Difference between revisions of "Primary Amyloidosis"

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(Definition / Description of Disease)
(Epidemiology / Prevalence)
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==Definition / Description of Disease==
 
==Definition / Description of Disease==
  
*A member of the group of “monoclonal immunoglobulin deposition diseases” that are characterized by visceral and soft tissue deposition of aberrant immunoglobulin (Ig), which subsequently results in organ dysfunction<ref>{{Cite journal|last=Aucouturier|first=Pierre|last2=Khamlichi|first2=Ahmed A.|last3=Touchard|first3=Guy|last4=Justrabo|first4=Eve|last5=Cogne|first5=Michel|last6=Chauffert|first6=Bruno|last7=Martin|first7=Francois|last8=Preud'homme|first8=Jean-Louis|date=1993|title=Heavy-Chain Deposition Disease|url=http://www.nejm.org/doi/abs/10.1056/NEJM199311043291905|journal=New England Journal of Medicine|language=en|volume=329|issue=19|pages=1389–1393|doi=10.1056/NEJM199311043291905|issn=0028-4793}}</ref><ref>{{Cite journal|last=J|first=Buxbaum|date=1992|title=Mechanisms of disease: monoclonal immunoglobulin deposition. Amyloidosis, light chain deposition disease, and light and heavy chain deposition disease|url=https://pubmed.ncbi.nlm.nih.gov/1582976/|language=en|pmid=1582976}}</ref><ref>{{Cite journal|last=Herzenberg|first=Andrew M.|last2=Lien|first2=John|last3=Magil|first3=Alex B.|date=1996|title=Monoclonal heavy chain (immunoglobulin G3) deposition disease: report of a case|url=https://linkinghub.elsevier.com/retrieve/pii/S0272638696901419|journal=American Journal of Kidney Diseases|language=en|volume=28|issue=1|pages=128–131|doi=10.1016/S0272-6386(96)90141-9}}</ref><ref>{{Cite journal|last=Kambham|first=Neeraja|last2=Markowitz|first2=Glen S.|last3=Appel|first3=Gerald B.|last4=Kleiner|first4=Morton J.|last5=Aucouturier|first5=Pierre|last6=D'Agati|first6=Vivette D.|date=1999|title=Heavy chain deposition disease: The disease spectrum|url=https://linkinghub.elsevier.com/retrieve/pii/S0272638699704324|journal=American Journal of Kidney Diseases|language=en|volume=33|issue=5|pages=954–962|doi=10.1016/S0272-6386(99)70432-4}}</ref><ref>{{Cite journal|last=Ra|first=Kyle|last2=Ma|first2=Gertz|date=1995|title=Primary systemic amyloidosis: clinical and laboratory features in 474 cases|url=https://pubmed.ncbi.nlm.nih.gov/7878478/|language=en|pmid=7878478}}</ref><ref>{{Cite journal|last=Preud'homme|first=Jean-Louis|last2=Aucouturier|first2=Pierre|last3=Touchard|first3=Guy|last4=Striker|first4=Liliane|last5=Khamlichi|first5=Ahmed Amine|last6=Rocca|first6=Anna|last7=Denoroy|first7=Luc|last8=Cogné|first8=Michel|date=1994|title=Monoclonal immunoglobulin deposition disease (Randall type). Relationship with structural abnormalities of immunoglobulin chains|url=https://linkinghub.elsevier.com/retrieve/pii/S0085253815586365|journal=Kidney International|language=en|volume=46|issue=4|pages=965–972|doi=10.1038/ki.1994.355}}</ref><ref>{{Cite journal|last=Preud'Homme|first=Jean-Louis|last2=Aucouturier|first2=Pierre|last3=Touchard|first3=Guy|last4=Khamlichi|first4=Amhed Amine|last5=Rocca|first5=Anna|last6=Denoroy|first6=Luc|last7=Cogne|first7=Michel|date=1994|title=Monoclonal immunoglobulin deposition disease: A review of immunoglobulin chain alterations|url=https://linkinghub.elsevier.com/retrieve/pii/0192056194900329|journal=International Journal of Immunopharmacology|language=en|volume=16|issue=5-6|pages=425–431|doi=10.1016/0192-0561(94)90032-9}}</ref><ref>{{Cite journal|last=Serpell|first=L. C.|last2=Sunde|first2=M.|last3=Blake|first3=C. C. F.|date=1997|title=The molecular basis of amyloidosis|url=http://link.springer.com/10.1007/s000180050107|journal=Cellular and Molecular Life Sciences|volume=53|issue=12|pages=871|doi=10.1007/s000180050107}}</ref><ref name=":0">McKenna RW, et al., (2017). Plasma cell neoplasms: Monoclonal immunoglobulin deposition diseases, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow, SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p254-255. </ref>.
