The WHO CNS Tumor Classification 2021 requires molecular parameters for accurate glioma diagnosis. An adult with IDH-wildtype glioma showing EGFR amplification, TERT promoter mutation, and +7/-10 chromosomal pattern is classified as:

• A Diffuse astrocytoma, IDH-wildtype, WHO Grade 2 — because histology lacks necrosis or vascular proliferation
• B Oligodendroglioma, IDH-wildtype, WHO Grade 2 — because EGFR amplification supports oligodendroglial lineage
• C Diffuse midline glioma, H3K27-altered, WHO Grade 4 — because EGFR amplification requires H3.3 K27M classification
• D Glioblastoma, IDH-wildtype, WHO Grade 4 — meeting molecular criteria even without histologic microvascular proliferation or necrosis ✓

Explanation

The 2021 WHO CNS5 classification introduced molecular criteria for diagnosing IDH-wildtype glioblastoma even in the absence of classic histological features (microvascular proliferation or necrosis). An IDH-wildtype diffuse astrocytic glioma with any one of the following molecular features is classified as Glioblastoma, IDH-wildtype, Grade 4: EGFR amplification, TERT promoter mutation combined with +7/-10 chromosomal pattern (gain of chromosome 7 and loss of chromosome 10), or CDKN2A/B homozygous deletion. This represents a paradigm shift from purely histological grading to integrated histomolecular classification. The histologically lower-grade appearance does not affect the Grade 4 classification if these molecular markers are present. Diffuse midline glioma requires H3 K27M or H3.3 G34 alteration, which is a separate entity.

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

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Written and medically reviewed by the StethoPrep medical team.