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Brain Tumor Histology - Quick Reference with Memory Tricks
Source: Robbins & Kumar Basic Pathology, Chapter 21
1. ASTROCYTOMA (IDH-mutant, Grade 2-4)
Origin: Astrocytes | Location: Cerebral hemispheres | Age: 4th-6th decade
Histology
- Gross: Poorly defined, gray, infiltrative mass - no discrete border. Expands without forming a nodule
- Micro (Grade 2): Mild to moderate increase in glial nuclei; nuclear pleomorphism; background has a fibrillary (cobweb-like) appearance from GFAP-positive astrocytic processes
- Micro (Grade 3): Denser cellularity + mitotic figures
- Micro (Grade 4 IDH-mutant): Cytological atypia, brisk mitoses, microvascular proliferation and/or necrosis - but less hemorrhage than GBM
- IHC: GFAP-positive; IDH1 mutant immunostain positive (shown in inset)
Molecular: IDH1/IDH2 mutation + TP53 + ATRX mutations
🧠 Memory Trick
"A for Astrocytes = A for Airy fibrillar background"
Grade 2 = Fine fibers, few nuclei | Grade 3 = add Mitoses | Grade 4 = add Necrosis + Vessels
IDH-mutant = better prognosis than GBM (think: IDH = I'm Doing better)
2. GLIOBLASTOMA (GBM, IDH-wild type, WHO Grade 4)
Origin: Astrocytes | Location: Cerebral hemispheres (temporal > parietal > frontal) | Age: 6th-8th decade
Histology
- Gross: Variegated - firm white areas + soft yellow necrotic areas + cystic/hemorrhagic zones = "butterfly glioma" when crosses corpus callosum
- Micro (the 4 hallmarks):
- High cellularity - pleomorphic, poorly differentiated cells
- Nuclear atypia + brisk mitotic activity
- Palisading necrosis - serpiginous (zigzag) bands of necrosis with tumor nuclei lined up ("palisaded") around the dead zones
- Microvascular (endothelial) proliferation - glomeruloid tufts of vessels
Molecular: IDH-wild type + TERT promoter mutation + EGFR amplification + CDKN2A deletion + MGMT methylation (chemosensitivity marker)
🧠 Memory Trick
"GBM = Gone Bad Maximally" - the 4 H's:
High cellularity + Hemorrhage/necrosis + Hyperplastic vessels + Hyperatypia
Palisading necrosis = think of soldiers in a trench (palisades) surrounding a war zone of dead cells
MGMT = Makes GBM Mild To chemo (methylated = responds to temozolomide)
3. OLIGODENDROGLIOMA (IDH-mutant + 1p/19q-codeleted, Grade 2-3)
Origin: Oligodendrocytes | Location: Frontal or temporal lobes | Age: 4th-5th decade
Histology
- Gross: Gelatinous gray mass; may show cysts, hemorrhage, and calcification
- Micro (the 3 hallmarks):
- "Fried egg" cells - round nuclei with clear cytoplasmic halo (artifact of formalin fixation)
- "Chicken-wire" vascular pattern - delicate anastomosing capillary network
- Calcification in up to 90% of cases (ranges from microscopic to massive)
- Mitotic activity is usually low (grade 2); grade 3 adds nuclear anaplasia, increased mitoses, microvascular proliferation
Molecular: IDH1/IDH2 mutation + 1p/19q codeletion (diagnostic) + TERT promoter mutation. Best prognosis among diffuse gliomas: 10-20 years (grade 2).