+
*A member of the group of “monoclonal immunoglobulin deposition diseases” that are characterized by visceral and soft tissue deposition of aberrant immunoglobulin (Ig), which subsequently results in organ dysfunction<ref>{{Cite journal|last=Aucouturier|first=Pierre|last2=Khamlichi|first2=Ahmed A.|last3=Touchard|first3=Guy|last4=Justrabo|first4=Eve|last5=Cogne|first5=Michel|last6=Chauffert|first6=Bruno|last7=Martin|first7=Francois|last8=Preud'homme|first8=Jean-Louis|date=1993|title=Heavy-Chain Deposition Disease|url=http://www.nejm.org/doi/abs/10.1056/NEJM199311043291905|journal=New England Journal of Medicine|language=en|volume=329|issue=19|pages=1389–1393|doi=10.1056/NEJM199311043291905|issn=0028-4793}}</ref><ref>{{Cite journal|last=J|first=Buxbaum|date=1992|title=Mechanisms of disease: monoclonal immunoglobulin deposition. Amyloidosis, light chain deposition disease, and light and heavy chain deposition disease|url=https://pubmed.ncbi.nlm.nih.gov/1582976/|language=en|pmid=1582976}}</ref><ref>{{Cite journal|last=Herzenberg|first=Andrew M.|last2=Lien|first2=John|last3=Magil|first3=Alex B.|date=1996|title=Monoclonal heavy chain (immunoglobulin G3) deposition disease: report of a case|url=https://linkinghub.elsevier.com/retrieve/pii/S0272638696901419|journal=American Journal of Kidney Diseases|language=en|volume=28|issue=1|pages=128–131|doi=10.1016/S0272-6386(96)90141-9}}</ref><ref>{{Cite journal|last=Kambham|first=Neeraja|last2=Markowitz|first2=Glen S.|last3=Appel|first3=Gerald B.|last4=Kleiner|first4=Morton J.|last5=Aucouturier|first5=Pierre|last6=D'Agati|first6=Vivette D.|date=1999|title=Heavy chain deposition disease: The disease spectrum|url=https://linkinghub.elsevier.com/retrieve/pii/S0272638699704324|journal=American Journal of Kidney Diseases|language=en|volume=33|issue=5|pages=954–962|doi=10.1016/S0272-6386(99)70432-4}}</ref><ref name=":3">{{Cite journal|last=Ra|first=Kyle|last2=Ma|first2=Gertz|date=1995|title=Primary systemic amyloidosis: clinical and laboratory features in 474 cases|url=https://pubmed.ncbi.nlm.nih.gov/7878478/|language=en|pmid=7878478}}</ref><ref>{{Cite journal|last=Preud'homme|first=Jean-Louis|last2=Aucouturier|first2=Pierre|last3=Touchard|first3=Guy|last4=Striker|first4=Liliane|last5=Khamlichi|first5=Ahmed Amine|last6=Rocca|first6=Anna|last7=Denoroy|first7=Luc|last8=Cogné|first8=Michel|date=1994|title=Monoclonal immunoglobulin deposition disease (Randall type). Relationship with structural abnormalities of immunoglobulin chains|url=https://linkinghub.elsevier.com/retrieve/pii/S0085253815586365|journal=Kidney International|language=en|volume=46|issue=4|pages=965–972|doi=10.1038/ki.1994.355}}</ref><ref>{{Cite journal|last=Preud'Homme|first=Jean-Louis|last2=Aucouturier|first2=Pierre|last3=Touchard|first3=Guy|last4=Khamlichi|first4=Amhed Amine|last5=Rocca|first5=Anna|last6=Denoroy|first6=Luc|last7=Cogne|first7=Michel|date=1994|title=Monoclonal immunoglobulin deposition disease: A review of immunoglobulin chain alterations|url=https://linkinghub.elsevier.com/retrieve/pii/0192056194900329|journal=International Journal of Immunopharmacology|language=en|volume=16|issue=5-6|pages=425–431|doi=10.1016/0192-0561(94)90032-9}}</ref><ref>{{Cite journal|last=Serpell|first=L. C.|last2=Sunde|first2=M.|last3=Blake|first3=C. C. F.|date=1997|title=The molecular basis of amyloidosis|url=http://link.springer.com/10.1007/s000180050107|journal=Cellular and Molecular Life Sciences|volume=53|issue=12|pages=871|doi=10.1007/s000180050107}}</ref><ref name=":0">McKenna RW, et al., (2017). Plasma cell neoplasms: Monoclonal immunoglobulin deposition diseases, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow, SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p254-255. </ref>
  
