According to the WHO Classification of Tumors of the Central Nervous System (5th edition, 2021), a 35-year-old patient with IDH1 R132H mutation, 1p/19q codeletion, and TERT promoter mutation, with an oligodendroglial morphology on histology, is classified as which entity and grade?

• A Diffuse astrocytoma, IDH-mutant — the IDH mutation places this in the astrocytic lineage regardless of 1p/19q status
• B Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, CNS WHO Grade 2 or 3 — grading is based on histological criteria (microvascular proliferation or necrosis, mitotic activity); molecular co-occurrence of IDH mutation + 1p/19q codeletion defines this entity and predicts better prognosis and response to procarbazine-lomustine-vincristine (PCV) chemotherapy ✓
• C Glioblastoma, IDH-mutant, CNS WHO Grade 4 — TERT promoter mutation with IDH mutation defines secondary GBM
• D Diffuse midline glioma, H3 K27M-altered — IDH mutations can be an epiphenomenon

Explanation

Per the 2021 WHO CNS5 classification, the defining molecular signature of oligodendroglioma is the combination of IDH mutation (IDH1 R132H or IDH2 R172X) AND 1p/19q codeletion (whole-arm codeletion mediated by t(1;19)(q10;p10) translocation). TERT promoter mutations are present in ~95% of oligodendrogliomas (but also in GBM) and are supportive but not definitional. WHO grade is now 2 or 3 based on histological features: Grade 3 requires significant mitotic activity (>6 mitoses/10 HPF) or anaplastic features. The molecular definition (IDH + 1p/19q) supersedes histology for diagnosis and predicts significantly better prognosis compared to IDH-mutant astrocytoma and GBM.

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

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