Lymphoplasmacytic lymphoma diagnostic study of choice: Difference between revisions

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== Overview ==
== Overview ==
The [[diagnosis]] of [[lymphoplasmacytic lymphoma]] is based on [[bone marrow biopsy]] and [[serum]] [[protein]] analysis.
The [[diagnosis]] of [[lymphoplasmacytic lymphoma]] is [[Based on Symptoms|based]] on [[bone marrow aspiration]] and [[biopsy]] and [[serum]] [[protein]] [[analysis]] [[Study design|studies]] such as [[immunohistochemistry|immunohistochemistry,]]  [[flow cytometry]] and [[cytogenetics]] to [[Differentiate|distinguish]] [[Lymphoplasmacytic lymphoma|LPL]] from other types of [[B-cell]] [[lymphomas]]. [[CSF]] [[flow cytometry]], [[protein electrophoresis]] and [[immunofixation]] is [[done]] for the [[diagnosis]] of [[Bing-Neel syndrome]] (a late, but severe, [[rare]] [[Complication (medicine)|complication]]).


== Diagnostic Study of Choice ==
== Diagnostic Study of Choice ==
There is no single [[diagnostic study of choice]] for the [[diagnosis]] of [[lymphoplasmacytic lymphoma]] (LPL), but '''bone marrow aspiration and biopsy''' is considered to be mandatory for assessment of patients with LPL and further supported by monoclonal protein/immunophenotypic studies like [[immunohistochemistry]], [[flow cytometry]] and [[cytogenetics]] to distinguish LPL from other types of [[B-cell]] [[lymphomas]].<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><ref name="pmid26980727">{{cite journal| author=Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R et al.| title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms. | journal=Blood | year= 2016 | volume= 127 | issue= 20 | pages= 2375-90 | pmid=26980727 | doi=10.1182/blood-2016-01-643569 | pmc=4874220 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26980727  }} </ref>
*There is no single [[diagnostic study of choice]] for the [[diagnosis]] of [[lymphoplasmacytic lymphoma]] (LPL), but '''[[bone marrow aspiration]]''' and '''[[biopsy]]''' is considered to be [[Mandatory labelling|mandatory]] for the [[Assessment and Plan|assessment]] of [[patients]] with LPL and further [[Support|supported]] by [[monoclonal]] [[protein]]/[[Immunophenotyping|immunophenotypic studies]] such as [[immunohistochemistry]], [[flow cytometry]] and [[cytogenetics]] to distinguish LPL from other types of [[B-cell]] [[lymphomas]].<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><ref name="pmid26980727">{{cite journal| author=Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R et al.| title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms. | journal=Blood | year= 2016 | volume= 127 | issue= 20 | pages= 2375-90 | pmid=26980727 | doi=10.1182/blood-2016-01-643569 | pmc=4874220 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26980727 }} </ref>
*Not all the [[diagnostic]] [[Test|tests]] mentioned are [[Performance status|performed]] in a [[patient]] with [[lymphoplasmacytic lymphoma]]. A [[Doctor of Medicine|doctor]] takes into account the following factors before choosing [[diagnostic]] [[Test|tests]] in a particular [[patient]]:
** Suspected type of [[cancer]]
** [[Signs and Symptoms|Signs]] and [[symptoms]]
** [[Age]]
** [[Medical condition]] of the [[patient]]
** [[Result|Results]] of earlier [[medical]] [[Test|tests]]
 
===Diagnostic Criteria:===
====Diagnostic criteria presented in second International Workshop, Greece, 2002====
 
* In September 26-30, 2002, in Athens, Greece,the Second International Workshop was held in which a [[Diagnosis|diagnostic]] criteria for [[Waldenström's macroglobulinemia|Waldenstrom's Macroglobulinemia]] was [[Proposition|proposed]]. According to this [[criteria]], the following findings on [[Performance status|performing]] [[Bone marrow examination|bone marrow biopsy]] and [[serum]] [[protein]] analysis are [[Confirmatory factor analysis|confirmatory]] of [[Waldenström macroglobulinemia]] and [[Exclusion criteria|exclude]] other small [[B cell]] [[lymphoid]] [[neoplasms]] with plasmacytic [[differentiation]]:<ref name="pmid15735132" /><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>


