Lymphoplasmacytic lymphoma pathophysiology: Difference between revisions

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{{Lymphoplasmacytic lymphoma}}
{{Lymphoplasmacytic lymphoma}}


{{CMG}}; {{AE}}{{S.M.}}  
{{CMG}}; {{AE}} {{S.M.}}  
==Overview==
==Overview==
[[Lymphoplasmacytic lymphoma]] (LPL) is an uncontrolled clonal [[proliferation]] of terminally differentiated [[B lymphocyte|B lymphocytes]], which are normally involved in [[humoral immunity]]. [[Genes]] involved in the [[pathogenesis]] of LPL include ''[[MYD88]]-L265P, and [[CXCR4]]''.
[[Lymphoplasmacytic lymphoma]] ([[Lymphoplasmacytic lymphoma|LPL]]) is an uncontrolled [[Clonal colony|clonal]] [[proliferation]] of terminally [[Differentiate|differentiated]] [[B lymphocyte|B lymphocytes]], which are [[Normal|normally]] involved in [[humoral immunity]]. Two main factors [[Mediation (biology)|mediating]] this [[disease]] include [[IgM]] [[paraprotein]] [[secretion]] and [[Tissue (biology)|tissue]] [[Infiltration (medical)|infiltration]] with [[neoplastic]] [[Lymphoplasmacytic lymphoma|lymphoplasmacytic]] [[cells]]. [[Genes]] involved in the [[pathogenesis]] of [[Lymphoplasmacytic lymphoma|LPL]] include ''[[MYD88]]-L265P, and [[CXCR4]]'' along with various other [[cytogenetic]] and [[epigenetic]] [[abnormalities]]. In [[patients]] of [[lymphoplasmacytic lymphoma]], there is an increased [[incidence]] of [[diffuse large B-cell lymphoma]], [[myelodysplastic syndrome]] ([[acute myeloid leukemia]]), [[Brain tumor|brain tumor,]] and [[MALT lymphoma|renal MALT lymphoma]]. Two [[histologic]] subtypes include lymphoplasmacytoid and [[Lymphoplasmacytic lymphoma|lymphoplasmacytic]] which [[Invasion|invade]] the [[lymphoid organs]] such as [[spleen]], [[lymph nodes]] and [[bone marrow]]. [[Bone marrow]] is [[Infiltration (medical)|infiltrated]] by small [[lymphocytes]], well-formed [[plasma cells]], and [[plasmacytoid]] [[lymphocytes]] in [[diffuse]], [[interstitial]], [[nodular]], paratrabecular, [[nodular]]-[[interstitial]] and mixed paratrabecular-[[nodular]] [[Pattern|patterns]]. [[Lymph nodes]] [[Infiltration (medical)|infiltration]] shows Dutcher and [[Russell bodies]], [[mast cells]], and [[hemosiderin]]-laden [[macrophages]]. [[Peripheral smear]] shows [[Circulation|circulating]] [[malignant]] [[Cells (biology)|cells]] with a [[plasmacytoid]] [[appearance]], having [[basophilic]] [[cytoplasm]], [[Perinuclear space|perinuclear]] [[Halo (medicine)|halo]], and [[nucleus]] with "clock-[[face]]" [[chromatin]] without [[nucleoli]]. [[Immunohistochemistry]] shows pan [[B-cell]] [[Surface chemistry|surface]] [[antigens]] such as [[Immunoglobulin|Ig]]+[[CD19]]+, [[CD20]]+, [[CD22]]+, [[CD79A]]+ and variable [[expression]] of some other [[antigens]].


==Pathophysiology==
==Pathophysiology==
*[[Lymphoplasmacytic lymphoma]] arises from [[Terminal deletion|terminally]] [[Differentiation|differentiated]] [[B cell|B lymphocytes]]. which are [[Normal|normally]] involved in [[humoral immunity]]
 
*[[Lymphoplasmacytic lymphoma]] arises from [[Terminal deletion|terminally]] [[Differentiation|differentiated]] [[B cell|B lymphocytes]]. Which are [[Normal|normally]] involved in [[humoral immunity]].


===B lymphocytes===
===B lymphocytes===
====Development====
====Development====
*[[B cells]] [[Development|develop]] from [[hematopoietic stem cells]] (HSCs) in [[bone marrow]]<ref name=":2">{{Cite journal|title = Lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors|journal = Immunological Reviews|date = 2010-11-01|issn = 1600-065X|pmc = 2975965|pmid = 20969583|pages = 37–46|volume = 238|issue = 1|doi = 10.1111/j.1600-065X.2010.00963.x|first = Motonari|last = Kondo}}</ref>
*[[B cells]] [[Development|develop]] from [[hematopoietic stem cells]] (HSCs) in [[bone marrow]]<ref name=":2">{{Cite journal|title = Lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors|journal = Immunological Reviews|date = 2010-11-01|issn = 1600-065X|pmc = 2975965|pmid = 20969583|pages = 37–46|volume = 238|issue = 1|doi = 10.1111/j.1600-065X.2010.00963.x|first = Motonari|last = Kondo}}</ref>
*Then undergo 2 types of [[selection]] in [[bone marrow]]:
*Then undergo 2 types of [[selection]] in [[bone marrow]]:
**Positive [[selection]] by [[antigen]]-[[Independent assortment|independent]] [[Signaling pathway|signaling]] involving both the pre-[[BCR]] and the [[BCR]]<ref name=":4">{{Cite journal|title = The pre-B cell receptor checkpoint|last = Martensson|first = Inga-Lill|date = 2010|journal = FEBS Letters|volume = 584|issue = 12|pages = 2572–9|doi = 10.1016/j.febslet.2010.04.057|pmid = 20420836|last2 = Almqvist|first2 = Nina|last3 = Grimsholm|first3 = Ola|last4 = Bernardi|first4 = Angelina}}</ref><ref name=":5">{{Cite journal|title = B lymphocytes: how they develop and function|journal = Blood|date = 2008-09-01|issn = 0006-4971|pmc = 2518873|pmid = 18725575|pages = 1570–1580|volume = 112|issue = 5|doi = 10.1182/blood-2008-02-078071|first = Tucker W.|last = LeBien|first2 = Thomas F.|last2 = Tedder}}</ref>
**The positive [[selection]] by [[antigen]]-[[Independent assortment|independent]] [[Signaling pathway|signaling]] involving both the pre-[[BCR]] and the [[BCR]]<ref name=":4">{{Cite journal|title = The pre-B cell receptor checkpoint|last = Martensson|first = Inga-Lill|date = 2010|journal = FEBS Letters|volume = 584|issue = 12|pages = 2572–9|doi = 10.1016/j.febslet.2010.04.057|pmid = 20420836|last2 = Almqvist|first2 = Nina|last3 = Grimsholm|first3 = Ola|last4 = Bernardi|first4 = Angelina}}</ref><ref name=":5">{{Cite journal|title = B lymphocytes: how they develop and function|journal = Blood|date = 2008-09-01|issn = 0006-4971|pmc = 2518873|pmid = 18725575|pages = 1570–1580|volume = 112|issue = 5|doi = 10.1182/blood-2008-02-078071|first = Tucker W.|last = LeBien|first2 = Thomas F.|last2 = Tedder}}</ref>
**[[Negative selection]] [[Lead|leads]] to a [[State (physics)|state]] of [[central tolerance]], by [[Binding (molecular)|binding]] of self-[[antigen]] with the [[BCR]] which if [[Binding|binds]] [[Strong|strongly]] to self-[[antigen]], [[Lead|leads]] to four [[Fate mapping|fates]] of [[B-cell]]:
**[[Negative selection]] [[Lead|leads]] to a [[State (physics)|state]] of [[central tolerance]], by [[Binding (molecular)|binding]] of self-[[antigen]] with the [[BCR]] which if [[Binding|binds]] [[Strong|strongly]] to self-[[antigen]], [[Lead|leads]] to four [[Fate mapping|fates]] of [[B-cell]]:
***[[Clonal selection|Clonal]] [[Deletion (genetics)|deletion]]
***[[Clonal selection|Clonal]] [[Deletion (genetics)|deletion]]
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*Immature [[B cells]] then migrate from [[bone marrow]] to secondary [[lymphoid organs]] (SLOs) such as [[spleen]] and [[lymph nodes]]
*Immature [[B cells]] then migrate from [[bone marrow]] to secondary [[lymphoid organs]] (SLOs) such as [[spleen]] and [[lymph nodes]]
*[[B cell]] [[Activation energy|activation]] begins when the [[B cell]] [[Binding (molecular)|binds]] to an [[antigen]] via its [[BCR]] in SLOs
*[[B cell]] [[Activation energy|activation]] begins when the [[B cell]] [[Binding (molecular)|binds]] to an [[antigen]] via its [[BCR]] in SLOs
====Function====
====Function====
[[B cells]] are:<ref name=":0">{{Cite book|title = Janeway's Immunobiology |edition=8th |last = Murphy |first = Kenneth |publisher = Garland Science |year = 2012|isbn = 9780815342434|location = New York}}</ref>
[[B cells]] are:<ref name=":0">{{Cite book|title = Janeway's Immunobiology |edition=8th |last = Murphy |first = Kenneth |publisher = Garland Science |year = 2012|isbn = 9780815342434|location = New York}}</ref>
*[[Lymphocyte]] subtype of [[white blood cells]]
*[[Lymphocyte]] subtype of [[white blood cells]]
*[[Function (biology)|Function]] as a part of [[humoral immunity]] which is a component of [[adaptive immune system]]
*[[Function (biology)|Function]] as a part of [[humoral immunity]] which is a component of [[adaptive immune system]]
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====Factors mediating lymphoplasmacytic lymphoma====
====Factors mediating lymphoplasmacytic lymphoma====
* It is understood that LPL is mediated by 2 major factors:
 
