Neuropathology

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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.

Gross image showing changes of a stroke. (WC/Marvin 101)

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.

Neuroanatomy

Main article: Neuroanatomy

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

Neuroradiology

Key factors to consider in evaluation:

  1. Location.
  2. Number of lesions - single versus multiple.
  3. Cystic versus solid lesion.
  4. Enhancement.

Lesion location

In neuroradiology and neuropathology, real estate is crucial. Lesion location can often narrow your differential.

Cortical lesions (gray matter):

Cortical-subcortical junction:

Subcortical lesions (white matter):

Deep gray matter lesions (e.g. basal ganglia):

Cerebellar lesions:

Intraventricular lesions:

Suprasellar (above the pituitary):

Number of lesions

If single lesion = think primary, neoplastic If multiple lesions = think metastatic, neoplastic or infectious NB: glioblastoma can be multifocal (and the foci can be quite far apart)

Cystic vs. solid lesions

Some tumours are classically cystic with a small solid component (so-called cyst with a mural nodule) -- e.g. pilocytic astrocytoma, ganglioglioma, hemangioblastoma

Enhancing vs. non-enhancing:

  • In adults, enhancing generally = high grade.
  • In pediatrics, it often depends on the pattern.

Two main patterns to be mindful of -- ring enhancing lesions, and cystic lesions with a mural nodule.

Ring enhancing lesions

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

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

Cyst with enhancing mural nodule

  • hemangioblastoma (#1 in adults)
  • pilocytic astrocytoma (#1 in peds)
  • pleomorphic xanthoastrocytoma
  • ganglioglioma

Grossing

This is covered in the neuroanatomy article.

Gross pathology

The gross usually useless for arriving at a definitive diagnosis.

Exceptions:[3]

Normal histology

Main article: Neurohistology

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

Histopathology

Neuronal changes

Anoxic neurons

  • AKA red neurons.

Features:

  • Intensely red cytoplasm.
  • Pyknosis = nuclear shrinkage + darker staining.
Images

  • Anoxic neurons (WC)

  • Neurons in an acute stroke. (WC)

www:

Central chromatolysis

Features:[6]

  • Central clearing.
    • Nucleus and Nissl substance are pushed to cell periphery.

DDx:

Images

  • Central chromatolysis - intermed. mag. (WC)

  • Central chromatolysis - NF stain - very high mag. (WC)

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:

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.[11]
  • Peripheral nucleus.

  • Reactive astrocytes - high mag. (WC)

Alzheimer type II astrocyte:[12]

  • Alzheimer type II astrocytes. (WC)

Creutzfeldt cell:[14]

  • Astrocyte that mimics a mitoses; has moderate (identifiable) cytoplasm.
  • Finding associated with demyelinating disease.
  • Image: Crutzfeldt cell (upmc.edu).[15]

Gemistocytic astrocytes:[16]

  • Distinct eosinophilic cytoplasm - with ground-glass appearance.

Tufted astrocytes:[17]

  • 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):[14]

  • Thin layer of cells (2-3 cells) with open nuclei that are larger than granular cell layer nuclei; seen with Purkinje cell loss.

  • Bergmann gliosis - intermed. mag. (WC)

  • Bergmann gliosis - high mag. (WC)

  • Bergmann gliosis due to compression by metastasis - intermed mag. (WC)

Image:

Reactive change vs. malignancy

Reactive changes vs. malignancy (mnemonic MIMICS):[18]

  • 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.
Gross
  • Frontal and temporal lobe - most common for HSV encephalitis.[19]
Microscopic

Features:[20]

  • Perivascular inflammation.
  • Microglia.
  • +/-Neuronophagia.
    • Phagocytosis of neurons.[21]
  • +/-Viral cytopathic changes.
  • +/-Perineuronal inflammation.

Notes:

  • Hemorrhage[22] and necrosis - characteristic of HSV encephalitis.

Image:

IHC

IHC stains for:

Architecture

Rosettes

  • Rosette = circular/flower-like arrangement of cells.[24]
  • Homer-Wright rosette = (circular) rosette with a small (~100 micrometers ???) meshwork of fibers (neuropil) at the centre.[24]
  • Pineocytomatous/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.[24]
  • Radial (cartwheel) profiles = neoplastic cells anchoring to stromal vessels, shorter processes than in ependymal pseudorosettes

  • Homer-Wright rosettes (WC).

  • Neurocytic rosettes (WC).