*These monoclonal Ig deposition diseases overlap as clinically similar conditions—but likely represent chemically distinctive manifestations of similar pathological processes, which can be placed into two major categories: 1) primary amyloidosis (detailed herein); 2) [http://www.ccga.io/index.php/Light_Chain_and_Heavy_Chain_Deposition_Disease light chain and heavy chain deposition diseases]<ref name=":0" /><ref name=":1">{{Cite journal|last=Ra|first=Kyle|last2=A|first2=Linos|last3=Cm|first3=Beard|last4=Rp|first4=Linke|last5=Ma|first5=Gertz|last6=Wm|first6=O'Fallon|last7=Lt|first7=Kurland|date=1992|title=Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989|url=https://pubmed.ncbi.nlm.nih.gov/1558973/|language=en|pmid=1558973}}</ref>.
+
*These monoclonal Ig deposition diseases overlap as clinically similar conditions—but likely represent chemically distinctive manifestations of similar pathological processes, which can be placed into two major categories: 1) primary amyloidosis (detailed herein); 2) [http://www.ccga.io/index.php/Light_Chain_and_Heavy_Chain_Deposition_Disease light chain and heavy chain deposition diseases]<ref name=":0" /><ref name=":1">{{Cite journal|last=Ra|first=Kyle|last2=A|first2=Linos|last3=Cm|first3=Beard|last4=Rp|first4=Linke|last5=Ma|first5=Gertz|last6=Wm|first6=O'Fallon|last7=Lt|first7=Kurland|date=1992|title=Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989|url=https://pubmed.ncbi.nlm.nih.gov/1558973/|language=en|pmid=1558973}}</ref>
*An acquired systemic amyloidosis, primary amyloidosis or the preferred term “AL amyloidosis,” results from a plasma cell or in rare instances, a lymphoplasmacytic neoplasm.
+
*An acquired systemic amyloidosis, primary amyloidosis or the preferred term “AL amyloidosis,” results from a plasma cell or in rare instances, a lymphoplasmacytic neoplasm
*AL amyloidosis is a rare clonal plasma cell dyscrasia, with a particularly devastating clinical phenotype that results from the extracellular amyloid fibril deposition in vital organs<ref>{{Cite journal|last=Ah|first=Bryce|last2=Rp|first2=Ketterling|last3=Ma|first3=Gertz|last4=M|first4=Lacy|last5=Ra|first5=Knudson|last6=S|first6=Zeldenrust|last7=S|first7=Kumar|last8=S|first8=Hayman|last9=F|first9=Buadi|date=2009|title=Translocation t(11;14) and survival of patients with light chain (AL) amyloidosis|url=https://pubmed.ncbi.nlm.nih.gov/19211640/|language=en|doi=10.3324/haematol.13369|pmc=PMC2649355|pmid=19211640}}</ref><ref>{{Cite journal|last=G|first=Merlini|date=2017|title=AL amyloidosis: from molecular mechanisms to targeted therapies|url=https://pubmed.ncbi.nlm.nih.gov/29222231/|language=en|doi=10.1182/asheducation-2017.1.1|pmc=PMC6142527|pmid=29222231}}</ref><ref>{{Cite journal|last=Ryšavá|first=Romana|date=2019|title=AL amyloidosis: advances in diagnostics and treatment|url=https://academic.oup.com/ndt/article/34/9/1460/5123556|journal=Nephrology Dialysis Transplantation|language=en|volume=34|issue=9|pages=1460–1466|doi=10.1093/ndt/gfy291|issn=0931-0509}}</ref>.
+
