Neuropathology

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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, muscle pathologies, neurohistology and neuroanatomy.

Neuroanatomy

This is a large topic. It covered in a separate article, that also covers grossing.

Neuroradiology

Enhancing vs. non-enhancing:

  • If it is tumour... enhancing usu. high grade, non-enhancing usu. low grade.

Ring enhancing lesions

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

  • Toxoplasmosis - most common.[1]

Ring enhancing lesion (DDx) - mnemonic MAGICAL DR:[2]

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

Grossing

This is covered in the neuroanatomy article.

Gross pathology

The gross usually useless for arriving at a definitive diagnosis.

Exceptions:[3]

  • Sausage shape lesion of filum terminale = myxopapillary ependymoma.
  • Soft & tan colour = pituitary adenoma.

Normal histology

This is a big topic. It is covered in a separate article called neurohistology.

Histopathology

Astrocyte changes

Reactive astrocytes.

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

Reactive changes vs. malignancy (mnemonic MIMICS):[4]

  • MIcrovesicular pattern.
  • Mitoses.
  • Irregular spacing.
  • Calcifications.
  • Satellitosis, perineuronal.
    • Large "crowds" of glial cells associated with nuclei.

Types

Alzheimer type II astrocyte:[5]

Bergmann gliosis (in the cerebellum):[6]

Creutzfeldt cell:[6]

  • Astrocyte that mimics a mitoses; has moderate (identifiable) cytoplasm.
  • Finding associated with demyelinating disease.

Gemistocytic astrocytes:[7]

  • Distinct eosinophilic cytoplasm - with ground-glass appearance.

Tufted astrocytes:[8]

  • Cellular processes loaded with tau protein (as may be seen with tau IHC or Gallyas silver stain); Parisian-star-like appearance with special stain.
  • +/-Multinucleated.
  • Classic features of progressive supranuclear palsy.

Architecture

  • Rosette = circular/flower-like arrangement of cells[9]
  • Pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre[9]
  • Rosenthal fibres = worm-like or corkscrew-like (brightly) eosinophilic bodies; 10-40 micrometers.
  • Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.[10]
  • Pseudopallisading

Notes: Good set of articles - [11]

Axonal swellings

H&E:

  • Eosinophilic (light pink) - ground glass-like appearance.
  • Shape:
    • Round if sectioned perpendicular to axis of axon.
      • Bound by cell membrane.
      • Large ~ typically 2-4x RBC diameter.
    • Sausage-shaped if cut in along axis.

Images:

IHC

  • APP.

Image:

Inclusion bodies

  • Negri bodies.
    • Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
    • Rabies.
    • Image: Negri bodies (WC/CDC).
  • Lewy bodies.
    • Eosinophilic cytoplasmic inclusion - composed mostly of alpha-synuclein.[14]
    • Image: Lewy body (WC).

Table of inclusions

Feature Appearance Associated disease Comment Image
Grumous bodies
AKA granular bodies
granular and eosinophilic ~50 micrometers neurodegenerative disease, neuroaxonal dystrophies, aging ?Comment ?Image
Cowdry type 1
AKA Cowdry type A
eosinophilic & round + halo herpes simplex virus can be confused with
Lewy body, Marinesco body
?Image
Lewy body round cytoplasmic eosinophilic
body +/- pale halo
Parkinsons disease, dementia with Lewy bodies morphology dependent on
location in brain; +ve for alpha-synuclein,
alpha-B crystallin, ubiquitin
[1]
Lafora body round myoclonic epilepsy look like corpora amylacea; location: dentate nucleus, liver, skeletal muscle, sweat glands ?Image
Lipofuscin yellow & granular aging olive, dendate ?Image
Negri body small eosinophic bodies rabies found in hippocampal neurons and Purkinje cells [2]
Hirano body concentric calcification/rod-shaped bright eosinophilic; overlap edge of neuron Alzheimer d., Pick d.[15] actin crystals, may look like capillaries; location: CA1 of hippocampus [3][16]
Neurofibrillary tangles flame-shaped cytoplasmic thingy
~30 micrometers
aging, Alzheimer's disease seen with silver stain [4][17], Schematic[16], [5][18]
Granulovacuolar degeneration cytoplasmic vacuoles 4-5 micrometers ageing, Alzheimer's disease,
Pick's disease
main found in Ammon horn[15] [6][18]
Pick bodies round, homogenous, intracytoplasmic, ~10 micrometers Pick's disease pyramidal neurons, dentate
granule cells (hippocampus); +ve for tau, tubulin, ubiquitin
[7]
Bunina body size of Nissl granules, eosinophilic ALS EM: membrane-bound bodies; ubiquitin +ve [8]