  • Perivascular pseudorosette (WC).

  • Multilayered rosettes (WC).

  • Ependymoblastous rosettes (WC/Marvin101).

  • True ependymal rosettes and pseudorosettes (WC).

  • Radial (cartwheel) profiles (WC).

Other

  • Rosenthal fibres = worm-like or corkscrew-like (brightly) eosinophilic bodies; 10-40 micrometers.
    • Key feature: variable thickness; helps separate from RBCs.
    • Well-seen on trichrome stains.

  • Rosenthal fibres. (WP)

  • Rosenthal fibres - smear (WC/AFIP)

  • Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.[26]
    • Image: [Image:Pilocytic_Micro.jpg EGBs (WC/AFIP)].
  • 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:

Inclusion bodies

  • Negri bodies.
    • Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
    • Rabies.

  • Negri bodies. (WC/CDC)

  • Owl eye inclusions.
    • Basiopilic neuronal inclusions in enlarged cells, typically seen in CMV encephalitis

  • Owl eye inclusions

  • Lewy bodies.
    • Eosinophilic cytoplasmic inclusion - composed mostly of alpha-synuclein.[27]

  • Lewy body. (WC)

Table of inclusions

Feature Appearance Associated disease Comment Image
Grumose 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 		Parkinson disease, dementia with Lewy bodies morphology dependent on
location in brain; +ve for alpha-synuclein,
alpha-B crystallin, ubiquitin
Lewy Koerperchen.JPG
, [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
Rabies encephalitis Negri bodies PHIL 3377 lores.jpg
Hirano body concentric calcification/rod-shaped bright eosinophilic; overlap edge of neuron Alzheimer disease, Pick disease[28] actin crystals, may look like capillaries; location: CA1 of hippocampus [2][29]
Neurofibrillary tangles flame-shaped cytoplasmic thingy
~30 micrometers 		aging, Alzheimer's disease seen with silver stain Schematic[29], [3][30]
Granulovacuolar degeneration cytoplasmic vacuoles 4-5 micrometers ageing, Alzheimer's disease,
Pick's disease 		main found in Ammon horn[28] [4][30]
Pick bodies round, homogenous, intracytoplasmic, ~10 micrometers Pick's disease pyramidal neurons, dentate
granule cells (hippocampus); +ve for tau, tubulin, ubiquitin 		[5]
Bunina body size of Nissl granules, eosinophilic amyotrophic lateral sclerosis (ALS) EM: membrane-bound bodies; ubiquitin +ve [6]

Image collection: Inclusion bodies (photobucket.com).

Immunohistochemistry

Main article: 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.
  • MAP2C. [31]
  • Ki-67 (MIB-1).

Useful additional markers:

  • IDH1(R132H) in Astrocytic/Oligodendroglial tumors. [32]
  • ATRX in mixed gliomas. [33]
  • EMA in Ependymal tumors. [34]
  • OLIG-2 usually -ve in Ependymomas. [35][36]

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.[37]

Others

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

Brain tumours

Main article: Neuropathology tumours

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

Non-tumour

Cerebral hemorrhage

See: Intracranial hematoma for intracranial bleeds

Includes discussion of:

Duret hematoma

  • AKA Duret hemorrhage.

General

  • Bleed in the upper brainstem (midbrain and pons).
    • Thought to be due to transtentorial herniation secondary to supratentorial mass effect (e.g. supratentorial tumour, intracranial hemorrhage).[38]
  • Often fatal.[39]

Gross

  • Extravasated blood in midbrain and pons - usu. ventral (anterior) and paramedian (adjacent to the midline).[38]

Image:

Microscopic

Features:

  • RBC extravasation.
  • +/-Hemosiderin-laden macrophages.
  • +/-Ischemic neurons.

Alcohol & CNS

Clinical

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

Pathology

Features:[41]

  • Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex[42] usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.[43]
  • Central pontine myelinolysis (CPM).[44]
    • Just what it sound like - myelin loss in the central pons.
    • Classically associated with rapid correction of hyponatremia.[45]
  • Mammillary body shrinkage.[46]
  • Anterior cerebellar vermis atrophy; weak finding - as also age-related.[47]
    • Vermis atrophy is also seen in schizophrenia.[48]

Marchiafava-Bignami Disease

  • Rare.
  • Demyelination of the corpus callosum.[43]

Wernicke's encephalopathy

General:

  • Due to thiamine deficiency.

