Plasma cell disorder: Difference between revisions
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==[[Plasma cell disorder overview|Overview]]== | ==[[Plasma cell disorder overview|Overview]]== | ||
Plasma cell disorders are a diverse type of blood disorders characterized by [[proliferation]] of a single clone of [[plasma cells]] that produces a [[homogeneous]] monoclonal (M) protein. | Plasma cell disorders are a diverse type of blood disorders characterized by [[proliferation]] of a single clone of [[plasma cells]] that produces a [[homogeneous]] monoclonal (M) protein. These monoclonal paraprotein are seen in the [[serum]] or urine. Monoclonal [[plasma cells]] are present in the [[bone marrow]] or, rarely, in other tissues. Plasma cell disorders include [[Monoclonal gammopathy of undetermined significance classification|monoclonal gammopathy of undetermined significance]] (MGUS)[[Multiple myeloma|, multiple myeloma]] (MM), [[lymphoplasmacytic lymphoma]]/ [[Waldenström's macroglobulinemia|Waldenstrom macroglobulinemia]] (LPL/WM), [[Lymphoproliferative disorders|lymphoproliferative disorders,]] smoldering multiple myeloma (SMM); solitary or extramedullary plasmacytoma, [[amyloidosis]], and [[POEMS syndrome]] ([[polyneuropathy]], [[Organomegaly|organomegaly,]] [[endocrinopathy]], monoclonal protein, and skin changes). These disorders have been defined by the International Myeloma Working Group in 2006. | ||
==[[Plasma cell disorder classification|Classification]]== | ==[[Plasma cell disorder classification|Classification]]== | ||
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| style="background:#F5F5F5;" align="center" + |Normal | | style="background:#F5F5F5;" align="center" + |Normal | ||
| style="background:#F5F5F5;" align="left" + | | | style="background:#F5F5F5;" align="left" + | | ||
* Solitory bone lesion due to plasma cell tumor | * Solitory bone lesion due to [[plasma cell]] tumor | ||
* Preserved levels of uninvolved immunoglobulins | * Preserved levels of uninvolved [[immunoglobulins]] | ||
* No [[anemia]], [[hypercalcemia]] or [[renal disease]] | * No [[anemia]], [[hypercalcemia]] or [[renal disease]] | ||
|- | |- | ||
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| style="background:#F5F5F5;" align="center" + |<10% | | style="background:#F5F5F5;" align="center" + |<10% | ||
| style="background:#F5F5F5;" align="left" + | | | style="background:#F5F5F5;" align="left" + | | ||
* No bone lesions | * No bone lesions | ||
* [[Nephrotic syndrome]] | * [[Nephrotic syndrome]] | ||
* [[Restrictive cardiomyopathy]] | * [[Restrictive cardiomyopathy]] | ||
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== Monoclonal gammopathies of undetermined significance (MGUS) == | == Monoclonal gammopathies of undetermined significance (MGUS) == | ||
* [[Monoclonal gammopathy of undetermined significance]] is a condition in which a low or non-quantifiable level of a [[monoclonal]] [[paraprotein]] is detected in the blood by means of [[protein electrophoresis]].<ref name="pmid16628189">{{cite journal |vauthors=Jego G, Bataille R, Geffroy-Luseau A, Descamps G, Pellat-Deceunynck C |title=Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors |journal=Leukemia |volume=20 |issue=6 |pages=1130–7 |date=June 2006 |pmid=16628189 |doi=10.1038/sj.leu.2404226 |url=}}</ref><ref name="pmid19181642">{{cite journal |vauthors=Dinarello CA |title=Targeting the pathogenic role of interleukin 1{beta} in the progression of smoldering/indolent myeloma to active disease |journal=Mayo Clin. Proc. |volume=84 |issue=2 |pages=105–7 |date=February 2009 |pmid=19181642 |pmc=2664579 |doi=10.4065/84.2.105 |url=}}</ref><ref name="pmid23233640">{{cite journal |vauthors=Merlini G, Palladini G |title=Differential diagnosis of monoclonal gammopathy of undetermined significance |journal=Hematology Am Soc Hematol Educ Program |volume=2012 |issue= |pages=595–603 |date=2012 |pmid=23233640 |doi=10.1182/asheducation-2012.1.595 |url=}}</ref> | * [[Monoclonal gammopathy of undetermined significance]] is a condition in which a low or non-quantifiable level of a [[monoclonal]] [[paraprotein]] is detected in the blood by means of [[protein electrophoresis]].