Difference between revisions of "Amyloid"

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Amyloid (view source)

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{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Image      = Cardiac amyloidosis very high mag he.jpg
| Width      =
| Caption    = Cardiac amyloidosis. [[H&E stain]].
| Micro      = typically extracellular, amorphous (no specific shape), acellular and pink (on [[H&E stain]]) -- cotton candy like, classically has a "cracked" appearance
| Subtypes  = multiple subclassifications: ''Robbins'' (AL amyloidosis, AA amyloidosis, non-AA and non-AL), ''set of six subtypes'' (primary (AL amyloidosis), secondary (AA amyloidosis, hemodialysis-related, localized), hereditary, senile systemic amyloidosis)
| LMDDx      = fibrin, collagen, smooth muscle
| Stains    = [[Congo red]] +ve
| IHC        =
| EM        = non-branching fine fibrils - usually 8-12 nm in diameter (accepted range 8-15 nm)
| Molecular  = beta sheet
| IF        =
| Gross      = waxy appearance
| Grossing  =
| Site      = pretty much anywhere, [[blood vessel]]s
| Assdx      = very many
| Syndromes  =
| Clinicalhx = variable
| Signs      =
| Symptoms  =
| Prevalence = uncommon
| Bloodwork  =
| Rads      =
| Endoscopy  =
| Prognosis  = dependent on subtype
| Other      =
| ClinDDx    =
}}
'''Amyloid''' is one of those things clinicians can put in many [[differential diagnoses]].  The [[pathologist]] can diagnose it.
'''Amyloid''' is one of those things clinicians can put in many [[differential diagnoses]].  The [[pathologist]] can diagnose it.
This article is a general overview of the topic. Links are provided to articles that deal with amyloidosis at specific sites, see ''[[Amyloid#Site specific|site specific]]'' section below.


=Overview=
=Overview=
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*May have a "cracked" appearance.{{fact}}
*May have a "cracked" appearance.{{fact}}


DDx - ''ABCs'' of pink:
Classic DDx - ''ABCs'' of pink:
*Amyloid.
*Amyloid.
*Blood (fibrin).
*Blood (fibrin).
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*Smooth muscle.
*Smooth muscle.


Stains:
Other considerations:
*[[Congo red stain]] - red (normal light), apple-green in polarized light.<ref name=pmid18076735>{{cite journal |author=Ebert EC, Nagar M |title=Gastrointestinal manifestations of amyloidosis |journal=Am. J. Gastroenterol. |volume=103 |issue=3 |pages=776-87 |year=2008 |month=March |pmid=18076735 |doi=10.1111/j.1572-0241.2007.01669.x |url=}}</ref>
*Foreign material, e.g. lifting agent "O'rise".<ref name=pmid31934919>{{cite journal |authors=Pezhouh MK, Burgart LJ, Chiu K, Cohen DA, Hutchings DA, Sanderson SO, Shirazi M, Stanich PP, VandenBussche CJ, Voltaggio L, Willhoit ED, Xue Y, Arnold CA |title=Characterization of Novel Injectable Lifting Agents Used in Colonic Polyp Removal: An Emerging Amyloid Mimic |journal=Am J Surg Pathol |volume=44 |issue=6 |pages=793–798 |date=June 2020 |pmid=31934919 |doi=10.1097/PAS.0000000000001435 |url=}}</ref>
*[[Thioflavin T stain]].<ref name=pmid18175051>{{cite journal |author=Nishi S, Alchi B, Imai N, Gejyo F |title=New advances in renal amyloidosis |journal=Clin. Exp. Nephrol. |volume=12 |issue=2 |pages=93-101 |year=2008 |month=April |pmid=18175051 |doi=10.1007/s10157-007-0008-3 |url=}}</ref>


Images:
====Images====
*[http://en.wikipedia.org/wiki/File:Small_bowel_duodenum_with_amyloid_deposition_congo_red_10X.jpg Amyloid - congo red stain] - wikipedia.org.
<gallery>
*[http://commons.wikimedia.org/wiki/File:Small_bowel_duodenum_with_amyloid_deposition_20X.jpg Amyloid - H&E stain] - wikimedia.org.
Image:Small_bowel_duodenum_with_amyloid_deposition_20X.jpg | Amyloid - H&E stain. (WC)
Image:Small bowel duodenum with amyloid deposition congo red 10X.jpg | Amyloid - congo red stain. (WC)
</gallery>


