CNS: WHO 2021 molecular classification
Free question published 09 October 2026
A 41-year-old man has a frontal lobe tumour resected. Histology shows a diffuse astrocytic glioma with brisk mitotic activity but no microvascular proliferation and no necrosis. Immunohistochemistry confirms an IDH1 R132H mutation and ATRX loss; 1p/19q is intact and CDKN2A/B is not homozygously deleted. Under the WHO 2021 classification of CNS tumours, which integrated diagnosis is most appropriate?
- ADiffuse astrocytoma, IDH-wildtype, WHO grade 2
- BAnaplastic oligoastrocytoma, NOS
- CAstrocytoma, IDH-mutant, WHO grade 3
- DOligodendroglioma, IDH-mutant and 1p/19q-codeleted, WHO grade 3
- EGlioblastoma, IDH-wildtype, WHO grade 4
Why C is correct
Under WHO 2021 (CNS5) and the EANO glioma guideline, an adult diffuse glioma with an IDH1 codon 132 mutation that is NOT 1p/19q-codeleted is classified as astrocytoma, IDH-mutant. Grading is then within tumour type: brisk mitotic activity with no microvascular proliferation, no necrosis and no CDKN2A/B homozygous deletion places this at WHO grade 3, since any of microvascular proliferation, necrosis or CDKN2A/B homozygous deletion would define grade 4. The presence of an IDH mutation excludes glioblastoma, IDH-wildtype, and the intact 1p/19q excludes oligodendroglioma.
And why the others are not
- AIncorrect: the tumour is IDH-mutant, not IDH-wildtype, and the brisk mitotic activity is incompatible with grade 2.
- BIncorrect: the combined oligoastrocytoma category has been abandoned in WHO 2021 in favour of molecularly defined entities.
- DIncorrect: oligodendroglioma requires both IDH mutation and 1p/19q codeletion, and 1p/19q is intact.
- EIncorrect: glioblastoma is reserved for IDH-wildtype astrocytic gliomas; the IDH1 R132H mutation here excludes that diagnosis.
Source WHO Classification of Tumours of the Central Nervous System, 5th edition (CNS5) — adult diffuse glioma criteria — Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231-1251.
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