Primary CNS tumors are classified by the World Health Organization (WHO) Classification of Tumours of the Central Nervous System, now in its 5th edition (2021). The classification integrates histology, IHC, and molecular markers to define tumor types and grades. Gliomas are the most common primary CNS tumors in adults.
Astrocytic Tumors
Glioblastoma, IDH-wildtype (WHO grade 4) — the most common and aggressive primary brain tumor in adults. Histology shows highly cellular astrocytic tumor with nuclear atypia, mitotic activity, microvascular proliferation, and pseudopalisading necrosis. IHC: GFAP-positive (variable), OLIG2-positive, ATRX retained (wildtype), p53 overexpression in 30%. Molecular markers: MGMT promoter methylation predicts response to temozolomide chemotherapy; EGFR amplification (40%) and TERT promoter mutation (80%) are diagnostic for glioblastoma, IDH-wildtype. The 2021 WHO classification diagnoses IDH-wildtype glioblastoma even in the absence of high-grade histological features if EGFR amplification, TERT promoter mutation, or +7/−10 chromosome copy number changes are present.
Astrocytoma, IDH-mutant (WHO grade 2-4) — IDH1/2 mutations define this lineage. Histological grade is determined by the presence of anaplasia: grade 2 (low cellularity, no mitosis), grade 3 (increased cellularity, mitosis), grade 4 (microvascular proliferation or necrosis = glioblastoma, IDH-mutant). IHC: IDH1 R132H antibody detects the most common IDH1 mutation (90% of IDH-mutant astrocytomas); ATRX loss (nuclear lost, 70%); p53 overexpression (60%). Prognosis is significantly better than IDH-wildtype glioblastoma.
Oligodendroglial Tumors
Oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO grade 2-3) — defined by the combination of IDH mutation and whole-arm loss of chromosome 1p and 19q. Histology shows monomorphic round nuclei with perinuclear halos (fried-egg appearance), chicken-wire capillary network, and microcalcifications. Grade 2 lacks necrosis and high mitotic activity; grade 3 shows increased mitoses and microvascular proliferation. IHC: OLIG2 strongly positive, GFAP-negative (tumor cells), IDH1 R132H positive (90%). FISH or chromosomal microarray confirms 1p/19q codeletion. Oligodendrogliomas are the most chemosensitive gliomas, with prolonged survival after procarbazine-CCNU-vincristine (PCV) or temozolomide therapy.
Ependymomas
Ependymomas arise from ependymal cells lining the ventricles and central canal. The 2021 WHO classification defines molecular subgroups: supratentorial ependymoma (ZFTA fusion or YAP1 fusion), posterior fossa ependymoma (PFA — poor prognosis, PFB — good prognosis), and spinal ependymoma (MYCN amplification in aggressive subset). Histology shows perivascular pseudorosettes (tumor cell processes radiating toward blood vessels) and true ependymal rosettes (central lumen). IHC: GFAP-positive, EMA-positive (dot-like perinuclear pattern), OLIG2-negative.
Neuronal and Mixed Neuronal-Glial Tumors
Ganglioglioma (WHO grade 1) — mixed tumor with dysmorphic ganglion cells (neoplastic neurons) and neoplastic glial cells. IHC: synaptophysin highlights the neuronal component; GFAP highlights the glial component. BRAF V600E mutation is present in 20-60% of cases. Gangliogliomas are associated with chronic epilepsy and have excellent prognosis after complete resection.
Dysembryoplastic neuroepithelial tumor (DNT, WHO grade 1) — benign, cortically based tumor of children and young adults with intractable epilepsy. Histology shows “specific glioneuronal element”: columns of oligodendrocyte-like cells perpendicular to the cortical surface with floating neurons. Molecular: BRAF V600E mutation in 30%; FGFR1 alterations in 30-50%.
Meningiomas
Meningiomas arise from meningothelial cells of the arachnoid mater. The 2021 WHO classification retains three grades based on histological criteria: grade 1 (benign, 80% — meningothelial, fibrous, transitional, psammomatous subtypes), grade 2 (atypical, 15-20% — 4-19 mitoses per 10 HPF, brain invasion, or 3+ of: sheeting architecture, small cells, macronucleoli, hypercellularity, spontaneous necrosis), grade 3 (anaplastic, 1-3% — ≥20 mitoses per 10 HPF or frank sarcoma-like or carcinoma-like histology). IHC: EMA-positive, progesterone receptor (PR)-positive in 70% of grade 1 tumors (prognostic for behavior). Molecular: NF2 mutation in 60% (all grades); TERT promoter mutation in grade 2/3; CDKN2A/B homozygous deletion in grade 3.
Intra-operative Consultation
Frozen section or smear preparation of CNS tumors provides immediate diagnosis during surgery. Smear preparation — a 1-2 mm piece of tumor is gently smeared between two slides, air-dried, and stained with toluidine blue or H&E. The smear preserves cellular detail and demonstrates fibrillary background (gliomas), cellular dyshesion (lymphoma), and papillary structures (choroid plexus tumors). The frozen section technique provides better tissue architecture but takes longer. Intra-operative consultation guides the surgeon — adequate tissue for diagnosis, confirmation of lesional tissue, and immediate preliminary diagnosis.
