Neuropathology

Neuropathology is the bane of many anatomical pathologists in teaching hospitals... 'cause they have to fill in for the neuropathologist when he or she is on vacation.

This article is an introduction to neuropathology. There are separate articles for brain tumours, the pituitary gland and muscle pathologies.

Normal histology

Normal cells

• Neuron:
  • Abundant cytoplasm - key feature.
  • Often very large cells, with angled edges.
  • Prominent nucleolus.
  • Nissl substance (granular perinuclear material - rough ER).
• Glial cells.
  • Oligodendrocyte.
    • Small round nuclei (lymphocyte-like nucleus) - key feature.
    • May resemble a fried egg on H&E (clear cytoplasm, central nucleus).
  • Astrocyte.
    • Irregular non-ovoid nucleus - key feature.
      • Image: astrocyte (med.unsw.edu.au) (in endocrine development).
    • Nuclei less dense than in oligodendrocyte.
    • Close to blood vessels.
    • Form blood-brain barrier.
    • Cytoplasm normally not visible.
  • Microglia - macrophage of the brain (derived from monocyte).
    • May be large.
    • May have vesicles.
• Ependyma.
  • Simple ciliated cuboidal epithelium.
  • Image: Ependyma (stonybrookmedicalcenter.org).

Histology - where

Subependyma

Features:

• Ependyma (simple ciliated cuboidal epithelium).
• Subependymal plate - connective tissue with blood vessels.

Pons

Features:

• Looks like bacon.
• Image: Pons (stonybrookmedicalcenter.org).

Caudate

Features:

• Neurons with adjacent ependymal lining.
  • The caudate forms lateral wall of lateral ventricle.

Putamen

Features:

• Histologically identical to the caudate - but not adjacent to a ventricle, i.e. an ependymal lining.

Globus pallidus

Features:

• Histologically distinct from caudate and putamen.

Hippocampus

Hippocampal formation:

1. Dentate gyrus.
   • "Dense" thin layer of nuclei.
   • Image: Dentate gyrus (stonybrookmedicalcenter.org).
2. Hippocampus proper (AKA Ammon's horn) - this is subdivided:
   • CA3 - superior.
   • CA1 - inferior.
   • CA2 - in between CA3 and CA1, lateral.
   • CA4 - medial.
3. Subicular complex.

Images:

• Hippocampus - frontal section (WP).
• Hippocampus - good schematic (WC).
• Hippocampus (ajnr.org).
• Hippocampus and subiculum (hu-berlin.de).
• Hippocampus - crappy schematic (ucsd.edu).

Important note: CA1 - weak link, dies in ischemia, affected by hypoglycemia.

Cerebellum

Main components:

• Cortex (superficial) - branches (Christmas tree-like).
• Dentate nucleus (deep) - looks like the bite impression of a molar.
  • Image: Cerebellum, cortex & dendate nucleus - low power (stonybrookmedicalcenter.org).

Cerebellar cortex:

• Layers (superficial to deep) - mnemonic MPG:
  1. Molecular layer -- "very pink" on H&E.
     • Inhibitory interneurons: stellate cells, basket cells.
  2. Purkinje cell layer.
     • One cell layer thick - hueuege cells.
  3. Granule cell layer -- "very blue" on H&E.
     • Granule cells (many), interneurons (Golgi cells --few in number). (???)
• Images:
  • Cerebellar cortex - micrograph (stonybrookmedicalcenter.org).
  • Cerebellar cortex - schematic (Gray's Anatomy - WC).

Histopathology

• Reactive astrocytes.
  • Eosinophilic cytoplasm.
  • Peripheral nucleus.
  • Well-defined cell border.
  • Many branching processes.

Alzheimer type II astrocytes:

• Large cleared nuclei.
• Indistinct cytoplasm.
• Images:
  • Alzheimer type II astrocytes (WC).
  • Alzheimer type II astrocytes (neuroquiz.com).
  • Alzheimer type II astrocytes (neuropathologyweb.org) .

• Axonal swellings
  • Image: Axonal swelling - neuropathologyweb.org.

Architecture

• Rosette = circular/flower-like arrangement of cells
• Pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre
• Rosenthal fibres = worm-like or corkscrew-like eosinophilic bodies.
  • Image: Rosenthal fibres - wikipedia.org.
• Pseudopallisading

Notes: Good set of articles -

Mass

In HIV/AIDS patients... mass on CT if infection:

• Toxoplasmosis - most common.