*It is understood that LPL is mediated by 2 major factors:
*#The [[secretion]] of [[IgM|IgM paraprotein]]:
*#The [[secretion]] of [[IgM|IgM paraprotein]]:
*#*[[Causes]] [[symptoms]] of [[hyperviscosity syndrome]]
*#*[[Causes]] [[symptoms]] of [[hyperviscosity syndrome]]
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==Genetics==
==Genetics==
*The exact [[pathogenesis]] of [[lymphoplasmacytic lymphoma]] is not completely understood; however, its [[Heredity|familial pattern]] of involvement [[Support|supports]] the role played by [[Genetics|genetic factors]] in the [[pathogenesis]] of this [[disease]]<ref name="pmid20308603">{{cite journal| author=Royer RH, Koshiol J, Giambarresi TR, Vasquez LG, Pfeiffer RM, McMaster ML| title=Differential characteristics of Waldenström macroglobulinemia according to patterns of familial aggregation. | journal=Blood | year= 2010 | volume= 115 | issue= 22 | pages= 4464-71 | pmid=20308603 | doi=10.1182/blood-2009-10-247973 | pmc=2881498 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20308603  }} </ref><ref name="pmid16357024">{{cite journal| author=Treon SP, Hunter ZR, Aggarwal A, Ewen EP, Masota S, Lee C et al.| title=Characterization of familial Waldenstrom's macroglobulinemia. | journal=Ann Oncol | year= 2006 | volume= 17 | issue= 3 | pages= 488-94 | pmid=16357024 | doi=10.1093/annonc/mdj111 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16357024  }} </ref>
*The exact [[pathogenesis]] of [[lymphoplasmacytic lymphoma]] is not completely understood; however, its [[Heredity|familial pattern]] of involvement [[Support|supports]] the role played by [[Genetics|genetic factors]] in the [[pathogenesis]] of this [[disease]]<ref name="pmid20308603">{{cite journal| author=Royer RH, Koshiol J, Giambarresi TR, Vasquez LG, Pfeiffer RM, McMaster ML| title=Differential characteristics of Waldenström macroglobulinemia according to patterns of familial aggregation. | journal=Blood | year= 2010 | volume= 115 | issue= 22 | pages= 4464-71 | pmid=20308603 | doi=10.1182/blood-2009-10-247973 | pmc=2881498 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20308603  }} </ref><ref name="pmid16357024">{{cite journal| author=Treon SP, Hunter ZR, Aggarwal A, Ewen EP, Masota S, Lee C et al.| title=Characterization of familial Waldenstrom's macroglobulinemia. | journal=Ann Oncol | year= 2006 | volume= 17 | issue= 3 | pages= 488-94 | pmid=16357024 | doi=10.1093/annonc/mdj111 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16357024  }} </ref>
*[[Development (biology)|Development]] of LPL is the [[result]] of multiple [[genetic mutations]]<ref name="UTDR">{{cite journal |vauthors=Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, Kohlhammer H, Xu W, Yang Y, Zhao H, Shaffer AL, Romesser P, Wright G, Powell J, Rosenwald A, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Staudt LM |title=Oncogenically active MYD88 mutations in human lymphoma |journal=Nature |volume=470 |issue=7332 |pages=115–9 |year=2011 |pmid=21179087 |doi=10.1038/nature09671 |url=}}</ref>
*[[Development (biology)|Development]] of LPL is the [[result]] of multiple [[genetic mutations]]<ref name="UTDR">{{cite journal |vauthors=Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, Kohlhammer H, Xu W, Yang Y, Zhao H, Shaffer AL, Romesser P, Wright G, Powell J, Rosenwald A, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Staudt LM |title=Oncogenically active MYD88 mutations in human lymphoma |journal=Nature |volume=470 |issue=7332 |pages=115–9 |year=2011 |pmid=21179087 |doi=10.1038/nature09671 |url=}}</ref>
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***[[Patients]] with [[lymphoplasmacytic lymphoma]] with co-existing [[mutation]] of [[MYD88]] & [[CXCR4]] are more likely to have [[hyperviscosity syndrome|hyper-viscosity syndrome]] and [[bone marrow]] involvement<ref name="UTDR" />
***[[Patients]] with [[lymphoplasmacytic lymphoma]] with co-existing [[mutation]] of [[MYD88]] & [[CXCR4]] are more likely to have [[hyperviscosity syndrome|hyper-viscosity syndrome]] and [[bone marrow]] involvement<ref name="UTDR" />
***[[Somatic hypermutation]] in IGHV/[[Immunoglobulin|IG]] [[gene]] [[rearrangement]]<ref name="pmid28366781">{{cite journal| author=Yun S, Johnson AC, Okolo ON, Arnold SJ, McBride A, Zhang L et al.| title=Waldenström Macroglobulinemia: Review of Pathogenesis and Management. | journal=Clin Lymphoma Myeloma Leuk | year= 2017 | volume= 17 | issue= 5 | pages= 252-262 | pmid=28366781 | doi=10.1016/j.clml.2017.02.028 | pmc=5413391 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28366781  }} </ref>
***[[Somatic hypermutation]] in IGHV/[[Immunoglobulin|IG]] [[gene]] [[rearrangement]]<ref name="pmid28366781">{{cite journal| author=Yun S, Johnson AC, Okolo ON, Arnold SJ, McBride A, Zhang L et al.| title=Waldenström Macroglobulinemia: Review of Pathogenesis and Management. | journal=Clin Lymphoma Myeloma Leuk | year= 2017 | volume= 17 | issue= 5 | pages= 252-262 | pmid=28366781 | doi=10.1016/j.clml.2017.02.028 | pmc=5413391 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28366781  }} </ref>
***ARIDA [[mutations]] (17%)
***AT-rich interactive domain-containing protein 1A gene (ARIDA) [[mutations]] (17%)
 
