cIMPACT-NOW Update 12: Refining pathology-based risk stratification and grading for IDH-mutant gliomas
Year: 2026
Type: article
Abstract: 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 ≥3 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.
Source: Neuro-Oncology
Institutions: Northwestern University, Mayo Clinic, Erasmus MC, Erasmus MC Cancer Institute, Harvard University, Mass General Brigham, University of Pennsylvania, Düsseldorf University Hospital, Heinrich Heine University Düsseldorf, Heidelberg University, University Hospital Heidelberg, Centre National de la Recherche Scientifique, Inserm, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Princess Máxima Center, Amsterdam University Medical Centers, Aix-Marseille Université, Institut de Neurophysiopathologie, Hôpital de la Timone
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7161738780