Waldenström's macroglobulinemia pathophysiology: Difference between revisions

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==Overview==
==Overview==
Waldenström macroglobulinemia is an uncontrolled clonal proliferation of terminally differentiated [[B lymphocyte]]s ([[plasma cells]]), which are normally involved in [[humoral immunity]]. [[Genes]] involved in the pathogenesis of Waldenström macroglobulinemia include ''[[MYD88]]-L265P, and [[CXCR4]]''.  
[[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]] 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 WM include ''[[MYD88]]-L265P, and [[CXCR4]]'' alongwith various other [[cytogenetic]] and [[epigenetic]] [[abnormalities]]. In [[patients]] of [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]], 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]]<nowiki/>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 paratrabacular-[[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==
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==Genetics==
==Genetics==
*The exact [[pathogenesis]] of [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]] 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 [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]] 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 WM 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 [[Waldenström's macroglobulinemia|WM]] 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>
*[[Somatic]] hypermutations of [[immunoglobulin]] [[Heavy chains|heavy chain]] [[gene]], without any intraclonal variation, [[Suggestion|suggests]] that the [[Cell (biology)|cell]] of [[origin]] is a post-[[germinal center]] [[B cell]] that has undergone [[affinity maturation]] as well as [[Chromosome abnormality|chromosomal abnormalities]] play a part in the [[pathogenesis]] of this [[disease]]:
*[[Somatic]] hypermutations of [[immunoglobulin]] [[Heavy chains|heavy chain]] [[gene]], without any intraclonal variation, [[Suggestion|suggests]] that the [[Cell (biology)|cell]] of [[origin]] is a post-[[germinal center]] [[B cell]] that has undergone [[affinity maturation]] as well as [[Chromosome abnormality|chromosomal abnormalities]] play a part in the [[pathogenesis]] of this [[disease]]:
**A [[mutation]] of the [[MYD88|MYD88 gene]] (L265P) has been found in more than 90% of [[patients]] with [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]], while it has [[Rare|rarely]] [[Presenting symptom|presented]] in [[patients]] with other types of mature [[B-cell]] [[tumors]]<ref name="TreonXu2012">{{cite journal|last1=Treon|first1=Steven P.|last2=Xu|first2=Lian|last3=Yang|first3=Guang|last4=Zhou|first4=Yangsheng|last5=Liu|first5=Xia|last6=Cao|first6=Yang|last7=Sheehy|first7=Patricia|last8=Manning|first8=Robert J.|last9=Patterson|first9=Christopher J.|last10=Tripsas|first10=Christina|last11=Arcaini|first11=Luca|last12=Pinkus|first12=Geraldine S.|last13=Rodig|first13=Scott J.|last14=Sohani|first14=Aliyah R.|last15=Harris|first15=Nancy Lee|last16=Laramie|first16=Jason M.|last17=Skifter|first17=Donald A.|last18=Lincoln|first18=Stephen E.|last19=Hunter|first19=Zachary R.|title=MYD88 L265P Somatic Mutation in Waldenström's Macroglobulinemia|journal=New England Journal of Medicine|volume=367|issue=9|year=2012|pages=826–833|issn=0028-4793|doi=10.1056/NEJMoa1200710}}</ref><ref name="pmid23355535">{{cite journal| author=Varettoni M, Arcaini L, Zibellini S, Boveri E, Rattotti S, Riboni R et al.| title=Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms. | journal=Blood | year= 2013 | volume= 121 | issue= 13 | pages= 2522-8 | pmid=23355535 | doi=10.1182/blood-2012-09-457101 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23355535  }} </ref><ref name="pmid26231802">{{cite journal| author=Shi M, Spurgeon S, Press R, Olson S, Fan G| title=MYD88 mutation analysis of a rare composite chronic lymphocyte leukemia and lymphoplasmacytic lymphoma by flow cytometry cell sorting. | journal=Ann Hematol | year= 2015 | volume= 94 | issue= 11 | pages= 1941-4 | pmid=26231802 | doi=10.1007/s00277-015-2460-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26231802  }} </ref><ref name="pmid23836557">{{cite journal| author=Yang G, Zhou Y, Liu X, Xu L, Cao Y, Manning RJ et al.| title=A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia. | journal=Blood | year= 2013 | volume= 122 | issue= 7 | pages= 1222-32 | pmid=23836557 | doi=10.1182/blood-2012-12-475111 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23836557  }} </ref><ref name="pmid21179087">{{cite journal| author=Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH et al.