====Diagnostic Criteria:====
In September 26-30, 2002, in Athens, Greece,the Second International Workshop was held in which a [[diagnostic criteria]] for [[Waldenström's macroglobulinemia|Waldenstrom's Macroglobulinemia]] was proposed. According to this criteria, the following findings on performing [[Bone marrow examination|bone marrow biopsy]] and '''serum protein analysis''' are confirmatory of [[Waldenström macroglobulinemia]] and exclude other small [[B cell]] [[lymphoid]] [[neoplasms]] with plasmacytic [[differentiation]]:<ref name="pmid15735132" />
#Presence of [[IgM]] monoclonal [[gammopathy]] of any concentration on [[serum]] protein analysis.
#A [[bone marrow]] [[biopsy]] demonstrating more than 10% infiltration by small [[lymphocytes]], plasmacytoid [[lymphocytes]], and [[plasma cells]], (with variable numbers of admixed immunoblasts), with an intertrabecular pattern consistent with [[lymphoplasmacytic lymphoma]].
#*[[Proliferation]] centers (pathognomonic of [[CLL]]/[[SLL]]) and paler-appearing marginal zone type [[differentiation]] (seen in marginal zone lymphoma) are absent.
#*[[IgM]] concentration widely varies in WM, and it is not possible to define a concentration that reliably distinguishes WM from other [[lymphoproliferative disorders]]. Hence, a diagnosis of WM can be made irrespective of [[IgM]] concentration if there is evidence of [[bone marrow]] [[Infiltration (medical)|infiltration]] by lymphoplasmacytoid [[lymphoma]] as defined by the Revised European-American [[Lymphoma]] [[classification]] and [[WHO]] criteria.<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> This is a [[tumor]] of small [[lymphocytes]] showing evidence of plasmacytoid or [[plasma cell]] [[differentiation]].
#*A recent study found that, in 39% of patients, the [[bone marrow]] [[aspirate]] contained a spectrum of small [[lymphocytes]], plasmacytoid [[lymphocytes]], and [[plasma cells]]; in 39% of patients, there was a predominance of small [[lymphocytes]] with fewer plasmacytoid [[lymphocytes]] or [[plasma cells]], and 22% of patients contained a mixture of small [[lymphocytes]] and [[plasma cells]], with rare plasmacytoid cells. [[Mast cells]] were increased in 26% of patients.<ref name="pmid12720133">{{cite journal| author=Remstein ED, Hanson CA, Kyle RA, Hodnefield JM, Kurtin PJ| title=Despite apparent morphologic and immunophenotypic heterogeneity, Waldenstrom's macroglobulinemia is consistently composed of cells along a morphologic continuum of small lymphocytes, plasmacytoid lymphocytes, and plasma cells. | journal=Semin Oncol | year= 2003 | volume= 30 | issue= 2 | pages= 182-6 | pmid=12720133 | doi=10.1053/sonc.2003.50073 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12720133  }} </ref>
#Intertrabecular pattern of [[bone marrow]] [[Infiltration (medical)|infiltration]].
#[[Immunophenotype]] of the lymphoplasmacytic infiltrate consistent with [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]]. This includes: [[IgM]]+, [[CD5]]-, [[CD10]]-, [[CD11c]]-, [[CD19]]+, [[CD20]]+, [[CD22]]+, [[CD23]]-, [[CD25]]+, [[CD27]]+, [[FMC7]]+, [[CD103]]- and [[CD138]]+.<ref name="pmid12720134">{{cite journal| author=San Miguel JF, Vidriales MB, Ocio E, Mateo G, Sánchez-Guijo F, Sánchez ML et al.| title=Immunophenotypic analysis of Waldenstrom's macroglobulinemia. | journal=Semin Oncol | year= 2003 | volume= 30 | issue= 2 | pages= 187-95 | pmid=12720134 | doi=10.1053/sonc.2003.50074 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12720134  }} </ref><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="pmid16191510">{{cite journal| author=Konoplev S, Medeiros LJ, Bueso-Ramos CE, Jorgensen JL, Lin P| title=Immunophenotypic profile of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. | journal=Am J Clin Pathol | year= 2005 | volume= 124 | issue= 3 | pages= 414-20 | pmid=16191510 | doi=10.1309/3G1X-DX0D-VHBN-VKB4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16191510  }} </ref>
{| class="wikitable"
{| class="wikitable"
|+
|+
! colspan="2" |
! colspan="3" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Diagnostic criteria presented in second International Workshop, Greece, 2002}}
!
|-
|-
| colspan="2" |Presence of [[IgM]] monoclonal [[gammopathy]] of any concentration on [[serum]] protein analysis.
| colspan="2" |'''1:'''[[Presenting symptom|Presence]] of [[Immunoglobulin M|IgM]] [[monoclonal gammopathy]] of any [[concentration]] on [[Serum protein electrophoresis|serum protein analysis]]
|Necessary criteria
|'''[[Necessary and sufficient|Necessary]]''' [[criteria]]
|-
|-
| rowspan="3" |A [[bone marrow]] [[biopsy]] demonstrating more than 10% infiltration by small [[lymphocytes]], plasmacytoid [[lymphocytes]], and [[plasma cells]], (with variable numbers of admixed immunoblasts), with an intertrabecular pattern consistent with [[lymphoplasmacytic lymphoma]].