*AL amyloidosis is a rare clonal plasma cell dyscrasia, with a particularly devastating clinical phenotype that results from the extracellular amyloid fibril deposition in vital organs<ref>{{Cite journal|last=Ah|first=Bryce|last2=Rp|first2=Ketterling|last3=Ma|first3=Gertz|last4=M|first4=Lacy|last5=Ra|first5=Knudson|last6=S|first6=Zeldenrust|last7=S|first7=Kumar|last8=S|first8=Hayman|last9=F|first9=Buadi|date=2009|title=Translocation t(11;14) and survival of patients with light chain (AL) amyloidosis|url=https://pubmed.ncbi.nlm.nih.gov/19211640/|language=en|doi=10.3324/haematol.13369|pmc=PMC2649355|pmid=19211640}}</ref><ref name=":4">{{Cite journal|last=G|first=Merlini|date=2017|title=AL amyloidosis: from molecular mechanisms to targeted therapies|url=https://pubmed.ncbi.nlm.nih.gov/29222231/|language=en|doi=10.1182/asheducation-2017.1.1|pmc=PMC6142527|pmid=29222231}}</ref><ref>{{Cite journal|last=Ryšavá|first=Romana|date=2019|title=AL amyloidosis: advances in diagnostics and treatment|url=https://academic.oup.com/ndt/article/34/9/1460/5123556|journal=Nephrology Dialysis Transplantation|language=en|volume=34|issue=9|pages=1460–1466|doi=10.1093/ndt/gfy291|issn=0931-0509}}</ref>
*The AL amyloid fibrils derive from ''N-''terminal region of monoclonal immunoglobulin light chains that consist of the whole or part of the variable (V<sub>I</sub>) domain<ref name=":2">{{Cite journal|date=2004|title=Guidelines on the diagnosis and management of AL amyloidosis|url=http://doi.wiley.com/10.1111/j.1365-2141.2004.04970.x|journal=British Journal of Haematology|language=en|volume=125|issue=6|pages=681–700|doi=10.1111/j.1365-2141.2004.04970.x|issn=0007-1048}}</ref>.
+
*The AL amyloid fibrils derive from ''N-''terminal region of monoclonal immunoglobulin light chains that consist of the whole or part of the variable (V<sub>I</sub>) domain<ref name=":2">{{Cite journal|date=2004|title=Guidelines on the diagnosis and management of AL amyloidosis|url=http://doi.wiley.com/10.1111/j.1365-2141.2004.04970.x|journal=British Journal of Haematology|language=en|volume=125|issue=6|pages=681–700|doi=10.1111/j.1365-2141.2004.04970.x|issn=0007-1048}}</ref>  
**The structure and unique nature of all monoclonal light chains influences their inherent propensity (for some) to form amyloid fibrils<ref name=":2" />.
+
**The structure and unique nature of all monoclonal light chains influences their inherent propensity (for some) to form amyloid fibrils<ref name=":2" />
**The amyloid formed from monoclonal light chains can exist in a partly unfolded state, which involves loss of tertiary or higher order structures<ref name=":2" />. Amyloids will readily aggregate in the ß-sheet structure to create protofilaments and fibril; this process is progressive as a ‘seeding” event serves as a template that facilities further amyloid deposition, which allows expansion of deposition by capturing further precursor molecules<ref name=":2" />.  
+
**The amyloid formed from monoclonal light chains can exist in a partly unfolded state, which involves loss of tertiary or higher order structures<ref name=":2" />. Amyloids will readily aggregate in the ß-sheet structure to create protofilaments and fibril; this process is progressive as a ‘seeding” event serves as a template that facilities further amyloid deposition, which allows expansion of deposition by capturing further precursor molecules<ref name=":2" />
  