<ref name="pmid16628189">{{cite journal |vauthors=Jego G, Bataille R, Geffroy-Luseau A, Descamps G, Pellat-Deceunynck C |title=Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors |journal=Leukemia |volume=20 |issue=6 |pages=1130–7 |date=June 2006 |pmid=16628189 |doi=10.1038/sj.leu.2404226 |url=}}</ref><ref name="pmid19181642">{{cite journal |vauthors=Dinarello CA |title=Targeting the pathogenic role of interleukin 1{beta} in the progression of smoldering/indolent myeloma to active disease |journal=Mayo Clin. Proc. |volume=84 |issue=2 |pages=105–7 |date=February 2009 |pmid=19181642 |pmc=2664579 |doi=10.4065/84.2.105 |url=}}</ref><ref name="pmid23233640">{{cite journal |vauthors=Merlini G, Palladini G |title=Differential diagnosis of monoclonal gammopathy of undetermined significance |journal=Hematology Am Soc Hematol Educ Program |volume=2012 |issue= |pages=595–603 |date=2012 |pmid=23233640 |doi=10.1182/asheducation-2012.1.595 |url=}}</ref> | ||
*<nowiki/>In addition, some patients develop a [[polyneuropathy]]<nowiki/>or other problems related to the secreted antibody. | *<nowiki/>In addition, some patients develop a [[polyneuropathy]]<nowiki/> or other problems related to the secreted antibody. | ||
* MGUS is a premalignant condition and is distinct fr<nowiki/>om [[multiple myeloma]]. | * MGUS is a premalignant condition and is distinct fr<nowiki/>om [[multiple myeloma]]. | ||
* Pathologically, the lesion in [[Monoclonal gammopathy of undetermined significance]] is in fact very similar to that in [[multiple myeloma]]. | * Pathologically, the lesion in [[Monoclonal gammopathy of undetermined significance]] is in fact very similar to that in [[multiple myeloma]]. | ||
For more information about Monoclonal gammopathies of undetermined significance '''[[Monoclonal gammopathies of undetermined significance |click here]]''' | For more information about Monoclonal gammopathies of undetermined significance '''[[Monoclonal gammopathies of undetermined significance |click here]].''' | ||
== Malignant monoclonal gammopathies == | == Malignant monoclonal gammopathies == | ||
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==== Symptomatic multiple myeloma ==== | ==== Symptomatic multiple myeloma ==== | ||
* People with [[Multiple myeloma classification|multiple myeloma]] with symptoms are categorized to have [[Multiple myeloma Classification|active multiple myeloma]] and will | * People with [[Multiple myeloma classification|multiple myeloma]] with symptoms are categorized to have [[Multiple myeloma Classification|active multiple myeloma]] and will exhibit any of the following features:<ref name="SergentanisZagouri2015">{{cite journal|last1=Sergentanis|first1=Theodoros N.|last2=Zagouri|first2=Flora|last3=Tsilimidos|first3=Gerasimos|last4=Tsagianni|first4=Anastasia|last5=Tseliou|first5=Melina|last6=Dimopoulos|first6=Meletios A.|last7=Psaltopoulou|first7=Theodora|title=Risk Factors for Multiple Myeloma: A Systematic Review of Meta-Analyses|journal=Clinical Lymphoma Myeloma and Leukemia|volume=15|issue=10|year=2015|pages=563–577.e3|issn=21522650|doi=10.1016/j.clml.2015.06.003}}</ref> | ||
** [[M protein]] in blood or urine | ** [[M protein]] in blood or urine | ||
** [[Bone marrow cells|Bone marrow]] [[plasma cells]] constitute more than 10% of the [[blood cells]] | ** [[Bone marrow cells|Bone marrow]] [[plasma cells]] constitute more than 10% of the [[blood cells]] | ||
** Presence of solitary [[plasmacytoma]] in bone | ** Presence of solitary [[plasmacytoma]] in bone | ||
** | ** ≥ 1 myeloma-defining event | ||
** CRAB features ( explained above) | ** CRAB features ( explained above) | ||
** Osteolytic lesions on bone x-ray | ** Osteolytic lesions on bone x-ray | ||
* Patients with active [[ | * Patients with active [[multiple myeloma]] usually require treatment to prevent progression of disease which can lead to death. | ||
==== Smoldering multiple myeloma ==== | ==== Smoldering multiple myeloma ==== | ||
* It is asymptomatic type of [[Multiple myeloma classification|multiple myeloma]]<ref name="pmid27291302">{{cite journal |vauthors=Rajkumar SV |title=Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=7 |pages=719–34 |date=July 2016 |pmid=27291302 |pmc=5291298 |doi=10.1002/ajh.24402 |url=}}</ref> | * It is asymptomatic type of [[Multiple myeloma classification|multiple myeloma]].<ref name="pmid27291302">{{cite journal |vauthors=Rajkumar SV |title=Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=7 |pages=719–34 |date=July 2016 |pmid=27291302 |pmc=5291298 |doi=10.1002/ajh.24402 |url=}}</ref> | ||