Image collection: Inclusion bodies (photobucket.com).

Immunohistochemistry

General

  • S-100.
    • Sensitive... but non-specific, e.g. also stains melanoma.

Glial

  • GFAP (glial fibrillary acidic protein) - should stain perikaryon.

Neuronal

  • Synaptophysin.
  • Chromogranin.

Carcinoma vs. glial tumours

  • AE1/AE3 often +ve in glial tumours (e.g. astrocytomas, oligodendrogliomas); CAM5.2 is usu. -ve in glial tumours.[19]

Others

  • APP (amyloid precursor protein) - detects axonal swellings.
  • NF (neurofilament) - detects axonal swellings.


Brain tumours

Tumours are a big part of neuropathology. The most common brain tumour is a metastasis. The most common primary tumour is glioblastoma which has a horrible prognosis.

Non-tumour

Alcohol & CNS

Clinical

  • Wernicke's encephalopathy
    • Mnemonic WACO:
      • Wernicke's.
      • Ataxia.
      • Confusion, confabulation -- Korsakoff.
      • Ocular Sx (CN IV palsy).
    • Cause: thiamine deficiency.

Pathology

Features:[20]

  • Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex[21] usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.[22]
  • Central pontine myelinolysis.
  • Mammillary body shrinkage.[23]
  • Anterior cerebellar vermis atrophy; weak finding - as also age-related.[24]
    • Vermis atrophy is also seen in schizophrenia.[25]
  • Marchiafava-Bignami Disease:
    • Rare.
    • Demyelination of the corpus callosum.[22]

Common non-specific findings

Abscess

General

  • May mimic malignancy clinically.

Microscopic

Features:

  • Sheets of neutrophils surrounded by fibrosing brain.
    • Fibrosing brain: pale (lighter pink than normal brain tissue), dense.

Image: Cerebral abscess (pathconsultddx.com).

Neurodegenerative diseases

This is a hueueuge topic. It is covered its own article and includes a general discussion of dementia.

Cysts

General

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

List of cysts

  • Colloid cyst.[26]
    • 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.

Stroke

Gross

  • Soft/mushy brain.
  • Older infarcts.
    • A "roof" is present - a thin submeningeal layer is preserved by the CSF.[27]
      • "Roof" is absent in trauma.
    • Cavity - in older infarcts.
      • Multiple sclerosis does not cavitate.
  • Laminar necrosis = (thin) chalky line replace grey mater.[28]

Hypoxic-ischemic encephalopathy

General

  • Often due to cardiac arrest, i.e. global ischemia.
  • Triple watershed area = parieto-occipital cortex, extrastriate occipital cortex.

Microscopic

Features:

  • Hippocampal ischemic changes:
    • Loss of neurons in CA1, CA3 and CA4 +/- "cavitation".
      • Neuronal loss: No blue (nuclei) where there should be some.
      • Cavitation: bubbles/clear spaces where there should be none.
    • CA2 neurons preserved.

Multiple sclerosis

General

  • A bread 'n butter disease of neurology in Canada.

Radiologic/Gross

Features:[31]

  • White matter lesions.
    • Cerebrum (classically): periventricular distribution.
    • Optic nerves (optic neuritis) - classic presentation.

Microscopic

Features:[32]

  • Perivascular inflammation.
  • Demyelination.
    • Subcortical myelinated fibers are often spared.