 
==Synonyms / Terminology==
 
==Synonyms / Terminology==
  
* Immunoglobulin light chain amyloidosis (AL)
+
*Immunoglobulin light chain amyloidosis (AL)
* AL amyloidosis (preferred in recent literature over Primary Amyloidosis, the WHO term)
+
*AL amyloidosis (preferred in recent literature over Primary Amyloidosis, the WHO term)
  
 
==Epidemiology / Prevalence==
 
==Epidemiology / Prevalence==
  
* AL amyloidosis is an uncommon disorder and its exact incidence is unknown<ref>{{Cite journal|last=Gertz|first=Morie A.|date=2018|title=Immunoglobulin light chain amyloidosis: 2018 Update on diagnosis, prognosis, and treatment: GERTZ|url=http://doi.wiley.com/10.1002/ajh.25149|journal=American Journal of Hematology|language=en|volume=93|issue=9|pages=1169–1180|doi=10.1002/ajh.25149}}</ref>.
+
*AL amyloidosis is an uncommon disorder and its exact incidence is unknown<ref>{{Cite journal|last=Gertz|first=Morie A.|date=2018|title=Immunoglobulin light chain amyloidosis: 2018 Update on diagnosis, prognosis, and treatment: GERTZ|url=http://doi.wiley.com/10.1002/ajh.25149|journal=American Journal of Hematology|language=en|volume=93|issue=9|pages=1169–1180|doi=10.1002/ajh.25149}}</ref>
  
* Within the US, the incidence is estimated at 9-14 cases per million person years, but the true prevalence may be higher due to under diagnosis<ref name=":1" /><ref>{{Cite journal|last=Staron|first=Andrew|last2=Connors|first2=Lawreen H.|last3=Ruberg|first3=Frederick L.|last4=Mendelson|first4=Lisa M.|last5=Sanchorawala|first5=Vaishali|date=2019|title=A new era of amyloidosis: the trends at a major US referral centre|url=https://www.tandfonline.com/doi/full/10.1080/13506129.2019.1640672|journal=Amyloid|language=en|volume=26|issue=4|pages=192–196|doi=10.1080/13506129.2019.1640672|issn=1350-6129}}</ref><ref>{{Cite journal|last=Vaxman|first=Iuliana|last2=Gertz|first2=Morie|date=2020|title=When to Suspect a Diagnosis of Amyloidosis|url=https://www.karger.com/Article/FullText/506617|journal=Acta Haematologica|language=en|pages=1–8|doi=10.1159/000506617|issn=0001-5792}}</ref>.
+
*Within the US, the incidence is estimated at 9-14 cases per million person years, but the true prevalence may be higher due to under diagnosis<ref name=":1" /><ref name=":5">{{Cite journal|last=Staron|first=Andrew|last2=Connors|first2=Lawreen H.|last3=Ruberg|first3=Frederick L.|last4=Mendelson|first4=Lisa M.|last5=Sanchorawala|first5=Vaishali|date=2019|title=A new era of amyloidosis: the trends at a major US referral centre|url=https://www.tandfonline.com/doi/full/10.1080/13506129.2019.1640672|journal=Amyloid|language=en|volume=26|issue=4|pages=192–196|doi=10.1080/13506129.2019.1640672|issn=1350-6129}}</ref><ref name=":6">{{Cite journal|last=Vaxman|first=Iuliana|last2=Gertz|first2=Morie|date=2020|title=When to Suspect a Diagnosis of Amyloidosis|url=https://www.karger.com/Article/FullText/506617|journal=Acta Haematologica|language=en|pages=1–8|doi=10.1159/000506617|issn=0001-5792}}</ref>
 +
*Considered a disease of the elderly, the incidence of AL amyloidosis increases with age<ref name=":1" /><ref name=":5" />
 +
**A small proportion of patients (~1.3%) are diagnosed under the age of 34, with the median age at diagnosis of 63 years of age<ref name=":7">{{Cite journal|last=Tp|first=Quock|last2=T|first2=Yan|last3=E|first3=Chang|last4=S|first4=Guthrie|last5=Ms|first5=Broder|date=2018|title=Epidemiology of AL amyloidosis: a real-world study using US claims data|url=https://pubmed.ncbi.nlm.nih.gov/29748430/|language=en|doi=10.1182/bloodadvances.2018016402|pmc=PMC5965052|pmid=29748430}}</ref>
 +
*There is a male predominance, with men reported in recent studies to account for 55-70% of patients<ref name=":3" /><ref name=":7" /><ref>{{Cite journal|last=Ra|first=Kyle|last2=Pr|first2=Greipp|last3=Wm|first3=O'Fallon|date=1986|title=Primary systemic amyloidosis: multivariate analysis for prognostic factors in 168 cases|url=https://pubmed.ncbi.nlm.nih.gov/3719098/|language=en|pmid=3719098}}</ref>
 +
*There is limited data regarding AL amyloidosis incidence across ethnic populations, however, the disease is known to occur in all races and geographical regions<ref name=":0" />
  