===Cytogenetics===
===Cytogenetics===
*Many [[Cytogenetics|cytogenetic]] [[abnormalities]] were [[Reporting disease cases|reported]] in [[lymphoplasmacytic lymphoma|lymphoplasmacytic lymphoma's]] [[patients]] including:
*Many [[Cytogenetics|cytogenetic]] [[abnormalities]] were [[Reporting disease cases|reported]] in [[lymphoplasmacytic lymphoma|lymphoplasmacytic lymphoma's]] [[patients]] including:
**[[Deletion]] of the long [[arm]] of [[Chromosome 6 (human)|chromosome 6]]q21-22.1 (most common, 50%)<ref name="TreonHunter2006">{{cite journal|last1=Treon|first1=S. P.|last2=Hunter|first2=Z. R.|last3=Aggarwal|first3=A.|last4=Ewen|first4=E. P.|last5=Masota|first5=S.|last6=Lee|first6=C.|last7=Santos|first7=D. Ditzel|last8=Hatjiharissi|first8=E.|last9=Xu|first9=L.|last10=Leleu|first10=X.|last11=Tournilhac|first11=O.|last12=Patterson|first12=C. J.|last13=Manning|first13=R.|last14=Branagan|first14=A. R.|last15=Morton|first15=C. C.|title=Characterization of familial Waldenström's macroglobulinemia|journal=Annals of Oncology|volume=17|issue=3|year=2006|pages=488–494|issn=1569-8041|doi=10.1093/annonc/mdj111}}</ref>
**[[Deletion]] of the long [[arm]] of [[Chromosome 6 (human)|chromosome 6]]q21-22.1 (most common, 50%)<ref name="TreonHunter2006">{{cite journal|last1=Treon|first1=S. P.|last2=Hunter|first2=Z. R.|last3=Aggarwal|first3=A.|last4=Ewen|first4=E. P.|last5=Masota|first5=S.|last6=Lee|first6=C.|last7=Santos|first7=D. Ditzel|last8=Hatjiharissi|first8=E.|last9=Xu|first9=L.|last10=Leleu|first10=X.|last11=Tournilhac|first11=O.|last12=Patterson|first12=C. J.|last13=Manning|first13=R.|last14=Branagan|first14=A. R.|last15=Morton|first15=C. C.|title=Characterization of familial Waldenström's macroglobulinemia|journal=Annals of Oncology|volume=17|issue=3|year=2006|pages=488–494|issn=1569-8041|doi=10.1093/annonc/mdj111}}</ref>
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===Epigenetics:===
===Epigenetics:===
*Three most common [[epigenetic]] causes are:
*Three most common [[epigenetic]] causes are:
**[[DNA methylation]], [[histone acetylation]], and [[non-coding RNA|non-codin]]<nowiki/>[[non-coding RNA|g RNA]]<nowiki/>s such as miRNAs<ref name="aa">Waldenström macroglobulinemia. International Waldenström Macroglobulinemia foundation (2015)http://www.iwmf.com/sites/default/files/docs/WM_Review_Ghobrial_Jan2014.pdf Accessed on November 12, 2015</ref>
**[[DNA methylation]], [[histone acetylation]], and [[non-coding RNA|non-codin]]<nowiki/>[[non-coding RNA|g RNA]]<nowiki/>s such as miRNAs<ref name="aa">Waldenström macroglobulinemia. International Waldenström Macroglobulinemia foundation (2015)http://www.iwmf.com/sites/default/files/docs/WM_Review_Ghobrial_Jan2014.pdf Accessed on November 12, 2015</ref>
*[[Upregulation]]<nowiki/> of miRNAs 155, 184, 206, 363, 494, and 542-3p occurs in [[Waldenström macroglobulinemia]]; among which miRNA-155 has a crucial role in [[tumor]] [[cell growth]] and [[proliferation]] in [[Waldenström macroglobulinemia]]
**[[Upregulation]] of miRNAs 155, 184, 206, 363, 494, and<nowiki/> 542-<nowiki/>3p occurs in [[Waldenström macroglobulinemia]]; among which miRNA-155 has a crucial role in [[tumor]] [[cell growth]] and [[proliferation]] in [[Waldenström macroglobulinemia]]
*
*[[Gene transcription]] through [[histone acetylation]] occurs following increased [[Gene expression|expression]] of miRNA-206 and reduced [[expression]] of miRNA-9
*[[Gene transcription]] through [[histone acetylation]] occurs following increased [[Gene expression|expression]] of miRNA-206 and reduced [[expression]] of miRNA-9


==Associated Conditions==
==Associated Conditions==
Several [[Study arms|studies]] showed an increased [[incidence]] of following [[second]] [[cancers]] in [[patients]] with [[lymphoplasmacytic lymphoma]]:<ref name="Acs">{{cite journal |vauthors=Morra E, Varettoni M, Tedeschi A, Arcaini L, Ricci F, Pascutto C, Rattotti S, Vismara E, Paris L, Cazzola M |title=Associated cancers in Waldenström macroglobulinemia: clues for common genetic predisposition |journal=Clin Lymphoma Myeloma Leuk |volume=13 |issue=6 |pages=700–3 |year=2013 |pmid=24070824 |doi=10.1016/j.clml.2013.05.008 |url=}}</ref>
Several [[Study arms|studies]] showed an increased [[incidence]] of following [[second]] [[cancers]] in [[patients]] with [[lymphoplasmacytic lymphoma]]:<ref name="Acs">{{cite journal |vauthors=Morra E, Varettoni M, Tedeschi A, Arcaini L, Ricci F, Pascutto C, Rattotti S, Vismara E, Paris L, Cazzola M |title=Associated cancers in Waldenström macroglobulinemia: clues for common genetic predisposition |journal=Clin Lymphoma Myeloma Leuk |volume=13 |issue=6 |pages=700–3 |year=2013 |pmid=24070824 |doi=10.1016/j.clml.2013.05.008 |url=}}</ref>
*[[Diffuse large B-cell lymphoma]]
*[[Diffuse large B-cell lymphoma]]
*[[Myelodysplastic syndrome]]/[[Acute myeloid leukemia]]  
*[[Myelodysplastic syndrome]]/[[Acute myeloid leukemia]]
*[[Brain tumor]]
*[[Brain tumor]]
*[[MALT lymphoma|Renal MALT lymphoma]] <ref name="AC">{{cite journal |vauthors=Chi PJ, Pei SN, Huang TL, Huang SC, Ng HY, Lee CT |title=Renal MALT lymphoma associated with Waldenström macroglobulinemia |journal=J. Formos. Med. Assoc. |volume=113 |issue=4 |pages=255–7 |year=2014 |pmid=24685302 |doi=10.1016/j.jfma.2011.02.007 |url=}}</ref>
*[[MALT lymphoma|Renal MALT lymphoma]] <ref name="AC">{{cite journal |vauthors=Chi PJ, Pei SN, Huang TL, Huang SC, Ng HY, Lee CT |title=Renal MALT lymphoma associated with Waldenström macroglobulinemia |journal=J. Formos. Med. Assoc. |volume=113 |issue=4 |pages=255–7 |year=2014 |pmid=24685302 |doi=10.1016/j.jfma.2011.02.007 |url=}}</ref>