Ring enhancing lesion (DDx) - mnemonic MAGICAL DR:

• Metstasis.
• Abscess.
• Glioblastoma.
• Infarct.
• Contusion.
• AIDS-related.
• Lymphoma + HIV assoc. disease (toxoplasma).
• Demyelination (e.g. multiple sclerosis).
• Resolving hematoma.

Alcohol & CNS

Pathology:

• Morel's laminar sclerosis
• central pontine myelinolysis
• Wernicke's encephalopathy
  • Mnemonic WACO:
    • Wernicke's.
    • Ataxia.
    • Confusion, confabulation -- Korsakoff.
    • Ocular Sx (CN IV palsy).
  • Cause: thiamine deficiency.
• Mammillary body shrinkage.

Acute disseminated encephalomyelitis

General

• Thought to be autoimmune.
• May mimic multiple sclerosis.
• Abbreviated "ADEM".

Diagnosis

• Need to r/o infection (with lumbar puncture).
• No old plaques on imaging (MRI).

Micro

• Spares subcortical fibres (???)

Tx

• Steroids.
• Plasmapheresis.

DDx

• Multiple sclerosis

Cysts

General:

• All are "benign", but some may be fatal due to spatial constraits.

• Colloid cyst
  • columnar epithelium.
• Arachnoid cyst - considered precursor of meningioma.
  • psammoma bodies.
  • clumps of cells.
  • whorled pattern.
• Dermoid cyst.
  • skin + adnexal structures.
  • ... think of ovarian dermoid.
• epidermoid.
• choriod cyst.
  • ?

• neuroenteric cyst.
• epithelial cyst.

Dementia

• Alzheimer's dementia.
• Vascular.
  • multi-infarct dementia.
• Parkinson's associated dementia.
• Lewy body dementia.
• Alcohol-related dementia.
• Fronto-temporal dementia (Pick disease).
• Multisystem atrophy.

Mnemonic VITAMIN D VEST:

• Vitamin deficiency (B12, folate, thiamine).
• Infection (HIV).
• Trauma.
• Anoxia.
• Metabolic (Diabetes).
• Intracranial tumour.
• Normal pressure hydrocephalus.
• Degenerative (Alzheimer's, Huntington's, CJD).
• Vascular.
• Endocrine.
• Space occupying lesion (chronic subdural hematoma).
• Toxins (alcohol).

Lewy body dementia

• Parkinsonian features.
• Hallucinations (visual).
• Progressive cog. decline with fluctuations.

Multiple system atrophy

• Alpha-synuclein-rich glial cytoplasmic inclusions - finding at autopsy.
  • Alpha-synuclein is implicated in a number of neurodegenerative diseases.

Brain tumours

Main article: Neuropathology tumours

Tumours are a big part of neuropathology.

Paediatric pathology

Joubert syndrome

• Malformation of the cerebellar vermis.

Epidemiology

• Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.

Histiocytoses

Features of histiocytoses:

	Histologic features	EM features	CD68	S-100	CD1a
Macrophage	epithelioid cells, giant cells	-	+	-	-
Erdheim-Chester disease	Touton giant cells	-	+	+/-	-
Rosai-Dorfman	Emperipolesis	-	+	+	-
Langerhans-histiocytosis	Reniform nuclei, eosinophilic cytoplasm	Birbeck granules	+	+	+

Stroke

Gross

• Soft/mushy brain.
• Older infarcts.
  • A "roof" is present - a thin submeningeal layer is preserved by the CSF.
    • "Roof" is absent in trauma.
  • Cavity - in older infarcts.
    • Multiple sclerosis does not cavitate.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

General

• Autosomal dominant disorder - the name implies.
• Cases strokes in 40-50 year-old.
• Characteristic MRI findings - present in asymptomatic individuals with mutation.

Etiology

• Mutation of Notch 3 gene.

Diagnosis

• Proven Notch3 mutation.

Histology

• Electron microscopy (skin biopsy):
  • Granular osmiophilic material (GOM).

See also

• Brain tumours.
• Pituitary gland.

External links

• Neuropathology (neuropathologyweb.org).
• Neuropathology cases (lib.umn.edu).
• Neuropathology micrographs - identifying the site (stonybrookmedicalcenter.org).