Lymphoplasmacytic lymphoma: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
 
(97 intermediate revisions by 3 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{SI}}
{{Lymphoplasmacytic lymphoma}}


{{CMG}}; {{AE}} {{S.M.}}
{{CMG}}; {{AE}} {{S.M.}}


{{SK}} Waldenstrom's macroglobulinemia; Waldenstrom's disease; Primary macroglobulinemia; Hyperviscosity syndrome  
{{SK}} Plasmacytoid lymphocytic [[lymphoma]]; Familial Waldenström's macroglobulinemia; Primary macroglobulinemia; Hyperviscosity syndrome; Lymphoplasmacytoid [[lymphoma]]


==Overview==
==[[Lymphoplasmacytic lymphoma overview|Overview]]==


==Historical Perspective==
==[[Lymphoplasmacytic lymphoma historical perspective|Historical Perspective]]==
*In 1936, Jens Bing and Axel Valdemar Neel, discovered a late and rare complication of WM known as Bing-Neel syndrome (BNS), who observed a case of 2 women, 56 and 39 years old, presenting with rapid neurodegeneration in the setting of hyperglobulinemia.
*In 1944, [[Jan G. Waldenstrom]], a Swedish doctor of internal medicine, first discovered Waldenstrom macroglobulinemia(WM). He reported an unusal presentation of fatigue, lymphadenopathy, bleeding from nose and mouth, worsening anemia, elevated sedimentation rate, low serum fibrinogen levels (hypofibrinogenemia), hyperviscosity, and hypergammaglobulinemia in two patients due to increased levels of a class of an abnormal high molecular weight serum protein called macroglobulins.<ref name="Waldenström2009">{{cite journal|last1=Waldenström|first1=Jan|title=Incipient myelomatosis or «essential« hyperglobulinemia with fibrinogenopenia - a new syndrome?|journal=Acta Medica Scandinavica|volume=117|issue=3-4|year=2009|pages=216–247|issn=00016101|doi=10.1111/j.0954-6820.1944.tb03955.x}}</ref><ref name="KonoplevMedeiros2005">{{cite journal|last1=Konoplev|first1=Sergej|last2=Medeiros|first2=L. Jeffrey|last3=Bueso-Ramos|first3=Carlos E.|last4=Jorgensen|first4=Jeffrey L.|last5=Lin|first5=Pei|title=Immunophenotypic Profile of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia|journal=American Journal of Clinical Pathology|volume=124|issue=3|year=2005|pages=414–420|issn=0002-9173|doi=10.1309/3G1XDX0DVHBNVKB4}}</ref>
*In 1962, the first report on familiality in WM was published, and since then many cohort studies as well as small case-control studies have been published showing familial aggregation of WM.<ref name="pmid13933388">{{cite journal| author=MASSARI R, FINE JM, METAIS R| title=Waldenstrom's macroglobulinaemia observed in two brothers. | journal=Nature | year= 1962 | volume= 196 | issue=  | pages= 176-8 | pmid=13933388 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13933388  }} </ref><ref name="pmid16224483">{{cite journal| author=Altieri A, Bermejo JL, Hemminki K| title=Familial aggregation of lymphoplasmacytic lymphoma with non-Hodgkin lymphoma and other neoplasms. | journal=Leukemia | year= 2005 | volume= 19 | issue= 12 | pages= 2342-3 | pmid=16224483 | doi=10.1038/sj.leu.2403991 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16224483  }} </ref><ref name="pmid6778280">{{cite journal| author=Blattner WA, Garber JE, Mann DL, McKeen EA, Henson R, McGuire DB et al.| title=Waldenström's macroglobulinemia and autoimmune disease in a family. | journal=Ann Intern Med | year= 1980 | volume= 93 | issue= 6 | pages= 830-2 | pmid=6778280 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6778280  }} </ref><ref name="pmid6805257">{{cite journal| author=Fine JM, Lambin P, Massari M, Leroux P| title=Malignant evolution of asymptomatic monoclonal IgM after seven and fifteen years in two siblings of a patient with Waldenström's macroglobulinemia. | journal=Acta Med Scand | year= 1982 | volume= 211 | issue= 3 | pages= 237-9 | pmid=6805257 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6805257  }} </ref><ref name="pmid3099545">{{cite journal| author=Fine JM, Muller JY, Rochu D, Marneux M, Gorin NC, Fine A et al.| title=Waldenström's macroglobulinemia in monozygotic twins. | journal=Acta Med Scand | year= 1986 | volume= 220 | issue= 4 | pages= 369-73 | pmid=3099545 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3099545  }} </ref><ref name="pmid408931">{{cite journal| author=Gétaz EP, Staples WG| title=Familial Waldenström's macroglobulinaemia: a case report. | journal=S Afr Med J | year= 1977 | volume= 51 | issue= 24 | pages= 891-2 | pmid=408931 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=408931  }} </ref><ref name="pmid8371587">{{cite journal| author=Linet MS, Humphrey RL, Mehl ES, Brown LM, Pottern LM, Bias WB et al.| title=A case-control and family study of Waldenstrom's macroglobulinemia. | journal=Leukemia | year= 1993 | volume= 7 | issue= 9 | pages= 1363-9 | pmid=8371587 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8371587  }} </ref><ref name="pmid8047841">{{cite journal| author=Ogmundsdóttir HM, Jóhannesson GM, Sveinsdóttir S, Einarsdóttir S, Hegeman A, Jensson O et al.| title=Familial macroglobulinaemia: hyperactive B-cells but normal natural killer function. | journal=Scand J Immunol | year= 1994 | volume= 40 | issue= 2 | pages= 195-200 | pmid=8047841 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8047841  }} </ref><ref name="pmid4143650">{{cite journal| author=Seligmann M, Danon F, Mihaesco C, Fudenberg HH| title=Immunoglobulin abnormalities in families of patients with Waldenström's macroglobulinemia. | journal=Am J Med | year= 1967 | volume= 43 | issue= 1 | pages= 66-83 | pmid=4143650 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4143650  }} </ref> <ref name="pmid1958390">{{cite journal| author=Taleb N, Tohme A, Abi Jirgiss D, Kattan J, Salloum E| title=Familial macroglobulinemia in a Lebanese family with two sisters presenting Waldenström's disease. | journal=Acta Oncol | year= 1991 | volume= 30 | issue= 6 | pages= 703-5 | pmid=1958390 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1958390  }} </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><ref name="pmid104746">{{cite journal| author=Youinou P, le Goff P, Saleun JP, Rivat L, Morin JF, Fauchier C et al.| title=Familial occurrence of monoclonal gammapathies. | journal=Biomedicine | year= 1978 | volume= 28 | issue= 4 | pages= 226-32 | pmid=104746 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=104746  }} </ref><ref name="pmid2505923">{{cite journal| author=Renier G, Ifrah N, Chevailler A, Saint-Andre JP, Boasson M, Hurez D| title=Four brothers with Waldenstrom's macroglobulinemia. | journal=Cancer | year= 1989 | volume= 64 | issue= 7 | pages= 1554-9 | pmid=2505923 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2505923  }} </ref>
*In 1994, a Revised European-American classification of lymphoid neaoplasms (REAL) was published by International Lymphoma Study Group which placed WM in the category of lymphoplasmacytic lymphoma (an indolent subtype of non-hodgkins lymphoma). The REAL classification is based on the morphology, immunophenotype, genetic features, and clinical features.<ref name="pmid10577857">{{cite journal| author=Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J et al.| title=World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. | journal=J Clin Oncol | year= 1999 | volume= 17 | issue= 12 | pages= 3835-49 | pmid=10577857 | doi=10.1200/JCO.1999.17.12.3835 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10577857  }} </ref><ref name="pmid8068936">{{cite journal| author=Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML et al.| title=A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. | journal=Blood | year= 1994 | volume= 84 | issue= 5 | pages= 1361-92 | pmid=8068936 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8068936  }} </ref>
*In 2001, WHO also classified the pathology of WM as lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia based on REAL classification.<ref name="KonoplevMedeiros2005">{{cite journal|last1=Konoplev|first1=Sergej|last2=Medeiros|first2=L. Jeffrey|last3=Bueso-Ramos|first3=Carlos E.|last4=Jorgensen|first4=Jeffrey L.|last5=Lin|first5=Pei|title=Immunophenotypic Profile of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia|journal=American Journal of Clinical Pathology|volume=124|issue=3|year=2005|pages=414–420|issn=0002-9173|doi=10.1309/3G1XDX0DVHBNVKB4}}</ref>
*In September 26-30, 2002, a consensus group at the Second International Workshop on WM in Athens, Greece, defined WM as a distinct clinicopathologic entity with characteristics of bone marrow infiltration associated with IgM monoclonal gammopathy by WM and proposed a diagnostic criteria forn WM.<ref name="KonoplevMedeiros2005">{{cite journal|last1=Konoplev|first1=Sergej|last2=Medeiros|first2=L. Jeffrey|last3=Bueso-Ramos|first3=Carlos E.|last4=Jorgensen|first4=Jeffrey L.|last5=Lin|first5=Pei|title=Immunophenotypic Profile of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia|journal=American Journal of Clinical Pathology|volume=124|issue=3|year=2005|pages=414–420|issn=0002-9173|doi=10.1309/3G1XDX0DVHBNVKB4}}</ref><ref name="pmid15735132">{{cite journal| author=Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP| title=Diagnosis and management of Waldenstrom's macroglobulinemia. | journal=J Clin Oncol | year= 2005 | volume= 23 | issue= 7 | pages= 1564-77 | pmid=15735132 | doi=10.1200/JCO.2005.03.144 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15735132  }} </ref>
*In 2009, in Arkansas, a patient of Bing-Neel syndrome discontinued the treatment for BNS which included, "intrathecal chemotherapy with several cycles of systemic chemotherapy followed by autologous stem cell-supported High-dose chemotherapy and bone marrow transplant|high-dose therapy transplant", and in 2013, was still asymptomatic when a follow-up report was published.<ref name="pmid23747080">{{cite journal| author=Abdallah AO, Atrash S, Muzaffar J, Abdallah M, Kumar M, Van Rhee F et al.| title=Successful treatment of Bing-Neel syndrome using intrathecal chemotherapy and systemic combination chemotherapy followed by BEAM auto-transplant: a case report and review of literature. | journal=Clin Lymphoma Myeloma Leuk | year= 2013 | volume= 13 | issue= 4 | pages= 502-6 | pmid=23747080 | doi=10.1016/j.clml.2013.03.002 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23747080  }} </ref>


