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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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===Light microscopy=== | ===Light microscopy=== | ||
Features:<ref>{{Ref_PBoD|259}}</ref> | Features:<ref>{{Ref_PBoD|259}}</ref> | ||
*Pink (on H&E stain). | *Pink (on [[H&E stain]]). | ||
*Extracellular location. | *Extracellular location. | ||
*Amorphous - no specific shape. | *Amorphous - no specific shape. | ||
*May have a "cracked" appearance.{{fact}} | |||
Classic DDx - ''ABCs'' of pink: | |||
*Amyloid. | |||
*Blood (fibrin). | |||
*Collagen. | |||
*Smooth muscle. | |||
Other considerations: | |||
* | *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> | ||
Images | ====Images==== | ||
<gallery> | |||
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== | |||
<pre> | |||
BONE LESION, RIGHT ILIAC, BIOPSY: | |||
- AMYLOID ASSOCIATED WITH HISTOCYTES, GIANT CELLS AND A FEW LYMPHOCYTES | |||
AND PLASMA CELLS. | |||
COMMENT: | |||
The presence of amyloid is confirmed with congo red staining and polarization. | |||
There are no histomorphologic findings suggestive of a plasma cell neoplasm | |||
in this biopsy. | |||
Clinical correlation with serum protein electrophoresis, urine protein electrophoresis | |||
and bone marrow sampling is suggested. | |||
</pre> | |||
=Associations - DDx= | =Associations - DDx= | ||
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#*Monoclonal light chains in serum and/or urine, may be due to plasma cell dyscrasia. | #*Monoclonal light chains in serum and/or urine, may be due to plasma cell dyscrasia. | ||
#Secondary (AA amyloidosis). | #Secondary (AA amyloidosis). | ||
#*Infections (osteomyelitis), neoplasia (Hodgkin's lymphoma). | #*Infections (osteomyelitis), neoplasia ([[Hodgkin's lymphoma]]). | ||
#Hemodialysis-related. | #Hemodialysis-related. | ||
#*Beta-2 microglobulin.<ref>{{Ref_PBoD|260}}</ref> | #*Beta-2 microglobulin.<ref>{{Ref_PBoD|260}}</ref> | ||
#Localized. | #Localized. | ||
#*''Abeta amyloid'' found in Alzheimer's disease. | #*''Abeta amyloid'' found in [[Alzheimer's disease]]. | ||
#*[[Pancreas|Pancreatic]] amyloid deposition associated with [[diabetes mellitus]] type 2.<ref>URL: [http://www.umm.edu/altmed/articles/amyloidosis-000007.htm http://www.umm.edu/altmed/articles/amyloidosis-000007.htm]. Accessed on: 23 October 2010.</ref> | #*[[Pancreas|Pancreatic]] amyloid deposition associated with [[diabetes mellitus]] type 2.<ref>URL: [http://www.umm.edu/altmed/articles/amyloidosis-000007.htm http://www.umm.edu/altmed/articles/amyloidosis-000007.htm]. Accessed on: 23 October 2010.</ref> | ||
#**Image: [http://library.med.utah.edu/WebPath/jpeg4/ENDO033.jpg Amyloid in DM (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html]. Accessed on: 6 December 2010.</ref> | #**Image: [http://library.med.utah.edu/WebPath/jpeg4/ENDO033.jpg Amyloid in DM (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html]. Accessed on: 6 December 2010.</ref> | ||
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===Biochemical techniques=== | ===Biochemical techniques=== | ||
*Pre-treated with potassium permanganate, to obliterate congo red reactivity, '''''was''''' though be definitive for AA amyloidosis;<ref name=pmid495695>{{cite journal |author=van Rijswijk MH, van Heusden CW |title=The potassium permanganate method. A reliable method for differentiating amyloid AA from other forms of amyloid in routine laboratory practice |journal=Am. J. Pathol. |volume=97 |issue=1 |pages=43–58 |year=1979 |month=October |pmid=495695 |pmc=2042379 |doi= |url=}}</ref> this is now generally considered to be unreliable.