oligodendroglioma

**Definition/Classification (WHO CNS 5th ed., 2021):** "Oligodendroglioma, IDH-mutant and 1p/19q-codeleted," CNS WHO grade 2 (well-differentiated) or grade 3 (anaplastic features: brisk mitoses, microvascular proliferation, necrosis). Molecular criteria are required for the diagnosis. An IDH-mutant glioma without 1p/19q codeletion is an astrocytoma, IDH-mutant, which usually has ATRX and TP53 mutations. Glioblastoma is IDH-wildtype.

**Epidemiology:** Mainly adults aged 35-50. About 4-5% of primary brain tumors. Slight male predominance.

**Pathophysiology/Genetics:** - IDH1 (R132H) or IDH2 mutation produces 2-hydroxyglutarate (an oncometabolite), which causes DNA hypermethylation (G-CIMP phenotype). - Codeletion of 1p and 19q (whole-arm translocation, t(1;19)(q10;p10)). - Frequent TERT promoter mutations. CIC (19q) and FUBP1 (1p) mutations are common. ATRX and TP53 are typically retained, which is the opposite of astrocytoma. - MGMT promoter methylation is common and contributes to chemosensitivity.

**Clinical presentation:** - Most commonly a **frontal lobe** tumor (then temporal), in the cerebral hemispheres with cortical/subcortical white matter involvement. - **Seizures** are the most common presentation (often the first symptom). - Also headache, focal deficits, and personality or cognitive changes.

**Imaging:** Cortical/subcortical mass, with **calcifications** in about 50-90% (best seen on CT). Variable or minimal enhancement, and cystic change or hemorrhage can occur. Calcified frontal mass in an adult with seizures is the classic stem.

**Histology (high-yield):** - Round, uniform nuclei with perinuclear clearing (**"fried egg" appearance**). This is partly a formalin-fixation artifact and is not seen on frozen section. - Delicate branching capillaries (**"chicken-wire" vasculature**). - Calcifications. Gliomas with microcalcifications are described as having "psammoma-like" calcifications. - Infiltrative growth. - Perineuronal satellitosis and secondary structures of Scherer.

**Treatment:** Maximal safe resection, followed by radiation plus chemotherapy (**PCV**: procarbazine, CCNU/lomustine, vincristine, or temozolomide) for higher-risk or grade 3 disease. Vorasidenib (an IDH1/2 inhibitor) is approved for grade 2 IDH-mutant gliomas after surgery. Antiepileptics are used for seizures. Oligodendroglioma is the glioma most sensitive to chemotherapy, which is linked to 1p/19q codeletion.

**Prognosis:** Best among diffuse gliomas. Median survival is more than 10-15 years for grade 2 and shorter for grade 3. 1p/19q codeletion and IDH mutation are favorable markers. Tumors can progress to higher grade.

**Differential/Board comparisons:** - Astrocytoma (IDH-mutant): ATRX/TP53 mutations, no 1p/19q codeletion. - Glioblastoma: IDH-wildtype, "pseudopalisading necrosis," "butterfly" lesion crossing the corpus callosum, GFAP+. - Ependymoma: perivascular pseudorosettes, fourth ventricle, in children. - Meningioma: psammoma bodies, dural tail, extra-axial. - Oligodendrocytes are the myelin-producing cells of the CNS (S100+, myelin-related markers), so oligodendroglioma cells can express Olig2 and S100.