Difference between revisions of "Neuropathology"

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*'''S'''atellitosis, perineuronal.
*'''S'''atellitosis, perineuronal.
**Large "crowds" of glial cells associated with nuclei.
**Large "crowds" of glial cells associated with nuclei.
===Inflammatory===
DDx:
*Autoimmune - [[Multiple sclerosis]].
*Neoplastic - [[Neuropathology tumours#CNS lymphoma|CNS lymphoma]].
*Infectious - [[HSV]].
====Encephalitis====
=====General=====
DDx:
*Viral encephalitis.
*Paraneoplastic syndromes.
=====Microscopic=====
Features:
*Perivascular and perineuronal inflammation.


===Architecture===
===Architecture===

Revision as of 14:52, 19 July 2011

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, the spine, the eye, 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

Neuronal changes

  • Central chromatolysis.[4]
    • Central clearing.
      • Nucleus and Nissl substance are pushed to cell periphery.
    • DDx: (traumatic) axonal injury,[5] vitamin deficiency (pellagra).[6]

Images:

Glial changes

Astrocyte changes

Reactive astrocytes:

  • Approximately equally-spaced; distance between neighbouring astrocytes is ~2x (or more) the cell size.
  • Well-defined cell border.
  • Eosinophilic cytoplasm with many branching processes.
    • Classically described as "funnel-shaped" in benign astrocytes.[7]
  • Peripheral nucleus.
  • Image: Reactive astrocytes - high mag. (WC).

Alzheimer type II astrocyte:[8]

Creutzfeldt cell:[10]

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

Gemistocytic astrocytes:[11]

  • Distinct eosinophilic cytoplasm - with ground-glass appearance.

Tufted astrocytes:[12]

  • 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.
  • A classic feature of progressive supranuclear palsy.

Other glial

Bergmann gliosis (in the cerebellum):[10]

Reactive change vs. malignancy

Reactive changes vs. malignancy (mnemonic MIMICS):[13]

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

Inflammatory

DDx:

Encephalitis

General

DDx:

  • Viral encephalitis.
  • Paraneoplastic syndromes.
Microscopic

Features:

  • Perivascular and perineuronal inflammation.

Architecture

All things rosette

  • Rosette = circular/flower-like arrangement of cells.[14]
  • Perivascular pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre.[14]
  • Homer-Wright rosette = (circular) rosette with a small (~100 micrometers ???) meshwork of fibers (neuropil) at the centre.[14]
  • Flexner-Wintersteiner rosette = rosette with empty centre (donut hole).[14]
    • Retinoblastomas.
    • Pineoblastomas.
    • Medulloepitheliomas.
  • True ependymal rosette = surrounds a space.[14]
    • Ependymoma.
  • Pineocytomatous/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.[14]
    • Similar to Homer-Wright rosette.
    • Pineocytoma.
    • Neurocytoma.

Other

  • 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.[16]
  • Pseudopalisading - picket fence-like alignment of cells; long axis of cells perpendicular to interface with other structures/cells.
    • Pseudopalisading of tumour cells (around necrotic regions) is seen in glioblastoma.

Note:

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.[19]
    • 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], [2]
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 [3]
Hirano body concentric calcification/rod-shaped bright eosinophilic; overlap edge of neuron Alzheimer d., Pick d.[20] actin crystals, may look like capillaries; location: CA1 of hippocampus [4][21]
Neurofibrillary tangles flame-shaped cytoplasmic thingy
~30 micrometers
aging, Alzheimer's disease seen with silver stain Schematic[21], [5][22]
Granulovacuolar degeneration cytoplasmic vacuoles 4-5 micrometers ageing, Alzheimer's disease,
Pick's disease
main found in Ammon horn[20] [6][22]
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.

Glial tumours

Standard work-up:

  • GFAP.
  • p53.
  • Ki-67.

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.[23]

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 (in adults) 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:[24]

  • Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex[25] usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.[26]
  • Central pontine myelinolysis (CPM).[27]
    • Just what it sound like - myelin loss in the central pons.
    • Classically associated with rapid correction of hyponatremia.[28]
  • Mammillary body shrinkage.[29]
  • Anterior cerebellar vermis atrophy; weak finding - as also age-related.[30]
    • Vermis atrophy is also seen in schizophrenia.[31]

Marchiafava-Bignami Disease

  • Rare.
  • Demyelination of the corpus callosum.[26]

Wernicke's encephalopathy

General:

  • Due to thiamine deficiency.

Features:

  • Neurons preserved - key.
  • Loss of myelin.
  • Hemorrhage.
  • Spongiosis.
  • Reactive blood vessels.


Common non-specific findings

Meningitis

General

  • Definition: inflammation of the meninges (pia mater, arachnoid membranes, dura mater).

