A 35-year-old man undergoes MRI for seizures showing a diffuse T2/FLAIR hyperintense mass involving the cortex and white matter of the left frontal lobe with minimal enhancement. Biopsy reveals a diffuse glioma with IDH1 R132H mutation, 1p/19q co-deletion, and TERT promoter mutation. According to WHO 2021 CNS classification, what is the diagnosis and grade?

• A Oligodendroglioma, IDH-mutant and 1p/19q co-deleted, WHO grade 2 — the defining molecular triad (IDH mutation + 1p/19q co-deletion + TERT promoter mutation) meets criteria for oligodendroglioma diagnosis ✓
• B IDH-mutant astrocytoma, WHO grade 2 — the 1p/19q co-deletion is irrelevant in astrocytomas
• C Glioblastoma, IDH-mutant, WHO grade 4 — IDH mutation does not prevent GBM diagnosis when imaging shows extensive involvement
• D Diffuse midline glioma, H3 K27M-altered — IDH mutation excludes this category

Explanation

WHO 2021 CNS classification mandates molecular diagnosis for diffuse gliomas. Oligodendroglioma is now defined by the co-occurrence of: (1) IDH1 or IDH2 mutation AND (2) whole-arm co-deletion of chromosomes 1p and 19q (1p/19q co-deletion). TERT promoter mutation is a near-universal co-occurring marker in oligodendroglioma, completing the molecular triad. Grading: grade 2 (no microvascular proliferation/necrosis) or grade 3 (with these features). This case lacks mitotic activity/necrosis/microvascular proliferation, making it grade 2. IDH-mutant astrocytomas by definition lack 1p/19q co-deletion (they typically have ATRX loss instead). IDH-mutant GBM requires grade 4 histological features. H3 K27M defines diffuse midline glioma (a separate entity).

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.