==Microscopic Pathology==
==Microscopic Pathology==
*LPL is a form of an indolent (slowly [[Growth|growing]]) [[Non hodgkin's lymphoma|non-hodgkin's lymphoma]]. LPL is called so because the [[lymphoma]] cells have the characteristics of both [[lymphocytes]] and [[plasma cells]].
*LPL is a form of an indolent (slowly [[Growth|growing]]) [[Non hodgkin's lymphoma|non-hodgkin's lymphoma]]. LPL is called so because the [[lymphoma]] cells have the characteristics of both [[lymphocytes]] and [[plasma cells]].
*Following [[lymphoid organs]] are involved in LPL:  
*Following [[lymphoid organs]] are involved in LPL:  
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***Paratrabecular
***Paratrabecular
***[[Nodular]]-[[interstitial]]
***[[Nodular]]-[[interstitial]]
***Mixed paratrabacular-[[nodular]]
***Mixed paratrabecular-[[nodular]]
*WM has two [[histologic]] subtypes:<ref name="pmid9366295">{{cite journal| author=Andriko JA, Aguilera NS, Chu WS, Nandedkar MA, Cotelingam JD| title=Waldenström's macroglobulinemia: a clinicopathologic study of 22 cases. | journal=Cancer | year= 1997 | volume= 80 | issue= 10 | pages= 1926-35 | pmid=9366295 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9366295  }} </ref>
*WM has two [[histologic]] subtypes:<ref name="pmid9366295">{{cite journal| author=Andriko JA, Aguilera NS, Chu WS, Nandedkar MA, Cotelingam JD| title=Waldenström's macroglobulinemia: a clinicopathologic study of 22 cases. | journal=Cancer | year= 1997 | volume= 80 | issue= 10 | pages= 1926-35 | pmid=9366295 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9366295  }} </ref>
**Lymphoplasmacytoid (73%)
**[[Lymphoplasmacytoid lymphoma|Lymphoplasmacytoid]] (73%)
**Lymphoplasmacytic (27%)
**[[Lymphoplasmacytic lymphoma|Lymphoplasmacytic]] (27%)
* The [[Cytological|cytologic]] [[Composition of Causes|composition]] and the [[Degree (angle)|degree]] of plasmacytic [[differentiation]] varies from case to case
*The [[Cytological|cytologic]] [[Composition of Causes|composition]] and the [[Degree (angle)|degree]] of plasmacytic [[differentiation]] varies from case to case
* The [[bone marrow]] contains variable numbers of [[pleomorphic]] [[lymphoid]] [[Cells (biology)|cells]]
*The [[bone marrow]] contains variable numbers of [[pleomorphic]] [[lymphoid]] [[Cells (biology)|cells]]
* [[Russell bodies]] ([[cytoplasmic]]) or Dutcher [[Body|bodies]] (pseudonuclear) which are positive for [[periodic acid Schiff]], can be seen due to accumulation of [[cytoplasmic]] [[IgM]] in some [[bone marrow]] [[Cells (biology)|cells]]
*[[Russell bodies]] ([[cytoplasmic]]) or Dutcher [[Body|bodies]] (pseudonuclear) which are positive for [[periodic acid Schiff]], can be seen due to accumulation of [[cytoplasmic]] [[IgM]] in some [[bone marrow]] [[Cells (biology)|cells]]
* [[Mast cell]] [[hyperplasia]] is common and may [[Stimulated emission|stimulate]] [[tumor cell]] [[proliferation]] and [[monoclonal]] [[IgM]] [[secretion]]
*[[Mast cell]] [[hyperplasia]] is common and may [[Stimulated emission|stimulate]] [[tumor cell]] [[proliferation]] and [[monoclonal]] [[IgM]] [[secretion]]
* [[Gene expression]] profiling has indicated that [[lymphoid]] [[Cells (biology)|cells]] of WM more closely resemble those of [[chronic lymphocytic leukemia]] than those of [[myeloma]]<ref name="pmid16804116">{{cite journal| author=Chng WJ, Schop RF, Price-Troska T, Ghobrial I, Kay N, Jelinek DF et al.| title=Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma. | journal=Blood | year= 2006 | volume= 108 | issue= 8 | pages= 2755-63 | pmid=16804116 | doi=10.1182/blood-2006-02-005488 | pmc=1895596 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16804116  }} </ref>
*[[Gene expression]] profiling has indicated that [[lymphoid]] [[Cells (biology)|cells]] of WM more closely resemble those of [[chronic lymphocytic leukemia]] than those of [[myeloma]]<ref name="pmid16804116">{{cite journal| author=Chng WJ, Schop RF, Price-Troska T, Ghobrial I, Kay N, Jelinek DF et al.| title=Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma. | journal=Blood | year= 2006 | volume= 108 | issue= 8 | pages= 2755-63 | pmid=16804116 | doi=10.1182/blood-2006-02-005488 | pmc=1895596 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16804116  }} </ref>
* '''[[Lymph nodes]]''' involvement has following characteristics:
*'''[[Lymph nodes]]''' involvement has following characteristics:
**Dutcher and [[Russell bodies]], [[mast cells]], and [[hemosiderin]]-laden [[macrophages]] comprise the typical characteristic [[lymph node]] involvement
**Dutcher and [[Russell bodies]], [[mast cells]], and [[hemosiderin]]-laden [[macrophages]] comprise the typical characteristic [[lymph node]] involvement
**Numerous non-[[caseating]] [[granulomas]] are [[Rare|rarely]] observed
**Numerous non-[[caseating]] [[granulomas]] are [[Rare|rarely]] observed
Line 153: Line 165:


{|  
{|  
|- valign="top"
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| [[File:Atypical Bcell gif.gif|thumb|200px|none|High-power field of peripheral blood smear revealing a large, atypical B cell with mild cytoplasmic expansion, coarse chromatin, multiple distinct nucleoli and peripheral vacuolation.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2944189_1752-1947-4-300-2&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=17 Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.]]]
[[File:Atypical Bcell gif.gif|thumb|200px|none|High-power field of peripheral blood smear revealing a large, atypical B cell with mild cytoplasmic expansion, coarse chromatin, multiple distinct nucleoli and peripheral vacuolation.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2944189_1752-1947-4-300-2&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=17 Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.]]]
| [[File:WM gif.gif|thumb|200px|none|Medium-power field of bone marrow aspirate demonstrating a population of small atypical lymphocytes admixed with normal cells of erythroid, myeloid and lymphoid lineage.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2944189_1752-1947-4-300-3&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=18 Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.]]]
|
| [[File:Splenic infiltrate gif.gif|thumb|200px|none| Low-power magnification of the splenic tissue. This slide displays significant distortion and diffuse infiltration of the splenic parenchyma by lymphoid cells. Of particular note is the expansion of the white pulp by this infiltrate. [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2944189_1752-1947-4-300-8&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=22 Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.]]]
[[File:Splenic infiltrate gif.gif|thumb|200px|none| Low-power magnification of the splenic tissue. This slide displays significant distortion and diffuse infiltration of the splenic parenchyma by lymphoid cells. Of particular note is the expansion of the white pulp by this infiltrate. [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2944189_1752-1947-4-300-8&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=22 Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.]]]
| [[File:Rouleaux formation gif.gif|thumb|300px|none|(A) Rouleaux formation, plasmacytoid cells, and lymphoid cells in the PBF (Leishman, ×1000). (B) Uni-binucleated plasmacytoid cells in the PBF (Leishman, ×1000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3443994_CRIM.PATHOLOGY2012-271407.001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=49 Source: Sethi B. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.]]]
|
| [[File:Bm aspirate gif.gif|thumb|300px|none| (A) Plasmacytoid cells in the bone marrow aspirates (Leishman, ×1000). (B) Tetranucleated plasmacytoid/plasma cell and lymphoid cell in the bone marrow aspirates (Leishman, ×1000). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC3443994_CRIM.PATHOLOGY2012-271407.002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=50 Source: Sethi B. et al, Department of Pathology, VCSGGMS & RI Srinagar, Pauri Garhwal, Uttarakhand, India.]]]
[[File:WM gif.gif|thumb|200px|none|Medium-power field of bone marrow aspirate demonstrating a population of small atypical lymphocytes admixed with normal cells of erythroid, myeloid and lymphoid lineage.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2944189_1752-1947-4-300-3&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=18 Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.]]]
|- valign="top"
|
| [[File:Wrights stain gif.gif|thumb|200px|none|Photomicrograph showing hypercellular bone marrow smears with the presence of mostly bare nuclei, few lymphoid cells, and plasmacytic cells (Wright's stain, ×1,000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3786287_br-48-230-g001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=24 Source: Pujani M. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.]]]
[[File:Rouleaux formation gif.gif|thumb|300px|none|(A) Rouleaux formation, plasmacytoid cells, and lymphoid cells in the PBF (Leishman, ×1000). (B) Uni-binucleated plasmacytoid cells in the PBF (Leishman, ×1000). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC3443994_CRIM.PATHOLOGY2012-271407.001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=49 Source: Sethi B. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.]]]
| [[File:Splenic lymphoid infiltrate gif.gif|thumb|200px|none|High-power magnification of splenic lymphoid infiltrate. This slide demonstrates that the infiltrate consists of small- and medium-sized atypical lymphocytes, which display dense chromatin clumping and prominent nucleoli.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2944189_1752-1947-4-300-9&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=23 Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.]]]
|
| [[File:Bone marrow infiltrate gif.gif|thumb|200px|none|Photomicrograph showing hypercellular marrow with diffuse infiltration by lymphoid cells, plasmacytoid lymphocytes, a few plasma cells, and mast cells (hematoxylin and eosin stain, ×1,000); inset photomicrograph showing strong cytoplasmic positivity for CD20 in the majority of the lymphoid cells (immunohistochemical stain for CD20, ×400).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3786287_br-48-230-g002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=25 Source: Pujani M. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.]]]
|}
| [[File:GM. kidneys gif.gif|thumb|200px|none| Light Microscopy. There is marked, global, homogeneous, eosinophilic thickening of the glomerular basement membrane with segmental accentuation. Homogeneous, eosinophilic globules are seen in the lumen of occasional capillary loops. The capillary lumina appear reduced in diameter but no inflammatory or proliferative changes are observed. The periglomerular interstitial space shows lymphocytic infiltration. Focal interstitial deposition of homogeneous eosinophilic material is present in the right upper corner of the picture (H&E × 400). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-1&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=31 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.]]]
{|
| [[File:Kidneys.immunoflorescence gif.gif|thumb|200px|none|Immunofluorescence. Global granular and homogeneous deposition of IgG along the glomerular basement membrane. Notice the presence of IgG containing globules in rare capillary loops. They seem to correspond to the eosinophilic globules seen by light microscopy and large electron dense deposits detected by electron microscopy (FITC labeled anti-IgG × 400).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-2&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=32 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.]]]
|
|- valign="top"
[[File:Bone marrow infiltrate gif.gif|thumb|200px|none|[[Photomicrograph]] showing hypercellular marrow with diffuse infiltration by lymphoid cells, plasmacytoid lymphocytes, a few plasma cells, and mast cells (hematoxylin and eosin stain, ×1,000); inset photomicrograph showing strong cytoplasmic positivity for CD20 in the majority of the lymphoid cells (immunohistochemical stain for CD20, ×400).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3786287_br-48-230-g002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=25 Source: Pujani M. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.]]]
| [[File:Kidneys. EM gif.gif|thumb|200px|none|Electron Microscopy. There is marked thickening of the glomerular basement membrane due to the presence of numerous electron dense deposits located at different levels. The deposits vary in size, tend to be spherical in shape and blend together. Under higher magnifications, they did not exhibit a fibrillary or micro-tubular substructure. Notice a thin subendothelial layer of duplicated basement membrane, also containing electron dense deposits, with cellular interposition. The capillary lumen appears significantly reduced in diameter. Also notice electron dense deposits present in the basement membrane of Bowman's capsule on the right upper corner (Uranyl acetate & lead citrate × 35,000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-3&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=33 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.]]]
|
| [[File:EM. kidneys gif.gif|thumb|200px|none|Electron Microscopy. This field illustrates a large subendothelial and several, much smaller, subepithelial electron dense deposits. This pattern is similar to that originally described in MPGN type III and also often seen in proliferative lupus GN. Notice the duplication of the glomerular basement membrane with cellular interposition. The duplicated segment also contains electron dense deposits. Occasionally giant, subendothelial, globular electron dense deposits reduced the capillary loop to a pin-point lumen. Probably they correspond to the globules seen by light and fluorescence microscopy (Uranyl acetate and lead citrate × 40,000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-4&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=34 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.]]]
[[File:Splenic lymphoid infiltrate gif.gif|thumb|200px|none|High-power magnification of splenic lymphoid infiltrate. This slide demonstrates that the infiltrate consists of small- and medium-sized atypical lymphocytes, which display dense chromatin clumping and prominent nucleoli. [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2944189_1752-1947-4-300-9&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=23 Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.]]]
| [[File:Renal biopsy immunoflorescence.gif|thumb|200px|none| Renal biopsy. (A) Immunofluorescent microscopic study showed 2+ reaction for IgM. (B) On the electron microscopic (EM) findings (× 20,000), there are subendothelial (arrow) and mesangial electron dense deposits revealing microtubular structures (25 nm in average diameter).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3102879_jkms-26-824-g001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=40 Source: Kim YL. et al, Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea]]]
|
[[File:Wrights stain gif.gif|thumb|200px|none|[[Photomicrograph]] showing hypercellular bone marrow smears with the presence of mostly bare nuclei, few lymphoid cells, and plasmacytic cells (Wright's stain, ×1,000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3786287_br-48-230-g001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=24 Source: Pujani M. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.]]]
|
[[File:Bm aspirate gif.gif|thumb|300px|none| (A) Plasmacytoid cells in the bone marrow aspirates (Leishman, ×1000). (B) Tetranucleated plasmacytoid/plasma cell and lymphoid cell in the bone marrow aspirates (Leishman, ×1000). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC3443994_CRIM.PATHOLOGY2012-271407.002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=50 Source: Sethi B. et al, Department of Pathology, VCSGGMS & RI Srinagar, Pauri Garhwal, Uttarakhand, India.]]]
|
|}
{|
|
[[File: Kidneys. EM gif.gif|thumb|200px|none|[[Electron microscope|Electron Microscopy]]. There is marked thickening of the glomerular basement membrane due to the presence of numerous electron-dense deposits located at different levels. The deposits vary in size, tend to be spherical in shape and blend together. Under higher magnifications, they did not exhibit a fibrillary or micro-tubular substructure. Notice a thin subendothelial layer of the duplicated basement membrane, also containing electron-dense deposits, with cellular interposition. The capillary lumen appears significantly reduced in diameter. Also notice electron-dense deposits present in the basement membrane of Bowman's capsule on the right upper corner (Uranyl acetate & lead citrate × 35,000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-3&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=33 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.]]]
|
[[File:EM. kidneys gif.gif|thumb|200px|none|[[Electron microscope|Electron Microscopy]]. This field illustrates a large subendothelial and several, much smaller, subepithelial electron-dense deposits. This pattern is similar to that originally described in MPGN type III and also often seen in proliferative lupus GN. Notice the duplication of the glomerular basement membrane with cellular interposition. The duplicated segment also contains electron-dense deposits. Occasionally giant, subendothelial, globular electron-dense deposits reduced the capillary loop to a pin-point lumen. Probably they correspond to the globules seen by light and fluorescence microscopy (Uranyl acetate and lead citrate × 40,000). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-4&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=34 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.]]]
|
[[File:GM. kidneys gif.gif|thumb|200px|none| Light Microscopy. There is marked, global, homogeneous, eosinophilic thickening of the glomerular basement membrane with segmental accentuation. Homogeneous, eosinophilic globules are seen in the lumen of occasional capillary loops. The capillary lumina appear reduced in diameter but no inflammatory or proliferative changes are observed. The periglomerular interstitial space shows lymphocytic infiltration. The focal interstitial deposition of homogeneous eosinophilic material is present in the right upper corner of the picture (H&E × 400). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-1&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=31 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.]]]
|
[[File:Kidneys.immunoflorescence gif.gif|thumb|200px|none|Immunofluorescence. Global granular and homogeneous deposition of IgG along the glomerular basement membrane. Notice the presence of IgG containing globules in rare capillary loops. They seem to correspond to the eosinophilic globules seen by light microscopy and large electron-dense deposits detected by electron microscopy (FITC labeled anti-IgG × 400).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-2&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=32 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.]]]
|
[[File:Renal biopsy immunoflorescence.gif|thumb|200px|none| Renal biopsy. (A) Immunofluorescent microscopic study showed a 2+ reaction for IgM. (B) On the electron microscopic (EM) findings (× 20,000), there are subendothelial (arrow) and mesangial electron-dense deposits revealing microtubular structures (25 nm in average diameter). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC3102879_jkms-26-824-g001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=40 Source: Kim YL. et al, Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea]]]
|
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Latest revision as of 17:11, 23 September 2020

