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 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.
    • Microglia - macrophage of the brain (derived from monocyte).
      • May be large.
      • May have vesicles.
  • Ependyma.

Normal cellular constituents in a table

Key feature Other features Image
Neuron cytoplasm Nissl substance
(prominent RER), "sharp" corners
in cell membrane 		red neurons (WC)
Astrocyte non-ovoid nucleus no cytoplasm (unsw.edu)
Oligodendrocyte round small nucleus peri-nuclear clearing
Microglia rod-like shape,
may have "bent" nucleus 		rarely seen in normal tissue (ucsf.edu),(vcu.edu)

Neurons

There are many types of 'em. Broadly, they can be classified as:

  1. Pyramidal - have a pyramidal shape.
    1. Dentrites go to molecular layer.
    2. Axons go to outside of cortex.
  2. Non-pyramidal.

Histology - where

Subependyma

Features:[1]

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

Pons

Features:

Caudate

Features:

  • Neurons with adjacent ependymal lining.[3]
    • 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:[4]

  1. Dentate gyrus.
  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:

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

Cerebellum

Main components:

Cerebellar cortex:

Cerebral cortex

Layers (superficial to deep):

  1. Molecular layer.
    • Empty appearing.
  2. Outer granular layer.
  3. Outer pyramidal layer.
  4. Inner granular layer.
    • Not prominent in frontal cortex.
    • Where the thalamic axons end.
  5. Inner pyramidal layer.
  6. Polymorphic layer.

Images:

Histopathology

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

Alzheimer type II astrocytes:[6]

Architecture

  • Rosette = circular/flower-like arrangement of cells[7]
  • Pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre[7]
  • Rosenthal fibres = worm-like or corkscrew-like eosinophilic bodies.
  • Pseudopallisading

Notes: Good set of articles - [8]

Mass

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

  • Toxoplasmosis - most common.[9]

Ring enhancing lesion (DDx) - mnemonic MAGICAL DR:[10]

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

Alcohol & CNS

Pathology:[11]

  • 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.[12]

Non-tumour

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[13]
    • 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:[14]

  • 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.[15]
    • Alpha-synuclein is implicated in a number of neurodegenerative diseases.[16]

Brain tumours

Main article: Neuropathology tumours

Tumours are a big part of neuropathology.

Paediatric pathology

Joubert syndrome

  • Malformation of the cerebellar vermis.[17]

Epidemiology

  • Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.[17]

Histiocytoses

Features of histiocytoses:[18]

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.[19]
      • "Roof" is absent in trauma.
    • Cavity - in older infarcts.
      • Multiple sclerosis does not cavitate.

Weird stuff

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

General

  • Autosomal dominant disorder - the name implies.[20]
  • Cases strokes in 40-50 year-old.
  • Characteristic MRI findings - present in asymptomatic individuals with mutation.

Etiology

  • Mutation of Notch 3 gene.[21]

Diagnosis

  • Proven Notch3 mutation.

Histology

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

See also

References

  1. ↑ Half-day. 28 June 2010.
  2. ↑ Half-day. 28 June 2010.
  3. ↑ URL: http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1. Accessed on: 2 July 2010.
  4. ↑ URL: http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1. Accessed on: 2 July 2010.
  5. ↑ URL: http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1. Accessed on: 2 July 2010.
  6. ↑ URL: http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html. Accessed on: 2 July 2010.
  7. ↑ 7.0 7.1 PMID 16551982
  8. ↑ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=PubMed&details_term=Neuropathology%20for%20the%20neuroradiologist
  9. ↑ MUN. Feb 3, 2009.
  10. ↑ TN2005 NS7.
  11. ↑ http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract
  12. ↑ Shear PK, Sullivan EV, Lane B, Pfefferbaum A (November 1996). "Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia". Alcohol. Clin. Exp. Res. 20 (8): 1489-95. PMID 8947329. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=1996&volume=20&issue=8&spage=1489.
  13. ↑ MUN. 11 Mar 2009.
  14. ↑ TN06 PS19
  15. ↑ Wenning, GK.; Stefanova, N.; Jellinger, KA.; Poewe, W.; Schlossmacher, MG. (Sep 2008). "Multiple system atrophy: a primary oligodendrogliopathy.". Ann Neurol 64 (3): 239-46. doi:10.1002/ana.21465. PMID 18825660.
  16. ↑ Uversky, VN. (Oct 2008). "Alpha-synuclein misfolding and neurodegenerative diseases.". Curr Protein Pept Sci 9 (5): 507-40. PMID 18855701.
  17. ↑ 17.0 17.1 http://www.ninds.nih.gov/disorders/joubert/joubert.htm
  18. ↑ Sternberg Surg. Path. P.479.
  19. ↑ MUN. 16 December 2009.
  20. ↑ Tikka, S.; Mykkänen, K.; Ruchoux, MM.; Bergholm, R.; Junna, M.; Pöyhönen, M.; Yki-Järvinen, H.; Joutel, A. et al. (Apr 2009). "Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients.". Brain 132 (Pt 4): 933-9. doi:10.1093/brain/awn364. PMID 19174371.
  21. ↑ Kalaria, RN.; Viitanen, M.; Kalimo, H.; Dichgans, M.; Tabira, T. (Nov 2004). "The pathogenesis of CADASIL: an update.". J Neurol Sci 226 (1-2): 35-9. doi:10.1016/j.jns.2004.09.008. PMID 15537516.

External links

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