* Shows presence of M-spike that quantitates > 3 g/dl on [[protein electrophoresis]] | * Shows presence of M-spike that quantitates > 3 g/dl on [[protein electrophoresis]]. | ||
* Presence of [[Bone marrow cells|bone marrow plasma cell]] burden of > 10% but < 60% | * Presence of [[Bone marrow cells|bone marrow plasma cell]] burden of > 10% but < 60%. | ||
* Absence of end-organ damage such as [[anemia]], [[hypercalcemia]], [[Renal dysfunction|renal dysfunction,]] or [[Osseous|osseous lesions]] | * Absence of end-organ damage such as [[anemia]], [[hypercalcemia]], [[Renal dysfunction|renal dysfunction,]] or [[Osseous|osseous lesions]]. | ||
* Patients with smoldering (asymptomatic) [[ | * Patients with smoldering (asymptomatic) [[multiple myeloma]] are managed by observation and undergoing follow up tests every 3 to 6 months. | ||
* There is high risk of developing [[ | * There is high risk of developing active [[multiple myeloma]]. | ||
==== Plasma-cell leukemia ==== | ==== Plasma-cell leukemia ==== | ||
* | * Characterized by large number of [[plasma cells]] circulating in the blood.<ref name="Rajkumar2016" /> | ||
* Rare condition, can develop in to most aggressive form of [[Multiple myeloma Classification|multiple myeloma]]. | * Rare condition, can develop in to most aggressive form of [[Multiple myeloma Classification|multiple myeloma]]. | ||
* Treatment options for [[plasma cell leukemia]] is [[chemotherapy]] or [[Hematopoietic stem cell transplantation|stem cell transplant]]. | * Treatment options for [[plasma cell leukemia]] is [[chemotherapy]] or [[Hematopoietic stem cell transplantation|stem cell transplant]]. | ||
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==== Non-secretory myeloma ==== | ==== Non-secretory myeloma ==== | ||
* Type of [[Multiple myeloma classification|multiple myeloma]] with less amount of [[M protein|M proteins]] secretion in [[blood]] or urine.<ref name="Rajkumar2016" /> | * Type of [[Multiple myeloma classification|multiple myeloma]] with less amount of [[M protein|M proteins]] secretion in [[blood]] or urine.<ref name="Rajkumar2016" /> | ||
* M protein is not detected by [[serum protein electrophoresis]] | * M protein is not detected by [[serum protein electrophoresis]]. | ||
* [[Bone marrow]] exibit [[Myeloma|myeloma cells]]. | * [[Bone marrow]] exibit [[Myeloma|myeloma cells]]. | ||
* Osteolytic bone lesions are seen on | * Osteolytic bone lesions are seen on X-ray. | ||
==== IgD myeloma ==== | ==== IgD myeloma ==== | ||
* IgD type constitues 2% of [[Multiple myeloma Classification|multiple myeloma]]<ref name="Rajkumar2016" /> | * IgD type constitues 2% of [[Multiple myeloma Classification|multiple myeloma]].<ref name="Rajkumar2016" /> | ||
* IgD [[Multiple myeloma classification|multiple myeloma]] has similar signs and symptoms as other types of [[Multiple myeloma classification|multiple myeloma]]. | * IgD [[Multiple myeloma classification|multiple myeloma]] has similar signs and symptoms as other types of [[Multiple myeloma classification|multiple myeloma]]. | ||
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==== Osteosclerotic myeloma ==== | ==== Osteosclerotic myeloma ==== | ||
* It is a rare disorder affecting multiple systems of the body<ref name="Rajkumar2016">{{cite journal|last1=Rajkumar|first1=S. Vincent|title=Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management|journal=American Journal of Hematology|volume=91|issue=7|year=2016|pages=719–734|issn=03618609|doi=10.1002/ajh.24402}}</ref> | * It is a rare disorder affecting multiple systems of the body.<ref name="Rajkumar2016">{{cite journal|last1=Rajkumar|first1=S. Vincent|title=Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management|journal=American Journal of Hematology|volume=91|issue=7|year=2016|pages=719–734|issn=03618609|doi=10.1002/ajh.24402}}</ref> | ||
* It is called POEMS syndrome: [[polyneuropathy]], [[Organomegaly|organomegaly,]] [[endocrinopathy]], monoclonal protein, skin changes | * It is called POEMS syndrome: [[polyneuropathy]], [[Organomegaly|organomegaly,]] [[endocrinopathy]], monoclonal protein, skin changes. | ||