<ref name=pmid20367306>{{Cite journal | last1 = Picken | first1 = MM. | title = Amyloidosis-where are we now and where are we heading? | journal = Arch Pathol Lab Med | volume = 134 | issue = 4 | pages = 545-51 | month = Apr | year = 2010 | doi = 10.1043/1543-2165-134.4.545 | PMID = 20367306 }}</ref> | *Pre-treated with potassium permanganate, to obliterate congo red reactivity, '''''was''''' though be definitive for AA amyloidosis;<ref name=pmid495695>{{cite journal |author=van Rijswijk MH, van Heusden CW |title=The potassium permanganate method. A reliable method for differentiating amyloid AA from other forms of amyloid in routine laboratory practice |journal=Am. J. Pathol. |volume=97 |issue=1 |pages=43–58 |year=1979 |month=October |pmid=495695 |pmc=2042379 |doi= |url=}}</ref> this is now generally considered to be unreliable.<ref name=pmid20367306>{{Cite journal | last1 = Picken | first1 = MM. | title = Amyloidosis-where are we now and where are we heading? | journal = Arch Pathol Lab Med | volume = 134 | issue = 4 | pages = 545-51 | month = Apr | year = 2010 | doi = 10.1043/1543-2165-134.4.545 | PMID = 20367306 }}</ref> | ||
===Immunohistochemistry=== | ===Immunohistochemistry=== | ||
*[[IHC]] may be useful for subclassification of | *[[IHC]] may be useful for the subclassification of amyloidoses.<ref name=pmid19756621>{{cite journal |author=Röcken C |title=[Update on immunohistological classification of amyloidoses] |language=German |journal=Pathologe |volume=30 Suppl 2 |issue= |pages=121–3 |year=2009 |month=December |pmid=19756621 |doi=10.1007/s00292-009-1183-7 |url=}}</ref> | ||
**The | **The reliability of IHC for the subclassification of amyloidoses is thought to be low.<ref name=pmid18181665>{{Cite journal | last1 = Solomon | first1 = A. | last2 = Murphy | first2 = CL. | last3 = Westermark | first3 = P. | title = Unreliability of immunohistochemistry for typing amyloid deposits. | journal = Arch Pathol Lab Med | volume = 132 | issue = 1 | pages = 14; author reply 14-5 | month = Jan | year = 2008 | doi = 10.1043/1543-2165(2008)132[14b:IR]2.0.CO;2 | PMID = 18181665 | url = http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165%282008%29132%5B14b%3AIR%5D2.0.CO%3B2 }}</ref><ref name=pmid11447744>{{cite journal |author=Murphy CL, Eulitz M, Hrncic R, ''et al.'' |title=Chemical typing of amyloid protein contained in formalin-fixed paraffin-embedded biopsy specimens |journal=Am. J. Clin. Pathol. |volume=116 |issue=1 |pages=135–42 |year=2001 |month=July |pmid=11447744 |doi=10.1309/TWBM-8L4E-VK22-FRH5 |url=}}</ref> | ||
***Extreme caution is advised when interpreting IHC results. | |||
Possibly useful immunostains: | |||
*Transthyretin | *Kappa. | ||
*Lambda. | |||
*Transthyretin. | |||
**The name ''transthyretin'' is from '''''trans'''ports '''thy'''roxine and '''retin'''ol'' (previous unknown as ''prealbumin''). | **The name ''transthyretin'' is from '''''trans'''ports '''thy'''roxine and '''retin'''ol'' (previous unknown as ''prealbumin''). | ||
===Mass spectroscopy=== | ===Mass spectroscopy=== | ||
*Can be typed using mass spectroscopy.<ref name=pmid20511161>{{Cite journal | last1 = Chee | first1 = CE. | last2 = Lacy | first2 = MQ. | last3 = Dogan | first3 = A. | last4 = Zeldenrust | first4 = SR. | last5 = Gertz | first5 = MA. | title = Pitfalls in the diagnosis of primary amyloidosis. | journal = Clin Lymphoma Myeloma Leuk | volume = 10 | issue = 3 | pages = 177-80 | month = Jun | year = 2010 | doi = 10.3816/CLML.2010.n.027 | PMID = 20511161 }}</ref> | *Can be typed using mass spectroscopy.<ref name=pmid20511161>{{Cite journal | last1 = Chee | first1 = CE. | last2 = Lacy | first2 = MQ. | last3 = Dogan | first3 = A. | last4 = Zeldenrust | first4 = SR. | last5 = Gertz | first5 = MA. | title = Pitfalls in the diagnosis of primary amyloidosis. | journal = Clin Lymphoma Myeloma Leuk | volume = 10 | issue = 3 | pages = 177-80 | month = Jun | year = 2010 | doi = 10.3816/CLML.2010.n.027 | PMID = 20511161 }}</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> | |||
**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: | ||
* | *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==== | ||
<gallery> | |||
Image:Cardiac_amyloidosis_very_high_mag_he.jpg | Senile systemic amyloidosis - H&E. (WC) | |||
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= | ||
==Abdomen== | |||
:''Abdominal fat pad biopsy'' redirects here. | |||
