Clinically-relevant pathological discordance in multicentric IDH-mutant gliomas: a single institution case series.

Authors

Thomas J Lai, Chuyin Yang, Bryan Zheng, Addison Fisher, Ryan Mostafavi, Samuel N Ashley, Terry J Prins, Alexander R Cohen, Linda M Liau, Robert A Chong, Phioanh L Nghiemphu, Timothy F Cloughesy, Negar Khanlou, Richard G Everson, Albert Lai

Published in

Journal of neuro-oncology. Volume 180. Issue 2. Nov 11, 2026. Epub Nov 11, 2026.

Abstract

Isocitrate dehydrogenase (IDH) mutations are truncal driver events in low-grade gliomas. While multifocal gliomas are presumed to spread metastatically and share identical pathology, the biological nature of IDH mutant multicentric gliomas remains poorly understood.
We retrospectively identified patients with radiographically distinct multicentric gliomas where ≥ 1 lesion was IDH-mutant. We analyzed the subset with multi​focal tissue sampling using available histopathology, immunohistochemistry, and next-generation sequencing across distinct foci to render updated CNS WHO diagnoses based on integrated molecular data.
Of 46 multicentric IDH-mutant gliomas, eight patients (17%) underwent multifocal sampling. Of six synchronous cases, three exhibited mismatched foundational drivers, one showed divergent clonal evolution (discordant 1p/19q codeletion), and two demonstrated asynchronous malignant progression. Differing pathology between the lesions directly influenced clinical decision-making in three of the synchronous cases. The remaining two cases presented metachronously. Structured review of surgical decision-making in 35 evaluable patients without multifocal sampling revealed that in 71% (25/35) of reviewed cases, tissue sampling of the additional lesion was not pursued for lesion-level (poor stereotactic target, diagnostic uncertainty) or patient-level reasons. In the remaining 29% (10/35), the additional lesion was determined to be amenable to biopsy or resection, yet sampling was deferred on the presumption of pathological concordance with the index lesion.
Multicentric IDH-mutant gliomas exhibit significant spatial and temporal heterogeneity driven by diverse oncogenic and clonal evolution. Because radiographic congruence does not guarantee histo-molecular congruence, multi​focal tissue acquisition with detailed morphologic and genetic profiling should become the standard clinical approach whenever feasible to prevent diagnostic misclassification and optimize individualized therapy.

PMID:
43013158
Bibliographic data and abstract were imported from PubMed on 12 Nov 2026.

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