* Treatment option for osteoclastic myeloma include: | * Treatment option for osteoclastic myeloma include: | ||
** [[Chemotherapy]] | ** [[Chemotherapy]] | ||
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==== Solitary plasmacytoma of bone ==== | ==== Solitary plasmacytoma of bone ==== | ||
* [[Plasmacytoma]] is collection of abnormal [[plasma cells]] forming a | * [[Plasmacytoma]] is collection of abnormal [[plasma cells]] forming a single tumor.<ref name="CaersPaiva2018">{{cite journal|last1=Caers|first1=J.|last2=Paiva|first2=B.|last3=Zamagni|first3=E.|last4=Leleu|first4=X.|last5=Bladé|first5=J.|last6=Kristinsson|first6=S. Y.|last7=Touzeau|first7=C.|last8=Abildgaard|first8=N.|last9=Terpos|first9=E.|last10=Heusschen|first10=R.|last11=Ocio|first11=E.|last12=Delforge|first12=M.|last13=Sezer|first13=O.|last14=Beksac|first14=M.|last15=Ludwig|first15=H.|last16=Merlini|first16=G.|last17=Moreau|first17=P.|last18=Zweegman|first18=S.|last19=Engelhardt|first19=M.|last20=Rosiñol|first20=L.|title=Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel|journal=Journal of Hematology & Oncology|volume=11|issue=1|year=2018|issn=1756-8722|doi=10.1186/s13045-017-0549-1}}</ref> | ||
* [[Plasmacytoma|Solitary plasmacytoma]] is | * [[Plasmacytoma|Solitary plasmacytoma]] is occurrence of single bone [[tumor]] made up of myeloma cells. | ||
* Xray shows an osteolytic lesion at the site of the [[Tumor|tumor.]] | * Xray shows an osteolytic lesion at the site of the [[Tumor|tumor.]] | ||
* [[Bone marrow]] plasma population remains less than 10% | * [[Bone marrow]] plasma population remains less than 10%. | ||
* One third of patients with solitary [[plasmacytoma]] will develop [[Multiple myeloma classification|multiple myeloma]]. | * One third of patients with solitary [[plasmacytoma]] will develop [[Multiple myeloma classification|multiple myeloma]]. | ||
==== Extramedullary plasmacytoma ==== | ==== Extramedullary plasmacytoma ==== | ||
* It is | * It is developed outside the [[bone marrow]] in soft tissues of the body<ref name="Rajkumar2016" /> | ||
* Most commonly seen in throat,[[paranasal sinuses]], [[nasal cavity]], [[larynx]], [[Gastrointestinal tract|GI tract,]] [[breast]] and [[brain]]. | * Most commonly seen in throat, [[paranasal sinuses]], [[nasal cavity]], [[larynx]], [[Gastrointestinal tract|GI tract,]] [[breast]], and [[brain]]. | ||
* Diagnosis is confirmed by [[biopsy]] of the [[Tumor|tumor.]] | * Diagnosis is confirmed by [[biopsy]] of the [[Tumor|tumor.]] | ||
* X-rays and | * X-rays and [[bone marrow]] [[biopsy]] is normal. | ||
* Treatment is done with either [[radiation therapy]] or surgery. | * Treatment is done with either [[radiation therapy]] or surgery. | ||
For more information about | For more information about [[multiple myeloma]], '''[[Multiple myeloma |click here]].''' | ||
=== Malignant lymphoproliferative disorders === | === Malignant lymphoproliferative disorders === | ||
==== Waldenstrom macroglobulinemia ==== | ==== Waldenstrom macroglobulinemia ==== | ||
* [[Waldenström's macroglobulinemia|Waldenstrom macroglobulinemia]] is a cancer involving | * [[Waldenström's macroglobulinemia|Waldenstrom macroglobulinemia]] is a cancer involving [[lymphocytes]].<ref name="pmid22773606">{{cite journal |vauthors=Braggio E, Philipsborn C, Novak A, Hodge L, Ansell S, Fonseca R |title=Molecular pathogenesis of Waldenstrom's macroglobulinemia |journal=Haematologica |volume=97 |issue=9 |pages=1281–90 |date=September 2012 |pmid=22773606 |pmc=3436227 |doi=10.3324/haematol.2012.068478 |url=}}</ref> | ||
* The main attributing [[antibody]] is [[IgM]]. | * The main attributing [[antibody]] is [[IgM]]. | ||
* It is a type of [[lymphoproliferative disease]] | * It is a type of [[lymphoproliferative disease]]. | ||
* It shares clinical characteristics with the indolent [[Non-Hodgkin lymphoma|non-Hodgkin lymphomas]]. | * It shares clinical characteristics with the indolent [[Non-Hodgkin lymphoma|non-Hodgkin lymphomas]]. | ||
* [[Waldenström's macroglobulinemia|Waldenstrom macroglobulinemia]] represents 1% of all hematological cancers | * [[Waldenström's macroglobulinemia|Waldenstrom macroglobulinemia]] represents 1% of all hematological cancers. | ||