===General=== | |||
*Abdominal fat pad biopsy - common screen for amyloidosis. | |||
**May be done with FNA. | |||
***Suffers for poor sensitivity.<ref name=pmid21760829>{{Cite journal | last1 = Devata | first1 = S. | last2 = Hari | first2 = P. | last3 = Markelova | first3 = N. | last4 = Li | first4 = R. | last5 = Komorowski | first5 = R. | last6 = Shidham | first6 = VB. | title = Detection of amyloid in abdominal fat pad aspirates in early amyloidosis: Role of electron microscopy and Congo red stained cell block sections. | journal = Cytojournal | volume = 8 | issue = | pages = 11 | month = | year = 2011 | doi = 10.4103/1742-6413.82278 | PMID = 21760829 }}</ref> | |||
===Microscopic=== | |||
Features: | |||
*Small-to-intermediate sized arteries with a thickened amorphous eosinophilic media. | |||
**Thickening classically nodular. | |||
**Apple green-birefringence -- with polarization. | |||
Note: | |||
*Evaluation of at least 15 small blood vessels is recommended.<ref name=pmid21760829/> | |||
===Sign out=== | |||
<pre> | |||
SOFT TISSUE, ABDOMEN, BIOPSY: | |||
- AMYLOIDOSIS. | |||
</pre> | |||
====Negative==== | |||
<pre> | |||
SOFT TISSUE, ABDOMEN, BIOPSY: | |||
- BENIGN FIBROADIPOSE TISSUE. | |||
- NEGATIVE FOR AMYLOIDOSIS WITH CONGO RED STAINING AND POLARIZED LIGHT. | |||
COMMENT: | |||
Correlation with serum protein electrophoresis, urine protein electrophoresis | |||
and bone marrow sampling should be considered within the clinical context. | |||
</pre> | |||
==Cardiac amyloidosis== | ==Cardiac amyloidosis== | ||
===General=== | ===General=== | ||
*Common cause of restrictive cardiomyopathy.<ref>Cardiac amyloidosis. Medlineplus.org. URL: [http://www.nlm.nih.gov/medlineplus/ency/article/000193.htm http://www.nlm.nih.gov/medlineplus/ency/article/000193.htm]. Accessed on: 3 December 2009.</ref> | *Common cause of [[restrictive cardiomyopathy]].<ref>Cardiac amyloidosis. Medlineplus.org. URL: [http://www.nlm.nih.gov/medlineplus/ency/article/000193.htm http://www.nlm.nih.gov/medlineplus/ency/article/000193.htm]. Accessed on: 3 December 2009.</ref> | ||
Cardiac amyloidosis - subtypes: | Cardiac amyloidosis - subtypes: | ||
#AL amyloidosis - associated with plasma cell dyscrasia - most common cardiac amyloidosis.<ref name=pmid18329550>{{Cite journal | last1 = Sharma | first1 = PP. | last2 = Payvar | first2 = S. | last3 = Litovsky | first3 = SH. | title = Histomorphometric analysis of intramyocardial vessels in primary and senile amyloidosis: epicardium versus endocardium. | journal = Cardiovasc Pathol | volume = 17 | issue = 2 | pages = 65-71 | month = | year = | doi = 10.1016/j.carpath.2007.05.008 | PMID = 18329550 }}</ref> | #AL amyloidosis - associated with plasma cell dyscrasia - most common cardiac amyloidosis.<ref name=pmid18329550>{{Cite journal | last1 = Sharma | first1 = PP. | last2 = Payvar | first2 = S. | last3 = Litovsky | first3 = SH. | title = Histomorphometric analysis of intramyocardial vessels in primary and senile amyloidosis: epicardium versus endocardium. | journal = Cardiovasc Pathol | volume = 17 | issue = 2 | pages = 65-71 | month = | year = | doi = 10.1016/j.carpath.2007.05.008 | PMID = 18329550 }}</ref> | ||
#Senile systemic amyloidosis - TTR-related amyloidosis (unmutated TTR). | #[[Senile systemic amyloidosis]] - TTR-related amyloidosis (unmutated TTR). | ||
#Hereditary amyloidosis. | #Hereditary amyloidosis. | ||
#AA amyloidosis is uncommon. | #[[AA amyloidosis]] is uncommon. | ||
Clinical: | Clinical: | ||
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*[[Immunotactoid glomerulopathy]]. | *[[Immunotactoid glomerulopathy]]. | ||
Images | ====Images==== | ||
<gallery> | |||
Image:Renal_amyloidosis_-_high_mag.jpg | Renal amyloidosis - high mag. (WC) | |||
Image:Renal_amyloidosis_-_2_-_high_mag.jpg | Renal amyloidosis - high mag. (WC) | |||
Image:Renal_amyloidosis_-_2_-_very_high_mag.jpg | Renal amyloidosis - very high mag. (WC) | |||
</gallery> | |||
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== | ||