Lymphoplasmacytic lymphoma Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]

Overview

Lymphoplasmacytic lymphoma (LPL) is an uncontrolled clonal proliferation of terminally differentiated B lymphocytes, which are normally involved in humoral immunity. Two main factors mediating this disease include IgM paraprotein secretion and tissue infiltration with neoplastic lymphoplasmacytic cells. Genes involved in the pathogenesis of LPL include MYD88-L265P, and CXCR4 along with various other cytogenetic and epigenetic abnormalities. In patients of lymphoplasmacytic lymphoma, there is an increased incidence of diffuse large B-cell lymphoma, myelodysplastic syndrome (acute myeloid leukemia), brain tumor, and renal MALT lymphoma. Two histologic subtypes include lymphoplasmacytoid and lymphoplasmacytic which invade the lymphoid organs such as spleen, lymph nodes and bone marrow. Bone marrow is infiltrated by small lymphocytes, well-formed plasma cells, and plasmacytoid lymphocytes in diffuse, interstitial, nodular, paratrabecular, nodular-interstitial and mixed paratrabecular-nodular patterns. Lymph nodes infiltration shows Dutcher and Russell bodies, mast cells, and hemosiderin-laden macrophages. Peripheral smear shows circulating malignant cells with a plasmacytoid appearance, having basophilic cytoplasm, perinuclear halo, and nucleus with "clock-face" chromatin without nucleoli. Immunohistochemistry shows pan B-cell surface antigens such as Ig+CD19+, CD20+, CD22+, CD79A+ and variable expression of some other antigens.

Pathophysiology

B lymphocytes

Development

Function

B cells are:[4]

Factors mediating lymphoplasmacytic lymphoma

Genetics

Cytogenetics

Epigenetics:

Associated Conditions

Several studies showed an increased incidence of following second cancers in patients with lymphoplasmacytic lymphoma:[22]

