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'''Amyloid''' is one of those things clinicians can put in many differential diagnoses.  The pathologist can diagnose it.
{{ 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.


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=
==Definition==
==Definition==
*Disorder of protein folding - structure: beta sheet.<ref name=pmid17190124>{{cite journal |author=Lachmann HJ, Hawkins PN |title=Amyloidosis and the lung |journal=Chron Respir Dis |volume=3 |issue=4 |pages=203-14 |year=2006 |pmid=17190124 |doi= |url=http://crd.sagepub.com/cgi/pmidlookup?view=long&pmid=17190124}}</ref>
*Disorder of protein folding - structure: beta sheet.<ref name=pmid17190124>{{cite journal |author=Lachmann HJ, Hawkins PN |title=Amyloidosis and the lung |journal=Chron Respir Dis |volume=3 |issue=4 |pages=203-14 |year=2006 |pmid=17190124 |doi= |url=http://crd.sagepub.com/cgi/pmidlookup?view=long&pmid=17190124}}</ref>


==Appearance==
==Appearance==
Features:<ref>PBoD P.259.</ref>
===Light microscopy===
*Pink (on H&E stain).
Features:<ref>{{Ref_PBoD|259}}</ref>
*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>


Stains:
====Images====
*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>
<gallery>
*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>
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===
Features:<ref name=fondazionedamico>URL: [http://www.fondazionedamico.org/biopsiarenale_atlas/seco/amil/amil21.htmv http://www.fondazionedamico.org/biopsiarenale_atlas/seco/amil/amil21.htm]. Accessed on: 9 November 2010.</ref>
*Fine fibrils, non-branching.
**Usually 8-12 nm in diameter; accepted range 8-15 nm.<ref name=pmid18045849>{{Cite journal | last1 = Alpers | first1 = CE. | last2 = Kowalewska | first2 = J. | title = Fibrillary glomerulonephritis and immunotactoid glomerulopathy. | journal = J Am Soc Nephrol | volume = 19 | issue = 1 | pages = 34-7 | month = Jan | year = 2008 | doi = 10.1681/ASN.2007070757 | PMID = 18045849 | URL = http://jasn.asnjournals.org/content/19/1/34.long }}</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.
*[http://www.fondazionedamico.org/biopsiarenale_atlas/seco/amil/amil22.htm Amyloid (fondazionedamico.org)].<ref name=fondazionedamico/>
*[http://commons.wikimedia.org/wiki/File:Small_bowel_duodenum_with_amyloid_deposition_20X.jpg Amyloid - H&E stain] - wikimedia.org.  
*[http://www.fondazionedamico.org/biopsiarenale_atlas/seco/amil/amil21.htm Amyloid (fondazionedamico.org)].
 