| title=Oncogenically active MYD88 mutations in human lymphoma. | journal=Nature | year= 2011 | volume= 470 | issue= 7332 | pages= 115-9 | pmid=21179087 | doi=10.1038/nature09671 | pmc=5024568 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21179087  }} </ref><ref name="pmid24224040">{{cite journal| author=Mori N, Ohwashi M, Yoshinaga K, Mitsuhashi K, Tanaka N, Teramura M et al.| title=L265P mutation of the MYD88 gene is frequent in Waldenström's macroglobulinemia and its absence in myeloma. | journal=PLoS One | year= 2013 | volume= 8 | issue= 11 | pages= e80088 | pmid=24224040 | doi=10.1371/journal.pone.0080088 | pmc=3818242 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24224040  }} </ref><ref name="pmid29080258">{{cite journal| author=Abeykoon JP, Paludo J, King RL, Ansell SM, Gertz MA, LaPlant BR et al.| title=MYD88 mutation status does not impact overall survival in Waldenström macroglobulinemia. | journal=Am J Hematol | year= 2018 | volume= 93 | issue= 2 | pages= 187-194 | pmid=29080258 | doi=10.1002/ajh.24955 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29080258  }} </ref><ref>{{Cite journal
**A [[mutation]] of the [[MYD88|MYD88 gene]] (L265P) has been found in more than 90% of [[patients]] with [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]], while it has [[Rare|rarely]] [[Presenting symptom|presented]] in [[patients]] with other types of mature [[B-cell]] [[tumors]]<ref name="TreonXu2012">{{cite journal|last1=Treon|first1=Steven P.|last2=Xu|first2=Lian|last3=Yang|first3=Guang|last4=Zhou|first4=Yangsheng|last5=Liu|first5=Xia|last6=Cao|first6=Yang|last7=Sheehy|first7=Patricia|last8=Manning|first8=Robert J.|last9=Patterson|first9=Christopher J.|last10=Tripsas|first10=Christina|last11=Arcaini|first11=Luca|last12=Pinkus|first12=Geraldine S.|last13=Rodig|first13=Scott J.|last14=Sohani|first14=Aliyah R.|last15=Harris|first15=Nancy Lee|last16=Laramie|first16=Jason M.|last17=Skifter|first17=Donald A.|last18=Lincoln|first18=Stephen E.|last19=Hunter|first19=Zachary R.|title=MYD88 L265P Somatic Mutation in Waldenström's Macroglobulinemia|journal=New England Journal of Medicine|volume=367|issue=9|year=2012|pages=826–833|issn=0028-4793|doi=10.1056/NEJMoa1200710}}</ref><ref name="pmid23355535">{{cite journal| author=Varettoni M, Arcaini L, Zibellini S, Boveri E, Rattotti S, Riboni R et al.| title=Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms. | journal=Blood | year= 2013 | volume= 121 | issue= 13 | pages= 2522-8 | pmid=23355535 | doi=10.1182/blood-2012-09-457101 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23355535  }} </ref><ref name="pmid26231802">{{cite journal| author=Shi M, Spurgeon S, Press R, Olson S, Fan G| title=MYD88 mutation analysis of a rare composite chronic lymphocyte leukemia and lymphoplasmacytic lymphoma by flow cytometry cell sorting. | journal=Ann Hematol | year= 2015 | volume= 94 | issue= 11 | pages= 1941-4 | pmid=26231802 | doi=10.1007/s00277-015-2460-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26231802  }} </ref><ref name="pmid23836557">{{cite journal| author=Yang G, Zhou Y, Liu X, Xu L, Cao Y, Manning RJ et al.| title=A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia. | journal=Blood | year= 2013 | volume= 122 | issue= 7 | pages= 1222-32 | pmid=23836557 | doi=10.1182/blood-2012-12-475111 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23836557  }} </ref><ref name="pmid21179087">{{cite journal| author=Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH et al.| title=Oncogenically active MYD88 mutations in human lymphoma. | journal=Nature | year= 2011 | volume= 470 | issue= 7332 | pages= 115-9 | pmid=21179087 | doi=10.1038/nature09671 | pmc=5024568 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21179087  }} </ref><ref name="pmid24224040">{{cite journal| author=Mori N, Ohwashi M, Yoshinaga K, Mitsuhashi K, Tanaka N, Teramura M et al.| title=L265P mutation of the MYD88 gene is frequent in Waldenström's macroglobulinemia and its absence in myeloma. | journal=PLoS One | year= 2013 | volume= 8 | issue= 11 | pages= e80088 | pmid=24224040 | doi=10.1371/journal.pone.0080088 | pmc=3818242 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24224040  }} </ref><ref name="pmid29080258">{{cite journal| author=Abeykoon JP, Paludo J, King RL, Ansell SM, Gertz MA, LaPlant BR et al.| title=MYD88 mutation status does not impact overall survival in Waldenström macroglobulinemia. | journal=Am J Hematol | year= 2018 | volume= 93 | issue= 2 | pages= 187-194 | pmid=29080258 | doi=10.1002/ajh.24955 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29080258  }} </ref><ref>{{Cite journal
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==Microscopic Pathology==
==Microscopic Pathology==
 
