Normal Histology
What You'll Learn
- The resident cells of the nervous system and how to recognize each
- Normal appearance of every compartment you'll be shown — cortex, white matter, basal ganglia, cerebellum, brainstem, cord, nerve, muscle, vessels, meninges
- The normal features that are easy to over-call as pathology (oligodendrocyte halos, corpora amylacea, neuromelanin)
- Know normal before abnormal. Most “what is this?” slides are answered by comparing to the normal architecture of that region.
- Perinuclear halos around oligodendrocytes are a normal fixation artifact — don't call oligodendroglioma unless there is a hypercellular infiltrating tumor.
- Corpora amylacea (subpial/perivascular PAS+ bodies) and neuromelanin (substantia nigra / locus coeruleus) are normal — increase with age.
- Purkinje cells sit in a single row between the molecular and granular layers; CA1 (Sommer sector) of the hippocampus is the most hypoxia-vulnerable.
- Muscle: normal fibers are polygonal with peripheral nuclei and a checkerboard of type I/II fibers on ATPase.
The Resident Cells
| Cell | Appearance | Marker | Role |
|---|
| Neuron | Large cell, open nucleus + prominent nucleolus, Nissl-rich cytoplasm | NeuN, synaptophysin, NSE | Excitable signaling cell; size/shape varies by region (pyramidal, Purkinje, motor) |
| Astrocyte | Star-shaped; pale nucleus; processes to vessels (foot processes) | GFAP | Homeostasis, BBB, glial scar; reactive forms hypertrophy |
| Oligodendrocyte | Small round nucleus, perinuclear clear halo (artifact); rows in white matter | Olig2 | CNS myelination |
| Microglia | Small elongated (“rod”) nucleus; inconspicuous when resting | CD68, Iba1 | Resident macrophage/immune surveillance |
| Ependyma | Cuboidal-columnar ciliated cells lining ventricles | GFAP, EMA (dot) | Line ventricles/central canal |
Cerebral Cortex & White Matter
- Cortex: six layers (molecular I → multiform VI); large pyramidal neurons in layers III and V (high metabolic demand → selective vulnerability, laminar necrosis).
- White matter: parallel myelinated axons with rows of oligodendrocytes and scattered astrocytes; stains blue on Luxol fast blue; pallor = myelin loss (true demyelination also shows macrophages with relative axonal sparing).
- Gray-white junction is sharp normally — blurring suggests edema, infiltrating tumor, or dysplasia.
Basal Ganglia, Brainstem & Cerebellum
- Basal ganglia: neuron-rich gray matter; physiologic iron accumulates with age (globus pallidus) — Perls+.
- Brainstem: cranial-nerve nuclei and tracts; the substantia nigra and locus coeruleus contain neuromelanin-pigmented neurons (brown on H&E) — depigmentation = Parkinson pathology.
- Cerebellum: three layers — molecular (outer, sparse), Purkinje (single row of large flask-shaped neurons), and granular (inner, densely packed small neurons). Bergmann glia sit at the Purkinje layer.
Spinal Cord
- Central H-shaped gray matter: large multipolar motor neurons in the anterior horn, sensory/relay neurons in the dorsal horn.
- Surrounding white-matter tracts (dorsal columns, corticospinal, spinothalamic) — selective tract pallor on LFB localizes disease (e.g., dorsal-column loss).
Peripheral Nerve & Skeletal Muscle
- Peripheral nerve (transverse): myelinated fibers of varied caliber within endoneurium; fascicles wrapped by perineurium; epineurium outside. Teased-fiber and semithin/toluidine-blue preps assess myelin; nodes of Ranvier separate internodes.
- Skeletal muscle (transverse): polygonal fibers of uniform size with peripheral nuclei; checkerboard type I (dark on NADH/slow) and type II fibers on ATPase; the neuromuscular junction is the motor endplate. Loss of the checkerboard (type grouping) = reinnervation.
Blood Vessels & Meninges
- Vessels: arteries (thick media), veins (thin wall), capillaries with a continuous endothelium + tight junctions = the blood-brain barrier; astrocyte foot processes invest capillaries.
- Meninges: dura (tough collagen), arachnoid (with arachnoid cap cells — the origin of meningioma; psammoma bodies are normal here), and pia (delicate, adherent to cortex). The subarachnoid space carries CSF and vessels.
| Structure | Normal you must know |
|---|
| Cortex | 6 layers; pyramidal neurons III/V vulnerable |
| Cerebellum | Molecular / Purkinje (single row) / granular |
| Hippocampus | CA1 = Sommer sector, most hypoxia-vulnerable |
| Substantia nigra | Neuromelanin-pigmented neurons (lost in PD) |
| Oligodendrocyte halo / corpora amylacea | Normal — do not over-call |
| Muscle | Polygonal fibers, peripheral nuclei, checkerboard I/II |
| Arachnoid cap cells | Origin of meningioma |
References
- Love S, Budka H, Ironside JW, Perry A. Greenfield's Neuropathology. 9th ed. CRC Press; 2015.
- Ellison D, Love S, et al. Neuropathology: A Reference Text of CNS Pathology. 3rd ed. Mosby; 2013.
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