Features:[49]

  • Neurons of mammillary bodies preserved - key.
  • Loss of myelin.
  • Hemorrhage.
  • Edema.
  • Reactive blood vessels.

Note:

  • The thalamus and inferior olives show neuronal loss.[49]

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.

CSF findings:

Type Glucose Protein Cells Cytopathology
Bacterial, acute low high neutrophils
 
Cytophathology
Viral normal slight elevation lymphocytes Cytophathology


Etiology

Bacterial meningitis - most probably cause by age:[50]

Age Organism
Neonate Escherichia coli, Group B Streptococcus
Infants, children Streptococcus pneumoniae
Adolescents, young adults Neisseria meningitidis
Elderly Streptococcus pneumoniae, Listeria monocytogenes

Gross

Features:

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

Image

  • Streptococcus Meningitis. (WC/Dr. Edwin P. Ewing, Jr.)

  • Hemophilus influenza Meningitis. (WC/CDC)

  • Pneumococcus Meningitis. (WC/Dr. Yale Rosen)

  • Bacterial Meningitis MRI (WC/MBq)

Microscopic

Features:

Main DDx:

Image

  • Bacterial meningitis. (WC/Marvin101)

Cerebral 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.

Images:

Neurodegenerative diseases

Main article: Neurodegenerative diseases

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

Epilepsy

Main article: Epilepsy

Cerebrovascular accident

  • Abbreviated CVA.
  • AKA stroke.
Main article: Cerebrovascular accident

Hypoxic-ischemic encephalopathy

  • Abbreviated HIE.
Main article: Hypoxic-ischemic encephalopathy

Multiple sclerosis

  • Abbreviated MS.
Main article: Multiple sclerosis

Cerebral amyloid angiopathy

General

  • Abbreviated CAA.
  • Disease of the old.
  • Strong association with lobar haemorrhage (bleeds of the cerebellar cortex and cerebral cortex).[52]

Etiology:

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

Gross

  • Bleeds typically superficial (cortex and subcortical white matter) and in the frontal lobe or parietal lobe.[53]

Microscopic

Features:

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

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.[54]

Images

  • CAA - congo red - very high mag. (WC)

  • CAA - congo red - low mag. (WC)

  • CAA - beta-amyloid - high mag. (WC)

Stains

IHC

  • Abeta-amyloid (AKA beta-amyloid).

Central pontine myelinolysis

  • Abbreviated CPM.
  • AKA pontine myelinolysis.

General

  • Classically in the pons, ergo "pontine" is in the name.
  • Classically midline, ergo "central" is in the name.
    • May occur elsewhere -- known as extrapontine myelinolysis.

Etiology:

  • Rapid correction of hyponatremia.[55]
  • Tacrolimus post-liver transplant.[56]
  • Associated with alcoholism and malnourishment.

Clinical:[57]

  • Decreased level of consciousness - most common.
  • Quadriplegia.
  • Poor prognosis.

Microscopic

Features:[58]

  • Myelin loss.
  • No inflammation.
  • Relative preservation of neurons.

Images:

Vascular malformations

Main article: Vascular malformations

Types:[59]

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

Also see: Sturge-Weber syndrome.

Cysts

General

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

List of cysts

  • Colloid cyst.
    • Columnar epithelium.
  • Arachnoid cyst - considered precursor of meningioma.
  • Dermoid cyst.
    • Skin + adnexal structures.
    • ... think of ovarian dermoid.
  • Epidermoid cyst.
  • Choroid plexus cyst.
  • Neuroenteric cyst.
    • Foregut cyst with connection to dura.[60]
      • Gastrointestinal tract epithelium.
      • Usually seen with vertebral anomalies.
  • Epithelial cyst.
  • Others.

Colloid cyst

General

Classic presentation:[61]

Gross

  • Fluid filled cyst - classically in the third ventricle.

Images

  • Colloid cyst at autopsy. (Shaktawat et al.[63])

www:

Microscopic

Features:[64]

  • Simple epithelium with ciliated cells and goblet cells.

Images

  • Colloid cyst. (WC)

www:

Paediatric pathology

Kernicterus

General

  • Due to hyperbilirubinemia.[65]

Gross

  • Yellow staining:[66]
    • Basal ganglia.[67]
    • Hippocampus.[68]
    • Subthalamic nucleus.

Note:

  • May not be specific.[65]

Image:

Microscopic

Features - similar to HIE:[66]

  • +/-Red neurons.
  • +/-Gliosis.

