astrocytoma

**Origin:** Neoplasm of astrocytes (GFAP-positive glial cells). Astrocytes maintain the blood-brain barrier, K+ buffering, and neurotransmitter reuptake.

**Major subtypes (high-yield):**

1. **Pilocytic astrocytoma (WHO grade 1)** - Most common primary brain tumor in children; usually posterior fossa (cerebellum), so presents with cerebellar signs (ataxia, dysmetria) and obstructive hydrocephalus (headache, vomiting). - Histology: biphasic pattern with **Rosenthal fibers** (eosinophilic, corkscrew-shaped) and microcysts. GFAP+. - Imaging: cystic mass with an enhancing mural nodule. - Genetics: **BRAF** alterations (KIAA1549-BRAF fusion); associated with NF1 (optic pathway glioma). - Prognosis: excellent; surgical resection is often curative.

2. **Diffuse astrocytoma, IDH-mutant (WHO grade 2-4)** - Affects young adults, typically cerebral hemispheres; seizures are a common presentation. - **IDH1/2 mutation** (produces 2-hydroxyglutarate), often with TP53 and ATRX loss. No 1p/19q codeletion. A codeletion would indicate oligodendroglioma. - Infiltrative and tends to progress to higher grade. Under the 2021 WHO classification, IDH-mutant astrocytomas are graded 2-4 (the term "secondary glioblastoma" is no longer used).

3. **Glioblastoma, IDH-wildtype (WHO grade 4)** - Most common and most malignant primary adult brain tumor; peak in older adults (about 60s). - Frontal/temporal lobes; can cross the corpus callosum ("butterfly glioma"). - Histology: **pseudopalisading necrosis** and **endothelial/microvascular proliferation**. GFAP+. - Imaging: ring-enhancing lesion with central necrosis and surrounding edema. - Genetics: EGFR amplification, TERT promoter mutation, +7/-10, PTEN loss. **MGMT promoter methylation** predicts better response to temozolomide. - Treatment: maximal safe resection, then radiation plus temozolomide. Median survival is about 12-18 months.

**Clinical presentation (general):** Headache, seizures, focal neurologic deficits, and signs of raised ICP depending on location.

**Key differentials for boards:** - Oligodendroglioma: "fried egg" cells, chicken-wire capillaries, calcifications, 1p/19q codeletion, IDH mutation. - Ependymoma: perivascular pseudorosettes, 4th ventricle. - Medulloblastoma: small blue cells, Homer-Wright rosettes, midline cerebellum in children. - Metastasis: gray-white junction, multiple lesions.

**Pearls:** Brain tumors in children are mostly infratentorial; in adults, mostly supratentorial. Astrocytomas are GFAP-positive. Glioblastoma is the classic answer for a ring-enhancing, crossing-the-midline lesion with pseudopalisading necrosis.