Difference between revisions of "Amyloid"

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'''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.


=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>
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**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>


==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>{{Ref_PBoD|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.
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*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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**Transthyretin - from '''''trans'''ports '''thy'''roxine and '''retin'''ol'' (previous ''prealbumin'').
**Transthyretin - from '''''trans'''ports '''thy'''roxine and '''retin'''ol'' (previous ''prealbumin'').


=Types=
==Secondary amyloidosis==
==Secondary amyloidosis==
*AKA ''AA amyloidosis''.
*AKA ''AA amyloidosis''.
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{{Main|Cerebral amyloid angiopathy}}
{{Main|Cerebral amyloid angiopathy}}
A common cause of [[lobar hemorrhage]] (cerebral cortex, cerebellar cortex) in the elderly.
A common cause of [[lobar hemorrhage]] (cerebral cortex, cerebellar cortex) in the elderly.
==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.


==Senile systemic amyloidosis==
==Senile systemic amyloidosis==
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*[http://commons.wikimedia.org/wiki/File:Cardiac_amyloidosis_intermed_mag.jpg Senile systemic amyloidosis - congo red (wikimedia.org)].
*[http://commons.wikimedia.org/wiki/File:Cardiac_amyloidosis_intermed_mag.jpg Senile systemic amyloidosis - congo red (wikimedia.org)].
*[http://commons.wikimedia.org/wiki/File:Cardiac_amyloidosis_very_high_mag_movat.jpg Senile systemic amyloidosis - Movat's (wikimedia.org)].
*[http://commons.wikimedia.org/wiki/File:Cardiac_amyloidosis_very_high_mag_movat.jpg Senile systemic amyloidosis - Movat's (wikimedia.org)].
=Site specific=
==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.


==Renal amyloidosis==
==Renal amyloidosis==
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</ref>
</ref>


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


==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]]

Revision as of 02:18, 11 December 2011

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

Overview

Definition

  • Disorder of protein folding - structure: beta sheet.[1]

Appearance

Light microscopy

Features:[2]

  • Pink (on H&E stain).
  • Extracellular location.
  • Amorphous - no specific shape.

Stains:

Images:

Electron microscopy

Features:[5]

  • Fine fibrils.
    • ~6-9 nanometers in diameter.

Images:

DDx

  • CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy).
    • Typically has basophilic granularity in the blood vessels.[6]

Associations - DDx

Classification

Amyloidosis can be classified a number of different ways.

Six subtypes classification

Amyloid classified into six groups:[3]

  1. Primary (AL amyloidosis).
    • Monoclonal light chains in serum and/or urine, may be due to plasma cell dyscrasia.
  2. Secondary (AA amyloidosis).
    • Infections (osteomyelitis), neoplasia (Hodgkin's lymphoma).
  3. Hemodialysis-related.
    • Beta-2 microglobulin.[10]
  4. Localized.
  5. Hereditary.
  6. Senile systemic amyloidosis.

How to remember: Two As = secondary amyloidosis.

Three main types - Robbins classification

Amyloid classified into three groups:[1]

  1. AL amyloidosis - "AL" = Amyloid Light chain.[13]
    • Primary amyloidosis.[7]
    • Bence Jones protein (light chains -- kappa or lambda) +ve -- necessary for amyloidosis but not sufficient.[14]
  2. AA amyloidosis - "AA" = Amyloid Associated.[15]
    • Secondary amyloidosis.
  3. Abeta amyloid - found in Alzheimer's disease.[16]

Additional types:

  • ATTR = Amyloid Transthyretin (TTR)
    • Transthyretin - serum protein that transport thyroxine and retinol; transthyretin AKA prealbumin.