==Classification==
==[[Lymphoplasmacytic lymphoma classification|Classification]]==
There is no established system for the classification of Waldenström's macroglobulinemia. However, according to a devised criteria based upon patient's symptoms, it can be classified into:<ref name="pmid15735132">{{cite journal| author=Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP| title=Diagnosis and management of Waldenstrom's macroglobulinemia. | journal=J Clin Oncol | year= 2005 | volume= 23 | issue= 7 | pages= 1564-77 | pmid=15735132 | doi=10.1200/JCO.2005.03.144 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15735132  }} </ref>
*Symptomatic Waldenstrom macroglobulinemia.
*Asymptomatic/Smoldering Waldenstrom macroglobulinemia (SWM).<ref name="pmid12720119">{{cite journal| author=Kyle RA, Treon SP, Alexanian R, Barlogie B, Björkholm M, Dhodapkar M et al.| title=Prognostic markers and criteria to initiate therapy in 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= 116-20 | pmid=12720119 | doi=10.1053/sonc.2003.50038 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12720119  }} </ref>
{| class="wikitable"
|+ '''Classification of WM and Related Disorders'''
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Criteria
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Symptomatic WM
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Asymptomatic WM
! style="background:#4479BA; color: #FFFFFF;" align="center" + |IgM-Related Disorders
! style="background:#4479BA; color: #FFFFFF;" align="center" + |MGUS
|-
| style="background:#DCDCDC;" align="center" + |IgM monoclonal protein
| style="background:#F5F5F5;" align="center" + |+
| style="background:#F5F5F5;" align="center" + |+
| style="background:#F5F5F5;" align="center" + |+
| style="background:#F5F5F5;" align="center" + |+
|-
| style="background:#DCDCDC;" align="center" + |Bone marrow infiltration
| style="background:#F5F5F5;" align="center" + |+
| style="background:#F5F5F5;" align="center" + |+
| style="background:#F5F5F5;" align="center" + |-
| style="background:#F5F5F5;" align="center" + |-
|-
| style="background:#DCDCDC;" align="center" + |Symptoms attributable to IgM
| style="background:#F5F5F5;" align="center" + |+
| style="background:#F5F5F5;" align="center" + |-
| style="background:#F5F5F5;" align="center" + |+
| style="background:#F5F5F5;" align="center" + |-
|-
| style="background:#DCDCDC;" align="center" + |Symptoms attributable to tumor infiltration
| style="background:#F5F5F5;" align="center" + |+
| style="background:#F5F5F5;" align="center" + |-
| style="background:#F5F5F5;" align="center" + |-
| style="background:#F5F5F5;" align="center" + |-
|}


==Pathophysiology==
==[[Lymphoplasmacytic lymphoma pathophysiology|Pathophysiology]]==
*Waldenström macroglobulinemia arises from terminally differentiated B [[Lymphocyte|lymphocytes]], which are normally involved in [[humoral immunity]].


* It is understood that Waldenström macroglobulinemia is mediated by 2 major factors:
==[[Lymphoplasmacytic lymphoma causes|Causes]]==
*#The secretion of [[IgM]] [[paraprotein]]
*#*Causes symptoms of [[hyperviscosity syndrome]]
*#The infiltration of tissues with [[neoplastic]] lymphoplasmacytic cells
*#*Mainly the [[bone marrow]], [[spleen]],and [[Lymph node|lymph nodes]]
*#*Sometimes the [[liver]], [[gastrointestinal tract]], [[Lung|lungs]], [[kidneys]], [[skin]], [[eyes]], and [[central nervous system]]
===Genetics===
*The exact pathogenesis of Waldenström macroglobulinemia is not completely understood; however, its [[Heredity|familial pattern]] of involvement 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 of Waldenström macroglobulinemia 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 mutations 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 macroglobulinemia, while it has rarely 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
| author = [[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]]
| title = MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia
| journal = [[The New England journal of medicine]]
| volume = 367
| issue = 9
| pages = 826–833
| year = 2012
| month = August
| doi = 10.1056/NEJMoa1200710
| pmid = 22931316
}}</ref>
***MYD88: The activating [[point mutation]] of MYD88 augments growth and survival of both normal and [[neoplastic]] B cells by preventing [[apoptosis]]. [[Point mutation]] of MYD88 leads to [[leucine]] to [[proline]] substitution in codon 265 (L265P) of MYD88 and produces constantly overactive protein causing proliferation of malignant cells that should normally undergo apoptosis.<ref /><ref />
***[[Monoclonal gammopathy of undetermined significance]] patients found to have MYD88 L265P mutation have significantly higher risk of progression to Waldenström macroglobulinemia or to other [[lymphoproliferative disorders]].<ref />
**Less commonly (30-35%), [[Nonsense mutation|nonsense]] or [[Frameshift mutation|frameshift mutations]] in the C-X-C chemokine receptor type 4 (CXCR4) 5338X gene have also been reported in patients with Waldenström macroglobulinemia.<ref>{{Cite journal
| author = [[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]]
| title = 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
| journal = [[Blood]]
| volume = 123
| issue = 11
| pages = 1637–1646
| year = 2014
| month = March
| doi = 10.1182/blood-2013-09-525808
| pmid = 24366360
}}</ref>
***Patients with Waldenström's macroglobulinemia 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]]/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.
====Cytogenetics====
*Many [[Cytogenetics|cytogenetic]] abnormalities were reported in Waldenström macroglobulinemia patients including:
**[[Deletion (genetics)]] 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 long arm of [[Chromosome 10 (human)|chromosome 10]], 12 0r 20.
**t(9;14)(p13;q32)(50%).<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>
**[[Trisomy]] 4(20%).<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>
**Trisomy 5.
**[[Monosomy]] 8.<ref>{{Cite journal
| author = [[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]]
| title = Waldenstrom macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions
| journal = [[Blood]]
| volume = 100
| issue = 8
| pages = 2996–3001
| year = 2002
| month = October
| doi = 10.1182/blood.V100.8.2996
| pmid = 12351413
}}</ref>
**Deletions of regions of 13q14 that include MIRN15A and MIRN16-1.<ref name="pmid19351844">{{cite journal| author=Braggio E, Keats JJ, Leleu X, Van Wier S, Jimenez-Zepeda VH, Valdez R et al.| title=Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenstrom's macroglobulinemia. | journal=Cancer Res | year= 2009 | volume= 69 | issue= 8 | pages= 3579-88 | pmid=19351844 | doi=10.1158/0008-5472.CAN-08-3701 | pmc=2782932 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19351844  }} </ref>
**t(11;18)(q21;q21) involving API-malt1.<ref name="pmid19351844">{{cite journal| author=Braggio E, Keats JJ, Leleu X, Van Wier S, Jimenez-Zepeda VH, Valdez R et al.| title=Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenstrom's macroglobulinemia. | journal=Cancer Res | year= 2009 | volume= 69 | issue= 8 | pages= 3579-88 | pmid=19351844 | doi=10.1158/0008-5472.CAN-08-3701 | pmc=2782932 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19351844  }} </ref>
**t(8;14).
**t(14;18).


