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Jensflorian (talk | contribs) (→Inflammation: +pic) |
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** Freeze most tissue in isopentane (-160°C) immersed in liquid nitrogen. | ** Freeze most tissue in isopentane (-160°C) immersed in liquid nitrogen. | ||
** Ultrastructural analyis might be required in some cases -> save something in 4% glutaraldehyde. | ** Ultrastructural analyis might be required in some cases -> save something in 4% glutaraldehyde. | ||
* FFPE | * [[FFPE]] specimens unsuitable for enzymatic stains. | ||
** Useful for morphology of inflammatory cells. | ** Useful for morphology of inflammatory cells. | ||
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** Formalin -> for IHC. | ** Formalin -> for IHC. | ||
** 4% Glutaraldehyde fixed -> for electron microscopy. | ** 4% Glutaraldehyde fixed -> for electron microscopy. | ||
====Skin biopsies==== | |||
* Punch biopsies (3mm) for small fiber neuropathy. | |||
** Paraformaldehyde-lysine-periodate -> for PGP9.5 immunofluorescence. | |||
=Muscle structure/histology= | =Muscle structure/histology= | ||
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Others: | Others: | ||
*Annular myofibrils ("ringbinden") = myopathic: Regeneration, myotonic dystrophy, tenotomy. Found in approx. 3% of unselected cases. | |||
Images: [http://frontalcortex.com/?page=image&topic=1&qid=987] - HE, NADH or MAD stains are useful. | |||
*Target fibre - "hole in middle of myofibres" = neurogenic. | *Target fibre - "hole in middle of myofibres" = neurogenic. | ||
**Images: [http://commons.wikimedia.org/w/index.php?title=File:Denervation_atrophy_-_very_high_mag.jpg Target fibres - very high mag. (WC)], [http://commons.wikimedia.org/wiki/File:Denervation_atrophy_-_sdh_-_very_high_mag.jpg Target fibres - SDH stain - very high mag. (WC)]. | **Images: [http://commons.wikimedia.org/w/index.php?title=File:Denervation_atrophy_-_very_high_mag.jpg Target fibres - very high mag. (WC)], [http://commons.wikimedia.org/wiki/File:Denervation_atrophy_-_sdh_-_very_high_mag.jpg Target fibres - SDH stain - very high mag. (WC)]. | ||
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===General=== | ===General=== | ||
Etiology:<ref>{{Cite journal | last1 = Prieto-González | first1 = S. | last2 = Grau | first2 = JM. | title = Diagnosis and classification of granulomatous myositis. | journal = Autoimmun Rev | volume = 13 | issue = 4-5 | pages = 372-4 | month = | year = | doi = 10.1016/j.autrev.2014.01.017 | PMID = 24424169 }}</ref> | Etiology:<ref>{{Cite journal | last1 = Prieto-González | first1 = S. | last2 = Grau | first2 = JM. | title = Diagnosis and classification of granulomatous myositis. | journal = Autoimmun Rev | volume = 13 | issue = 4-5 | pages = 372-4 | month = | year = | doi = 10.1016/j.autrev.2014.01.017 | PMID = 24424169 }}</ref> | ||
* [[Sarcoidosis]] | * [[Sarcoidosis]]. | ||
* Idiopathic | * Idiopathic. | ||
* Infectious ([[Tuberculosis]], Syphillis, Brucellosis | * Infectious ([[Tuberculosis]], Syphillis, Brucellosis. | ||
* Foreign-body reaction | * Foreign-body reaction. | ||
* [[Thymoma]] - myasthenia gravis | * [[Thymoma]] - myasthenia gravis. | ||
* [[Lymphoma]] - paraneoplastic | * [[Lymphoma]] - paraneoplastic. | ||
* [[Primary biliary | * [[Primary biliary cholangitis]]. | ||
<gallery> | <gallery> | ||
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File:Granulomatous myositis.jpg | Granulomatous myositis ([[H&E]]) | File:Granulomatous myositis.jpg | Granulomatous myositis ([[H&E]]) | ||
</gallery> | </gallery> | ||
==Spinal muscular atrophy== | |||
* Autosomal recessive disease by SMN1 gene deletion on chromosome 5q. | |||
* Centromeric gene copy (SMN2) whose product can mitigate disease severity. | |||
* Variability in severity and age of onset of disease (SMA type 1-4). | |||
* Neurogenic muscle atrophy, weakness, loss of reflexes, tongue fasciculation and tremor. | |||
** Usu. groups of atrophic fibers. | |||
** Few compensatorirc hypertrophic fibers. | |||
===Diagnostic relevance=== | |||
* Antisense-oligonucleotide that increase full-length protein product derived from SMN2 (Nusinersen). | |||