Microscopic Pathology

High-power field of peripheral blood smear revealing a large, atypical B cell with mild cytoplasmic expansion, coarse chromatin, multiple distinct nucleoli and peripheral vacuolation.Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.
Low-power magnification of the splenic tissue. This slide displays significant distortion and diffuse infiltration of the splenic parenchyma by lymphoid cells. Of particular note is the expansion of the white pulp by this infiltrate. Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.
Medium-power field of bone marrow aspirate demonstrating a population of small atypical lymphocytes admixed with normal cells of erythroid, myeloid and lymphoid lineage.Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.
(A) Rouleaux formation, plasmacytoid cells, and lymphoid cells in the PBF (Leishman, ×1000). (B) Uni-binucleated plasmacytoid cells in the PBF (Leishman, ×1000). Source: Sethi B. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.
Photomicrograph showing hypercellular marrow with diffuse infiltration by lymphoid cells, plasmacytoid lymphocytes, a few plasma cells, and mast cells (hematoxylin and eosin stain, ×1,000); inset photomicrograph showing strong cytoplasmic positivity for CD20 in the majority of the lymphoid cells (immunohistochemical stain for CD20, ×400).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3786287_br-48-230-g002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=25 Source: Pujani M. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.
]
High-power magnification of splenic lymphoid infiltrate. This slide demonstrates that the infiltrate consists of small- and medium-sized atypical lymphocytes, which display dense chromatin clumping and prominent nucleoli. Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.
Photomicrograph showing hypercellular bone marrow smears with the presence of mostly bare nuclei, few lymphoid cells, and plasmacytic cells (Wright's stain, ×1,000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3786287_br-48-230-g001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=24 Source: Pujani M. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.
]
(A) Plasmacytoid cells in the bone marrow aspirates (Leishman, ×1000). (B) Tetranucleated plasmacytoid/plasma cell and lymphoid cell in the bone marrow aspirates (Leishman, ×1000). Source: Sethi B. et al, Department of Pathology, VCSGGMS & RI Srinagar, Pauri Garhwal, Uttarakhand, India.
Electron Microscopy. There is marked thickening of the glomerular basement membrane due to the presence of numerous electron-dense deposits located at different levels. The deposits vary in size, tend to be spherical in shape and blend together. Under higher magnifications, they did not exhibit a fibrillary or micro-tubular substructure. Notice a thin subendothelial layer of the duplicated basement membrane, also containing electron-dense deposits, with cellular interposition. The capillary lumen appears significantly reduced in diameter. Also notice electron-dense deposits present in the basement membrane of Bowman's capsule on the right upper corner (Uranyl acetate & lead citrate × 35,000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-3&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=33 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.
]
Electron Microscopy. This field illustrates a large subendothelial and several, much smaller, subepithelial electron-dense deposits. This pattern is similar to that originally described in MPGN type III and also often seen in proliferative lupus GN. Notice the duplication of the glomerular basement membrane with cellular interposition. The duplicated segment also contains electron-dense deposits. Occasionally giant, subendothelial, globular electron-dense deposits reduced the capillary loop to a pin-point lumen. Probably they correspond to the globules seen by light and fluorescence microscopy (Uranyl acetate and lead citrate × 40,000). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-4&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=34 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.
]
Light Microscopy. There is marked, global, homogeneous, eosinophilic thickening of the glomerular basement membrane with segmental accentuation. Homogeneous, eosinophilic globules are seen in the lumen of occasional capillary loops. The capillary lumina appear reduced in diameter but no inflammatory or proliferative changes are observed. The periglomerular interstitial space shows lymphocytic infiltration. The focal interstitial deposition of homogeneous eosinophilic material is present in the right upper corner of the picture (H&E × 400). Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.
Immunofluorescence. Global granular and homogeneous deposition of IgG along the glomerular basement membrane. Notice the presence of IgG containing globules in rare capillary loops. They seem to correspond to the eosinophilic globules seen by light microscopy and large electron-dense deposits detected by electron microscopy (FITC labeled anti-IgG × 400).Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.
Renal biopsy. (A) Immunofluorescent microscopic study showed a 2+ reaction for IgM. (B) On the electron microscopic (EM) findings (× 20,000), there are subendothelial (arrow) and mesangial electron-dense deposits revealing microtubular structures (25 nm in average diameter). Source: Kim YL. et al, Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea

Immunohistochemistry

Malignant cells in lymphoplasmacytic lymphoma have following immunophenotypic characteristics:[27][7]