====Epigenetics====
==[[Lymphoplasmacytic lymphoma differential diagnosis|Differentiating Lymphoplasmacytic lymphoma from other Diseases]]==
*Three most common [[epigenetic]] causes are [[DNA methylation]], [[histone acetylation]], and [[non-coding 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>
*Up-regulation 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.
*Gene [[transcription]] through histone [[acetylation]] occurs following increased [[Gene expression|expression]] of miRNA-206 and reduced expression of miRNA-9.
===Associated Conditions===
Several studies showed an increased incidence of following second cancers in patients with Waldenström macroglobulinemia:<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]]
*[[Myelodysplastic syndrome]]/[[Acute myeloid leukemia]]
*[[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>
===Microscopic Pathology===
WM/LPL is a form of an indolent (slowly growing) non-hodgkin lymphoma. LPL is called so because the lymphoma cells have the characteristics of both lymphocytes and plasma cells. After a detailed clinicopathological assessment and review of the published 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>
*IgM monoclonal gammopathy of any concentration.
*Bone marrow 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>
**Small lymphocytes with clumped chromatin, inconspicuous nucleoli, and sparse cytoplasm.
**Well-formed plasma cells.
**Plasmacytoid lymphocytes (have cytologic features intermediate between above 2 extremes), in following patterns:<ref name="pmid11554171">{{cite journal| author=Owen RG, Barrans SL, Richards SJ, O'Connor SJ, Child JA, Parapia LA et al.| title=Waldenström macroglobulinemia. Development of diagnostic criteria and identification of prognostic factors. | journal=Am J Clin Pathol | year= 2001 | volume= 116 | issue= 3 | pages= 420-8 | pmid=11554171 | doi=10.1309/4LCN-JMPG-5U71-UWQB | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11554171  }} </ref><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>
***Diffuse.
***Interstitial.
***Nodular.
***Paratrabecular.
***Nodular-interstitial.
***Mixed paratrabacular-nodular.
*Following lymphoid organs are involved in WM:
**Bone marrow.
**Lymph nodes(nodal involvement is characterized by paracortical and hilar infiltration with frequent sparing of the subscapular and marginal sinuses).
**Spleen.
*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%).
**Lymphoplasmacytic (27%).
*The cytologic composition and the degree of plasmacytic differentiation varies from case to case.
*The bone marrow contains variable numbers of pleomorphic lymphoid cells.
*Dutcher bodies may be seen in plasma cells, as intracytoplasmic inclusions positive for periodic acid Schiff.
*Mast cell hyperplasia is common and may stimulate tumor cell proliferation and monoclonal IgM secretion.
*Gene expression profiling has indicated that lymphoid 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>
===Immunohistochemistry===
Malignant cells in Waldenström macroglobulinemia have following immunophenotypic characteristics:<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>
<ref name="UTDR" />
*Express pan B-cell antigens surface with following immunophenotype:<ref name="pmid19047284">{{cite journal| author=Dimopoulos MA, Gertz MA, Kastritis E, Garcia-Sanz R, Kimby EK, Leblond V et al.| title=Update on treatment recommendations from the Fourth International Workshop on Waldenstrom's Macroglobulinemia. | journal=J Clin Oncol | year= 2009 | volume= 27 | issue= 1 | pages= 120-6 | pmid=19047284 | doi=10.1200/JCO.2008.17.7865 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19047284  }} </ref><ref name="pmid17303694">{{cite journal| author=Vijay A, Gertz MA| title=Waldenström macroglobulinemia. | journal=Blood | year= 2007 | volume= 109 | issue= 12 | pages= 5096-103 | pmid=17303694 | doi=10.1182/blood-2006-11-055012 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17303694  }} </ref><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>
**Ig+[[CD19]]+
**[[CD20]]+
**[[CD22]]+
**[[CD79A]]+
*Variable expression of:
**[[CD11c]]+
**[[CD43]]+
**[[CD38]]+
**[[CD45]]+
**[[CD138]]+
**[[CD25]]+
**[[CD27]]+
**[[FMC7]]+
**[[PAX5]]+
**[[CD38]]+
**[[Bcl2]]+
*Following aren't expressed:
**[[CD5]]-
**[[CD10]]-
**[[CD23]]-
**[[CD103]]-
**[[Bcl6]]-
**[[CD75]]-
*[[IgM]] positive (mostly).
*[[IgG]] positive (few).
*[[Immunoglobulin A|IgA]] (rare).
*[[Immunoglobulin D|IgD]] negative (lack).


==Causes==
==[[Lymphoplasmacytic lymphoma epidemiology and demographics|Epidemiology and Demographics]]==
=== Genetic Causes ===
*Waldenström Macroglobulinemia is most probably caused by a [[somatic mutation]] in the [[MYD88]] gene (seen in 90% of cases) or CXR4 gene (seen in 30% of cases).<ref name=":0">{{Cite journal
| author = [[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]]
| title = MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia
| journal = [[The New England journal of medicine]]
| volume = 367
| issue = 9
| pages = 826–833
| year = 2012
| month = August
| doi = 10.1056/NEJMoa1200710
| pmid = 22931316
}}</ref><ref>{{Cite journal
| author = [[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]]
| title = 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
| journal = [[Blood]]
| volume = 123
| issue = 11
| pages = 1637–1646
| year = 2014
| month = March
| doi = 10.1182/blood-2013-09-525808
| pmid = 24366360
}}</ref>


