Pathology · CNS Pathology (Tumors, Degenerative, Infections)

A 35-year-old presents with seizures. MRI shows a cortical-subcortical mass with 'fried egg' cells on biopsy. Immunostaining is positive for IDH1 R132H, ATRX-negative, and p53 overexpressing. 1p/19q co-deletion is absent. Per WHO 2021 CNS classification, which diagnosis is most appropriate?

  • A Oligodendroglioma, IDH-mutant with 1p/19q co-deletion, CNS WHO grade 2
  • B Astrocytoma, IDH-mutant, CNS WHO grade 2 or 3 (depending on histological grade and CDKN2A/B status)
  • C Glioblastoma, IDH-wildtype, CNS WHO grade 4
  • D Diffuse midline glioma, H3 K27-altered, CNS WHO grade 4
Correct answer: B. Astrocytoma, IDH-mutant, CNS WHO grade 2 or 3 (depending on histological grade and CDKN2A/B status)

Explanation

Per WHO 2021 CNS classification, IDH-mutant diffuse gliomas are categorized by the presence or absence of 1p/19q co-deletion. IDH mutation + absent 1p/19q co-deletion + ATRX loss + TP53 mutation defines Astrocytoma, IDH-mutant. Grade is determined by histology (grade 2 = diffuse, grade 3 = anaplastic with mitoses) and molecular features — specifically, CDKN2A/B homozygous deletion automatically confers grade 4. IDH-wildtype glioblastoma shows EGFR amplification, TERT promoter mutation, and +7/-10 copy number changes without IDH mutation. Oligodendroglioma requires IDH mutation AND 1p/19q co-deletion.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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