===DDx===
*[[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>
 
==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=
*Infections.<ref name=merck>Amyloidosis. Merck Manual. URL: [http://www.merck.com/mmpe/sec12/ch160/ch160a.html http://www.merck.com/mmpe/sec12/ch160/ch160a.html]. Accessed on: 3 December 2009.</ref><ref>PBoD P.261.</ref>
*Infections:<ref name=merck>Amyloidosis. Merck Manual. URL: [http://www.merck.com/mmpe/sec12/ch160/ch160a.html http://www.merck.com/mmpe/sec12/ch160/ch160a.html]. Accessed on: 3 December 2009.</ref><ref>{{Ref_PBoD|261}}</ref>
**Tuberculosis.
**[[Tuberculosis]].
**Leprosy.
**[[Leprosy]].
**Chronic osteomyelitis.
**Chronic [[osteomyelitis]].
**Bronchiectasis.
**[[Bronchiectasis]].
*Idiopathic conditions:
*Idiopathic conditions:
**Rheumatoid arthritis - relatively common (compared to others below).
**[[Rheumatoid arthritis]] - relatively common (compared to others below).
**Anklyosing spondylitis - renal amyloidosis.
**Anklyosing spondylitis - renal amyloidosis.
**Crohn's disease.<ref name=merck/>
**[[Crohn's disease]].<ref name=merck/>
**Familial Mediterranean fever.<ref name=merck/>
**Familial Mediterranean fever.<ref name=merck/>
*Malignancy.
*Malignancy.
**Plasmacytoma.
**[[Plasmacytoma]].
***5-15% of patients with multiple myeloma develop amyloidosis<ref>PBoD P.261.</ref> - some say 10-20%.<ref name=merck>Amyloidosis. Merck Manual. URL: [http://www.merck.com/mmpe/sec12/ch160/ch160a.html http://www.merck.com/mmpe/sec12/ch160/ch160a.html]. Accessed on: 3 December 2009.</ref>
***5-15% of patients with [[multiple myeloma]] develop amyloidosis<ref>{{Ref_PBoD|261}}</ref> - some say 10-20%.<ref name=merck>Amyloidosis. Merck Manual. URL: [http://www.merck.com/mmpe/sec12/ch160/ch160a.html http://www.merck.com/mmpe/sec12/ch160/ch160a.html]. Accessed on: 3 December 2009.</ref>
**Medullary thyroid carcinoma.
**[[Medullary thyroid carcinoma]].
**Renal cell carcinoma.
**[[Renal cell carcinoma]].
*Many other conditions...
*Many other conditions...


==Classification==
=Classification=
Amyloidosis can be classified a number of different ways.
Amyloidosis can be classified a number of different ways.


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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, neoplasia.
#*Infections (osteomyelitis), neoplasia ([[Hodgkin's lymphoma]]).
#Hemodialysis-related.
#Hemodialysis-related.
#*Beta-2 microglobulin.<ref>PBoD P.260.</ref>
#*Beta-2 microglobulin.<ref>{{Ref_PBoD|260}}</ref>
#Localized.
#*''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>
#**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>
#Hereditary.
#Hereditary.
#Senile.
#Senile systemic amyloidosis.
#Localized.


How to remember: Two ''A''s = secondary amyloidosis.
How to remember: Two ''A''s = secondary amyloidosis.
Line 57: Line 140:
#AL amyloidosis - "AL" = ''Amyloid Light chain''.<ref name=pmid9573002>{{Cite journal  | last1 = Comenzo | first1 = RL. | last2 = Vosburgh | first2 = E. | last3 = Falk | first3 = RH. | last4 = Sanchorawala | first4 = V. | last5 = Reisinger | first5 = J. | last6 = Dubrey | first6 = S. | last7 = Dember | first7 = LM. | last8 = Berk | first8 = JL. | last9 = Akpek | first9 = G. | title = Dose-intensive melphalan with blood stem-cell support for the treatment of AL (amyloid light-chain) amyloidosis: survival and responses in 25 patients. | journal = Blood | volume = 91 | issue = 10 | pages = 3662-70 | month = May | year = 1998 | doi =  | PMID = 9573002 }}</ref>
#AL amyloidosis - "AL" = ''Amyloid Light chain''.<ref name=pmid9573002>{{Cite journal  | last1 = Comenzo | first1 = RL. | last2 = Vosburgh | first2 = E. | last3 = Falk | first3 = RH. | last4 = Sanchorawala | first4 = V. | last5 = Reisinger | first5 = J. | last6 = Dubrey | first6 = S. | last7 = Dember | first7 = LM. | last8 = Berk | first8 = JL. | last9 = Akpek | first9 = G. | title = Dose-intensive melphalan with blood stem-cell support for the treatment of AL (amyloid light-chain) amyloidosis: survival and responses in 25 patients. | journal = Blood | volume = 91 | issue = 10 | pages = 3662-70 | month = May | year = 1998 | doi =  | PMID = 9573002 }}</ref>
#*Primary amyloidosis.<ref name=merck>Amyloidosis. Merck Manual. URL: [http://www.merck.com/mmpe/sec12/ch160/ch160a.html http://www.merck.com/mmpe/sec12/ch160/ch160a.html]. Accessed on: 3 December 2009.</ref>
#*Primary amyloidosis.<ref name=merck>Amyloidosis. Merck Manual. URL: [http://www.merck.com/mmpe/sec12/ch160/ch160a.html http://www.merck.com/mmpe/sec12/ch160/ch160a.html]. Accessed on: 3 December 2009.</ref>
#*Bence Jones protein (light chains -- kappa or lambda) +ve -- necessary for amyloidosis but not sufficient.<ref>PBoD P.261.</ref>
#*Bence Jones protein (light chains -- kappa or lambda) +ve -- necessary for amyloidosis but not sufficient.<ref>{{Ref_PBoD|261}}</ref>
#AA amyloidosis - "AA" = ''Amyloid Associated''.<ref>PBoD P.259.</ref>
#AA amyloidosis - "AA" = ''Amyloid Associated''.<ref>{{Ref_PBoD|259}}</ref>
#*Secondary amyloidosis.
#*Secondary amyloidosis.
#Abeta amyloid - found in Alzheimer's disease.<ref>PBoD P.259.</ref>
#Abeta amyloid - found in Alzheimer's disease.<ref>{{Ref_PBoD|259}}</ref>