Joubert syndrome

  • Malformation of the cerebellar vermis.[69]

Epidemiology

  • Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.[69]

Weird stuff

Acute disseminated encephalomyelitis

  • Abbreviated ADEM.
Main article: Acute disseminated encephalomyelitis

Neuromyelitis optica

  • Abbreviated NMO.

General

  • Rare autoimmune disease - once considered a variant of multiple sclerosis.
    • Autoantibodies directed at aquaporin-4.[70]

Diagnosis:

  • NMO-IgG.

Clinical - preferentially:

  • Eye (optic neuritis).
  • Spinal cord (myelitis).

Microscopic

Features:

  • Inflammation - lymphocytes, macrophages.
  • Reactive astrocytes.

Images:

IHC

  • Mixed lymphocyte population with CD3 > CD20.
  • Aquaporin-4 loss.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

  • Commonly abbreviated CADASIL.
Main article: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Progressive multifocal leukoencephalopathy

  • Abbreviated PML.
Main article: Progressive multifocal leukoencephalopathy

See also

References

  1. ↑ MUN. Feb 3, 2009.
  2. ↑ Yeung, J.C.; Leonard, Blair J. N. (2005). The Toronto Notes 2005 - Review for the MCCQE and Comprehensive Medical Reference (2005 ed.). The Toronto Notes Inc. for Medical Students Inc.. pp. NS7. ISBN 978-0968592854.
  3. ↑ R. Kiehl. 8 November 2010.
  4. ↑ URL: http://neuropathology-web.org/chapter2/chapter2aHIE.html. Accessed on: 10 December 2014.
  5. ↑ URL: http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm and http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm. Accessed on: 31 October 2010.
  6. ↑ URL: http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html. Accessed on: 22 December 2010.
  7. ↑ Holland GR (1996). "Experimental trigeminal nerve injury". Crit. Rev. Oral Biol. Med. 7 (3): 237–58. PMID 8909880.
  8. ↑ Piercecchi-Marti MD, Pélissier-Alicot AL, Leonetti G, Tervé JP, Cianfarani F, Pellissier JF (December 2004). "Pellagra: a rare disease observed in a victim of mental and physical abuse". Am J Forensic Med Pathol 25 (4): 342–4. PMID 15577526.
  9. ↑ URL: http://frontalcortex.com/?page=oll&topic=24&qid=602. Accessed on: 3 November 2010.
  10. ↑ Finnie JW, Manavis J, Blumbergs PC, Kuchel TR (November 2000). "Axonal and neuronal amyloid precursor protein immunoreactivity in the brains of guinea pigs given tunicamycin". Vet. Pathol. 37 (6): 677–80. PMID 11105962. http://vet.sagepub.com/content/37/6/677.full.
  11. ↑ MUN. 15 November 2010.
  12. ↑ URL: http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html. Accessed on: 2 July 2010.
  13. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 202. ISBN 978-1416002741.
  14. ↑ 14.0 14.1 Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 18. ISBN 978-0443069826.
  15. ↑ URL: http://path.upmc.edu/cases/case336.html. Accessed on: 15 January 2012.
  16. ↑ URL: http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html. Accessed on: 7 November 2010.
  17. ↑ Gray, Francoise; Poirier, Jacques; De Girolami, Umberto (2003). Escourolle and Poirier's Manual of Basic Neuropathology (4th ed.). Churchill Livingstone. pp. 173. ISBN 978-0750674058.
  18. ↑ Weedman Molavi, Diana (2008). The Practice of Surgical Pathology: A Beginner's Guide to the Diagnostic Process (1st ed.). Springer. pp. 254. ISBN 978-0387744858.
  19. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 416 Q47. ISBN 978-1416025887.
  20. ↑ Takei, H.; Wilfong, A.; Malphrus, A.; Yoshor, D.; Hunter, JV.; Armstrong, DL.; Bhattacharjee, MB. (Aug 2010). "Dual pathology in Rasmussen's encephalitis: a study of seven cases and review of the literature.". Neuropathology 30 (4): 381-91. doi:10.1111/j.1440-1789.2009.01079.x. PMID 20051019.
  21. ↑ URL: http://medical-dictionary.thefreedictionary.com/neuronophagia. Accessed on: 11 April 2012.
