to tumors that are IDH wild type; the reclassification of tumors previously diagnosed as IDH-mutated glioblastomas as astrocytomas IDH mutated, grade 4; and the requirement for the presence of IDH mutations to classify tumors as astrocytomas or oligodendrogliomas.

Conclusions and Relevance  The 2021 World Health Organization central nervous system tumor classification is a major advance toward improving the diagnosis of brain tumors. It will provide clinicians with more accurate guidance on prognosis and optimal therapy for patients and ensure that more homogenous patient populations are enrolled in clinical trials, potentially facilitating the development of more effective therapies.

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Article Information

Accepted for Publication: May 24, 2022.

Published Online: August 25, 2022. doi:10.1001/jamaoncol.2022.2844

Corresponding Author: Ugonma N. Chukwueke, MD, MPH, Division of Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02420 (ugonma_chukwueke@dfci.harvard.edu).

Author Contributions: Dr Chukwueke had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: Lang-Orsini.

Drafting of the manuscript: Berger, Wen, Lang-Orsini.

Critical revision of the manuscript for important intellectual content: Berger, Lang-Orsini, Chukwueke.

Administrative, technical, or material support: Berger, Lang-Orsini, Chukwueke.

Supervision: Chukwueke.

Conflict of Interest Disclosures: Dr Wen reported receiving grants from AstraZeneca, BeiGene, Bristol-Myers Squibb, Chimerix, Eli Lilly, Kazia, MediciNova, Merck, Nuvation Bio, Puma, Servier, Vascular Biogenics, VBI Vaccines, and Bayer; advisory board fees from AstraZeneca, Black Diamond, Boehringer Ingelheim, Celularity, Chimerix, Genenta, GlaxoSmithKline, Karyopharm, Merck, Mundipharma, Novartis, Novocure, Prelude Therapeutics, and Servier; data safety monitoring board fees from Day One Bio and Novocure; and consultant fees from Nuvation Bio, Vascular Biogenics, and Sapience outside the submitted work. No other disclosures were reported.

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