Treatment

The very short version:

  • AL - chemotherapy & stem cell transplant.[3]
  • AA - treat underlying cause.[3]

Classification of amyloid - differentiation

AA amyloidosis does not stain with congo red if pre-treated with potassium permanganate.[17] in other words,

References

  1. van Rijswijk MH, van Heusden CW (October 1979). "The potassium permanganate method. A reliable method for differentiating amyloid AA from other forms of amyloid in routine laboratory practice". Am. J. Pathol. 97 (1): 43–58. PMC 2042379. PMID 495695. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042379/.
  2. Murphy CL, Eulitz M, Hrncic R, et al. (July 2001). "Chemical typing of amyloid protein contained in formalin-fixed paraffin-embedded biopsy specimens". Am. J. Clin. Pathol. 116 (1): 135–42. doi:10.1309/TWBM-8L4E-VK22-FRH5. PMID 11447744.
  3. Murphy CL, Wang S, Williams T, Weiss DT, Solomon A (2006). "Characterization of systemic amyloid deposits by mass spectrometry". Meth. Enzymol. 412: 48–62. doi:10.1016/S0076-6879(06)12004-2. PMID 17046651.
  4. Vrana JA, Gamez JD, Madden BJ, Theis JD, Bergen HR, Dogan A (December 2009). "Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens". Blood 114 (24): 4957–9. doi:10.1182/blood-2009-07-230722. PMID 19797517.

IHC

  • Can be classified based on IHC.[18]
    • Transthyretin - from transports thyroxine and retinol (previous prealbumin).

Types

Secondary amyloidosis

  • AKA AA amyloidosis.
  • Pathophysiology: acute-phase reactant serum amyloid A (SAA) - degraded + deposits.[7][19]

Cerebral amyloid angiopathy

Main article: Cerebral amyloid angiopathy

A common cause of lobar hemorrhage (cerebral cortex, cerebellar cortex) in the elderly.

Senile systemic amyloidosis

  • Abbreviated SSA.

General

  • Previously known as senile cardiac amyloidosis.[20]
  • May be referred to as ATTR = amyloidosis TTR; in SSA the TTR is not mutated.
    • There is a hereditary form of amyloidosis with mutated TTR deposition known as ATTR type FAP = ATTR type Familial Amyloid Polyneuropathy.

Epidemiology:

  • Common in the elderly, as the word senile suggests.
  • Found in approx. 25% of elderly over 80 years old,[20] and in upto 65% of patients over 90 years old.[21]

Treatment:

  • No effective treatment.

Gross pathology

  • Grey/black "peppering" of left atrial endocardium - in fixed specimens.[22]
    • "Peppering" should be present if severe.

Microscopic

Features:

  • 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.
    • Amyloid vs. Fibrosis? Subendocardial fibrosis may have rim of (diffusion) preserved myocytes. (???)
  • Amyloid often present in the subepicardial tissue[21] - less commonly affected by ischemia.

Images:

Site specific

Cardiac amyloidosis

General

  • Common cause of restrictive cardiomyopathy.[23]

Cardiac amyloidosis - subtypes:

  1. AL amyloidosis - associated with plasma cell dyscrasia - most common cardiac amyloidosis.[21]
  2. Senile systemic amyloidosis - TTR-related amyloidosis (unmutated TTR).
  3. Hereditary amyloidosis.
  4. AA amyloidosis is uncommon.

Clinical:

  • CHF, conduction abnormalities.
  • Kidney disease (proteinuria) - associated with AL amyloidosis.

Renal amyloidosis

Both AL and AA amyloidosis can affect the kidney.[4]

GI amyloidosis

GI amyloidosis can lead to obstruction and usually is greatest in the small bowel.[3]

Liver amyloidosis

Features:

  • Parenchymal deposition (common).
  • Portal triad deposition (less common).

Bone

Amyloid is reported in association with:

See also

References

  1. ↑ 1.0 1.1 Lachmann HJ, Hawkins PN (2006). "Amyloidosis and the lung". Chron Respir Dis 3 (4): 203-14. PMID 17190124. http://crd.sagepub.com/cgi/pmidlookup?view=long&pmid=17190124.
  2. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 259. ISBN 0-7216-0187-1.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Ebert EC, Nagar M (March 2008). "Gastrointestinal manifestations of amyloidosis". Am. J. Gastroenterol. 103 (3): 776-87. doi:10.1111/j.1572-0241.2007.01669.x. PMID 18076735.
  4. ↑ 4.0 4.1 Nishi S, Alchi B, Imai N, Gejyo F (April 2008). "New advances in renal amyloidosis". Clin. Exp. Nephrol. 12 (2): 93-101. doi:10.1007/s10157-007-0008-3. PMID 18175051.
  5. ↑ 5.0 5.1 URL: http://www.fondazionedamico.org/biopsiarenale_atlas/seco/amil/amil21.htm. Accessed on: 9 November 2010.
  6. ↑ Kleinschmidt-DeMasters BK, Prayson RA (November 2006). "An algorithmic approach to the brain biopsy--part I". Arch. Pathol. Lab. Med. 130 (11): 1630–8. PMID 17076524.
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 Amyloidosis. Merck Manual. URL: http://www.merck.com/mmpe/sec12/ch160/ch160a.html. Accessed on: 3 December 2009.
  8. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 261. ISBN 0-7216-0187-1.
  9. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 261. ISBN 0-7216-0187-1.
  10. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 260. ISBN 0-7216-0187-1.
  11. ↑ URL: http://www.umm.edu/altmed/articles/amyloidosis-000007.htm. Accessed on: 23 October 2010.
  12. ↑ URL: http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html. Accessed on: 6 December 2010.
  13. ↑ Comenzo, RL.; Vosburgh, E.; Falk, RH.; Sanchorawala, V.; Reisinger, J.; Dubrey, S.; Dember, LM.; Berk, JL. et al. (May 1998). "Dose-intensive melphalan with blood stem-cell support for the treatment of AL (amyloid light-chain) amyloidosis: survival and responses in 25 patients.". Blood 91 (10): 3662-70. PMID 9573002.
  14. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 261. ISBN 0-7216-0187-1.
  15. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 259. ISBN 0-7216-0187-1.
  16. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 259. ISBN 0-7216-0187-1.
  17. ↑ van Rijswijk MH, van Heusden CW (October 1979). "The potassium permanganate method. A reliable method for differentiating amyloid AA from other forms of amyloid in routine laboratory practice". Am. J. Pathol. 97 (1): 43–58. PMC 2042379. PMID 495695. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042379/.
  18. ↑ Röcken C (December 2009). "[Update on immunohistological classification of amyloidoses]" (in German). Pathologe 30 Suppl 2: 121–3. doi:10.1007/s00292-009-1183-7. PMID 19756621.
  19. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 260. ISBN 0-7216-0187-1.
  20. ↑ 20.0 20.1 Ikeda, S. (Dec 2004). "Cardiac amyloidosis: heterogenous pathogenic backgrounds.". Intern Med 43 (12): 1107-14. PMID 15645642.
  21. ↑ 21.0 21.1 21.2 Sharma, PP.; Payvar, S.; Litovsky, SH.. "Histomorphometric analysis of intramyocardial vessels in primary and senile amyloidosis: epicardium versus endocardium.". Cardiovasc Pathol 17 (2): 65-71. doi:10.1016/j.carpath.2007.05.008. PMID 18329550.
  22. ↑ Pomerance, A. (Sep 1965). "Senile cardiac amyloidosis.". Br Heart J 27 (5): 711-8. PMID 5829755. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC469777/pdf/brheartj00340-0085.pdf.
  23. ↑ Cardiac amyloidosis. Medlineplus.org. URL: http://www.nlm.nih.gov/medlineplus/ency/article/000193.htm. Accessed on: 3 December 2009.
  24. ↑ Petruzziello, F.; Zeppa, P.; Catalano, L.; Cozzolino, I.; Gargiulo, G.; Musto, P.; D'Auria, F.; Liso, V. et al. (May 2010). "Amyloid in bone marrow smears of patients affected by multiple myeloma.". Ann Hematol 89 (5): 469-74. doi:10.1007/s00277-009-0857-9. PMID 19894050.
  25. ↑ Alabi, ZO.; Ojo, OS.; Odesanmi, WO. (1991). "Secondary amyloidosis in chronic osteomyelitis.". Int Orthop 15 (1): 21-2. PMID 2071276.
  26. ↑ Miossec, P.; Lormeau, B.; Valensi, P.; Arthuis, F.; Amouroux, J.; Attali, JR. (Sep 1999). "Bone amyloidoma in a diabetic patient with morbid obesity.". Diabetes Metab 25 (3): 261-3. PMID 10499196.


External links

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