  22. ↑ Vossough, A.; Zimmerman, RA.; Bilaniuk, LT.; Schwartz, EM. (Apr 2008). "Imaging findings of neonatal herpes simplex virus type 2 encephalitis.". Neuroradiology 50 (4): 355-66. doi:10.1007/s00234-007-0349-3. PMID 18246335.
  23. ↑ URL: http://neuropathology-web.org/chapter5/chapter5dViruses.html. Accessed on: 27 January 2012.
  24. ↑ 24.0 24.1 24.2 24.3 24.4 24.5 Wippold FJ, Perry A (March 2006). "Neuropathology for the neuroradiologist: rosettes and pseudorosettes". AJNR Am J Neuroradiol 27 (3): 488–92. PMID 16551982.
  25. ↑ URL: http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17. Accessed on: 3 December 2010.
  26. ↑ Gray, Francoise; Poirier, Jacques; De Girolami, Umberto (2003). Escourolle and Poirier's Manual of Basic Neuropathology (4th ed.). Churchill Livingstone. pp. 11. ISBN 978-0750674058.
  27. ↑ Marui W, Iseki E, Kato M, Akatsu H, Kosaka K (August 2004). "Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease". Acta Neuropathol. 108 (2): 121–8. doi:10.1007/s00401-004-0869-4. PMID 15235805.
  28. ↑ 28.0 28.1 Gray, Francoise; Poirier, Jacques; De Girolami, Umberto (2003). Escourolle and Poirier's Manual of Basic Neuropathology (4th ed.). Churchill Livingstone. pp. 5. ISBN 978-0750674058.
  29. ↑ 29.0 29.1 URL: http://www.pakmed.net/academic/age/alz/alz030.htm. Accessed on: 12 November 2010.
  30. ↑ 30.0 30.1 URL: http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm. Accessed on: 13 November 2010.
  31. ↑ Blümcke, I.; Müller, S.; Buslei, R.; Riederer, BM.; Wiestler, OD. (Aug 2004). "Microtubule-associated protein-2 immunoreactivity: a useful tool in the differential diagnosis of low-grade neuroepithelial tumors.". Acta Neuropathol 108 (2): 89-96. doi:10.1007/s00401-004-0873-8. PMID 15146346.
  32. ↑ Paulus, W. (Nov 2009). "GFAP, Ki67 and IDH1: perhaps the golden triad of glioma immunohistochemistry.". Acta Neuropathol 118 (5): 603-4. doi:10.1007/s00401-009-0600-6. PMID 19847448.
  33. ↑ Reuss, DE.; Sahm, F.; Schrimpf, D.; Wiestler, B.; Capper, D.; Koelsche, C.; Schweizer, L.; Korshunov, A. et al. (Jan 2015). "ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated" diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma.". Acta Neuropathol 129 (1): 133-46. doi:10.1007/s00401-014-1370-3. PMID 25427834.
  34. ↑ Hasselblatt, M.; Paulus, W. (Oct 2003). "Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas.". Acta Neuropathol 106 (4): 385-8. doi:10.1007/s00401-003-0752-8. PMID 12898159.
  35. ↑ Ishizawa, K.; Komori, T.; Shimada, S.; Hirose, T.. "Olig2 and CD99 are useful negative markers for the diagnosis of brain tumors.". Clin Neuropathol 27 (3): 118-28. PMID 18552083.
  36. ↑ Otero, JJ.; Rowitch, D.; Vandenberg, S. (Sep 2011). "OLIG2 is differentially expressed in pediatric astrocytic and in ependymal neoplasms.". J Neurooncol 104 (2): 423-38. doi:10.1007/s11060-010-0509-x. PMID 21193945.
  37. ↑ Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 12. ISBN 978-0443069826.
  38. ↑ 38.0 38.1 Parizel, PM.; Makkat, S.; Jorens, PG.; Ozsarlak, O.; Cras, P.; Van Goethem, JW.; van den Hauwe, L.; Verlooy, J. et al. (Jan 2002). "Brainstem hemorrhage in descending transtentorial herniation (Duret hemorrhage).". Intensive Care Med 28 (1): 85-8. doi:10.1007/s00134-001-1160-y. PMID 11819006.
  39. ↑ Fujimoto, Y.; Aguiar, PH.; Freitas, AB.; de Andrade, AF.; Marino Júnior, R. (Oct 2000). "Recovery from Duret hemorrhage: a rare complication after craniotomy--case report.". Neurol Med Chir (Tokyo) 40 (10): 508-10. PMID 11098635.
  40. ↑ URL: http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html. Accessed on: 4 December 2011.
  41. ↑ http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract
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