Classification of MS lesions:

  • Early active.
  • Inactive.
  • Early remyelinating.
  • Late remyelinating.

Vascular malformations

Types:[33]

  1. Arteriovenous malformation.
    • Most important clinically - highest risk of bleeding.
  2. Varix.
    • One large (dilated) vein.
  3. Venous angioma.
    • Many small veins.
  4. Caverous malformation.
    • Vessels are back-to-back (no intervening parenchyma).

Also see: Sturge-Weber syndrome.

Arteriovenous malformation

General

  • High risk for bleeding vis-a-vis other vascular malformations.

Gross

Features:[33]

  • Classically wedge-shaped - with base toward superficial aspect and apex toward deep aspect (like pulmonary infarcts).
  • Usually middle cerebral artery distribution.

Microscopic

Features:

  • Large vessels with eccentric wall thickening.
    • "Large" = ~ 0.5 mm (0.25-1.0 mm).
      • 0.25 mm = ~ 31 RBC diameters across.

Image: Cerebral AVM (WC).

Notes:

  • There is usually one feeding artery.
    • The artery is often not seen.
  • Arteries have internal elastic lamina (best seen on elastic trichrome).

Paediatric pathology

Joubert syndrome

  • Malformation of the cerebellar vermis.[34]

Epidemiology

  • Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.[34]

Weird stuff

Acute disseminated encephalomyelitis

General

  • Thought to be autoimmune; often associated with/preceded by by viral illness.[35]
  • May mimic multiple sclerosis.
  • Abbreviated "ADEM".

Diagnosis

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

Microscopic

Features:

  • Spares subcortical fibres (???)

Tx

  • Steroids.
  • Plasmapheresis.

DDx

  • Multiple sclerosis.

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

General

  • Autosomal dominant disorder - as the name implies.[36]
  • Cases strokes in 40-50 year-old.
  • Characteristic MRI findings - present in asymptomatic individuals with mutation.

Etiology

  • Mutation of Notch 3 gene.[37]

Diagnosis

  • Proven Notch 3 mutation.
  • Can be diagnosed on a skin biopsy.
  • IHC for Notch 3 -- +ve staining in Notch 3 mutants.

Histology

Features:

  • Subcortical infarcts.
    • Patches of (non-myelinated) tissue within the white matter deep to the cortex with abundant macrophages.
  • Blood vessels typically have a basophilic granularity.[38]

Note:

  • No cortical involvement -- this is unlike multiple sclerosis.

DDx:

  • Amyloidosis.
  • Binswanger's disease - multi-infarct dementia affecting subcortical white matter.
    • Often diagnosed as Alzheimer's disease in the past.

Electron microscopy

  • Granular osmiophilic material (GOM).

Binswanger's disease

General

  • Multi-infarct dementia affecting subcortical white matter.
  • Waste-basket diagnosis; diagnosed if CADASIL and amyloidosis have been excluded.
  • Diagnosis has been controversial -- most with this entity (in the past) were diagnosed with Alzheimer's disease.

Microscopic

Features:

  • Subcortical lesions that replace the myelin consisting of macrophages.

Prion diseases

Etiology:[39]

  • Misfolded cell-surface protein called PrP(C).

Includes:[39]

  • Creutzfeldt-Jakob disease (CJD).
  • Sporadic fatal insomnia (sFI).

Creutzfeldt-Jakob disease

General

  • Commonly abbreviated as CJD.
  • Rare.
  • Incurable disease.
  • Usually diagnosed clinically.
    • Characteristic findings:
      • Very rapid decline (3-4 months).
      • Characteristic (cortex findings on) neuroradiology.

Variant Creutzfeldt-Jakob disease (vCJD)

  • Associated with bovine spongiform encephalopathy.
  • Should sample: spleen, lymph nodes, tonsils.[40]

Microscopic

Features:

  • Spongy appearance (cytoplasmic vacuolization[41]).

Images:

See also

References

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  2. TN2005 NS7.
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External links