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Updated: May 20, 2026

A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas
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A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas

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cIMPACT-NOW update 12: Refining Pathology-based Risk Stratification and Grading for IDH-mutant Gliomas.

Daniel J Brat1, Kenneth Aldape2, Pim J French3

  • 1Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Neuro-Oncology
|May 19, 2026
PubMed
Summary

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This summary is machine-generated.

New criteria for grading IDH-mutant gliomas improve risk stratification. Genetic alterations and mitotic counts help distinguish CNS WHO grades 3 and 4, guiding treatment decisions for these brain tumors.

Area of Science:

  • Neuro-oncology
  • Pathology
  • Genetics

Background:

  • Accurate risk stratification and grading of IDH-mutant gliomas are crucial for effective clinical management.
  • Current grading systems require refinement, particularly at the boundary between CNS WHO grades 2 and 3.
  • Understanding novel glioma subgroups and multidisciplinary treatment considerations is essential.

Purpose of the Study:

  • To evaluate literature for improved pathology-based risk stratification and grading of IDH-mutant gliomas.
  • To identify genetic alterations and molecular signatures associated with specific glioma grades.
  • To propose refined criteria for CNS WHO grading, especially for IDH-mutant astrocytomas.

Main Methods:

  • Literature review and analysis of genetic alterations in IDH-mutant gliomas.
Keywords:
AstrocytomaBrain TumorGliomaIDH-mutantOligodendroglioma

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  • Evaluation of DNA methylation signatures (G-CIMP-low, A_IDH_HG).
  • Assessment of specific genetic alterations including PDGFRA amplification, PIK3 mutations, EGFR amplification, MYCN amplification, and RB pathway alterations.

    • Main Results:

    • PDGFRA amplification is linked to aggressive IDH-mutant astrocytomas (CNS WHO grade 4).
    • Genetic alterations like PIK3 mutations, EGFR amplification, and RB pathway alterations suggest intermediate risk (CNS WHO grade 3).
    • A mitotic count of ≥3 per 2.4 mm² is proposed as a CNS WHO grade 3 criterion; specific methylation signatures correlate with higher grades.

    Conclusions:

    • Implementing evidence-based criteria, including specific genetic markers and mitotic counts, will enhance risk stratification for IDH-mutant gliomas.
    • Refined grading improves guidance for clinical decision-making in neuro-oncology.
    • Further research may uncover grading improvements for oligodendrogliomas, though some grade 3 tumors show favorable outcomes.