* Gene transfer with scAAV9-SMN (Zolgensma). | |||
==Metabolic myopathy== | ==Metabolic myopathy== | ||
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===General=== | ===General=== | ||
*Most common biopsy: sural nerve. | *Most common biopsy: sural nerve. | ||
**Approx. 20-30% of the biopsies are diagnostic or may alter treatment decisions. | |||
** Far less common: Superficial peroneal nerve. | |||
*Metabolic, toxic and nutritional causes account for 50% of neuropathies. | |||
*Inflammatory neuropathies (mostly GBS, CIDP or vasculitis): 10-20%. | |||
*Familial neuropathy: 10-20%. | |||
*Neoplasm-associated neuropathy: 5-10%. | |||
===Nerve structure=== | |||
*Nerve (surrounded by epineurium). | |||
*Fascicle (surrounded by perineurium). | |||
** Usu 6-15 fascicles in sural nerve. | |||
*Nerve fibre (surrounded by endoneurium). | |||
**Myelinated axons. | |||
**Unmyelinated axons and their Schwann cells together are called Remak bundles. | |||
Epineurium: | |||
* Capillaries, arterioles and venules. | |||
* Fibroblasts (CD34+/-ve, EMA-ve, S100-ve). | |||
* Macrophages (CD68+ve, CD168+ve). | |||
* Mast cells (metachromatic granules). | |||
* Leukocytes (usu. less than 10 CD3+ve Lymphocytes/mm²). | |||
* Pacinian corpuscles (no pathological relevance). | |||
Perineurium: | |||
* Fascicles may separated by perineurial septae. | |||
*Occasional perineurial calcifications (no pathological relevance). | |||
*Renaut bodies (subperineurial whorled structures consisting of fibroblasts). | |||
<gallery> | |||
Image:N_renaut_body_semithin.jpg|Renaut body in a fascicle. | |||
File:Pacinian Corpuscle (36298105211).jpg|Pacinian corpuscle. | |||
</gallery> | |||
===Stains=== | ===Stains=== | ||
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*Axon = green. | *Axon = green. | ||
*Myelin = red. | *Myelin = red. | ||
Toluidine blue staion: | |||
*Plastic embedded semithin sections (1µm). | |||
===Artifacts=== | |||
*Myelin splits: stretching. | |||
*Neurokeratin: Formalin fixation (longitudinal: "herringbone", cross section: "wagon-wheels"). | |||
*Dark staining myelin: crushing. | |||
*Pale expanding myelin sheets: delayed fixation. | |||
*Uneven myelin staining: osmication problems. | |||
*Shrunken crescentic fascicles: Hyperosmolarity. | |||
===Reactive changes=== | ===Reactive changes=== | ||
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===Degenerative changes=== | ===Degenerative changes=== | ||
Types:<ref>URL: [http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/nervepath.html http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/nervepath.html]. Accessed on: 9 November 2010.</ref> | Types:<ref>URL: [http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/nervepath.html http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/nervepath.html]. Accessed on: 9 November 2010.</ref> | ||
* | *Axonal degeneration. | ||
* | *Wallerian degeneration. | ||
*Segmental demyelination. | *Segmental demyelination. | ||
====Axonal degeneration==== | |||
*Axonal swelling. | |||
*Intra-axonal filamentous aggregates. | |||
*Mitochondrial abnormalities. | |||
*Aggregation of organelles and dense bodies. | |||
====Wallerian degeneration==== | ====Wallerian degeneration==== | ||
*Watery axon and granular disintegration (distal). | |||
*Macrophage accumulation (3-4d after transsection). | |||
*Many lysosomes (CD68+ve). | |||
*Endoneurial proliferation. | |||
*Digestion chambers - '''key feature'''. | *Digestion chambers - '''key feature'''. | ||
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</gallery> | </gallery> | ||
===Regeneration=== | |||
*Axon sprouts (regenerating clusters): Three or more closely apposed myelinated axons. | |||
*Thin myelin sheaths. | |||
===Inflammation=== | ===Inflammation=== | ||
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*[[Leprosy]] (Leprous neuropathy). | *[[Leprosy]] (Leprous neuropathy). | ||
*[[Sarcoidosis]]. | *[[Sarcoidosis]]. | ||
*CMV neuritis in immuncompromised patients. | |||
*[[Vasculitis]]. | |||
*Paraprotein-associated neuropathy. | |||
*Neuropathy with macrophage-induced demyelination (CIDP, GBS). | |||