* Common causes of [[Waldenström's macroglobulinemia]] include [[genetic]], environmental, and [[autoimmune]] factors. | * Common causes of [[Waldenström's macroglobulinemia]] include [[genetic]], environmental, and [[autoimmune]] factors. | ||
* Common [[risk factors]] in the development of [[Waldenström's macroglobulinemia]] are [[ | * Common [[risk factors]] in the development of [[Waldenström's macroglobulinemia]] are [[monoclonal gammopathies of undetermined significance]]. | ||
For more information about Waldenström's macroglobulinemia | For more information about [[Waldenström's macroglobulinemia]], '''[[Waldenström's macroglobulinemia |click here]].''' | ||
==== Malignant lymphoma ==== | ==== Malignant lymphoma ==== | ||
* Type of [[cancer]] that originates in [[Lymphocyte|lymphocytes]]<ref name="isbn92-832-2411-6">{{cite book |author= |title=Pathology and Genetics of Haemo (World Health Organization Classification of Tumours S.) |publisher=Oxford Univ Pr |location= |year= |pages= |isbn=92-832-2411-6 |oclc= |doi=}}</ref> | * Type of [[cancer]] that originates in [[Lymphocyte|lymphocytes]].<ref name="isbn92-832-2411-6">{{cite book |author= |title=Pathology and Genetics of Haemo (World Health Organization Classification of Tumours S.) |publisher=Oxford Univ Pr |location= |year= |pages= |isbn=92-832-2411-6 |oclc= |doi=}}</ref> | ||
* Also called [[Hematological malignancy|hematological neoplasms]]. | * Also called [[Hematological malignancy|hematological neoplasms]]. | ||
* | * Primary types include [[Hodgkin lymphoma]] and [[non-Hodgkin lymphoma]]. | ||
For more information about lymphoma '''[[lymphoma |click here]]''' | For more information about malignant lymphoma, '''[[lymphoma |click here]].''' | ||
=== Chronic lymphocytic leukemia === | === Chronic lymphocytic leukemia === | ||
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* [[Prognosis]] is generally good, and the 5-year survival rate of patients with [[chronic lymphocytic leukemia]] is approximately 81.7%. | * [[Prognosis]] is generally good, and the 5-year survival rate of patients with [[chronic lymphocytic leukemia]] is approximately 81.7%. | ||
* The mainstay of therapy for [[symptomatic]] [[chronic lymphocytic leukemia]] patients is immunochemotherapy. | * The mainstay of therapy for [[symptomatic]] [[chronic lymphocytic leukemia]] patients is immunochemotherapy. | ||
For more information about chronic lymphocytic leukemia '''[[ chronic lymphocytic leukemia|click here]]''' | For more information about [[chronic lymphocytic leukemia]], '''[[ chronic lymphocytic leukemia|click here]]''' | ||
== Heavy-chain diseases == | == Heavy-chain diseases == | ||
* Heavy chain diseases are [[ | * Heavy chain diseases are [[plasma cell]] [[neoplasia]] featuring overproduction of [[Immunoglobulin|immunoglobulin heavy chains]].<ref name="MunshiCabot2008">{{cite journal|last1=Munshi|first1=Nikhil C.|last2=Cabot|first2=Richard C.|last3=Harris|first3=Nancy Lee|last4=Shepard|first4=Jo-Anne O.|last5=Rosenberg|first5=Eric S.|last6=Cort|first6=Alice M.|last7=Ebeling|first7=Sally H.|last8=Peters|first8=Christine C.|last9=Digumarthy|first9=Subba|last10=Rahemtullah|first10=Aliyah|title=Case 13-2008|journal=New England Journal of Medicine|volume=358|issue=17|year=2008|pages=1838–1848|issn=0028-4793|doi=10.1056/NEJMcpc0800959}}</ref> | ||
=== γHCD === | === γHCD === | ||
Revision as of 18:25, 19 September 2018
|
Plasma cell disorders |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nazia Fuad M.D., Anmol Pitliya, M.B.B.S. M.D.[2]
Overview
Plasma cell disorders are a diverse type of blood disorders characterized by proliferation of a single clone of plasma cells that produces a homogeneous monoclonal (M) protein. These monoclonal paraprotein are seen in the serum or urine. Monoclonal plasma cells are present in the bone marrow or, rarely, in other tissues. Plasma cell disorders include monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), lymphoplasmacytic lymphoma/ Waldenstrom macroglobulinemia (LPL/WM), lymphoproliferative disorders, smoldering multiple myeloma (SMM); solitary or extramedullary plasmacytoma, amyloidosis, and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). These disorders have been defined by the International Myeloma Working Group in 2006.