*Following [[lymphoid organs]] are involved in [[Waldenström's macroglobulinemia|WM]]:  
*Following [[lymphoid organs]] are involved in WM:  
**[[Bone marrow]]
**[[Bone marrow]]
**[[Lymph nodes]] ([[Nodal (protein)|nodal]] involvement is [[Characterization (mathematics)|characterized]] by paracortical and [[hilar]] [[Infiltration (medical)|infiltration]] with [[Frequentist|frequent]] sparing of the [[subscapular]] and [[Marginal distribution|marginal]] [[sinuses]])
**[[Lymph nodes]] ([[Nodal (protein)|nodal]] involvement is [[Characterization (mathematics)|characterized]] by paracortical and [[hilar]] [[Infiltration (medical)|infiltration]] with [[Frequentist|frequent]] sparing of the [[subscapular]] and [[Marginal distribution|marginal]] [[sinuses]])
**[[Spleen]]
**[[Spleen]]
*After a [[Detailed balance|detailed]] clinicopathological [[Assessment and Plan|assessment]] and [[review]] of the published [[Literature review|literature]], the following [[diagnostic criteria]] was proposed for WM:<ref name="pmid12720135">{{cite journal| author=Owen RG| title=Developing diagnostic criteria in Waldenstrom's macroglobulinemia. | journal=Semin Oncol | year= 2003 | volume= 30 | issue= 2 | pages= 196-200 | pmid=12720135 | doi=10.1053/sonc.2003.50069 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12720135  }} </ref>
*After a [[Detailed balance|detailed]] clinicopathological [[Assessment and Plan|assessment]] and [[review]] of the published [[Literature review|literature]], the following [[diagnostic criteria]] was proposed for [[Waldenström's macroglobulinemia|WM]]:<ref name="pmid12720135">{{cite journal| author=Owen RG| title=Developing diagnostic criteria in Waldenstrom's macroglobulinemia. | journal=Semin Oncol | year= 2003 | volume= 30 | issue= 2 | pages= 196-200 | pmid=12720135 | doi=10.1053/sonc.2003.50069 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12720135  }} </ref>
*[[IgM]] [[monoclonal gammopathy]] of any [[concentration]]
*[[IgM]] [[monoclonal gammopathy]] of any [[concentration]]
*'''[[Bone marrow]]''' [[Infiltration (medical)|infiltration]] by:<ref name="pmid19287458">{{cite journal| author=Morice WG, Chen D, Kurtin PJ, Hanson CA, McPhail ED| title=Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenström's macroglobulinemia. | journal=Mod Pathol | year= 2009 | volume= 22 | issue= 6 | pages= 807-16 | pmid=19287458 | doi=10.1038/modpathol.2009.34 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19287458  }} </ref><ref name="pmid12720118">{{cite journal| author=Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML et al.| title=Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. | journal=Semin Oncol | year= 2003 | volume= 30 | issue= 2 | pages= 110-5 | pmid=12720118 | doi=10.1053/sonc.2003.50082 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12720118  }} </ref><ref name="AnsellKyle2010">{{cite journal|last1=Ansell|first1=Stephen M.|last2=Kyle|first2=Robert A.|last3=Reeder|first3=Craig B.|last4=Fonseca|first4=Rafael|last5=Mikhael|first5=Joseph R.|last6=Morice|first6=William G.|last7=Bergsagel|first7=P. Leif|last8=Buadi|first8=Francis K.|last9=Colgan|first9=Joseph P.|last10=Dingli|first10=David|last11=Dispenzieri|first11=Angela|last12=Greipp|first12=Philip R.|last13=Habermann|first13=Thomas M.|last14=Hayman|first14=Suzanne R.|last15=Inwards|first15=David J.|last16=Johnston|first16=Patrick B.|last17=Kumar|first17=Shaji K.|last18=Lacy|first18=Martha Q.|last19=Lust|first19=John A.|last20=Markovic|first20=Svetomir N.|last21=Micallef|first21=Ivana N.M.|last22=Nowakowski|first22=Grzegorz S.|last23=Porrata|first23=Luis F.|last24=Roy|first24=Vivek|last25=Russell|first25=Stephen J.|last26=Short|first26=Kristen E. Detweiler|last27=Stewart|first27=A. Keith|last28=Thompson|first28=Carrie A.|last29=Witzig|first29=Thomas E.|last30=Zeldenrust|first30=Steven R.|last31=Dalton|first31=Robert J.|last32=Rajkumar|first32=S. Vincent|last33=Gertz|first33=Morie A.|title=Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines|journal=Mayo Clinic Proceedings|volume=85|issue=9|year=2010|pages=824–833|issn=00256196|doi=10.4065/mcp.2010.0304}}</ref>