=== Less Common Causes ===
==[[Lymphoplasmacytic lymphoma risk factors|Risk Factors]]==
Less common causes of Waldenström macroglobulinemia may include:<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><ref>{{Cite journal
| author = [[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]]
| title = Waldenstrom macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions
| journal = [[Blood]]
| volume = 100
| issue = 8
| pages = 2996–3001
| year = 2002
| month = October
| doi = 10.1182/blood.V100.8.2996
| pmid = 12351413
}}</ref>
*[[Chromosomal abnormalities]]: deletions of 6q23 and 13q14, and gains of 3q13-q28, 6p and 18q.
*Personal and family history of [[autoimmune diseases]] with autoantibodies and chronic immune stimulation leads to 2-3 fold higher risk of developing WM, especially elevated risks are associated with following:
**Hepatitis C virus infection (overall 20-30% increased risk for non-Hodgkin lymohoma and 3-fold increased risk for WM).<ref name="pmid18703425">{{cite journal| author=Kristinsson SY, Björkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O| title=Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population-based study in Sweden. | journal=Blood | year= 2008 | volume= 112 | issue= 8 | pages= 3052-6 | pmid=18703425 | doi=10.1182/blood-2008-06-162768 | pmc=2569164 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18703425  }} </ref><ref name="pmid18809818">{{cite journal| author=Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O| title=Chronic immune stimulation and subsequent Waldenström macroglobulinemia. | journal=Arch Intern Med | year= 2008 | volume= 168 | issue= 17 | pages= 1903-9 | pmid=18809818 | doi=10.1001/archinternmed.2008.4 | pmc=2670401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18809818  }} </ref><ref name="pmid18387498">{{cite journal| author=de Sanjose S, Benavente Y, Vajdic CM, Engels EA, Morton LM, Bracci PM et al.| title=Hepatitis C and non-Hodgkin lymphoma among 4784 cases and 6269 controls from the International Lymphoma Epidemiology Consortium. | journal=Clin Gastroenterol Hepatol | year= 2008 | volume= 6 | issue= 4 | pages= 451-8 | pmid=18387498 | doi=10.1016/j.cgh.2008.02.011 | pmc=3962672 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18387498  }} </ref>
**HIV.<ref name="pmid18809818">{{cite journal| author=Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O| title=Chronic immune stimulation and subsequent Waldenström macroglobulinemia. | journal=Arch Intern Med | year= 2008 | volume= 168 | issue= 17 | pages= 1903-9 | pmid=18809818 | doi=10.1001/archinternmed.2008.4 | pmc=2670401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18809818  }} </ref>
**Rickettsiosis.<ref name="pmid18809818">{{cite journal| author=Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O| title=Chronic immune stimulation and subsequent Waldenström macroglobulinemia. | journal=Arch Intern Med | year= 2008 | volume= 168 | issue= 17 | pages= 1903-9 | pmid=18809818 | doi=10.1001/archinternmed.2008.4 | pmc=2670401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18809818  }} </ref>
**Sjogren syndrome.<ref name="pmid20181958">{{cite journal| author=Kristinsson SY, Koshiol J, Björkholm M, Goldin LR, McMaster ML, Turesson I et al.| title=Immune-related and inflammatory conditions and risk of lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. | journal=J Natl Cancer Inst | year= 2010 | volume= 102 | issue= 8 | pages= 557-67 | pmid=20181958 | doi=10.1093/jnci/djq043 | pmc=2857799 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20181958  }} </ref><ref name="pmid18263783">{{cite journal| author=Ekström Smedby K, Vajdic CM, Falster M, Engels EA, Martínez-Maza O, Turner J et al.| title=Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. | journal=Blood | year= 2008 | volume= 111 | issue= 8 | pages= 4029-38 | pmid=18263783 | doi=10.1182/blood-2007-10-119974 | pmc=2288717 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18263783  }} </ref>
**Autoimmune hemolytic anemia.<ref name="pmid20181958">{{cite journal| author=Kristinsson SY, Koshiol J, Björkholm M, Goldin LR, McMaster ML, Turesson I et al.| title=Immune-related and inflammatory conditions and risk of lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. | journal=J Natl Cancer Inst | year= 2010 | volume= 102 | issue= 8 | pages= 557-67 | pmid=20181958 | doi=10.1093/jnci/djq043 | pmc=2857799 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20181958  }} </ref><ref name="pmid18263783">{{cite journal| author=Ekström Smedby K, Vajdic CM, Falster M, Engels EA, Martínez-Maza O, Turner J et al.| title=Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. | journal=Blood | year= 2008 | volume= 111 | issue= 8 | pages= 4029-38 | pmid=18263783 | doi=10.1182/blood-2007-10-119974 | pmc=2288717 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18263783  }} </ref>
**Sarcoidosis.<ref name="pmid16985251">{{cite journal| author=Landgren O, Engels EA, Pfeiffer RM, Gridley G, Mellemkjaer L, Olsen JH et al.| title=Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia. | journal=J Natl Cancer Inst | year= 2006 | volume= 98 | issue= 18 | pages= 1321-30 | pmid=16985251 | doi=10.1093/jnci/djj361 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16985251  }} </ref>
**SLE.<ref name="pmid18263783">{{cite journal| author=Ekström Smedby K, Vajdic CM, Falster M, Engels EA, Martínez-Maza O, Turner J et al.| title=Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. | journal=Blood | year= 2008 | volume= 111 | issue= 8 | pages= 4029-38 | pmid=18263783 | doi=10.1182/blood-2007-10-119974 | pmc=2288717 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18263783  }} </ref>
*Hay fever.
*[[Environmental factor|Environmental factors]]:
**According to some recent studies, exposure to following environmental factors seems to have association with the development of WM:<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="pmid25174029">{{cite journal| author=Vajdic CM, Landgren O, McMaster ML, Slager SL, Brooks-Wilson A, Smith A et al.| title=Medical history, lifestyle, family history, and occupational risk factors for lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. | journal=J Natl Cancer Inst Monogr | year= 2014 | volume= 2014 | issue= 48 | pages= 87-97 | pmid=25174029 | doi=10.1093/jncimonographs/lgu002 | pmc=4155457 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25174029  }} </ref>
***Occupational (Farming).
***[[Pesticides]].
***Paint.
***Rubber dyes.
***Benzene.
***Coal dust.
***Leather manufacturing.
***Wood dust.
***Organic solvents.


==Differentiating Lymphoplasmacytic Lymphoma from Other B cell lymphoid neoplasms==
==[[Lymphoplasmacytic lymphoma screening|Screening]]==
Waldenström macroglobulinemia must be differentiated from other B cell lymphoid neoplasms including:


*[[Chronic lymphocytic leukemia]]/[[small lymphocytic lymphoma]]:
==[[Lymphoplasmacytic lymphoma natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
:*Always express CD5
:*Usually CD23 positive<ref name="CLL">{{cite journal |vauthors=Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ |title=Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines |journal=Blood |volume=111 |issue=12 |pages=5446–56 |year=2008 |pmid=18216293 |pmc=2972576 |doi=10.1182/blood-2007-06-093906 |url=}}</ref>
 
*[[B-cell prolymphocytic leukemia]]:
:*Express bright surface [[Immunoglobulin M|IgM]], [[CD20]] and other B-cell antigens ([[CD19]], [[CD22]], [[CD79a]], [[FMC7]])<ref name=",m">{{cite journal |vauthors=Del Giudice I, Davis Z, Matutes E, Osuji N, Parry-Jones N, Morilla A, Brito-Babapulle V, Oscier D, Catovsky D |title=IgVH genes mutation and usage, ZAP-70 and CD38 expression provide new insights on B-cell prolymphocytic leukemia (B-PLL) |journal=Leukemia |volume=20 |issue=7 |pages=1231–7 |year=2006 |pmid=16642047 |doi=10.1038/sj.leu.2404238 |url=}}</ref><ref name="njl">{{cite journal |vauthors=Ravandi F, O'Brien S |title=Chronic lymphoid leukemias other than chronic lymphocytic leukemia: diagnosis and treatment |journal=Mayo Clin. Proc. |volume=80 |issue=12 |pages=1660–74 |year=2005 |pmid=16342661 |doi=10.4065/80.12.1660 |url=}}</ref>
 
*[[Follicular lymphoma]]:
:*Express [[CD10]], [[HLA-DR]], pan B-cell antigens (CD19, CD20, CD79a), CD21, and surface IgM, [[Immunoglobulin G|IgG]], or [[IgA]]
:*Rearrangement of Bcl-2<ref name="FL">{{cite journal |vauthors=Karube K, Guo Y, Suzumiya J, Sugita Y, Nomura Y, Yamamoto K, Shimizu K, Yoshida S, Komatani H, Takeshita M, Kikuchi M, Nakamura N, Takasu O, Arakawa F, Tagawa H, Seto M, Ohshima K |title=CD10-MUM1+ follicular lymphoma lacks BCL2 gene translocation and shows characteristic biologic and clinical features |journal=Blood |volume=109 |issue=7 |pages=3076–9 |year=2007 |pmid=17138820 |doi=10.1182/blood-2006-09-045989 |url=}}</ref><ref name="FL1">{{cite journal |vauthors=Anderson KC, Bates MP, Slaughenhoupt BL, Pinkus GS, Schlossman SF, Nadler LM |title=Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation |journal=Blood |volume=63 |issue=6 |pages=1424–33 |year=1984 |pmid=6609729 |doi= |url=}}
:*Bone marrow infiltration of small, cleaved cells that are usually paratrabecular
</ref>
 
*[[Multiple myeloma]]:
:*Express CD138, CD38, CD79a, VS38c and CD56 (70%)
:*Presence of plasmacytic cell infiltration of bone marrow, osteolytic lesions, and [[renal insufficiency]]
:*Translocation involving chromosome 11 (t11;14)<ref name="UTD">{{cite journal |vauthors=Pangalis GA, Kyrtsonis MC, Kontopidou FN, Vassilakopoulos TP, Siakantaris MP, Dimopoulou MN, Kittas C, Angelopoulou MK |title=Differential diagnosis of Waldenstrom's macroglobulinemia from other low-grade B-cell lymphoproliferative disorders |journal=Semin. Oncol. |volume=30 |issue=2 |pages=201–5 |year=2003 |pmid=12720136 |doi=10.1053/sonc.2003.50046 |url=}}</ref>
 