 
==Clinical Features==
 
==Clinical Features==
  
Put your text here
+
* The signs and symptoms that raise the clinical suspicion for a possible diagnosis of amyloidosis are generally nonspecific; therefore, the establishment of an AL amyloidosis is difficult and is highly reliant upon a clinical suspicion<ref name=":6" />
 +
* Clinical presentations vary, ranging from more rapidly progressive symptoms to slowly evolving or a paucity of symptoms among others<ref name=":5" />
 +
* Nearly 25% of patients are diagnosed late, and many present with advanced, irreversible cardiac damage, and often succumb to within 12 months of the diagnosis<ref name=":4" />
 +
* Clinical presentations generally relate and are of a consequence of amyloid in organs and tissues, and it is often the presentation of symptoms within a particular organ that predominate, which initiates the diagnosis<ref name=":4" /><ref name=":6" />
 +
* Signs of the disease in the early stages include peripheral neuropathy (~15-20%), carpal tunnel syndrome (~21%), and bone pain (~5%)<ref name=":0" />. Other major symptoms, in addition to the extremely common presenting symptoms of fatigue and weight loss, relate to congestive heart failure (~15-20%), nephrotic syndrome (~28%), or malabsorption (~5%) are common<ref name=":3" /><ref name=":0" />
 +
* Physical observations include hepatomegaly (~25-30%), macroglossia (~10%), and purpura, commonly of periorbital or facial presentation (~15%)<ref name=":3" />
 +
* Individuals with congestive heart failure or nephrotic syndrome often present with edema<ref name=":3" />
 +
* Few patients present with splenomegaly, lymphadenopathy, skin and soft tissue thickening, a hoarse voice (due to vocal cord infiltration), hypoadrenalism or hypothyroidism (due to deposits within the adrenal gland or thyroid, respectively)<ref>{{Cite journal|last=Mahmood|first=S.|last2=Palladini|first2=G.|last3=Sanchorawala|first3=V.|last4=Wechalekar|first4=A.|date=2014|title=Update on treatment of light chain amyloidosis|url=http://www.haematologica.org/cgi/doi/10.3324/haematol.2013.087619|journal=Haematologica|language=en|volume=99|issue=2|pages=209–221|doi=10.3324/haematol.2013.087619|issn=0390-6078|pmc=PMC3912950|pmid=24497558}}</ref>
  
 
==Sites of Involvement==
 
==Sites of Involvement==

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Primary Author(s)*

Put your text here

Cancer Category/Type

Mature B-cell neoplasms

Cancer Sub-Classification / Subtype

Monoclonal immunoglobulin deposition disease

Definition / Description of Disease

  • A member of the group of “monoclonal immunoglobulin deposition diseases” that are characterized by visceral and soft tissue deposition of aberrant immunoglobulin (Ig), which subsequently results in organ dysfunction[1][2][3][4][5][6][7][8][9]
  • These monoclonal Ig deposition diseases overlap as clinically similar conditions—but likely represent chemically distinctive manifestations of similar pathological processes, which can be placed into two major categories: 1) primary amyloidosis (detailed herein); 2) light chain and heavy chain deposition diseases[9][10]
  • An acquired systemic amyloidosis, primary amyloidosis or the preferred term “AL amyloidosis,” results from a plasma cell or in rare instances, a lymphoplasmacytic neoplasm
  • AL amyloidosis is a rare clonal plasma cell dyscrasia, with a particularly devastating clinical phenotype that results from the extracellular amyloid fibril deposition in vital organs[11][12][13]
  • The AL amyloid fibrils derive from N-terminal region of monoclonal immunoglobulin light chains that consist of the whole or part of the variable (VI) domain[14]
    • The structure and unique nature of all monoclonal light chains influences their inherent propensity (for some) to form amyloid fibrils[14]
    • The amyloid formed from monoclonal light chains can exist in a partly unfolded state, which involves loss of tertiary or higher order structures[14]. Amyloids will readily aggregate in the ß-sheet structure to create protofilaments and fibril; this process is progressive as a ‘seeding” event serves as a template that facilities further amyloid deposition, which allows expansion of deposition by capturing further precursor molecules[14]

Synonyms / Terminology

  • Immunoglobulin light chain amyloidosis (AL)
  • AL amyloidosis (preferred in recent literature over Primary Amyloidosis, the WHO term)