===Electron microscopy===
===Electron microscopy===
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*[[CADASIL]] (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy).
*[[CADASIL]] (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy).
**Typically has basophilic granularity in the blood vessels.<ref name=pmid17076524>{{cite journal |author=Kleinschmidt-DeMasters BK, Prayson RA |title=An algorithmic approach to the brain biopsy--part I |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1630–8 |year=2006 |month=November |pmid=17076524 |doi= |url=}}</ref>
**Typically has basophilic granularity in the blood vessels.<ref name=pmid17076524>{{cite journal |author=Kleinschmidt-DeMasters BK, Prayson RA |title=An algorithmic approach to the brain biopsy--part I |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1630–8 |year=2006 |month=November |pmid=17076524 |doi= |url=}}</ref>
==Stains==
*[[Congo red]] +ve.
**Positive:<ref name=pmid18076735>{{cite journal |author=Ebert EC, Nagar M |title=Gastrointestinal manifestations of amyloidosis |journal=Am. J. Gastroenterol. |volume=103 |issue=3 |pages=776-87 |year=2008 |month=March |pmid=18076735 |doi=10.1111/j.1572-0241.2007.01669.x |url=}}</ref>
***Orange/light red (non-polarized light).
***Apple green birefringence ([[polarized light]]).
**Negative:
***Blue birefringence (polarized light) = collagen fibers.<ref name=pmid21760829/>
*[[Thioflavin T stain]].<ref name=pmid18175051>{{cite journal |author=Nishi S, Alchi B, Imai N, Gejyo F |title=New advances in renal amyloidosis |journal=Clin. Exp. Nephrol. |volume=12 |issue=2 |pages=93-101 |year=2008 |month=April |pmid=18175051 |doi=10.1007/s10157-007-0008-3 |url=}}</ref>
*Sodium sulphate-Alcian Blue stain +ve.<ref name=pmid55419>{{Cite journal  | last1 = Pomerance | first1 = A. | last2 = Slavin | first2 = G. | last3 = McWatt | first3 = J. | title = Experience with the sodium sulphate-Alcian Blue stain for amyloid in cardiac pathology. | journal = J Clin Pathol | volume = 29 | issue = 1 | pages = 22-6 | month = Jan | year = 1976 | doi =  | PMID = 55419 }}</ref>


==Sign out==
==Sign out==
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**Considered to be the definitive test.<ref name=pmid11447744/><ref name=pmid17046651>{{cite journal |author=Murphy CL, Wang S, Williams T, Weiss DT, Solomon A |title=Characterization of systemic amyloid deposits by mass spectrometry |journal=Meth. Enzymol. |volume=412 |issue= |pages=48–62 |year=2006 |pmid=17046651 |doi=10.1016/S0076-6879(06)12004-2 |url=}}</ref>
**Considered to be the definitive test.<ref name=pmid11447744/><ref name=pmid17046651>{{cite journal |author=Murphy CL, Wang S, Williams T, Weiss DT, Solomon A |title=Characterization of systemic amyloid deposits by mass spectrometry |journal=Meth. Enzymol. |volume=412 |issue= |pages=48–62 |year=2006 |pmid=17046651 |doi=10.1016/S0076-6879(06)12004-2 |url=}}</ref>
***High specificity and sensitivity vis-à-vis clinicopathologic correlation.<ref name=pmid19797517>{{cite journal |author=Vrana JA, Gamez JD, Madden BJ, Theis JD, Bergen HR, Dogan A |title=Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens |journal=Blood |volume=114 |issue=24 |pages=4957–9 |year=2009 |month=December |pmid=19797517 |doi=10.1182/blood-2009-07-230722 |url=}}</ref>
***High specificity and sensitivity vis-à-vis clinicopathologic correlation.<ref name=pmid19797517>{{cite journal |author=Vrana JA, Gamez JD, Madden BJ, Theis JD, Bergen HR, Dogan A |title=Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens |journal=Blood |volume=114 |issue=24 |pages=4957–9 |year=2009 |month=December |pmid=19797517 |doi=10.1182/blood-2009-07-230722 |url=}}</ref>
**May be done on formalin-fixed paraffin embedded (FFPE) material.<ref name=pmid19797517/>
**May be done on [[formalin-fixed paraffin embedded]] (FFPE) material.<ref name=pmid19797517/>


