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Updated: Jan 30, 2026
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A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas
Published on: May 9, 2025
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The Misclassification of Diffuse Gliomas: Rates and Outcomes
J Bryan Iorgulescu1,2,3,4, Matthew Torre5,2, Maya Harary2,3
1Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. jiorgulescu@bwh.harvard.edu.
Summary
Histologic diagnosis of diffuse gliomas leads to significant misclassification, impacting patient outcomes. Accurate molecular profiling is crucial for reliable diagnosis and clinical trial interpretation.
Area of Science:
- Neuro-oncology
- Cancer diagnostics
- Molecular pathology
Background:
- The 2016 WHO classification integrated histopathology and molecular data for central nervous system tumors, improving accuracy.
- Despite advancements, the extent and impact of misclassifying histologically diagnosed diffuse gliomas remain unclear.
Purpose of the Study:
- To determine the frequency and clinical consequences of misclassification in histologically diagnosed diffuse gliomas.
- To assess misclassification rates based on WHO grade and molecular markers like 1p/19q, IDH, ATRX, and p53 status.
Main Methods:
- Analysis of newly diagnosed diffuse gliomas (2010-2015) from the National Cancer Database.
- Assessment of misclassification rates and overall survival (OS) by WHO grade and 1p/19q status.
- Examination of misclassification rates by IDH, ATRX, and p53 statuses in an analogous multi-institutional cohort.
Main Results:
- Significant misclassification rates were observed: 21%-35% for oligodendrogliomas, 6%-9% for astrocytomas, and 9% for glioblastomas based on molecular markers.
- Molecularly characterized oligodendrogliomas showed lower-than-expected 1p/19q-codeletion rates (74.4%-78.8%).
- Overall survival was significantly influenced by accurate WHO grading and 1p/19q status.
Conclusions:
- Histologic misclassification of diffuse gliomas is common and has significant clinical implications.
- Findings challenge the interpretation of historical data and contemporary trials relying solely on histology.
- Accurate molecular profiling is essential for precise diffuse glioma diagnosis and reliable clinical trial outcomes.
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