*[[Mantle cell lymphoma]]:
:* Expresses CD5+ and CD23+
:* Expresses surface IgM, IgD, and cyclin D1 in majority of cases
:*Infiltration of bone marrow by monomorphous small lymphoid cells with irregular nuclei<ref name="MCL">{{cite journal |vauthors=Dorfman DM, Pinkus GS |title=Distinction between small lymphocytic and mantle cell lymphoma by immunoreactivity for CD23 |journal=Mod. Pathol. |volume=7 |issue=3 |pages=326–31 |year=1994 |pmid=8058704 |doi= |url=}}</ref><ref name="MCL1">{{cite journal |vauthors=DiRaimondo F, Albitar M, Huh Y, O'Brien S, Montillo M, Tedeschi A, Kantarjian H, Lerner S, Giustolisi R, Keating M |title=The clinical and diagnostic relevance of CD23 expression in the chronic lymphoproliferative disease |journal=Cancer |volume=94 |issue=6 |pages=1721–30 |year=2002 |pmid=11920534 |doi= |url=}}</ref>
 
*[[Marginal zone lymphoma]]:
:*Expresses B cell markers CD19, CD20, and CD22
:*Infiltrates the bone marrow with a characteristic intertrabecular and intrasinusoidal pattern
:*Most common cytogenetic abnormalities are loss of 7q (19%) along with +3q (19%) and +5q (10% )<ref name="add">{{cite journal |vauthors=Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD |title=World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997 |journal=J. Clin. Oncol. |volume=17 |issue=12 |pages=3835–49 |year=1999 |pmid=10577857 |doi= |url=}}</ref><ref name="asdf">{{cite journal |vauthors=Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC |title=A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group |journal=Blood |volume=84 |issue=5 |pages=1361–92 |year=1994 |pmid=8068936 |doi= |url=}}</ref>
 
==Epidemiology and Demographics==
*Lymphoplasmacytic lymphoma is one of the rare subtypes of NHL accounting just 1-2% of it.
===Prevalence===
* The prevalence of Waldenström macroglobulinemia is estimated to be 1000-1,500 cases in United States annually.<ref name="pmid22139816">{{cite journal| author=Wang H, Chen Y, Li F, Delasalle K, Wang J, Alexanian R et al.| title=Temporal and geographic variations of Waldenstrom macroglobulinemia incidence: a large population-based study. | journal=Cancer | year= 2012 | volume= 118 | issue= 15 | pages= 3793-800 | pmid=22139816 | doi=10.1002/cncr.26627 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22139816  }} </ref><ref name="pmid9506352">{{cite journal| author=Groves FD, Travis LB, Devesa SS, Ries LA, Fraumeni JF| title=Waldenström's macroglobulinemia: incidence patterns in the United States, 1988-1994. | journal=Cancer | year= 1998 | volume= 82 | issue= 6 | pages= 1078-81 | pmid=9506352 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9506352  }} </ref>
 
===Incidence===
*WM accounts for approximately 1% to 2% of hematologic cancers.<ref name="pmid8219203">{{cite journal| author=Herrinton LJ, Weiss NS| title=Incidence of Waldenström's macroglobulinemia. | journal=Blood | year= 1993 | volume= 82 | issue= 10 | pages= 3148-50 | pmid=8219203 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8219203  }} </ref><ref name="pmid9506352">{{cite journal| author=Groves FD, Travis LB, Devesa SS, Ries LA, Fraumeni JF| title=Waldenström's macroglobulinemia: incidence patterns in the United States, 1988-1994. | journal=Cancer | year= 1998 | volume= 82 | issue= 6 | pages= 1078-81 | pmid=9506352 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9506352  }} </ref>
*World-wide, the overall age-adjusted incidence of Waldenström macroglobulinemia is 0.38 cases per 100,000 persons annually, increasing with age to 2.85 in patients above 80 years (or 5 cases per 1 million persons per year).<ref name="pmid23901022">{{cite journal| author=Monge J, Braggio E, Ansell SM| title=Genetic factors and pathogenesis of Waldenström's macroglobulinemia. | journal=Curr Oncol Rep | year= 2013 | volume= 15 | issue= 5 | pages= 450-6 | pmid=23901022 | doi=10.1007/s11912-013-0331-7 | pmc=PMC3807757 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23901022  }} </ref>
*The age-adjusted incidence rate for males is 0.92 per 100,000 person-years.<ref name="KyleLarson2018">{{cite journal|last1=Kyle|first1=Robert A.|last2=Larson|first2=Dirk R.|last3=McPhail|first3=Ellen D.|last4=Therneau|first4=Terry M.|last5=Dispenzieri|first5=Angela|last6=Kumar|first6=Shaji|last7=Kapoor|first7=Prashant|last8=Cerhan|first8=James R.|last9=Rajkumar|first9=S. Vincent|title=Fifty-Year Incidence of Waldenström Macroglobulinemia in Olmsted County, Minnesota, From 1961 Through 2010: A Population-Based Study With Complete Case Capture and Hematopathologic Review|journal=Mayo Clinic Proceedings|volume=93|issue=6|year=2018|pages=739–746|issn=00256196|doi=10.1016/j.mayocp.2018.02.011}}</ref>
*The age-adjusted incidence rate for females is 0.30 per 100,000 person-years.<ref name="KyleLarson2018">{{cite journal|last1=Kyle|first1=Robert A.|last2=Larson|first2=Dirk R.|last3=McPhail|first3=Ellen D.|last4=Therneau|first4=Terry M.|last5=Dispenzieri|first5=Angela|last6=Kumar|first6=Shaji|last7=Kapoor|first7=Prashant|last8=Cerhan|first8=James R.|last9=Rajkumar|first9=S. Vincent|title=Fifty-Year Incidence of Waldenström Macroglobulinemia in Olmsted County, Minnesota, From 1961 Through 2010: A Population-Based Study With Complete Case Capture and Hematopathologic Review|journal=Mayo Clinic Proceedings|volume=93|issue=6|year=2018|pages=739–746|issn=00256196|doi=10.1016/j.mayocp.2018.02.011}}</ref>
*Combined age and sex-adjusted incidence is 0.57 per 100,000 person-years.<ref name="KyleLarson2018">{{cite journal|last1=Kyle|first1=Robert A.|last2=Larson|first2=Dirk R.|last3=McPhail|first3=Ellen D.|last4=Therneau|first4=Terry M.|last5=Dispenzieri|first5=Angela|last6=Kumar|first6=Shaji|last7=Kapoor|first7=Prashant|last8=Cerhan|first8=James R.|last9=Rajkumar|first9=S. Vincent|title=Fifty-Year Incidence of Waldenström Macroglobulinemia in Olmsted County, Minnesota, From 1961 Through 2010: A Population-Based Study With Complete Case Capture and Hematopathologic Review|journal=Mayo Clinic Proceedings|volume=93|issue=6|year=2018|pages=739–746|issn=00256196|doi=10.1016/j.mayocp.2018.02.011}}</ref>
 
===Age===
* The incidence of Waldenström's macroglobulinemia increases after 50 years of age.<ref name="RF">Waldenström's macroglobulinemia. American Cancer Society (2015)http://www.cancer.org/cancer/waldenstrommacroglobulinemia/detailedguide/waldenstrom-macroglobulinemia-risk-factors Accessed on November 6, 2015</ref>
 
* The median age at diagnosis is 65 years.<ref name="pmid22139816">{{cite journal| author=Wang H, Chen Y, Li F, Delasalle K, Wang J, Alexanian R et al.| title=Temporal and geographic variations of Waldenstrom macroglobulinemia incidence: a large population-based study. | journal=Cancer | year= 2012 | volume= 118 | issue= 15 | pages= 3793-800 | pmid=22139816 | doi=10.1002/cncr.26627 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22139816  }} </ref><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><ref name="pmid8219203">{{cite journal| author=Herrinton LJ, Weiss NS| title=Incidence of Waldenström's macroglobulinemia. | journal=Blood | year= 1993 | volume= 82 | issue= 10 | pages= 3148-50 | pmid=8219203 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8219203  }} </ref>
 
