{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T19:58:44Z","timestamp":1794081524137,"version":"4.8.0"},"reference-count":160,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A working group of cIMPACT-NOW evaluated the literature on IDH-mutant gliomas for opportunities to improve pathology-based risk stratification and grading, especially at the interface of CNS WHO grades 2 and 3, since therapeutic decisions depend on risk assessment for clinical management. The group also evaluated newly described IDH-mutant glioma subgroups and considered multidisciplinary aspects of therapeutic decision-making. PDGFRA amplification was associated with highly aggressive clinical behavior of IDH-mutant astrocytomas, consistent with CNS WHO grade 4. Other genetic alterations associated with intermediate risk and most consistent with CNS WHO grade 3 included PIK3 mutations; EGFR alteration; MYCN amplification; and specific retinoblastoma pathway alterations, including CDK4, CDK6, and CCND2 amplification, RB1 homozygous deletion or mutation, and mutation of CDKN2A. DNA methylation signatures of G-CIMP-low or A_IDH_HG were consistent with CNS WHO grade 3 or 4, depending upon other grading criteria. We suggest a mitotic count of \u22653 per 2.4 mm2 could be considered as a CNS WHO grade 3 criterion. Our review did not uncover features to improve the grading of oligodendroglioma, IDH-mutant and 1p\/19q-codeleted, although CNS WHO grade 3 tumors with elevated mitotic rates, yet lacking necrosis, microvascular proliferation, CDKN2A\/B homozygous deletion, and MRI contrast enhancement, may be associated with extended survival. Implementing evidence-based criteria for risk stratification and grading will improve guidance for clinical decision-making.<\/jats:p>","DOI":"10.1093\/neuonc\/noag108","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T12:05:19Z","timestamp":1778760319000},"page":"2069-2089","source":"Crossref","is-referenced-by-count":19,"title":["cIMPACT-NOW Update 12: Refining pathology-based risk stratification and grading for IDH-mutant gliomas"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-6563","authenticated-orcid":false,"given":"Daniel J","family":"Brat","sequence":"first","affiliation":[{"name":"Department of Pathology, Northwestern University Feinberg School of Medicine , Chicago, Illinois,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5119-7550","authenticated-orcid":false,"given":"Kenneth","family":"Aldape","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, Minnesota,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0668-9529","authenticated-orcid":false,"given":"Pim J","family":"French","sequence":"additional","affiliation":[{"name":"Brain Tumor Center, Department of Neurology, Erasmus MC Cancer Institute, University Medical Center , Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9423-4099","authenticated-orcid":false,"given":"David N","family":"Louis","sequence":"additional","affiliation":[{"name":"Department of Pathology, Mass General Brigham, Harvard Medical School , Boston, Massachusetts,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4861-0898","authenticated-orcid":false,"given":"MacLean P","family":"Nasrallah","sequence":"additional","affiliation":[{"name":"Department of Pathology, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, Pennsylvania,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1419-9837","authenticated-orcid":false,"given":"Guido","family":"Reifenberger","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, Heinrich Heine University Medical Faculty and University Hospital D\u00fcsseldorf , D\u00fcsseldorf,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4573-6033","authenticated-orcid":false,"given":"David E","family":"Reuss","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, University of Heidelberg , Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5910-7799","authenticated-orcid":false,"given":"Mehdi","family":"Touat","sequence":"additional","affiliation":[{"name":"Department of Neuro-oncology, Sorbonne University, Inserm, CNRS, UMRS 1127, Paris Brain Institute (PBI), AP-HP Sorbonne University, La Piti\u00e9 Salp\u00eatri\u00e8re - Charles Foix Hospital Group , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5710-5127","authenticated-orcid":false,"given":"Martin J","family":"van den Bent","sequence":"additional","affiliation":[{"name":"Brain Tumor Center, Department of Neurology, Erasmus MC Cancer Institute, University Medical Center , Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5453-5201","authenticated-orcid":false,"given":"Pieter","family":"Wesseling","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam University Medical Centers , Amsterdam,","place":["The Netherlands"]},{"name":"Princess M\u00e1xima Center for Pediatric Oncology , Utrecht,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3604-887X","authenticated-orcid":false,"given":"Dominique","family":"Figarella-Branger","sequence":"additional","affiliation":[{"name":"Aix-Marseille Univ, APHM, CNRS, INP, Institut de Neurophysiopathologie, GlioME Team, CHU Timone, Service d\u2019Anatomie Pathologique et de Neuropathologie , Marseille,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"2026091010362911000_noag108-B1","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization classification of tumors of the Central nervous system: a summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol"},{"key":"2026091010362911000_noag108-B2","volume-title":"World Health Organization Histological Classification of Tumours of the Central Nervous System","author":"DN OH","year":"2016","edition":"4th"},{"key":"2026091010362911000_noag108-B3","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO classification of tumors of the Central nervous system: a summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro Oncol"},{"key":"2026091010362911000_noag108-B4","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s00401-020-02127-9","article-title":"cIMPACT-NOW update 5: recommended grading criteria and terminologies for IDH-mutant astrocytomas","volume":"139","author":"Brat","year":"2020","journal-title":"Acta Neuropathol"},{"key":"2026091010362911000_noag108-B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-016-1646-x","article-title":"Announcing cIMPACT-NOW: the consortium to inform molecular and practical approaches to CNS tumor taxonomy","volume":"133","author":"Louis","year":"2017","journal-title":"Acta Neuropathol"},{"key":"2026091010362911000_noag108-B6","volume-title":"World Health Organization of Tumours Editoril Board. 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