Classification
| Plasma cell disorder | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary amyloidosis | Malignant monoclonal gammopathy | Chronic lymphocytic leukemia | Heavy chain diseases (HCD) | Cryoglobulinemia | Monoclonal gammopathy of undetermined significance (MGUS) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Multiple myeloma | Malignant lymphoproliferative disorders | γHCD | αHCD | μHCD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Benign (IgG, IgA, IgD, IgM, and, rarely, free light chains) | Associated neoplasms or other diseases not known to produce monoclonal proteins | Biclonal and triclonal gammopathies | Idiopathic (Bence Jones proteinuria) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Waldenstrom macroglobulinemia | Malignant lymphoma | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Symptomatic multiple myeloma | Smoldering multiple myeloma | Plasma-cell leukemia | Non-secretory myeloma | Solitary plasmacytoma of bone | Osteosclerotic myeloma | Extramedullary plasmacytoma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Differential Diagnosis
| Disease | IgM | IgG | IgA | IgE | IgD | Monoclonal Ig level | SFLC | Bone marrow plasma cells | Other criteria |
|---|---|---|---|---|---|---|---|---|---|
| IgM MGUS | + | − | − | − | − | < 3gm/dl | N/A | <10% |
|
| Non igM MGUS | + | − | + | − | − | < 3gm/dl | N/A | <10% |
|
| Smoldering MM | − | + | + | − | − | > 3gm/dl | N/A | 10-60% |
|
| Light chain MGUS | − | − | − | − | − | <500 mg/24 hrs (urine) | Free kappa or lambda light chain Abnormal ratio (<0.26 or >1.65) Increase in involved light chain concentration |
<10% |
|
| Active symptomatic Multiple myeloma | − | + | + | + | + | >3gm/dl | >100 | >60% |
|
| Waldenstrom macroglobulinemia | + | − | − | − | − | Variable | N/A | >10% |
|
| Solitary Plasmacytoma | + | − | − | − | − | <3mg/dl | Abnormal in 47% cases | Normal |
|
| Primary amyloidosis | − | − | − | − | − | <3md/dl | Light chains of immunoglobulines | <10% |
|
| |||||||||
Monoclonal gammopathies of undetermined significance (MGUS)
- Monoclonal gammopathy of undetermined significance is a condition in which a low or non-quantifiable level of a monoclonal paraprotein is detected in the blood by means of protein electrophoresis.[1][2][3]
- In addition, some patients develop a polyneuropathy or other problems related to the secreted antibody.
- MGUS is a premalignant condition and is distinct from multiple myeloma.
- Pathologically, the lesion in Monoclonal gammopathy of undetermined significance is in fact very similar to that in multiple myeloma.
For more information about Monoclonal gammopathies of undetermined significance click here.
Malignant monoclonal gammopathies
Multiple myeloma
Symptomatic multiple myeloma
- People with multiple myeloma with symptoms are categorized to have active multiple myeloma and will exhibit any of the following features:[4]
- M protein in blood or urine
- Bone marrow plasma cells constitute more than 10% of the blood cells
- Presence of solitary plasmacytoma in bone
- ≥ 1 myeloma-defining event
- CRAB features ( explained above)
- Osteolytic lesions on bone x-ray
- Patients with active multiple myeloma usually require treatment to prevent progression of disease which can lead to death.
Smoldering multiple myeloma
- It is asymptomatic type of multiple myeloma.[5]
- Shows presence of M-spike that quantitates > 3 g/dl on protein electrophoresis.
- Presence of bone marrow plasma cell burden of > 10% but < 60%.
- Absence of end-organ damage such as anemia, hypercalcemia, renal dysfunction, or osseous lesions.
- Patients with smoldering (asymptomatic) multiple myeloma are managed by observation and undergoing follow up tests every 3 to 6 months.
- There is high risk of developing active multiple myeloma.
Plasma-cell leukemia
- Characterized by large number of plasma cells circulating in the blood.[6]
- Rare condition, can develop in to most aggressive form of multiple myeloma.
- Treatment options for plasma cell leukemia is chemotherapy or stem cell transplant.
Non-secretory myeloma
- Type of multiple myeloma with less amount of M proteins secretion in blood or urine.[6]
- M protein is not detected by serum protein electrophoresis.
- Bone marrow exibit myeloma cells.
- Osteolytic bone lesions are seen on X-ray.
IgD myeloma
- IgD type constitues 2% of multiple myeloma.[6]
- IgD multiple myeloma has similar signs and symptoms as other types of multiple myeloma.
- IgD myeloma mostly affect people of younger age.
Osteosclerotic myeloma
- It is a rare disorder affecting multiple systems of the body.[6]
- It is called POEMS syndrome: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes.
