Histologic Patterns
What You'll Learn
- The recurring reactions the nervous system shows to any insult — recognize the pattern, then reach for the disease
- What each pattern looks like, the stain that confirms it, and what causes it
- The basic architectural patterns of neoplasia and the logic of grading
- Patterns beat lists. A slide shows a reaction (injury / gliosis / demyelination / inflammation / necrosis / neoplasia) long before it shows a specific disease.
- Red neurons = acute ischemia (12–24 h). Gitter cells (foamy macrophages) = subacute clean-up (infarct, demyelination).
- Demyelination = myelin loss (LFB pallor) with macrophages and relative axonal preservation; contrast with axonal loss.
- Spongiform change (prion) = fine neuropil vacuolation without inflammation; confirm with PrP — don't confuse with edema/status spongiosus.
- For a tumor, read architecture → cytology → grade features (mitoses, microvascular proliferation, necrosis).
Neuronal Injury
| Pattern | On the slide | Cause |
|---|
| Red (eosinophilic) neuron | Shrunken, bright-pink cytoplasm, pyknotic nucleus (H&E) | Acute ischemia/hypoxia (12–24 h) |
| Chromatolysis | Swollen soma, eccentric nucleus, Nissl dissolution | Axonal injury (axotomy) |
| Neuronophagia | Microglia engulfing a dying neuron | Viral infection, acute injury |
| Simple atrophy | Small dark neurons + gliosis, neuron loss | Chronic neurodegeneration |
Glial & Macrophage Reactions
| Pattern | On the slide | Cause / meaning |
|---|
| Reactive gliosis | Hypertrophic GFAP+ astrocytes (gemistocytes), glial scar | Any chronic CNS injury (the CNS “scar”) |
| Alzheimer type II astrocyte | Swollen pale nucleus, no cytoplasm | Hyperammonemia / hepatic encephalopathy |
| Rosenthal fibers | Eosinophilic corkscrew GFAP+ inclusions | Chronic gliosis, pilocytic astrocytoma, Alexander disease |
| Microglial nodule / rod cells | Clusters/rows of activated microglia | Viral encephalitis (HIV, CMV), neurosyphilis |
| Gitter cells (foamy macrophages) | Lipid-laden macrophages (LFB-PAS+, CD68+) | Infarct clean-up, active demyelination |
Demyelination & Axonal Degeneration
- Demyelination: LFB pallor with sheets of myelin-laden macrophages and relative axonal sparing; perivenular in MS. Contrast with dysmyelination (leukodystrophies).
- Axonal degeneration (Wallerian): axon + myelin fragment distal to injury; macrophages clear debris; axonal spheroids/torpedoes mark disrupted axons.
Inflammation Patterns
| Pattern | On the slide | Points to |
|---|
| Perivascular cuffing | Lymphocytes ringing vessels (Virchow-Robin) | Viral encephalitis, MS, vasculitis, lymphoma (angiocentric) |
| Neutrophilic exudate | PMNs in subarachnoid space / abscess | Bacterial meningitis, abscess |
| Granulomatous | Epithelioid histiocytes ± giant cells, ± caseation | TB, sarcoid, fungal |
| Vasculitis | Transmural vessel-wall inflammation ± fibrinoid necrosis | Primary CNS or systemic vasculitis |
Necrosis, Edema, Hemorrhage, Calcification
| Pattern | On the slide / stain | Meaning |
|---|
| Ischemic necrosis (CNS → liquefactive) | Red neurons early, then macrophage-mediated liquefaction/cavitation — the brain liquefies (unlike coagulative necrosis elsewhere) | Infarct |
| Liquefactive necrosis | Cystic cavity + macrophages | Evolving/old infarct, abscess |
| Caseous necrosis | Amorphous eosinophilic debris in a granuloma | TB, fungal |
| Vasogenic edema | Pale, loose white matter around vessels | Tumor/abscess (steroid-responsive) |
| Hemorrhage / hemosiderin | Fresh RBCs vs blue iron on Prussian blue | Acute vs old bleed |
| Calcification | Basophilic; von Kossa+ | Dystrophic (old lesions), psammoma bodies, Fahr |
Protein Inclusions & Spongiform Change
Inclusions are a pattern of their own — recognize location (nuclear vs cytoplasmic) and the stain (full table in the Neurodegenerative chapter). Key ones: Lewy body (α-synuclein, cytoplasmic), neurofibrillary tangle (tau, silver+), Negri body (rabies, cytoplasmic), owl-eye / Cowdry A (viral, intranuclear).
Spongiform change: fine vacuolation of gray-matter neuropil without inflammation; PrP immunostain confirms prion disease. Do not confuse with edema artifact or the status spongiosus of severe neuronal loss.
Neoplasia — Basic Architectural Patterns
| Architecture | What it is | Classic tumor |
|---|
| True rosette (central lumen) | Cells around a lumen | Ependymoma (canals), retinoblastoma (Flexner-Wintersteiner) |
| Homer-Wright rosette (neuropil core) | Cells around fibrillar core, no lumen | Medulloblastoma, neuroblastoma |
| Perivascular pseudorosette | Processes radiating to a vessel | Ependymoma |
| Palisading | Nuclei in parallel rows (Verocay), or around necrosis | Schwannoma; glioblastoma (pseudopalisading necrosis) |
| Whorls | Concentric cell wraps ± psammoma | Meningioma |
| Papillae / fronds | Fibrovascular cores lined by cells | Choroid plexus papilloma, papillary ependymoma |
| Sheets of monomorphic cells | Diffuse uniform cells | Lymphoma, pituitary adenoma, oligodendroglioma |
Grading logic (read after architecture): hypercellularity → nuclear atypia → mitoses → microvascular proliferation → necrosis. The last two mark the highest grade (e.g., glioblastoma). Molecular markers (IDH, 1p/19q, ATRX) then refine the diagnosis — see the Tumors chapter.
| Pattern | Buzzword |
|---|
| Red neurons | Acute ischemia, 12–24 h |
| Gitter cells | Foamy macrophages clearing debris |
| Alzheimer type II astrocyte | Hyperammonemia / hepatic encephalopathy |
| Perivascular cuffing | Viral encephalitis / MS / angiocentric lymphoma |
| Spongiform change | Prion (PrP+), no inflammation |
| Pseudopalisading necrosis + MVP | Glioblastoma (highest grade) |
References
- Love S, Budka H, Ironside JW, Perry A. Greenfield's Neuropathology. 9th ed. CRC Press; 2015.
- Prayson RA. Neuropathology. 2nd ed. Elsevier; 2012.
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