References

  1. ↑ Kondo, Motonari (2010-11-01). "Lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors". Immunological Reviews. 238 (1): 37–46. doi:10.1111/j.1600-065X.2010.00963.x. ISSN 1600-065X. PMC 2975965. PMID 20969583.
  2. ↑ Martensson, Inga-Lill; Almqvist, Nina; Grimsholm, Ola; Bernardi, Angelina (2010). "The pre-B cell receptor checkpoint". FEBS Letters. 584 (12): 2572–9. doi:10.1016/j.febslet.2010.04.057. PMID 20420836.
  3. ↑ LeBien, Tucker W.; Tedder, Thomas F. (2008-09-01). "B lymphocytes: how they develop and function". Blood. 112 (5): 1570–1580. doi:10.1182/blood-2008-02-078071. ISSN 0006-4971. PMC 2518873. PMID 18725575.
  4. ↑ Murphy, Kenneth (2012). Janeway's Immunobiology (8th ed.). New York: Garland Science. ISBN 9780815342434.
  5. ↑ Royer RH, Koshiol J, Giambarresi TR, Vasquez LG, Pfeiffer RM, McMaster ML (2010). "Differential characteristics of Waldenström macroglobulinemia according to patterns of familial aggregation". Blood. 115 (22): 4464–71. doi:10.1182/blood-2009-10-247973. PMC 2881498. PMID 20308603.
  6. ↑ Treon SP, Hunter ZR, Aggarwal A, Ewen EP, Masota S, Lee C; et al. (2006). "Characterization of familial Waldenstrom's macroglobulinemia". Ann Oncol. 17 (3): 488–94. doi:10.1093/annonc/mdj111. PMID 16357024.
  7. ↑ 7.0 7.1 7.2 Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, Kohlhammer H, Xu W, Yang Y, Zhao H, Shaffer AL, Romesser P, Wright G, Powell J, Rosenwald A, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Staudt LM (2011). "Oncogenically active MYD88 mutations in human lymphoma". Nature. 470 (7332): 115–9. doi:10.1038/nature09671. PMID 21179087.
  8. ↑ Treon, Steven P.; Xu, Lian; Yang, Guang; Zhou, Yangsheng; Liu, Xia; Cao, Yang; Sheehy, Patricia; Manning, Robert J.; Patterson, Christopher J.; Tripsas, Christina; Arcaini, Luca; Pinkus, Geraldine S.; Rodig, Scott J.; Sohani, Aliyah R.; Harris, Nancy Lee; Laramie, Jason M.; Skifter, Donald A.; Lincoln, Stephen E.; Hunter, Zachary R. (2012). "MYD88 L265P Somatic Mutation in Waldenström's Macroglobulinemia". New England Journal of Medicine. 367 (9): 826–833. doi:10.1056/NEJMoa1200710. ISSN 0028-4793.
  9. ↑ Varettoni M, Arcaini L, Zibellini S, Boveri E, Rattotti S, Riboni R; et al. (2013). "Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms". Blood. 121 (13): 2522–8. doi:10.1182/blood-2012-09-457101. PMID 23355535.
  10. ↑ Shi M, Spurgeon S, Press R, Olson S, Fan G (2015). "MYD88 mutation analysis of a rare composite chronic lymphocyte leukemia and lymphoplasmacytic lymphoma by flow cytometry cell sorting". Ann Hematol. 94 (11): 1941–4. doi:10.1007/s00277-015-2460-6. PMID 26231802.
  11. ↑ Yang G, Zhou Y, Liu X, Xu L, Cao Y, Manning RJ; et al. (2013). "A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia". Blood. 122 (7): 1222–32. doi:10.1182/blood-2012-12-475111. PMID 23836557.
  12. ↑ Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH; et al. (2011). "Oncogenically active MYD88 mutations in human lymphoma". Nature. 470 (7332): 115–9. doi:10.1038/nature09671. PMC 5024568. PMID 21179087.
  13. ↑ Mori N, Ohwashi M, Yoshinaga K, Mitsuhashi K, Tanaka N, Teramura M; et al. (2013). "L265P mutation of the MYD88 gene is frequent in Waldenström's macroglobulinemia and its absence in myeloma". PLoS One. 8 (11): e80088. doi:10.1371/journal.pone.0080088. PMC 3818242. PMID 24224040.
  14. ↑ Abeykoon JP, Paludo J, King RL, Ansell SM, Gertz MA, LaPlant BR; et al. (2018). "MYD88 mutation status does not impact overall survival in Waldenström macroglobulinemia". Am J Hematol. 93 (2): 187–194. doi:10.1002/ajh.24955. PMID 29080258.
  15. ↑ Steven P. Treon, Lian Xu, Guang Yang, Yangsheng Zhou, Xia Liu, Yang Cao, Patricia Sheehy, Robert J. Manning, Christopher J. Patterson, Christina Tripsas, Luca Arcaini, Geraldine S. Pinkus, Scott J. Rodig, Aliyah R. Sohani, Nancy Lee Harris, Jason M. Laramie, Donald A. Skifter, Stephen E. Lincoln & Zachary R. Hunter (2012). "MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia". The New England journal of medicine. 367 (9): 826–833. doi:10.1056/NEJMoa1200710. PMID 22931316. Unknown parameter |month= ignored (help)
  16. ↑ Zachary R. Hunter, Lian Xu, Guang Yang, Yangsheng Zhou, Xia Liu, Yang Cao, Robert J. Manning, Christina Tripsas, Christopher J. Patterson, Patricia Sheehy & Steven P. Treon (2014). "The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis". Blood. 123 (11): 1637–1646. doi:10.1182/blood-2013-09-525808. PMID 24366360. Unknown parameter |month= ignored (help)
  17. ↑ 17.0 17.1 17.2 Yun S, Johnson AC, Okolo ON, Arnold SJ, McBride A, Zhang L; et al. (2017). "Waldenström Macroglobulinemia: Review of Pathogenesis and Management". Clin Lymphoma Myeloma Leuk. 17 (5): 252–262. doi:10.1016/j.clml.2017.02.028. PMC 5413391. PMID 28366781.
  18. ↑ Treon, S. P.; Hunter, Z. R.; Aggarwal, A.; Ewen, E. P.; Masota, S.; Lee, C.; Santos, D. Ditzel; Hatjiharissi, E.; Xu, L.; Leleu, X.; Tournilhac, O.; Patterson, C. J.; Manning, R.; Branagan, A. R.; Morton, C. C. (2006). "Characterization of familial Waldenström's macroglobulinemia". Annals of Oncology. 17 (3): 488–494. doi:10.1093/annonc/mdj111. ISSN 1569-8041.
  19. ↑ Roelandt F. J. Schop, W. Michael Kuehl, Scott A. Van Wier, Gregory J. Ahmann, Tammy Price-Troska, Richard J. Bailey, Syed M. Jalal, Ying Qi, Robert A. Kyle, Philip R. Greipp & Rafael Fonseca (2002). "Waldenstrom macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions". Blood. 100 (8): 2996–3001. doi:10.1182/blood.V100.8.2996. PMID 12351413. Unknown parameter |month= ignored (help)
  20. ↑ 20.0 20.1 Braggio E, Keats JJ, Leleu X, Van Wier S, Jimenez-Zepeda VH, Valdez R; et al. (2009). "Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenstrom's macroglobulinemia". Cancer Res. 69 (8): 3579–88. doi:10.1158/0008-5472.CAN-08-3701. PMC 2782932. PMID 19351844.
  21. ↑ Waldenström macroglobulinemia. International Waldenström Macroglobulinemia foundation (2015)http://www.iwmf.com/sites/default/files/docs/WM_Review_Ghobrial_Jan2014.pdf Accessed on November 12, 2015
  22. ↑ Morra E, Varettoni M, Tedeschi A, Arcaini L, Ricci F, Pascutto C, Rattotti S, Vismara E, Paris L, Cazzola M (2013). "Associated cancers in Waldenström macroglobulinemia: clues for common genetic predisposition". Clin Lymphoma Myeloma Leuk. 13 (6): 700–3. doi:10.1016/j.clml.2013.05.008. PMID 24070824.
  23. ↑ Chi PJ, Pei SN, Huang TL, Huang SC, Ng HY, Lee CT (2014). "Renal MALT lymphoma associated with Waldenström macroglobulinemia". J. Formos. Med. Assoc. 113 (4): 255–7. doi:10.1016/j.jfma.2011.02.007. PMID 24685302.
  24. ↑ Owen RG (2003). "Developing diagnostic criteria in Waldenstrom's macroglobulinemia". Semin Oncol. 30 (2): 196–200. doi:10.1053/sonc.2003.50069. PMID 12720135.
  25. ↑ Morice WG, Chen D, Kurtin PJ, Hanson CA, McPhail ED (2009). "Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenström's macroglobulinemia". Mod Pathol. 22 (6): 807–16. doi:10.1038/modpathol.2009.34. PMID 19287458.
  26. ↑ Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML; et al. (2003). "Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia". Semin Oncol. 30 (2): 110–5. doi:10.1053/sonc.2003.50082. PMID 12720118.
  27. ↑ 27.0 27.1 Ansell, Stephen M.; Kyle, Robert A.; Reeder, Craig B.; Fonseca, Rafael; Mikhael, Joseph R.; Morice, William G.; Bergsagel, P. Leif; Buadi, Francis K.; Colgan, Joseph P.; Dingli, David; Dispenzieri, Angela; Greipp, Philip R.; Habermann, Thomas M.; Hayman, Suzanne R.; Inwards, David J.; Johnston, Patrick B.; Kumar, Shaji K.; Lacy, Martha Q.; Lust, John A.; Markovic, Svetomir N.; Micallef, Ivana N.M.; Nowakowski, Grzegorz S.; Porrata, Luis F.; Roy, Vivek; Russell, Stephen J.; Short, Kristen E. Detweiler; Stewart, A. Keith; Thompson, Carrie A.; Witzig, Thomas E.; Zeldenrust, Steven R.; Dalton, Robert J.; Rajkumar, S. Vincent; Gertz, Morie A. (2010). "Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines". Mayo Clinic Proceedings. 85 (9): 824–833. doi:10.4065/mcp.2010.0304. ISSN 0025-6196.
  28. ↑ Owen RG, Barrans SL, Richards SJ, O'Connor SJ, Child JA, Parapia LA; et al. (2001). "Waldenström macroglobulinemia. Development of diagnostic criteria and identification of prognostic factors". Am J Clin Pathol. 116 (3): 420–8. doi:10.1309/4LCN-JMPG-5U71-UWQB. PMID 11554171.
  29. ↑ 29.0 29.1 Andriko JA, Aguilera NS, Chu WS, Nandedkar MA, Cotelingam JD (1997). "Waldenström's macroglobulinemia: a clinicopathologic study of 22 cases". Cancer. 80 (10): 1926–35. PMID 9366295.
  30. ↑ Chng WJ, Schop RF, Price-Troska T, Ghobrial I, Kay N, Jelinek DF; et al. (2006). "Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma". Blood. 108 (8): 2755–63. doi:10.1182/blood-2006-02-005488. PMC 1895596. PMID 16804116.
  31. ↑ Dimopoulos MA, Gertz MA, Kastritis E, Garcia-Sanz R, Kimby EK, Leblond V; et al. (2009). "Update on treatment recommendations from the Fourth International Workshop on Waldenstrom's Macroglobulinemia". J Clin Oncol. 27 (1): 120–6. doi:10.1200/JCO.2008.17.7865. PMID 19047284.
  32. ↑ Vijay A, Gertz MA (2007). "Waldenström macroglobulinemia". Blood. 109 (12): 5096–103. doi:10.1182/blood-2006-11-055012. PMID 17303694.
  33. ↑ Owen RG (2003). "Developing diagnostic criteria in Waldenstrom's macroglobulinemia". Semin Oncol. 30 (2): 196–200. doi:10.1053/sonc.2003.50069. PMID 12720135.

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