- Treatment option for osteoclastic myeloma include:
Solitary plasmacytoma of bone
- Plasmacytoma is collection of abnormal plasma cells forming a single tumor.[7]
- Solitary plasmacytoma is occurrence of single bone tumor made up of myeloma cells.
- Xray shows an osteolytic lesion at the site of the tumor.
- Bone marrow plasma population remains less than 10%.
- One third of patients with solitary plasmacytoma will develop multiple myeloma.
Extramedullary plasmacytoma
- It is developed outside the bone marrow in soft tissues of the body[6]
- Most commonly seen in throat, paranasal sinuses, nasal cavity, larynx, GI tract, breast, and brain.
- Diagnosis is confirmed by biopsy of the tumor.
- X-rays and bone marrow biopsy is normal.
- Treatment is done with either radiation therapy or surgery.
For more information about multiple myeloma, click here.
Malignant lymphoproliferative disorders
Waldenstrom macroglobulinemia
- Waldenstrom macroglobulinemia is a cancer involving lymphocytes.[8]
- The main attributing antibody is IgM.
- It is a type of lymphoproliferative disease.
- It shares clinical characteristics with the indolent non-Hodgkin lymphomas.
- Waldenstrom macroglobulinemia represents 1% of all hematological cancers.
- Common causes of Waldenström's macroglobulinemia include genetic, environmental, and autoimmune factors.
- Common risk factors in the development of Waldenström's macroglobulinemia are monoclonal gammopathies of undetermined significance.
For more information about Waldenström's macroglobulinemia, click here.
Malignant lymphoma
- Type of cancer that originates in lymphocytes.[9]
- Also called hematological neoplasms.
- Primary types include Hodgkin lymphoma and non-Hodgkin lymphoma.
For more information about malignant lymphoma, click here.
Chronic lymphocytic leukemia
- Chronic lymphocytic leukemia arises from pre-follicular center B cells, normally involved in immunoglobulins production.[10]
- Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote both malignant leukemic proliferation and apoptotic resistance of mature B cells.
- Chronic lymphocytic leukemia must be differentiated from hairy cell leukaemia, prolymphocytic leukaemia, follicular lymphoma, and mantle cell lymphoma.
- Prognosis is generally good, and the 5-year survival rate of patients with chronic lymphocytic leukemia is approximately 81.7%.
- The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is immunochemotherapy.
For more information about chronic lymphocytic leukemia, click here
Heavy-chain diseases
- Heavy chain diseases are plasma cell neoplasia featuring overproduction of immunoglobulin heavy chains.[11]
γHCD
- Gamma chain or IgG heavy chain disease
- Primarily seen in elderly men but can occur in children.
- High levels of IgG with reduction of normal immunoglobulin level
- Lymphadenopathy, hepatosplenomegaly and recurrent infections are common features
- Vincristine, corticosteroids and radiation therapy may produce remission.
αHCD
- Alpha chain or IgA heavy chain
- Appears between age 10-30 as an immune response to a microorganism
- Patients present with diffuse abdominal lymphoma and malabsorption.
- Course is variable, some patients die in 1-2 yrs, others go in to remission lasting for many years.
- Serum protein electrophoresis detect increased α & β fraction.
- Treatment is corticosteroids, cytotoxic drugs and broadspectrum antibiotics
μHCD
- MU chain or IGM heavy chain disease
- Mainly affects individuals > 50 yrs
- Spleen, liver and abdominal lymph nodes involvement is more common than peripheral lymphadenopathy
- Serum protein electrophoresis exibit hypogammaglobulinemia.
- Vacuolated plasma cells are pathognomic on bone marrow exam.
- Treatment consists of alkylating agents and corticosteroids.
Cryoglobulinemia
- Cryoglobulinemia is the presence of high amount of heavy globulins (e.g. IgM) in the bloodstream which thicken on exposure to cold.[12][13][14][15]
- Cryoglobulins are circulating immunoglobulins or proteins that become insoluble at less than 4 degrees Celsius.
- Cryoglobulinemia can lead to a medium-sized vessel vasculitis due to vascular deposition of circulating immune complexes.
- This leads to the triad of palpable purpura, arthralgias and peripheral neuropathy
- Common causes ofCryoglobulinemia are primarily hematologic, oncologic, and rheumatic
For more information on Cryoglobulinemia click here
Primary amyloidosis
- The "AL" refers to amyloid light chain.[16][17]
- AL amyloidosis is the most common form of systemic amyloidosis in the US.
- Occurs in 5 to 15% of people with multiple myeloma.
- Treatment can involve application of chemotherapy similar to that used in multiple myeloma
For more information on primary amyloidosis click here
References
- ↑ Jego G, Bataille R, Geffroy-Luseau A, Descamps G, Pellat-Deceunynck C (June 2006). "Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors". Leukemia. 20 (6): 1130–7. doi:10.1038/sj.leu.2404226. PMID 16628189.
