The WHO 2021 CNS tumour classification has incorporated molecular markers into glioma grading. IDH-mutant astrocytoma is now graded 2–4 based on which molecular feature that upgrades a grade 3 IDH-mutant astrocytoma to grade 4?

• A MGMT promoter methylation
• B CDKN2A/B homozygous deletion ✓
• C TERT promoter mutation
• D ATRX mutation

Explanation

WHO 2021 CNS classification introduced molecular criteria: IDH-mutant astrocytoma Grade 4 is defined by CDKN2A/B homozygous deletion (or other aggressive molecular features), even in the absence of histological necrosis or microvascular proliferation (traditional grade 4 criteria). This upgrades some tumours previously classified as grade 3 to grade 4. MGMT methylation predicts chemosensitivity but does not change grading. ATRX loss and TERT mutations are diagnostic markers, not grading criteria for IDH-mutant astrocytomas.

Reference: Bailey & Love's Short Practice of Surgery, 27th ed.

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