Epidemiology / Prevalence

  • AL amyloidosis is an uncommon disorder and its exact incidence is unknown[15]
  • Within the US, the incidence is estimated at 9-14 cases per million person years, but the true prevalence may be higher due to under diagnosis[10][16][17]
  • Considered a disease of the elderly, the incidence of AL amyloidosis increases with age[10][16]
    • A small proportion of patients (~1.3%) are diagnosed under the age of 34, with the median age at diagnosis of 63 years of age[18]
  • There is a male predominance, with men reported in recent studies to account for 55-70% of patients[5][18][19]
  • There is limited data regarding AL amyloidosis incidence across ethnic populations, however, the disease is known to occur in all races and geographical regions[9]

Clinical Features

  • The signs and symptoms that raise the clinical suspicion for a possible diagnosis of amyloidosis are generally nonspecific; therefore, the establishment of an AL amyloidosis is difficult and is highly reliant upon a clinical suspicion[17]
  • Clinical presentations vary, ranging from more rapidly progressive symptoms to slowly evolving or a paucity of symptoms among others[16]
  • Nearly 25% of patients are diagnosed late, and many present with advanced, irreversible cardiac damage, and often succumb to within 12 months of the diagnosis[12]
  • Clinical presentations generally relate and are of a consequence of amyloid in organs and tissues, and it is often the presentation of symptoms within a particular organ that predominate, which initiates the diagnosis[12][17]
  • Signs of the disease in the early stages include peripheral neuropathy (~15-20%), carpal tunnel syndrome (~21%), and bone pain (~5%)[9]. Other major symptoms, in addition to the extremely common presenting symptoms of fatigue and weight loss, relate to congestive heart failure (~15-20%), nephrotic syndrome (~28%), or malabsorption (~5%) are common[5][9]
  • Physical observations include hepatomegaly (~25-30%), macroglossia (~10%), and purpura, commonly of periorbital or facial presentation (~15%)[5]
  • Individuals with congestive heart failure or nephrotic syndrome often present with edema[5]
  • Few patients present with splenomegaly, lymphadenopathy, skin and soft tissue thickening, a hoarse voice (due to vocal cord infiltration), hypoadrenalism or hypothyroidism (due to deposits within the adrenal gland or thyroid, respectively)[20]

Sites of Involvement

Put your text here

Morphologic Features

Put your text here

Immunophenotype

Put your text here and/or fill in the table

Finding Marker
Positive (universal) EXAMPLE CD1
Positive (subset) EXAMPLE CD2
Negative (universal) EXAMPLE CD3
Negative (subset) EXAMPLE CD4

Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence
EXAMPLE t(9;22)(q34;q11.2) EXAMPLE 3'ABL1 / 5'BCR EXAMPLE der(22) EXAMPLE 5%
EXAMPLE t(8;21)(q22;q22) EXAMPLE 5'RUNX1 / 3'RUNXT1 EXAMPLE der(8) EXAMPLE 5%

Characteristic Chromosomal Aberrations / Patterns

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Genomic Gain/Loss/LOH

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Chromosome Number Gain/Loss/Amp/LOH Region
EXAMPLE 8 EXAMPLE Gain EXAMPLE chr8:0-1000000
EXAMPLE 7 EXAMPLE Loss EXAMPLE chr7:0-1000000

Gene Mutations (SNV/INDEL)

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Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)
EXAMPLE TP53 EXAMPLE R273H EXAMPLE Tumor Suppressor EXAMPLE LOF EXAMPLE 20%

Other Mutations

Type Gene/Region/Other
Concomitant Mutations EXAMPLE IDH1 R123H
Secondary Mutations EXAMPLE Trisomy 7
Mutually Exclusive EXAMPLE EGFR Amplification

Epigenomics (Methylation)

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Genes and Main Pathways Involved

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Diagnostic Testing Methods

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Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

