Last Minute Review
Pathology — Last Minute Review
Rapid Review
A last-minute review of high-yield neuropathology facts for the RITE and board exams. Tables, key associations, and must-know one-liners — designed for a quick pass the night before.
CNS Tumors
| Tumor | WHO Grade | Location | Histology / Marker | Key Fact |
|---|---|---|---|---|
| Glioblastoma (GBM) | 4 | Cerebral hemispheres (adults) | Pseudopalisading necrosis, microvascular proliferation; GFAP+; IDH-wildtype | Most common primary malignant brain tumor in adults; “butterfly” pattern crosses corpus callosum |
| Astrocytoma, IDH-mutant | 2–4 | Cerebral hemispheres (young adults) | IDH1 R132H mutation; TP53 mutation (nuclear p53 accumulation on IHC); ATRX loss | Better prognosis than IDH-wildtype; 2-HG oncometabolite produced |
| Oligodendroglioma | 2–3 | Frontal lobe (adults) | “Fried egg” cells, chicken-wire vasculature; 1p/19q codeletion + IDH-mutant | Calcifications on imaging; chemosensitive (PCV); seizures common |
| Ependymoma | 2–3 | 4th ventricle (children), spinal cord (adults) | Perivascular pseudorosettes, true rosettes; GFAP+ | Posterior fossa → fills 4th ventricle; ZFTA fusion in supratentorial |
| Medulloblastoma | 4 | Posterior fossa (cerebellum, children) | Homer Wright rosettes; synaptophysin+ | Most common malignant pediatric brain tumor; WHO 2021 molecular subgroups: WNT (best prognosis, ~10%); SHH (PTCH1/SMO/SUFU; ~30%; subset = Gorlin syndrome; split into TP53-wildtype vs TP53-mutant per CNS5); Group 3 (~25%, MYC amplification, worst); Group 4 (~35%, MYCN amplification, isochromosome 17q) |
| Meningioma | 1–3 | Dura (convexity, parasagittal, sphenoid wing) | Psammoma bodies, whorls; EMA+; loss of NF2/merlin | Most common primary intracranial tumor overall; extra-axial, dural tail sign |
| Schwannoma | 1 | CN VIII (vestibular, CPA); spinal nerve roots | Verocay bodies, Antoni A (compact) & B (loose); S100+ | Bilateral vestibular schwannomas → NF2; benign, encapsulated |
| Craniopharyngioma (Adamantinomatous) | 1 | Suprasellar (children & adolescents) | Wet keratin, calcifications, cholesterol crystals; β-catenin mutation (CTNNB1) | Bimodal age (5–14, 50–74); “machinery oil” cyst fluid; hypothalamic/pituitary dysfunction |
| Craniopharyngioma (Papillary) | 1 | Suprasellar / 3rd ventricle (adults) | Well-differentiated squamous epithelium; BRAF V600E mutation | Adults only; no calcification; solid; responds to BRAF inhibitors |
| Pituitary Adenoma (WHO 2022: pituitary neuroendocrine tumor, PitNET) | 1 | Sella turcica | Monomorphic cells; specific hormone stains; no reticulin network | Most common sellar tumor; prolactinoma most common functional type; bitemporal hemianopia from optic chiasm compression |
| Hemangioblastoma | 1 | Posterior fossa (cerebellar), spinal cord | Stromal cells with lipid vacuoles, rich capillary network | Associated with VHL syndrome (chromosome 3p); may cause secondary polycythemia (EPO production) |
| PCNSL | High-grade | Periventricular white matter (deep structures) | Diffuse large B-cell lymphoma; CD20+; perivascular cuffing | Immunocompromised (HIV/EBV) or elderly immunocompetent; “ghost tumor” — shrinks with steroids; avoid steroids BEFORE biopsy if PCNSL suspected — steroids cause rapid tumor lysis and reduce diagnostic yield. Biopsy first, then treat |
| DNET (Dysembryoplastic Neuroepithelial Tumor) | 1 | Temporal lobe cortex (children/young adults) | Specific glioneuronal element, floating neurons in mucin pools | Chronic epilepsy; cortical-based, bubbly/multicystic on MRI; excellent prognosis |
| Ganglioglioma | 1–3 | Temporal lobe (children/young adults) | Ganglion cells + glial cells; CD34+; BRAF V600E common | Most common tumor causing chronic epilepsy in children; cystic + mural nodule |
| Pilocytic Astrocytoma | 1 | Posterior fossa / cerebellum (children); optic pathway | Rosenthal fibers, eosinophilic granular bodies; BRAF-KIAA1549 fusion | Most common pediatric glioma / most common benign pediatric CNS tumor (medulloblastoma is most common malignant); cystic + enhancing mural nodule; optic pathway glioma → NF1 |
| Choroid Plexus Papilloma | 1 | Lateral ventricle (children), 4th ventricle (adults) | Papillary fronds, single-layer cuboidal epithelium | Overproduction of CSF → hydrocephalus; transthyretin+ |
| Pineoblastoma | 4 | Pineal region (children) | Small round blue cells; synaptophysin+ | Trilateral retinoblastoma = bilateral retinoblastoma + pineoblastoma (RB1 loss) |
| Pineocytoma | 1 | Pineal region (adults) | Pineocytomatous rosettes; well-differentiated | Benign; Parinaud syndrome (dorsal midbrain compression) |
