Difference between revisions of "Amyloid"

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(→‎Classification of amyloid - differentiation: more - potassium permanganate method no good)
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==Classification of amyloid - differentiation==
==Classification of amyloid - differentiation==
AA amyloidosis does '''not''' stain with congo red if pre-treated with potassium permanganate.<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> in other words,
===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>


===References===
===References===
# {{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=}}
# {{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=}}
# {{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=}}
# {{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=}}
# {{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=}}

Revision as of 01:56, 1 February 2012

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, non-branching.
    • Usually 8-12 nm in diameter; accepted range 8-15 nm.[6]

Images:

DDx

  • CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy).
    • Typically has basophilic granularity in the blood vessels.[7]

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.[11]
  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.[14]
    • Primary amyloidosis.[8]
    • Bence Jones protein (light chains -- kappa or lambda) +ve -- necessary for amyloidosis but not sufficient.[15]
  2. AA amyloidosis - "AA" = Amyloid Associated.[16]
    • Secondary amyloidosis.
  3. Abeta amyloid - found in Alzheimer's disease.[17]

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

Biochemical techniques

  • Pre-treated with potassium permanganate, to obliterate congo red reactivity, was though be definitive for AA amyloidosis;[18] this is now generally considered to be unreliable.[19]

References

  1. 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.
  2. 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.
  3. 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.[20]
    • Transthyretin - from transports thyroxine and retinol (previous prealbumin).

Other

  • Can be typed using mass spectroscopy.[21]

Types

Secondary amyloidosis

  • AKA AA amyloidosis.
  • Pathophysiology: acute-phase reactant serum amyloid A (SAA) - degraded + deposits.[8][22]

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.[23]
  • 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,[23] and in upto 65% of patients over 90 years old.[24]

Treatment:

  • No effective treatment.

Gross pathology

  • Grey/black "peppering" of left atrial endocardium - in fixed specimens.[25]
    • "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[24] - less commonly affected by ischemia.

Images:

Site specific

Cardiac amyloidosis

General

  • Common cause of restrictive cardiomyopathy.[26]

Cardiac amyloidosis - subtypes:

  1. AL amyloidosis - associated with plasma cell dyscrasia - most common cardiac amyloidosis.[24]
  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]

Images:

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. Alpers, CE.; Kowalewska, J. (Jan 2008). "Fibrillary glomerulonephritis and immunotactoid glomerulopathy.". J Am Soc Nephrol 19 (1): 34-7. doi:10.1681/ASN.2007070757. PMID 18045849.
  7. 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.
  8. 8.0 8.1 8.2 8.3 8.4 8.5 Amyloidosis. Merck Manual. URL: http://www.merck.com/mmpe/sec12/ch160/ch160a.html. Accessed on: 3 December 2009.
  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. 261. ISBN 0-7216-0187-1.
  11. 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.
  12. URL: http://www.umm.edu/altmed/articles/amyloidosis-000007.htm. Accessed on: 23 October 2010.
  13. URL: http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html. Accessed on: 6 December 2010.
  14. 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.
  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. 261. 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. 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.
  18. 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/.
  19. Picken, MM. (Apr 2010). "Amyloidosis-where are we now and where are we heading?". Arch Pathol Lab Med 134 (4): 545-51. doi:10.1043/1543-2165-134.4.545. PMID 20367306.
  20. 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.
  21. Chee, CE.; Lacy, MQ.; Dogan, A.; Zeldenrust, SR.; Gertz, MA. (Jun 2010). "Pitfalls in the diagnosis of primary amyloidosis.". Clin Lymphoma Myeloma Leuk 10 (3): 177-80. doi:10.3816/CLML.2010.n.027. PMID 20511161.
  22. 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.
  23. 23.0 23.1 Ikeda, S. (Dec 2004). "Cardiac amyloidosis: heterogenous pathogenic backgrounds.". Intern Med 43 (12): 1107-14. PMID 15645642.
  24. 24.0 24.1 24.2 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.
  25. 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.
  26. Cardiac amyloidosis. Medlineplus.org. URL: http://www.nlm.nih.gov/medlineplus/ency/article/000193.htm. Accessed on: 3 December 2009.
  27. 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.
  28. Alabi, ZO.; Ojo, OS.; Odesanmi, WO. (1991). "Secondary amyloidosis in chronic osteomyelitis.". Int Orthop 15 (1): 21-2. PMID 2071276.
  29. 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