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Familial Forms

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Other Information

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Links

Monoclonal Immunoglobulin Deposition Diseases

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References

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  1. Aucouturier, Pierre; et al. (1993). "Heavy-Chain Deposition Disease". New England Journal of Medicine. 329 (19): 1389–1393. doi:10.1056/NEJM199311043291905. ISSN 0028-4793.
  2. J, Buxbaum (1992). "Mechanisms of disease: monoclonal immunoglobulin deposition. Amyloidosis, light chain deposition disease, and light and heavy chain deposition disease". PMID 1582976.
  3. Herzenberg, Andrew M.; et al. (1996). "Monoclonal heavy chain (immunoglobulin G3) deposition disease: report of a case". American Journal of Kidney Diseases. 28 (1): 128–131. doi:10.1016/S0272-6386(96)90141-9.
  4. Kambham, Neeraja; et al. (1999). "Heavy chain deposition disease: The disease spectrum". American Journal of Kidney Diseases. 33 (5): 954–962. doi:10.1016/S0272-6386(99)70432-4.
  5. 5.0 5.1 5.2 5.3 5.4 Ra, Kyle; et al. (1995). "Primary systemic amyloidosis: clinical and laboratory features in 474 cases". PMID 7878478.
  6. Preud'homme, Jean-Louis; et al. (1994). "Monoclonal immunoglobulin deposition disease (Randall type). Relationship with structural abnormalities of immunoglobulin chains". Kidney International. 46 (4): 965–972. doi:10.1038/ki.1994.355.
  7. Preud'Homme, Jean-Louis; et al. (1994). "Monoclonal immunoglobulin deposition disease: A review of immunoglobulin chain alterations". International Journal of Immunopharmacology. 16 (5–6): 425–431. doi:10.1016/0192-0561(94)90032-9.
  8. Serpell, L. C.; et al. (1997). "The molecular basis of amyloidosis". Cellular and Molecular Life Sciences. 53 (12): 871. doi:10.1007/s000180050107.
  9. 9.0 9.1 9.2 9.3 9.4 McKenna RW, et al., (2017). Plasma cell neoplasms: Monoclonal immunoglobulin deposition diseases, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow, SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p254-255.
  10. 10.0 10.1 10.2 Ra, Kyle; et al. (1992). "Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989". PMID 1558973.
  11. Ah, Bryce; et al. (2009). "Translocation t(11;14) and survival of patients with light chain (AL) amyloidosis". doi:10.3324/haematol.13369. PMC 2649355. PMID 19211640.CS1 maint: PMC format (link)
  12. 12.0 12.1 12.2 G, Merlini (2017). "AL amyloidosis: from molecular mechanisms to targeted therapies". doi:10.1182/asheducation-2017.1.1. PMC 6142527. PMID 29222231.CS1 maint: PMC format (link)
  13. Ryšavá, Romana (2019). "AL amyloidosis: advances in diagnostics and treatment". Nephrology Dialysis Transplantation. 34 (9): 1460–1466. doi:10.1093/ndt/gfy291. ISSN 0931-0509.
  14. 14.0 14.1 14.2 14.3 "Guidelines on the diagnosis and management of AL amyloidosis". British Journal of Haematology. 125 (6): 681–700. 2004. doi:10.1111/j.1365-2141.2004.04970.x. ISSN 0007-1048.
  15. Gertz, Morie A. (2018). "Immunoglobulin light chain amyloidosis: 2018 Update on diagnosis, prognosis, and treatment: GERTZ". American Journal of Hematology. 93 (9): 1169–1180. doi:10.1002/ajh.25149.
  16. 16.0 16.1 16.2 Staron, Andrew; et al. (2019). "A new era of amyloidosis: the trends at a major US referral centre". Amyloid. 26 (4): 192–196. doi:10.1080/13506129.2019.1640672. ISSN 1350-6129.
  17. 17.0 17.1 17.2 Vaxman, Iuliana; et al. (2020). "When to Suspect a Diagnosis of Amyloidosis". Acta Haematologica: 1–8. doi:10.1159/000506617. ISSN 0001-5792.
  18. 18.0 18.1 Tp, Quock; et al. (2018). "Epidemiology of AL amyloidosis: a real-world study using US claims data". doi:10.1182/bloodadvances.2018016402. PMC 5965052. PMID 29748430.CS1 maint: PMC format (link)
  19. Ra, Kyle; et al. (1986). "Primary systemic amyloidosis: multivariate analysis for prognostic factors in 168 cases". PMID 3719098.
  20. Mahmood, S.; et al. (2014). "Update on treatment of light chain amyloidosis". Haematologica. 99 (2): 209–221. doi:10.3324/haematol.2013.087619. ISSN 0390-6078. PMC 3912950. PMID 24497558.CS1 maint: PMC format (link)

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