====Guillain–Barré syndrome==== | |||
*Acute inflammatory demyelinating polyneuropathy (AIDP) | |||
*Preceding infection (RSV, EBV, CMV, HIV, Mycoplasma). | |||
*Monophasic course of motor / sensory deficits. | |||
*Hours to 4 weeks. | |||
*Elevated CSF protein but normal cell count. | |||
*Mononuclear ednoneurial perivascular inflammatory infiltrate (mostly CD4+ve). | |||
*Destructive myelin stripping by macrophages. | |||
*Reduced fiber density. | |||
*Uncompacted myelin / Widely spaced myelin. | |||
====Chronic inflammatory demyelinating polyneuropathy (CIDP)==== | |||
*Progredient course longer than 8 weeks.<ref>URL: [http://path.upmc.edu/cases/case426.html http://path.upmc.edu/cases/case426.html]. Accessed on: 14 | |||
November 2010.</ref> | |||
*Progressive or relapsing and remitting course. | |||
*Multifocal affections of proximal nerves (motor and sensory symptoms). | |||
*Responsive to steroids. | |||
*Enlargement of affected nerve. | |||
*Variation of fiber density between fascicles / reduced axon numbers. | |||
*CD4+ve/CD8+ve inflammatory infiltrates(approx. 65% cases). | |||
*Demyelination (thinly myelinated axons, macrophages). | |||
*Onion-bulb formations (15-40%, chronic recurrent demyelination and remyelination). | |||
DDx: Familial hypertrophic neuropathy. | |||
====Neurosarcoidosis==== | |||
*Neurological symptoms in 5% of sarcoidosis cases. | |||
*Granulomas may be endoneurial or epineurial. | |||
*Compact mass of epitheloid cells. | |||
*Perilesional fibrosis and lymphocytic infiltrates. | |||
*Axonal loss and regenerating fibers. | |||
*Segmental demyelination and remyelination. | |||
====Vasculitic neuropathy==== | |||
*Endoneurial and epineurial mircrovessels, arterioles and venules. | |||
*Ischemia of nerve: thrombosis and fibrinoid necrosis. | |||
*Signs of previous vasculitis: Vessel narrowing, fragmentation of elastica, fibrous obliteration and recanalization. | |||
*Often nerve involvement in systemic vasculitis: | |||
**Medium-sized epineurial vessels: mostly classic polyarteritis nodosa. | |||
**Small and medium-sized vessels and eosinophilia: Churg-Strauss angitis. | |||
**Small vessels and necrotizing: ANCA-associated microscopic polyangitis. | |||
<gallery> | <gallery> | ||
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===Other Diseases=== | ===Other Diseases=== | ||
* | *Amyloid neuropathy: Amorphic endoneurial deposits. | ||
* | **TTR amyloidosis is of specific interest, because treatment options exist.<ref>{{Cite journal | last1 = Adams | first1 = D. | last2 = Koike | first2 = H. | last3 = Slama | first3 = M. | last4 = Coelho | first4 = T. | title = Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. | journal = Nat Rev Neurol | volume = 15 | issue = 7 | pages = 387-404 | month = Jul | year = 2019 | doi = 10.1038/s41582-019-0210-4 | PMID = 31209302 }}</ref> | ||
** | **Example of amyloid deposits [https://www.nature.com/articles/s41582-019-0210-4/figures/3 here] | ||
*Neuropathy associated with paraproteinemia: Alterations in myelin periodicity, nerve fiber loss. | |||
**[[MGUS]] - Monoclonal gammopathy of unknown significance. | |||
** Multiple myeloma. | |||
**[[POEMS]] syndrome. | |||
**[[LCDD]] - light chain deposition diesease. | |||
*Toxic polyneuropathy (drug toxicity).<ref>URL: [http://path.upmc.edu/cases/case173.html http://path.upmc.edu/cases/case173.html]. Accessed on: 8 January 2012.</ref> | *Toxic polyneuropathy (drug toxicity).<ref>URL: [http://path.upmc.edu/cases/case173.html http://path.upmc.edu/cases/case173.html]. Accessed on: 8 January 2012.</ref> | ||
*Polyglucosan body disease. | |||
===Neoplasms=== | |||
=== | |||
''Main article: [[Peripheral nerve sheath tumours]]'' | ''Main article: [[Peripheral nerve sheath tumours]]'' | ||
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**[[Neurofibroma]] | **[[Neurofibroma]] | ||
**[[Perineurioma]] | **[[Perineurioma]] | ||
**[[Nerve sheath myxoma]] | |||
**[[Malignant peripheral nerve sheath tumour]] | **[[Malignant peripheral nerve sheath tumour]] | ||
*Non neurogenic-tumors of the nerve: | *Non neurogenic-tumors of the nerve: |
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