In diffuse gliomas, the 2021 WHO CNS Tumor Classification now requires molecular profiling for definitive diagnosis. IDH-mutant astrocytoma is distinguished from IDH-mutant oligodendroglioma by which molecular alteration?

• A TERT promoter mutation favours astrocytoma; IDH mutation defines oligodendroglioma
• B EGFR amplification in astrocytoma; PDGFRA amplification in oligodendroglioma
• C H3 K27M mutation in astrocytoma; IDH2 R172K mutation in oligodendroglioma
• D ATRX loss and TP53 mutation favour astrocytoma; 1p/19q co-deletion defines oligodendroglioma ✓

Explanation

Per the 2021 WHO CNS Classification, IDH-mutant gliomas are classified as oligodendroglioma when they have 1p/19q co-deletion (with TERT promoter mutation and IDH mutation). IDH-mutant astrocytoma is defined by IDH mutation WITH ATRX loss and/or TP53 mutation but WITHOUT 1p/19q co-deletion. ATRX and TP53 mutations are mutually exclusive with 1p/19q co-deletion and serve as surrogate markers for astrocytic differentiation.

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

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