===Gender===
* Men are twice more likely than women to develop WM(5.4 vs. 2.7 per million, respectively). <ref name="pmid22139816">{{cite journal| author=Wang H, Chen Y, Li F, Delasalle K, Wang J, Alexanian R et al.| title=Temporal and geographic variations of Waldenstrom macroglobulinemia incidence: a large population-based study. | journal=Cancer | year= 2012 | volume= 118 | issue= 15 | pages= 3793-800 | pmid=22139816 | doi=10.1002/cncr.26627 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22139816  }} </ref><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><ref name="pmid17488966">{{cite journal| author=Giordano TP, Henderson L, Landgren O, Chiao EY, Kramer JR, El-Serag H et al.| title=Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. | journal=JAMA | year= 2007 | volume= 297 | issue= 18 | pages= 2010-7 | pmid=17488966 | doi=10.1001/jama.297.18.2010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17488966  }} </ref><ref name="pmid8219203">{{cite journal| author=Herrinton LJ, Weiss NS| title=Incidence of Waldenström's macroglobulinemia. | journal=Blood | year= 1993 | volume= 82 | issue= 10 | pages= 3148-50 | pmid=8219203 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8219203  }} </ref>
 
===Race===
*Higher incidence in whites (4.1 per million per year) comparative to blacks (1.8 per million per year) and in past 20 years, incidence in whites has elevated.<ref name="pmid22139816">{{cite journal| author=Wang H, Chen Y, Li F, Delasalle K, Wang J, Alexanian R et al.| title=Temporal and geographic variations of Waldenstrom macroglobulinemia incidence: a large population-based study. | journal=Cancer | year= 2012 | volume= 118 | issue= 15 | pages= 3793-800 | pmid=22139816 | doi=10.1002/cncr.26627 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22139816  }} </ref><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><ref name="pmid16150940">{{cite journal| author=Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS| title=Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. | journal=Blood | year= 2006 | volume= 107 | issue= 1 | pages= 265-76 | pmid=16150940 | doi=10.1182/blood-2005-06-2508 | pmc=1895348 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16150940  }} </ref><ref name="pmid8219203">{{cite journal| author=Herrinton LJ, Weiss NS| title=Incidence of Waldenström's macroglobulinemia. | journal=Blood | year= 1993 | volume= 82 | issue= 10 | pages= 3148-50 | pmid=8219203 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8219203  }} </ref>
 
=== Epidemiology and demographics of Smoldering Waldenstrom macroglobulinemia ===
According to a recent study done in 2017, the following data was found out regarding epidemiology and demographics of SWM.<ref name="PophaliBartley2017">{{cite journal|last1=Pophali|first1=Priyanka Avinash|last2=Bartley|first2=Adam C.|last3=Kapoor|first3=Prashant|last4=Gonsalves|first4=Wilson I.|last5=Ashrani|first5=Aneel A.|last6=Marshall|first6=Ariela L.|last7=Siddiqui|first7=Mustaqeem Ahmad|last8=Go|first8=Ronald S.|title=Smoldering Waldenström’s macroglobulinemia (SWM): Analysis from the National Cancer Database (NCDB).|journal=Journal of Clinical Oncology|volume=35|issue=15_suppl|year=2017|pages=1573–1573|issn=0732-183X|doi=10.1200/JCO.2017.35.15_suppl.1573}}</ref>
 
{| class="wikitable"
|+ ''' Epidemiology and demographics of Smoldering Waldenstrom macroglobulinemia according to Sex, Race and Age'''
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Risk factors
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Proportion of SWM
|-
| style="background:#DCDCDC;" align="center" + |Sex
| style="background:#F5F5F5;" align="center" + |Males:27.72%, Females:28.31%
|-
| style="background:#DCDCDC;" align="center" + |Race
| style="background:#F5F5F5;" align="center" + |White, non-hispanic:28.97%, White, Hispanic:24.79%, Black:21.01%, Asian:20.41%, Other:26.08%.
|-
| style="background:#DCDCDC;" align="center" + |Age in years
| style="background:#F5F5F5;" align="center" + |18-49:18.32%, 50-64:25.91%, 65-79:30.8%, ≥80 : 27.26%
|-
|}
 