Additional types:
Additional types:
Line 72: Line 155:


==Classification of amyloid - differentiation==
==Classification of amyloid - differentiation==
If resistant to congo red with pre-treatment of potassium permanganate likely non-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>
===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>
 
===Immunohistochemistry===
*[[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 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:
*Kappa.
*Lambda.
*Transthyretin.
**The name ''transthyretin'' is from '''''trans'''ports '''thy'''roxine and '''retin'''ol'' (previous unknown as ''prealbumin'').


===References===
===Mass spectroscopy===
# van Rijswijk MH and van Heusden CWGJ. The potassium permanganate method. A reliable method for differentiating amyloid AA from other forms of amyloid in routine laboratory practice. Am J Pathol 1979; 97: 43-58. PMID 495695.
*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>
# Murphy CL, Eulitz M, Hrncic R, Sletten K, Westermark P, Williams T, Macy SD, Wooliver C, Wall J, Weiss DT and Solomon A. Chemical typing of amyloid protein contained in formalin-fixed paraffin-embedded biopsy specimens. Am J Clin Pathol 2001; 116: 135-142.  
**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>
# Murphy CL, Wang S, Williams T, Weiss DT and Solomon A. Characterization of systemic amyloid deposits by mass spectroscopy. Methods Enzymol 2006; 412: 48-62.  
***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>
# Vrana JA, Gamez JD, Madden BJ, Theis JD, Robert Bergen III H, and Dogan A. Classification of amyloidosis by laser microdissection and mass spectometry-based proteomic analysis in clinical biopsy specimens. Blood 2009; 114: 4957-4959.
**May be done on [[formalin-fixed paraffin embedded]] (FFPE) material.<ref name=pmid19797517/>


=Types=
==Secondary amyloidosis==
==Secondary amyloidosis==
*AKA ''AA amyloidosis''.
*AKA ''AA amyloidosis''.
*Pathophysiology: acute-phase reactant '''serum amyloid A''' (SAA) - degraded + deposits.<ref name=merck/><ref>PBoD P.260.</ref>
*Pathophysiology: acute-phase reactant '''serum amyloid A''' (SAA) - degraded + deposits.<ref name=merck/><ref>{{Ref_PBoD|260}}</ref>
 
==Cardiac amyloidosis==
===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>
 
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>
#Senile systemic amyloidosis - TTR-related amyloidosis (unmutated TTR).
#Hereditary amyloidosis.
#AA amyloidosis is uncommon.