*'''[[Bone marrow]]''' [[Infiltration (medical)|infiltration]] by:<ref name="pmid19287458">{{cite journal| author=Morice WG, Chen D, Kurtin PJ, Hanson CA, McPhail ED| title=Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenström's macroglobulinemia. | journal=Mod Pathol | year= 2009 | volume= 22 | issue= 6 | pages= 807-16 | pmid=19287458 | doi=10.1038/modpathol.2009.34 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19287458  }} </ref><ref name="pmid12720118">{{cite journal| author=Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML et al.| title=Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. | journal=Semin Oncol | year= 2003 | volume= 30 | issue= 2 | pages= 110-5 | pmid=12720118 | doi=10.1053/sonc.2003.50082 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12720118  }} </ref><ref name="AnsellKyle2010">{{cite journal|last1=Ansell|first1=Stephen M.|last2=Kyle|first2=Robert A.|last3=Reeder|first3=Craig B.|last4=Fonseca|first4=Rafael|last5=Mikhael|first5=Joseph R.|last6=Morice|first6=William G.|last7=Bergsagel|first7=P. Leif|last8=Buadi|first8=Francis K.|last9=Colgan|first9=Joseph P.|last10=Dingli|first10=David|last11=Dispenzieri|first11=Angela|last12=Greipp|first12=Philip R.|last13=Habermann|first13=Thomas M.|last14=Hayman|first14=Suzanne R.|last15=Inwards|first15=David J.|last16=Johnston|first16=Patrick B.|last17=Kumar|first17=Shaji K.|last18=Lacy|first18=Martha Q.|last19=Lust|first19=John A.|last20=Markovic|first20=Svetomir N.|last21=Micallef|first21=Ivana N.M.|last22=Nowakowski|first22=Grzegorz S.|last23=Porrata|first23=Luis F.|last24=Roy|first24=Vivek|last25=Russell|first25=Stephen J.|last26=Short|first26=Kristen E. Detweiler|last27=Stewart|first27=A. Keith|last28=Thompson|first28=Carrie A.|last29=Witzig|first29=Thomas E.|last30=Zeldenrust|first30=Steven R.|last31=Dalton|first31=Robert J.|last32=Rajkumar|first32=S. Vincent|last33=Gertz|first33=Morie A.|title=Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines|journal=Mayo Clinic Proceedings|volume=85|issue=9|year=2010|pages=824–833|issn=00256196|doi=10.4065/mcp.2010.0304}}</ref>
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{|  
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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.]]]
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| [[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.]]]
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|- 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.]]]
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|}
{|
|
[[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: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.]]]
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[[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]]]
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Latest revision as of 18:22, 15 August 2019

Waldenström's macroglobulinemia 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], Roukoz A. Karam, M.D.[3], Mirdula Sharma, MBBS [4]; Grammar Reviewer: Natalie Harpenau, B.S.[5]

Overview

Waldenstrom's macroglobulinemia 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 WM include MYD88-L265P, and CXCR4 alongwith various other cytogenetic and epigenetic abnormalities. In patients of Waldenstrom's macroglobulinemia, 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 nodesand 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 paratrabacular-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, perinuclearhalo, 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 Waldenstrom's macroglobulinemia

Genetics

Cytogenetics

Epigenetics:

Associated Conditions

Several studies showed an increased incidence of following second cancers in patients with Waldenstrom's macroglobulinemia:[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).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).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 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).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).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. 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 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 Waldenstrom's macroglobulinemia 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.
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