🧠 Memory Trick
"OLIGO = Old Looking Fried Egg Cells"
Remember the 3 C's of oligodendroglioma: Clear halos (fried egg) + Chicken-wire vessels + Calcification
1p/19q codeletion = the chromosomes are "deleted like the first and last" parts of 19 = 1p (first arm) and 19q (last chromosome arm listed)
4. MEDULLOBLASTOMA (WHO Grade 4)
Origin: Primitive neuroectodermal cells | Location: Midline cerebellum (vermis in children; lateral in adults) | Age: Children predominantly
Histology
- Gross: Well-circumscribed, gray, friable mass in cerebellar midline; may extend to leptomeninges; "drop metastases" via CSF
- Micro:
- Classic "small blue cell" tumor - densely cellular sheets of monomorphic cells
- Small cells with little cytoplasm, hyperchromatic nuclei, abundant mitoses
- Homer-Wright rosettes - primitive tumor cells arranged in a circle surrounding central neuropil (pink tangled neuronal processes) - NO lumen (differentiates from ependymoma)
- Neuronal markers positive (synaptophysin, NeuN); GFAP usually negative
- Drop metastases to spinal cord via CSF seeding
Molecular subtypes: WNT-activated (best - ~100% 5-yr survival) | SHH-activated | TP53-mutant (worst)
🧠 Memory Trick
"MedulloBLASToma = BLAST of small blue cells in the BACK (cerebellum)"
Homer-Wright rosette = Homer (from Homer Simpson) sits around a donut with PINK filling (neuropil, no lumen)
Contrast: Ependymoma rosettes have a LUMEN (true rosette) + perivascular pseudorosettes
Radiosensitive = think "medulloBLAST was BLASTED by radiation" (exquisitely sensitive)
CSF spread = "DROP" metastases - drops of tumor fall down the spine
5. MENINGIOMA (WHO Grade 1, 2, 3)
Origin: Arachnoid cap cells (meninges) | Location: Dura-based, parasagittal, sphenoid ridge, olfactory groove | Age: Middle-aged adults; F > M
Histology
- Gross: Well-defined, lobulated, dura-based mass that compresses but does NOT invade the brain; may show hyperostosis of overlying bone
- Micro (key subtypes):
| Subtype | Key Feature |
|---|
| Meningothelial | Syncytium-like lobules, cells with no visible membranes |
| Fibroblastic | Elongated cells + abundant collagen |
| Transitional | Mix of meningothelial + fibroblastic |
| Psammomatous | Multiple psammoma bodies (concentric calcified rings) |
| Secretory | PAS-positive eosinophilic glandular material |
- Whorled pattern of cell growth is characteristic
- Psammoma bodies = concentrically laminated calcifications ("onion-skin rings")
Molecular: NF2 mutations most common
🧠 Memory Trick
"MeninGIOMA = sits on the DURA like a G.I. (general) on a throne, squishing the brain below"
Psammoma bodies = think "Psammo = Sand" (from Greek psammos = sand) - calcified whorls that look like sand dollars
WHIRL = the key word: whorled cells + psammoma bodies (whorled calcifications)
Grade 2 = Brain invasion or chordoid/clear cell subtype | Grade 3 = looks like sarcoma/carcinoma
Quick-Reference Comparison Table
| Tumor | Hallmark Feature | Memory Hook |
|---|
| Astrocytoma | Fibrillary background, GFAP+, infiltrative | "Airy/Fibrillar" background |
| GBM | Palisading necrosis + microvascular proliferation | "Palisade + Glomeruloid vessels" |
| Oligodendroglioma | Fried egg + chicken-wire + calcification | "3 C's: Clear halo, Chicken-wire, Calcification" |
| Medulloblastoma | Small blue cells + Homer-Wright rosettes | "Blue BLAST + Homer's Pink donut" |
| Meningioma | Whorled cells + psammoma bodies | "WHIRL + Sand dollars" |
Rosette Cheat Sheet (Easy Confusion!)
| Rosette | Tumor | Center Content |
|---|
| Homer-Wright | Medulloblastoma, Neuroblastoma | Neuropil (pink fibers) - NO lumen |
| True (Flexner-Wintersteiner) | Retinoblastoma, Ependymoma | Central lumen |
| Perivascular pseudorosette | Ependymoma | Fibrillary processes radiating to a blood vessel |
Trick: "Homer Wright = Pink neuropil, NO hole" / "True rosette = TRUE lumen/hole"
Robbins & Kumar Basic Pathology, pp. 858-864