Clinical:
==Cerebral amyloid angiopathy==
*CHF, conduction abnormalities.
{{Main|Cerebral amyloid angiopathy}}
*Kidney disease (proteinuria) - associated with AL amyloidosis.
A common cause of [[lobar hemorrhage]] (cerebral cortex, cerebellar cortex) in the elderly.


===Senile systemic amyloidosis===
==Senile systemic amyloidosis==
*Abbreviated ''SSA''.
*Abbreviated ''SSA''.
===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 Polyneuropahty.
**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:
Line 108: Line 196:
*Found in approx. 25% of elderly over 80 years old,<ref name=pmid15645642/> and in upto 65% of patients over 90 years old.<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>
*Found in approx. 25% of elderly over 80 years old,<ref name=pmid15645642/> and in upto 65% of patients over 90 years old.<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>


Gross pathology:
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===
*Grey/black "peppering" of left atrial endocardium - in fixed specimens.<ref name=pmid5829755>{{Cite journal  | last1 = Pomerance | first1 = A. | title = Senile cardiac amyloidosis. | journal = Br Heart J | volume = 27 | issue = 5 | pages = 711-8 | month = Sep | year = 1965 | doi =  | PMID = 5829755 | url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC469777/pdf/brheartj00340-0085.pdf }}</ref>  
*Grey/black "peppering" of left atrial endocardium - in fixed specimens.<ref name=pmid5829755>{{Cite journal  | last1 = Pomerance | first1 = A. | title = Senile cardiac amyloidosis. | journal = Br Heart J | volume = 27 | issue = 5 | pages = 711-8 | month = Sep | year = 1965 | doi =  | PMID = 5829755 | url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC469777/pdf/brheartj00340-0085.pdf }}</ref>  
**"Peppering" should be present if severe.
**"Peppering" should be present if severe.


Histology:
===Microscopic===
Features:
*Heart most commonly involved, followed by lungs and then by kidney (renal papilla).
*Heart most commonly involved, followed by lungs and then by kidney (renal papilla).
*DDx of pink of H&E is important to remember: amyloid, muscle, collagen, clotted blood.
*DDx of pink of H&E is important to remember: amyloid, muscle, collagen, clotted blood.
Line 118: Line 210:
*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.


Treatment:
====Images====
*No effective treatment.
<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=
==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==
===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>
 
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>
#[[Senile systemic amyloidosis]] - TTR-related amyloidosis (unmutated TTR).
#Hereditary amyloidosis.
#[[AA amyloidosis]] is uncommon.
 
Clinical:
*[[CHF]], conduction abnormalities.
*Kidney disease (proteinuria) - associated with AL amyloidosis.


Images:
==Pulmonary amyloidosis==
*[http://commons.wikimedia.org/wiki/File:Cardiac_amyloidosis_very_high_mag_he.jpg Senile systemic amyloidosis - H&E (wikimedia.org)].
{{Main|Pulmonary amyloidosis}}
*[http://commons.wikimedia.org/wiki/File:Cardiac_amyloidosis_intermed_mag.jpg Senile systemic amyloidosis - congo red (wikimedia.org)].
*Very rare.
*[http://commons.wikimedia.org/wiki/File:Cardiac_amyloidosis_very_high_mag_movat.jpg Senile systemic amyloidosis - Movat's (wikimedia.org)].


==Renal amyloidosis==
==Renal amyloidosis==
Both AL and AA amyloidosis can affect the kidney.<ref name=pmid18175051/>
{{Main|Medical kidney diseases}}
===General===
*Both AL and AA amyloidosis can affect the kidney.<ref name=pmid18175051/>
 