- ↑ Dinarello CA (February 2009). "Targeting the pathogenic role of interleukin 1{beta} in the progression of smoldering/indolent myeloma to active disease". Mayo Clin. Proc. 84 (2): 105–7. doi:10.4065/84.2.105. PMC 2664579. PMID 19181642.
- ↑ Merlini G, Palladini G (2012). "Differential diagnosis of monoclonal gammopathy of undetermined significance". Hematology Am Soc Hematol Educ Program. 2012: 595–603. doi:10.1182/asheducation-2012.1.595. PMID 23233640.
- ↑ Sergentanis, Theodoros N.; Zagouri, Flora; Tsilimidos, Gerasimos; Tsagianni, Anastasia; Tseliou, Melina; Dimopoulos, Meletios A.; Psaltopoulou, Theodora (2015). "Risk Factors for Multiple Myeloma: A Systematic Review of Meta-Analyses". Clinical Lymphoma Myeloma and Leukemia. 15 (10): 563–577.e3. doi:10.1016/j.clml.2015.06.003. ISSN 2152-2650.
- ↑ Rajkumar SV (July 2016). "Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management". Am. J. Hematol. 91 (7): 719–34. doi:10.1002/ajh.24402. PMC 5291298. PMID 27291302.
- ↑ 6.0 6.1 6.2 6.3 6.4 Rajkumar, S. Vincent (2016). "Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management". American Journal of Hematology. 91 (7): 719–734. doi:10.1002/ajh.24402. ISSN 0361-8609.
- ↑ Caers, J.; Paiva, B.; Zamagni, E.; Leleu, X.; Bladé, J.; Kristinsson, S. Y.; Touzeau, C.; Abildgaard, N.; Terpos, E.; Heusschen, R.; Ocio, E.; Delforge, M.; Sezer, O.; Beksac, M.; Ludwig, H.; Merlini, G.; Moreau, P.; Zweegman, S.; Engelhardt, M.; Rosiñol, L. (2018). "Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel". Journal of Hematology & Oncology. 11 (1). doi:10.1186/s13045-017-0549-1. ISSN 1756-8722.
- ↑ Braggio E, Philipsborn C, Novak A, Hodge L, Ansell S, Fonseca R (September 2012). "Molecular pathogenesis of Waldenstrom's macroglobulinemia". Haematologica. 97 (9): 1281–90. doi:10.3324/haematol.2012.068478. PMC 3436227. PMID 22773606.
- ↑ Pathology and Genetics of Haemo (World Health Organization Classification of Tumours S.). Oxford Univ Pr. ISBN 92-832-2411-6.
- ↑ Hallek, Michael (2015). "Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment". American Journal of Hematology. 90 (5): 446–460. doi:10.1002/ajh.23979. ISSN 0361-8609.
- ↑ Munshi, Nikhil C.; Cabot, Richard C.; Harris, Nancy Lee; Shepard, Jo-Anne O.; Rosenberg, Eric S.; Cort, Alice M.; Ebeling, Sally H.; Peters, Christine C.; Digumarthy, Subba; Rahemtullah, Aliyah (2008). "Case 13-2008". New England Journal of Medicine. 358 (17): 1838–1848. doi:10.1056/NEJMcpc0800959. ISSN 0028-4793.
- ↑ Scotto G, Cibelli DC, Saracino A, Prato R, Palumbo E, Fazio V; et al. (2006). "Cryoglobulinemia in subjects with HCV infection alone, HIV infection and HCV/HIV coinfection". J Infect. 52 (4): 294–9. doi:10.1016/j.jinf.2005.05.025. PMID 16026843.
- ↑ Suszek D, Majdan M (2018). "[Cryoglobulins and cryoglobulinemic vasculitis]". Wiad Lek. 71 (1 pt 1): 59–63. PMID 29558353.
- ↑ Blank N, Lorenz HM (2016). "[Cryoglobulinemic vasculitis]". Z Rheumatol. 75 (3): 303–15. doi:10.1007/s00393-016-0076-4. PMID 27034078.
- ↑ Ramos-Casals M, Trejo O, García-Carrasco M, Cervera R, Font J (2000). "Mixed cryoglobulinemia: new concepts". Lupus. 9 (2): 83–91. doi:10.1191/096120300678828127. PMID 10787003.
- ↑ Gertz MA (2004). "The classification and typing of amyloid deposits". Am. J. Clin. Pathol. 121 (6): 787–9. doi:10.1309/TR4L-GLVR-JKAM-V5QT. PMID 15198347. Unknown parameter
|month=ignored (help) - ↑ "Amyloidosis Causes, Diagnosis, Symptoms, and Treatment on MedicineNet.com".