The 2021 WHO Classification of CNS Tumors made a paradigm shift in glioma classification. Under the new classification, IDH-mutant astrocytomas are graded by specific molecular criteria. Which molecular alteration, when present in an IDH-mutant astrocytoma, automatically upgrades it to WHO grade 4 even without microvascular proliferation or necrosis?
- A CDKN2A/B homozygous deletion ✓
- B TERT promoter mutation
- C 1p/19q codeletion
- D MGMT promoter methylation
Explanation
The 2021 WHO CNS5 classification grades IDH-mutant astrocytomas (grades 2-4) using molecular criteria. Grade 4 astrocytoma (IDH-mutant) can be assigned not only by classical histological criteria (microvascular proliferation or necrosis) but also by molecular criteria alone: CDKN2A/B homozygous deletion automatically confers grade 4, as it has the same poor prognosis as classically defined GBM regardless of histological appearance. TERT mutations are features of IDH-wildtype GBM; 1p/19q codeletion defines oligodendroglioma; MGMT methylation is a predictive biomarker for temozolomide response.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.