Clinical:
*Usually [[nephrotic syndrome|Nephrotic]] range proteinuria.<ref name=pmid17550319>{{Cite journal  | last1 = Satoskar | first1 = AA. | last2 = Burdge | first2 = K. | last3 = Cowden | first3 = DJ. | last4 = Nadasdy | first4 = GM. | last5 = Hebert | first5 = LA. | last6 = Nadasdy | first6 = T. | title = Typing of amyloidosis in renal biopsies: diagnostic pitfalls. | journal = Arch Pathol Lab Med | volume = 131 | issue = 6 | pages = 917-22 | month = Jun | year = 2007 | doi = 10.1043/1543-2165(2007)131[917:TOAIRB]2.0.CO;2 | PMID = 17550319 | url=http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2007)131%5B917:TOAIRB%5D2.0.CO;2 }}</ref>
 
===Microscopic===
Features:
*Paucicellular mesangial expansion.
*Fluffy hyaline material in medium-sized blood vessels.
<!-- ??? Location: between ''internal elastic lamina'' and ''tunica media'' smooth muscle. -->
 
DDx:
*[[Diabetic nephropathy]].
*[[Idiopathic nodular glomerulosclerosis]].
*[[Light chain deposition disease]].
*[[Fibrillary glomerulopathy]].
*[[Immunotactoid glomerulopathy]].
 
====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==
GI amyloidosis can lead to obstruction and usually is greatest in the [[small bowel]].<ref name=pmid18076735/>
*GI amyloidosis can lead to obstruction and usually is greatest in the [[small bowel]].<ref name=pmid18076735/>


===Liver amyloidosis===
===Liver amyloidosis===
{{Main|Liver amyloidosis}}
Features:
Features:
*Parenchymal deposition (common).
*Parenchymal deposition (common).
*Portal triad deposition (less common).
*Portal triad deposition (less common).


===Gastric amyloidosis===
{{Main|Amyloidosis of the stomach}}
==Bone==
Amyloid is reported in association with:
*[[Multiple myeloma]] ~40% of patients in one series.<ref name=pmid19894050>{{Cite journal  | last1 = Petruzziello | first1 = F. | last2 = Zeppa | first2 = P. | last3 = Catalano | first3 = L. | last4 = Cozzolino | first4 = I. | last5 = Gargiulo | first5 = G. | last6 = Musto | first6 = P. | last7 = D'Auria | first7 = F. | last8 = Liso | first8 = V. | last9 = Rizzi | first9 = R. | title = Amyloid in bone marrow smears of patients affected by multiple myeloma. | journal = Ann Hematol | volume = 89 | issue = 5 | pages = 469-74 | month = May | year = 2010 | doi = 10.1007/s00277-009-0857-9 | PMID = 19894050 }}</ref>
*[[Chronic osteomyelitis]] ~10% of patients in one series.<ref name=pmid2071276>{{Cite journal  | last1 = Alabi | first1 = ZO. | last2 = Ojo | first2 = OS. | last3 = Odesanmi | first3 = WO. | title = Secondary amyloidosis in chronic osteomyelitis. | journal = Int Orthop | volume = 15 | issue = 1 | pages = 21-2 | month =  | year = 1991 | doi =  | PMID = 2071276 }}</ref>
*Diabetes (one case).<ref name=pmid10499196>{{Cite journal  | last1 = Miossec | first1 = P. | last2 = Lormeau | first2 = B. | last3 = Valensi | first3 = P. | last4 = Arthuis | first4 = F. | last5 = Amouroux | first5 = J. | last6 = Attali | first6 = JR. | title = Bone amyloidoma in a diabetic patient with morbid obesity. | journal = Diabetes Metab | volume = 25 | issue = 3 | pages = 261-3 | month = Sep | year = 1999 | doi =  | PMID = 10499196 }}
</ref>


==See also==
=See also=
*[[Basics]]
*[[Basics]].
*[[Neuropathology]]
*[[Neuropathology]].
*[[Fibrillary glomerulonephritis]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}




==External links==
=External links=
*[http://en.wikipedia.org/wiki/Amyloidosis Amyloidosis] - wikipedia.org.
*[http://en.wikipedia.org/wiki/Amyloidosis Amyloidosis] - wikipedia.org.


[[Category:Weird stuff]]
[[Category:Weird stuff]]
Michael
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