Classic clinical presentation:

  • Neck stiffness.
  • Fever.
  • +/-Headache.
  • +/-Decreased level of consciousness.

Etiology:

  • Infectious.
    • Bacterial.
    • Viral.
    • Parasitic
  • Autoimmune.
  • Toxic.

Gross

Features:

  • +/-Clouded appearance of the meninges.
  • +/-Pus.
  • +/-Petechiae.
  • +/-Cerebral edema.

Image:

Microscopic

Features:

  • Inflammation of the meninges.
  • Infectious meningitis:
    • Microorganisms (bacteria, fungi).

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.

Epilepsy

General

  • Seizure that are "idiopathic", i.e. no brain tumour, no mass lesion, no brain injury.
  • Most common form: temporal lobe epilepsy.[32]

Microscopic

Features:[33]

  • Mesial temporal sclerosis = scarring of the medial temporal lobe.
    • Involves: hippocampus, parahippocampal gyrus and amygdala.
      • Hippocampus: CA1 and CA4 affected.

Notes:

  • Changes in CA1 & CA4 of the hippocampus - DDx:
    • Epilpsy.
    • Dementia.

Cysts

General

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

List of cysts

  • Colloid cyst.[34]
    • 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.[35]
      • "Roof" is absent in trauma.
    • Cavity - in older infarcts.
      • Multiple sclerosis does not cavitate.
  • Laminar necrosis = (thin) chalky line replaces grey mater.[36]
    • AKA pseudolaminar necrosis - as it is not localized to a specific layer of the cortex.[37]

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 (in adults):
    • 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/resistant.
  • Purkinje cell loss in the cerebellum and Bergmann gliosis.
  • "Anoxic neurons".[38]
    • Shrunken neurons with intensely eosinophilic cytoplasm and pyknotic (shrunken) nuclei.
  • Pseudolaminar necrosis - (uncontrolled) cell death in the cerebral cortex in a band-like pattern,[39] with a relative preservation of cells immediately adjacent to the meninges.

Images:

Notes:

  • Neurons of subiculum in adults - usu. normal (as they are resistant to ischemic changes).

Multiple sclerosis

General

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

Clinical:

  • CSF: oligoclonal bands of immunoglobulin.[42]

Radiologic/Gross

Features:[43]

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

Microscopic

Features:[44]

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

Classification of MS lesions:

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

Cerebral amyloid angiopathy

General

  • Abbreviated CAA.
  • Disease of the old.
  • Strong association with lobar haemorrhage.[45]
    • Cerebellar cortex.
    • Cerebral cortex.

Etiology:

  • Amyloid deposition in the basal lamina of smooth muscle (in the cerebellar cortex and cerebral cortex).

Microscopic

Features:

  • Amorphous, acellular eosinophilic material within walls of small arteries.
    • This is a high power diagnosis with congo red staining.

Special stains:

Notes:

  • Amyloidosis is seen in all individuals with Alzheimer's disease; the amount of amyloid is what differs -- in CAA it is lots and lots.
  • The white matter is typically spared by CAA.[46]

Images:

Vascular malformations

Types:[47]

  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.

Paediatric pathology

Joubert syndrome

  • Malformation of the cerebellar vermis.[48]

Epidemiology

  • Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.[48]

Weird stuff

Acute disseminated encephalomyelitis

General

  • Thought to be autoimmune; often associated with/preceded by by viral illness.[49]
  • May mimic multiple sclerosis.
  • Abbreviated "ADEM".

Treatment:

  • Steroids.
  • Plasmapheresis.

Diagnosis:

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

Microscopic

Features:[50]

  • Myelin loss with sparing of axons.
  • Inflammation:
    • Early: neutrophils.
    • Late: mononuclear cells (lymphocytes, plasma cells).
  • Lipid-laden macrophages.

DDx

  • Multiple sclerosis.
    • Age of lesions differs.
  • Acute necrotizing hemorrhagic encephalomyelitis (ANHE).

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

General

  • Autosomal dominant disorder - as the name implies.[51]
  • Causes strokes in 40-50 year-old.
  • Characteristic MRI findings - present in asymptomatic individuals with mutation.
  • Increased risk of myocardial infarction.[52]

Etiology

  • Mutation of Notch 3 gene.[53]
    • Diagnosis: proven Notch 3 mutation.

Microscopic

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.[54]

IHC

  • Notch 3: smooth muscle and pericytes punctate +ve.[52]

Image: Notch 3 staining in CADASIL (WC).

Notes:

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

DDx:

Skin biopsy diagnosis

  • Can be diagnosed on a skin biopsy.[55]

Electron microscopy

  • Granular osmiophilic material (GOM).

See also

References

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  2. TN2005 NS7.
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