==Risk Factors==
*History of WM/LPL or other B-cell disorders in first-degree relatives of patient with WM.<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><ref name="pmid17785558">{{cite journal| author=McMaster ML, Csako G, Giambarresi TR, Vasquez L, Berg M, Saddlemire S et al.| title=Long-term evaluation of three multiple-case Waldenstrom macroglobulinemia families. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 17 | pages= 5063-9 | pmid=17785558 | doi=10.1158/1078-0432.CCR-07-0299 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17785558  }} </ref><ref name="pmid18703425">{{cite journal| author=Kristinsson SY, Björkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O| title=Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population-based study in Sweden. | journal=Blood | year= 2008 | volume= 112 | issue= 8 | pages= 3052-6 | pmid=18703425 | doi=10.1182/blood-2008-06-162768 | pmc=2569164 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18703425  }} </ref>
*History of precursor condition of IgM Monoclonal gammopathy of undetermined significance (MGUS) in patient of WM.<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="pmid12881316">{{cite journal| author=Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR et al.| title=Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. | journal=Blood | year= 2003 | volume= 102 | issue= 10 | pages= 3759-64 | pmid=12881316 | doi=10.1182/blood-2003-03-0801 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12881316  }} </ref><ref name="pmid12881316">{{cite journal| author=Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR et al.| title=Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. | journal=Blood | year= 2003 | volume= 102 | issue= 10 | pages= 3759-64 | pmid=12881316 | doi=10.1182/blood-2003-03-0801 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12881316  }} </ref><ref name="pmid16034042">{{cite journal| author=Baldini L, Goldaniga M, Guffanti A, Broglia C, Cortelazzo S, Rossi A et al.| title=Immunoglobulin M monoclonal gammopathies of undetermined significance and indolent Waldenstrom's macroglobulinemia recognize the same determinants of evolution into symptomatic lymphoid disorders: proposal for a common prognostic scoring system. | journal=J Clin Oncol | year= 2005 | volume= 23 | issue= 21 | pages= 4662-8 | pmid=16034042 | doi=10.1200/JCO.2005.06.147 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16034042  }} </ref><ref name="pmid12881316">{{cite journal| author=Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR et al.| title=Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. | journal=Blood | year= 2003 | volume= 102 | issue= 10 | pages= 3759-64 | pmid=12881316 | doi=10.1182/blood-2003-03-0801 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12881316  }} </ref><ref name="pmid19182202">{{cite journal| author=Landgren O, Kristinsson SY, Goldin LR, Caporaso NE, Blimark C, Mellqvist UH et al.| title=Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden. | journal=Blood | year= 2009 | volume= 114 | issue= 4 | pages= 791-5 | pmid=19182202 | doi=10.1182/blood-2008-12-191676 | pmc=2716021 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19182202  }} </ref>
*Age older than 60 years.<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>
*Personal and family history of autoimmune diseases with autoantibodies leads to 2-3 fold higher risk of developing WM, especially elevated risks are associated with following:
**Hepatitis C virus infection (overall 20-30% increased risk for non-Hodgkin lymohoma and 3-fold increased risk for WM).<ref name="pmid18703425">{{cite journal| author=Kristinsson SY, Björkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O| title=Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population-based study in Sweden. | journal=Blood | year= 2008 | volume= 112 | issue= 8 | pages= 3052-6 | pmid=18703425 | doi=10.1182/blood-2008-06-162768 | pmc=2569164 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18703425  }} </ref><ref name="pmid18809818">{{cite journal| author=Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O| title=Chronic immune stimulation and subsequent Waldenström macroglobulinemia. | journal=Arch Intern Med | year= 2008 | volume= 168 | issue= 17 | pages= 1903-9 | pmid=18809818 | doi=10.1001/archinternmed.2008.4 | pmc=2670401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18809818  }} </ref><ref name="pmid18387498">{{cite journal| author=de Sanjose S, Benavente Y, Vajdic CM, Engels EA, Morton LM, Bracci PM et al.| title=Hepatitis C and non-Hodgkin lymphoma among 4784 cases and 6269 controls from the International Lymphoma Epidemiology Consortium. | journal=Clin Gastroenterol Hepatol | year= 2008 | volume= 6 | issue= 4 | pages= 451-8 | pmid=18387498 | doi=10.1016/j.cgh.2008.02.011 | pmc=3962672 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18387498  }} </ref>
**HIV.<ref name="pmid18809818">{{cite journal| author=Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O| title=Chronic immune stimulation and subsequent Waldenström macroglobulinemia. | journal=Arch Intern Med | year= 2008 | volume= 168 | issue= 17 | pages= 1903-9 | pmid=18809818 | doi=10.1001/archinternmed.2008.4 | pmc=2670401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18809818  }} </ref>
**Rickettsiosis.<ref name="pmid18809818">{{cite journal| author=Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O| title=Chronic immune stimulation and subsequent Waldenström macroglobulinemia. | journal=Arch Intern Med | year= 2008 | volume= 168 | issue= 17 | pages= 1903-9 | pmid=18809818 | doi=10.1001/archinternmed.2008.4 | pmc=2670401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18809818  }} </ref>
**Sjogren syndrome.<ref name="pmid20181958">{{cite journal| author=Kristinsson SY, Koshiol J, Björkholm M, Goldin LR, McMaster ML, Turesson I et al.| title=Immune-related and inflammatory conditions and risk of lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. | journal=J Natl Cancer Inst | year= 2010 | volume= 102 | issue= 8 | pages= 557-67 | pmid=20181958 | doi=10.1093/jnci/djq043 | pmc=2857799 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20181958  }} </ref><ref name="pmid18263783">{{cite journal| author=Ekström Smedby K, Vajdic CM, Falster M, Engels EA, Martínez-Maza O, Turner J et al.| title=Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. | journal=Blood | year= 2008 | volume= 111 | issue= 8 | pages= 4029-38 | pmid=18263783 | doi=10.1182/blood-2007-10-119974 | pmc=2288717 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18263783  }} </ref>
**Autoimmune hemolytic anemia.<ref name="pmid20181958">{{cite journal| author=Kristinsson SY, Koshiol J, Björkholm M, Goldin LR, McMaster ML, Turesson I et al.| title=Immune-related and inflammatory conditions and risk of lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. | journal=J Natl Cancer Inst | year= 2010 | volume= 102 | issue= 8 | pages= 557-67 | pmid=20181958 | doi=10.1093/jnci/djq043 | pmc=2857799 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20181958  }} </ref><ref name="pmid18263783">{{cite journal| author=Ekström Smedby K, Vajdic CM, Falster M, Engels EA, Martínez-Maza O, Turner J et al.| title=Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. | journal=Blood | year= 2008 | volume= 111 | issue= 8 | pages= 4029-38 | pmid=18263783 | doi=10.1182/blood-2007-10-119974 | pmc=2288717 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18263783  }} </ref>
**Sarcoidosis.<ref name="pmid16985251">{{cite journal| author=Landgren O, Engels EA, Pfeiffer RM, Gridley G, Mellemkjaer L, Olsen JH et al.| title=Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia. | journal=J Natl Cancer Inst | year= 2006 | volume= 98 | issue= 18 | pages= 1321-30 | pmid=16985251 | doi=10.1093/jnci/djj361 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16985251  }} </ref>
**SLE.<ref name="pmid18263783">{{cite journal| author=Ekström Smedby K, Vajdic CM, Falster M, Engels EA, Martínez-Maza O, Turner J et al.| title=Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. | journal=Blood | year= 2008 | volume= 111 | issue= 8 | pages= 4029-38 | pmid=18263783 | doi=10.1182/blood-2007-10-119974 | pmc=2288717 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18263783  }} </ref>
*Hay fever.
*Male gender.<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><ref name="pmid17488966">{{cite journal| author=Giordano TP, Henderson L, Landgren O, Chiao EY, Kramer JR, El-Serag H et al.| title=Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. | journal=JAMA | year= 2007 | volume= 297 | issue= 18 | pages= 2010-7 | pmid=17488966 | doi=10.1001/jama.297.18.2010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17488966  }} </ref>
*White race/ethnicity.<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><ref name="pmid16150940">{{cite journal| author=Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS| title=Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. | journal=Blood | year= 2006 | volume= 107 | issue= 1 | pages= 265-76 | pmid=16150940 | doi=10.1182/blood-2005-06-2508 | pmc=1895348 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16150940  }} </ref>
===Environmental Factors===
According to some recent studies, exposure to following environmental factors seems to have association with the development of WM:<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="pmid25174029">{{cite journal| author=Vajdic CM, Landgren O, McMaster ML, Slager SL, Brooks-Wilson A, Smith A et al.| title=Medical history, lifestyle, family history, and occupational risk factors for lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. | journal=J Natl Cancer Inst Monogr | year= 2014 | volume= 2014 | issue= 48 | pages= 87-97 | pmid=25174029 | doi=10.1093/jncimonographs/lgu002 | pmc=4155457 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25174029  }} </ref>
*Occupational (Farming).
*Pesticides.
*Wood dust.
*Organic solvents.
 
There are no established risk factors for [disease name].
 
OR
 
The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].
 
OR
 
Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
 
OR
 
Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
 
==Screening==
There is insufficient evidence to recommend routine screening for [disease/malignancy].
 
OR
 
According to the [guideline name], screening for [disease name] is not recommended.
 
OR
 
According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].
 
==Natural History, Complications, and Prognosis==
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
 
OR
 
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
 
OR
 
Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.


==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
OR
The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
OR


The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
[[Lymphoplasmacytic lymphoma diagnostic study of choice|Diagnostic study of choice]] | [[Lymphoplasmacytic lymphoma history and symptoms|History and Symptoms]] | [[Lymphoplasmacytic lymphoma physical examination|Physical Examination]] | [[Lymphoplasmacytic lymphoma laboratory findings|Laboratory Findings]] | [[Lymphoplasmacytic lymphoma electrocardiogram|Electrocardiogram]] | [[Lymphoplasmacytic lymphoma x ray|X-Ray Findings]] | [[Lymphoplasmacytic lymphoma echocardiography and ultrasound|Echocardiography and Ultrasound]] | [[Lymphoplasmacytic lymphoma CT scan|CT-Scan Findings]] | [[Lymphoplasmacytic lymphoma MRI|MRI Findings]] | [[Lymphoplasmacytic lymphoma other imaging findings|Other Imaging Findings]] | [[Lymphoplasmacytic lymphoma other diagnostic studies|Other Diagnostic Studies]]
 
OR
 
There are no established criteria for the diagnosis of [disease name].
 
===History and Symptoms===
*Sometimes, Waldenstrom macroglobulinemia (WM) isn’t causing any symptoms when it’s first found. Instead, it’s found when the person has blood tests done for some other reason. WM found this way is sometimes called asymptomatic or smoldering WM.
*Hyperviscosity Syndrome:
The lymphoma cells make varying amounts of a protein called immunoglobulin M (IgM, or macroglobulin). Higher amounts of this protein than normal in blood tends to make it thick leading to hyperviscosity syndrome (when blood becomes thick, it is harder for blood to flow through small blood vessels), and when this occurs, the condition is termed as Waldenstrom macroglobulinemia. This excess amount of IgM antibodies can be ultimately associated with circulatory problems leading to less blood flow to the brain, the eyes or other organs, which may cause any of the following:
**Symptoms resembling those of stroke.
**Dizziness.
**Headache.
**Blurred vision or loss of vision.
**Shortness of breath.
**Numbness and tingling of the fingers or toes (called peripheral neuropathy).
**Muscle weakness.
**Confusion.
*Amyloidosis (due to IgM deposits in kidney and heart tissues lwading to problems with these organs).
*Cryoglobulinemia and vasculitis (inflammation of small blood vessels occurs when IgM antibody forms immune complexes with cold exposure (called cryoglobulin) in cooler parts of body like tip of nose, ears, fingers and toes. This leads to pain and other problems in these body parts upon exposure to cold temperature).
*Not all people with WM develop hyperviscosity, cryoglobulins, or amyloidosis.
 
