WHO 2021 CNS tumor classification introduced integrated molecular-morphological diagnoses. Glioblastoma, IDH-wildtype, CNS WHO grade 4, requires at least ONE of three molecular criteria (even without necrosis or microvascular proliferation). Which three molecular features define IDH-wildtype glioma as glioblastoma per WHO 2021?
- A MGMT promoter methylation, CDKN2A/B deletion, and chromosome 1p/19q co-deletion
- B IDH1 R132H mutation, ATRX loss, and TP53 mutation
- C TERT promoter mutation, EGFR amplification, and/or +7/−10 chromosomal copy number changes ✓
- D H3 K27M mutation, PDGFRA amplification, and monosomy 10
Explanation
WHO 2021 CNS classification defines IDH-wildtype astrocytoma as glioblastoma, CNS WHO grade 4, if the tumor shows ANY of three molecular features — TERT promoter mutation, EGFR gene amplification, and/or combined +7/−10 copy number alteration (gain of chromosome 7, loss of chromosome 10) — regardless of the presence of classic histological features (necrosis, microvascular proliferation). This reflects molecular-prognostic equivalence with histological GBM. MGMT promoter methylation predicts temozolomide response but is a prognostic/predictive marker, not diagnostic; 1p/19q co-deletion is found in oligodendroglioma; IDH1 R132H/ATRX/TP53 are astrocytoma IDH-mutant features; H3 K27M defines diffuse midline glioma.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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