| Chordoma | Locally aggressive | Clivus / sacrum (midline) | Physaliphorous cells (bubbly, vacuolated); brachyury+ | Arises from notochord remnants; locally destructive; high recurrence |
| Colloid Cyst | Benign | Anterior 3rd ventricle (foramen of Monro) | Simple cuboidal/columnar epithelium; mucin-filled | Positional headaches; acute obstructive hydrocephalus → sudden death risk |
| Brain Metastases | N/A | Gray-white junction (hematogenous) | Resembles primary tumor; cytokeratin/TTF-1/etc. | Most common brain tumors overall; lung > breast > melanoma > renal > colon; melanoma & renal → hemorrhagic mets |
| Diffuse Midline Glioma, H3 K27-altered | 4 | Midline (thalamus, brainstem/DIPG, spinal cord; children) | H3K27M most common; H3K27me3 loss on IHC; diffuse infiltrative astrocytoma | WHO 2021 CNS5 entity; very poor prognosis; DIPG = pontine variant; not amenable to resection |
| ATRT (Atypical Teratoid/Rhabdoid Tumor) | 4 | Posterior fossa (infants <3 yrs) | Rhabdoid cells; INI1/SMARCB1 loss on IHC (rarely SMARCA4) | Pediatric embryonal tumor; very poor prognosis; mimics medulloblastoma clinically; SMARCB1 germline = rhabdoid tumor predisposition syndrome |
💎 Board Pearl
- IDH-mutant = better prognosis in gliomas — always check IDH status first
- 1p/19q codeletion is diagnostic of oligodendroglioma (must have both codeletion + IDH mutation)
- WHO 2021 classification: molecular markers trump histology for diagnosis
- Butterfly GBM: tumor crossing the corpus callosum — classic imaging finding
- MGMT promoter methylation → better temozolomide response in GBM
- TERT promoter mutations: oligodendroglioma (1p/19q codel), IDH-wildtype GBM, and atypical/anaplastic meningioma
- Vorasidenib (FDA Aug 2024): IDH1/2 inhibitor for adults and pediatric patients ≥12 years with grade 2 astrocytoma or oligodendroglioma harboring a susceptible IDH1/2 mutation following surgery (biopsy, subtotal resection, or gross total resection); INDIGO trial
- Stupp protocol (standard GBM): RT 60 Gy / 30 fractions + concurrent temozolomide × 6 weeks, then 6 cycles adjuvant TMZ
- RT + PCV (procarbazine/CCNU/vincristine): RTOG 9402 & EORTC 26951 for 1p/19q-codeleted anaplastic oligodendroglioma; RTOG 9802 for high-risk grade 2 glioma
Neurocutaneous Syndromes (Phakomatoses)
| Syndrome | Gene | Chromosome | Inheritance | Key Features | Associated Tumors |
|---|---|---|---|---|---|
| NF1 (von Recklinghausen) | NF1 (neurofibromin) | 17q11 | AD | ≥6 café-au-lait macules, axillary freckling, Lisch nodules, bony dysplasia | Neurofibromas (plexiform), optic pathway glioma, MPNST, pheochromocytoma |
| NF2-related schwannomatosis (NF2) | NF2 (merlin/schwannomin) | 22q12 | AD | Bilateral vestibular schwannomas (diagnostic hallmark; mosaic/segmental NF2-related schwannomatosis may lack bilateral VS), cataracts, hearing loss | Schwannomas, meningiomas, ependymomas |
| Tuberous Sclerosis (TSC) | TSC1 (hamartin) / TSC2 (tuberin) | 9q34 / 16p13 | AD | Cortical tubers, ash-leaf spots, shagreen patch, facial angiofibromas, seizures, intellectual disability | Subependymal giant cell astrocytoma (SEGA), cardiac rhabdomyoma, renal angiomyolipoma |
| VHL | VHL | 3p25 | AD | Hemangioblastomas (CNS/retina), renal cysts, pheochromocytoma, secondary polycythemia | Hemangioblastomas, clear cell renal cell carcinoma, pheochromocytoma |
| Sturge-Weber | GNAQ (somatic) | 9q21 | Sporadic (not inherited) | Port-wine stain (V1), leptomeningeal angiomatosis, tram-track calcifications, seizures, glaucoma | No associated tumors; vascular malformation |
| Ataxia-Telangiectasia | ATM | 11q22 | AR | Cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, radiosensitivity, ↑ AFP | ↑ risk lymphoma & leukemia; DNA repair defect |
| Cowden Syndrome | PTEN | 10q23 | AD | Mucocutaneous lesions, macrocephaly, Lhermitte-Duclos (dysplastic gangliocytoma of cerebellum) | Breast, thyroid, endometrial carcinomas |
| Gorlin Syndrome (Basal Cell Nevus) | PTCH1 | 9q22 | AD | Multiple basal cell carcinomas, jaw keratocysts, calcified falx cerebri, skeletal anomalies | Medulloblastoma (desmoplastic/SHH subtype), basal cell carcinomas |
💎 Board Pearl
- NF1 = chromosome 17 (“17 letters in von Recklinghausen”); NF2 = chromosome 22 (“NF2 → 22”)
- Sturge-Weber is the only phakomatosis that is NOT inherited — somatic GNAQ mutation
- TSC: mTOR pathway → treated with everolimus (mTOR inhibitor) for SEGA
- Ataxia-telangiectasia: ↑ AFP + ↓ IgA + radiosensitivity = classic triad
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