===Common symptoms of WM===
*Mucous membrane bleeding (oronasal).
*Fatigue
*Weakness (due to anemia associated with IgM binding to RBCs).
*Loss of appetite.
*B symptoms as seen in other types of NHL:
**Unexplained fever.
**Drenching night sweats.
**Unexplained weight loss.
**Enlarged lymph nodes.
*Numbness and tingling (painful pins and needle sensation) of the fingers or toes (called peripheral neuropathy).
===Less common signs and symptoms of WM===
*Enlarged lymph nodes (appearing as 1-2 inches sized lumps under the skin in neck, groin or the armpits).
*Swollen belly/abdomen (due to hepatosplenomegaly).
*Problems with circulation system leading to:
**Headache.
**Confusion.
**Dizziness.
**Symptoms resembling stroke like slurred speech or weakness on one side of body (such patients are advised to consult from their doctor right away).
*Abnormal mucous membrane bleeding (epistaxis, bleeding gums).
*Vision problems (blurred vision or blind spots).
*Kidney problems (leading to weakness, trouble breathing and fluid buildup in body tissues associated with accumulation of excess salt, fluid and waste products in blood secondary to amyloidosis).
*Heart problems (Secondary to amyloidosis, build up of M protein in heart affects its pumping ability, and also the heart has to work harder to pump the thick blood ultimately leading to CHF with following symptoms).
**Palpitations.
**Feeling of tiredness and weakness.
**Cough.
**Shortness of breath.
**Rapid weight gain.
**Swelling of feet and legs.
*Infections (high levels of abnormal antibody in WM slows down the production of normal antibodies).
*Digestive problems (due to M protein build up in intestines):
**Diarrhea.
**Poor absorption of vitamins.
**GIT bleeding (blood in stools/dark stools).
*Sensitivity to cold (due to cryoglobulinemia which is associated with reduced blood flow leading to pain, itching, bluish discoloration or sores in following body parts).
**Tip of nose.
**Ears.
**Fingers.
**Toes.
 
 
 
Read more: http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/more-types-of-nhl/lymphoplasmacytic-lymphoma/?region=on#ixzz5eavoTzUH
The majority of patients with [disease name] are asymptomatic.
 
OR
 
The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
 
===Physical Examination===
Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].
 
OR
 
Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
The presence of [finding(s)] on physical examination is diagnostic of [disease name].
 
OR
 
The presence of [finding(s)] on physical examination is highly suggestive of [disease name].
 
===Laboratory Findings===
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
 
OR
 
Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
 
OR
 
[Test] is usually normal among patients with [disease name].
 
OR
 
Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
 
OR
 
There are no diagnostic laboratory findings associated with [disease name].
 
===Electrocardiogram===
There are no ECG findings associated with [disease name].
 
OR
 
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
===X-ray===
There are no x-ray findings associated with [disease name].
 
OR
 
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
 
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound findings associated with [disease name].
 
OR
 
Echocardiography/ultrasound  may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no echocardiography/ultrasound  findings associated with [disease name]. However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
 
===CT scan===
There are no CT scan findings associated with [disease name].
 
OR
 
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
 
===MRI===
There are no MRI findings associated with [disease name].
 
OR
 
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
 
===Other Imaging Findings===
There are no other imaging findings associated with [disease name].
 
OR
 
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
===Other Diagnostic Studies===
There are no other diagnostic studies associated with [disease name].
 
OR
 
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].


==Treatment==
==Treatment==
One or more of the following treatments can be given for lymphoplasmacytic lymphoma.
[[Lymphoplasmacytic lymphoma medical therapy|Medical Therapy]] | [[Lymphoplasmacytic lymphoma surgery|Surgery]] | [[Lymphoplasmacytic lymphoma primary prevention|Primary Prevention]] | [[Lymphoplasmacytic lymphoma secondary prevention|Secondary Prevention]] | [[Lymphoplasmacytic lymphoma cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Lymphoplasmacytic lymphoma future or investigational therapies|Future or Investigational Therapies]]
===Watchful waiting===
Watchful waiting (also called active surveillance) may be offered for lymphoplasmacytic lymphoma because it develops slowly and may not need to be treated right away. The healthcare team will carefully monitor the person with lymphoplasmacytic lymphoma and start treatment when symptoms appear, such as hyperviscosity syndrome, or there are signs that the disease is progressing more quickly.
===Chemotherapy===
*People with lymphoplasmacytic lymphoma who have symptoms or hyperviscosity syndrome are usually given chemotherapy. Chemotherapy drugs that may be used with or without prednisone include:
**Chlorambucil (Leukeran)
**Fludarabine (Fludara)
**Bendamustine (Treanda)
**Cyclophosphamide (Cytoxan, Procytox)
 
*Combinations of chemotherapy drugs that may be used include:
**DRC – dexamethasone (Decadron, Dexasone), rituximab (Rituxan) and cyclophosphamide
**BRD – bortezomib (Velcade) and rituximab, with or without dexamethasone
**CVP – cyclophosphamide, vincristine (Oncovin) and prednisone
**R-CVP – CVP with rituximab
**Thalidomide (Thalomid) and rituximab
 
===Targeted therapy===
*Targeted therapy uses drugs to target specific molecules (such as proteins) on the surface of cancer cells. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells while limiting harm to normal cells.
*Targeted therapy drugs used alone or in combination to treat lymphoplasmacytic lymphoma include rituximab, bortezomib and ibrutinib (Imbruvica).
===Immunotherapy===
*Immunotherapy works by stimulating, boosting, restoring or acting like the body’s immune system to create a response against cancer cells. Immunomodulatory drugs are a type of immunotherapy that interferes with the growth and division of cancer cells.
*Thalidomide is a type of immunomodulatory drug that may be used to treat lymphoplasmacytic lymphoma.
===Radiation therapy===
External beam radiation therapy may be used to treat lymphoplasmacytic lymphoma that develops outside of the lymphatic system (called extralymphatic disease), but this is rare.
===Stem cell transplant===
*Some people with lymphoplasmacytic lymphoma may be offered a stem cell transplant.
*It may be used if the lymphoma comes back (recurs) after treatment or doesn’t respond to other treatments (called refractory disease).
*Many people with lymphoplasmacytic lymphoma are older or may not be in good health, so a stem cell transplant may not be a good treatment option for them.
 
 
Read more: http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/more-types-of-nhl/lymphoplasmacytic-lymphoma/?region=on#ixzz5eb6iT7G6
===Medical Therapy===
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
 
OR
 
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
 
OR
 
The majority of cases of [disease name] are self-limited and require only supportive care.
 
OR
 
[Disease name] is a medical emergency and requires prompt treatment.
 
OR
 
The mainstay of treatment for [disease name] is [therapy].
 
OR
 
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
 
OR
 
[Therapy] is recommended among all patients who develop [disease name].
 
OR
 
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
 
OR
 
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
 
OR
 
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
 
OR
 
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
 
===Surgery===
Surgical intervention is not recommended for the management of [disease name].
 
OR
 
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
 
OR
 
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
 
OR
 
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
 
OR
 
Surgery is the mainstay of treatment for [disease or malignancy].
 
===Primary Prevention===
There are no established measures for the primary prevention of [disease name].
 
OR
 
There are no available vaccines against [disease name].
 
OR
 
Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
 
OR
 
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].
 
===Secondary Prevention===
There are no established measures for the secondary prevention of [disease name].
 
OR


Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
==Case Studies==
[[Lymphoplasmacytic lymphoma case study one|Case #1]]


==References==
[[Category: (name of the system)]]
{{reflist|2}}

Latest revision as of 20:45, 19 August 2020

Lymphoplasmacytic lymphoma Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Lymphoplasmacytic Lymphoma from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Lymphoplasmacytic lymphoma On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Lymphoplasmacytic lymphoma

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Lymphoplasmacytic lymphoma

CDC on Lymphoplasmacytic lymphoma

Lymphoplasmacytic lymphoma in the news

Blogs on Lymphoplasmacytic lymphoma

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for Lymphoplasmacytic lymphoma

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

Synonyms and keywords: Plasmacytoid lymphocytic lymphoma; Familial Waldenström's macroglobulinemia; Primary macroglobulinemia; Hyperviscosity syndrome; Lymphoplasmacytoid lymphoma

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Lymphoplasmacytic lymphoma from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic study of choice | History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | X-Ray Findings | Echocardiography and Ultrasound | CT-Scan Findings | MRI Findings | Other Imaging Findings | Other Diagnostic Studies

Treatment

Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

Case Studies

Case #1

Retrieved from "https://www.wikidoc.org/index.php?title=Lymphoplasmacytic_lymphoma&oldid=1653407"