=Types=
=Types=
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===General===
===General===
*Previously known as ''senile cardiac amyloidosis''.<ref name=pmid15645642>{{Cite journal  | last1 = Ikeda | first1 = S. | title = Cardiac amyloidosis: heterogenous pathogenic backgrounds. | journal = Intern Med | volume = 43 | issue = 12 | pages = 1107-14 | month = Dec | year = 2004 | doi =  | PMID = 15645642 }}</ref>
*Previously known as ''senile cardiac amyloidosis''.<ref name=pmid15645642>{{Cite journal  | last1 = Ikeda | first1 = S. | title = Cardiac amyloidosis: heterogenous pathogenic backgrounds. | journal = Intern Med | volume = 43 | issue = 12 | pages = 1107-14 | month = Dec | year = 2004 | doi =  | PMID = 15645642 }}</ref>
*May be referred to as ''ATTR'' = amyloidosis TTR; in SSA the TTR is not mutated.
*May be referred to as ''ATTR'' = amyloidosis TTR; in SSA the TTR is not mutated, some call it:  wt transthyretin amyloidosis (ATTR).
**There is a hereditary form of amyloidosis with mutated TTR deposition known as ''ATTR type FAP'' = ATTR type Familial Amyloid Polyneuropathy.
**There is a hereditary form of amyloidosis with mutated TTR deposition known as ''ATTR type FAP'' = ATTR type Familial Amyloid Polyneuropathy.
***Hereditary TTR: deposits in the heart, nerves and leptomeningeal amyloidosis.


Epidemiology:
Epidemiology:
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Treatment:
Treatment:
*No effective treatment.
*Liver transplantation, RNAi therapy (patisiran) and antisense oligonucleotides (inotersen).<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>


===Gross pathology===
===Gross pathology===
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*Amyloid often present in the subepicardial tissue<ref name=pmid18329550/> - less commonly affected by ischemia.
*Amyloid often present in the subepicardial tissue<ref name=pmid18329550/> - less commonly affected by ischemia.


Images:
====Images====
*[http://commons.wikimedia.org/wiki/File:Cardiac_amyloidosis_very_high_mag_he.jpg Senile systemic amyloidosis - H&E (wikimedia.org)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Cardiac_amyloidosis_intermed_mag.jpg Senile systemic amyloidosis - congo red (wikimedia.org)].
Image:Cardiac_amyloidosis_very_high_mag_he.jpg | Senile systemic amyloidosis - H&E. (WC)
*[http://commons.wikimedia.org/wiki/File:Cardiac_amyloidosis_very_high_mag_movat.jpg Senile systemic amyloidosis - Movat's (wikimedia.org)].
Image:Cardiac_amyloidosis_intermed_mag.jpg | Senile systemic amyloidosis - congo red. (WC)
Image:Cardiac_amyloidosis_very_high_mag_movat.jpg | Senile systemic amyloidosis - Movat's. (WC)
</gallery>


=Site specific=
=Site specific=
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Note:
Note:
*Evaluation of at least 15 small blood vessels is recommended.<ref name=pmid21760829/>
*Evaluation of at least 15 small blood vessels is recommended.<ref name=pmid21760829/>
===Stains===
*[[Congo red]] +ve.
**Positive:
***Orange/light red (non-polarizaed light).
***Apple green birefringence (polarized light).
**Negative:
***Blue birefringence (polarized light) = collagen fibers.<ref name=pmid21760829/>


===Sign out===
===Sign out===
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*[[Immunotactoid glomerulopathy]].
*[[Immunotactoid glomerulopathy]].


Images:
====Images====
*[[WC]]:
<gallery>
**[http://commons.wikimedia.org/wiki/File:Renal_amyloidosis_-_high_mag.jpg Renal amyloidosis - high mag. (WC)].
Image:Renal_amyloidosis_-_high_mag.jpg | Renal amyloidosis - high mag. (WC)
**[http://commons.wikimedia.org/wiki/File:Renal_amyloidosis_-_2_-_high_mag.jpg Renal amyloidosis - high mag. (WC)].
Image:Renal_amyloidosis_-_2_-_high_mag.jpg | Renal amyloidosis - high mag. (WC)
**[http://commons.wikimedia.org/wiki/File:Renal_amyloidosis_-_2_-_very_high_mag.jpg Renal amyloidosis - very high mag. (WC)].
Image:Renal_amyloidosis_-_2_-_very_high_mag.jpg | Renal amyloidosis - very high mag. (WC)
*www:
</gallery>
**[http://path.upmc.edu/cases/case125.html Renal amyloidosis - several images (upmc.edu)].
www:
*[http://path.upmc.edu/cases/case125.html Renal amyloidosis - several images (upmc.edu)].
 
==Urinary bladder amyloidosis==
{{Main|Urinary bladder amyloidosis}}


==GI amyloidosis==
==GI amyloidosis==
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*Parenchymal deposition (common).
*Parenchymal deposition (common).
*Portal triad deposition (less common).
*Portal triad deposition (less common).
===Gastric amyloidosis===
{{Main|Amyloidosis of the stomach}}


==Bone==
==Bone==
Michael
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