| rowspan="3" |'''2:'''A [[bone marrow]] [[biopsy]] demonstrating more than 10% [[Infiltration (medical)|infiltration]] by small [[lymphocytes]], [[plasmacytoid]] [[lymphocytes]], and [[plasma cells]], (with [[variable]] [[Number|numbers]] of admixed [[Immunoblast|immunoblasts]]), with an intertrabecular [[pattern]] consistent with [[lymphoplasmacytic lymphoma]]
|[[Proliferation]] centers (pathognomonic of [[CLL]]/[[SLL]]) and paler-appearing marginal zone type [[differentiation]] (seen in marginal zone lymphoma) are absent.
|[[Proliferation]] centers ([[pathognomonic]] of [[CLL]]/[[SLL]]) and [[Paleness|paler]]-[[Appearance|appearing]] [[marginal zone]] type [[differentiation]] (seen in [[marginal zone lymphoma]]) are absent
| rowspan="3" |Necessary criteria
| rowspan="3" |'''[[Necessary and sufficient|Necessary]]''' [[criteria]]
|-
|-
|[[IgM]] concentration widely varies in WM, and it is not possible to define a concentration that reliably distinguishes WM from other [[lymphoproliferative disorders]]. Hence, a diagnosis of WM can be made irrespective of [[IgM]] concentration if there is evidence of [[bone marrow]] [[Infiltration (medical)|infiltration]] by lymphoplasmacytoid [[lymphoma]] as defined by the Revised European-American [[Lymphoma]] [[classification]] and [[WHO]] criteria.<ref name="pmid8068936" /> This is a [[tumor]] of small [[lymphocytes]] showing evidence of plasmacytoid or [[plasma cell]] [[differentiation]].
|[[IgM]] [[concentration]] [[Wide and fast|widely]] [[Variable|varies]] in [[Waldenström's macroglobulinemia|WM]], and it is not [[Possibility theory|possible]] to define a [[concentration]] that reliably distinguishes [[Waldenström's macroglobulinemia|WM]] from other [[lymphoproliferative disorders]]. Hence, a [[diagnosis]] of [[Waldenström's macroglobulinemia|WM]] can be made irrespective of [[IgM]] [[concentration]] if there is an [[evidence]] of [[bone marrow]] [[Infiltration (medical)|infiltration]] by lymphoplasmacytoid [[lymphoma]] as defined by the Revised European-American [[Lymphoma]] [[classification]] and [[WHO]] [[criteria]]. This is a [[tumor]] of small [[lymphocytes]] showing [[evidence]] of [[plasmacytoid]] or [[plasma cell]] [[differentiation]].
|-
|-
|A recent study found that, in 39% of patients, the [[bone marrow]] [[aspirate]] contained a spectrum of small [[lymphocytes]], plasmacytoid [[lymphocytes]], and [[plasma cells]]; in 39% of patients, there was a predominance of small [[lymphocytes]] with fewer plasmacytoid [[lymphocytes]] or [[plasma cells]], and 22% of patients contained a mixture of small [[lymphocytes]] and [[plasma cells]], with rare plasmacytoid cells. [[Mast cells]] were increased in 26% of patients.<ref name="pmid12720133" />
|A [[Recent changes|recent]] [[Study design|study]] found that, in 39% of [[patients]], the [[bone marrow]] [[aspirate]] contained a [[spectrum]] of small [[lymphocytes]], [[plasmacytoid]] [[lymphocytes]], and [[plasma cells]]; in 39% of [[patients]], there was a [[Predominance diagram|predominance]] of small [[lymphocytes]] with [[Fewmets|fewer]] [[plasmacytoid]] [[lymphocytes]] or [[plasma cells]], and 22% of the [[patients]] contained a [[mixture]] of small [[lymphocytes]] and [[plasma cells]], with [[rare]] [[plasmacytoid]] [[Cells (biology)|cells]]. [[Mast cells]] were increased in 26% of [[patients]].
|-
|-
| colspan="2" |Intertrabecular pattern of [[bone marrow]] [[Infiltration (medical)|infiltration]].
| colspan="2" |'''3:'''Intertrabecular [[pattern]] of [[bone marrow]] [[Infiltration (medical)|infiltration]]
|Supportive criteria
|'''[[Support|Supportive]]''' [[criteria]]
|-
|-
| colspan="2" |[[Immunophenotype]] of the lymphoplasmacytic infiltrate consistent with [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]]. This includes: [[IgM]]+, [[CD5]]-, [[CD10]]-, [[CD11c]]-, [[CD19]]+, [[CD20]]+, [[CD22]]+, [[CD23]]-, [[CD25]]+, [[CD27]]+, [[FMC7]]+, [[CD103]]- and [[CD138]]+.<ref name="pmid12720134" /><ref name="pmid11554171" /><ref name="pmid16191510" />
| colspan="2" |'''4:'''[[Immunophenotype]] of the [[Lymphoplasmacytic lymphoma|lymphoplasmacytic]] [[Infiltration (medical)|infiltrate]] consistent with [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]]. This includes: [[IgM]]+, [[CD5]]-, [[CD10]]-, [[CD11c]]-, [[CD19]]+, [[CD20]]+, [[CD22]]+, [[CD23]]-, [[CD25]]+, [[CD27]]+, [[FMC7]]+, [[CD103]]- and [[CD138]]+
|Supportive criteria
|'''[[Support|Supportive]]''' [[criteria]]
|}
|}
(3,4 are supportive of but not necessary for WM diagnosis).
====mSMART guidelines for diagnosis of Waldenstrom macroglobulinemia and associated disorders====
*Another diagnostic Criteria for Waldenström Macroglobulinemia and associated [[disorders]] is as follow:<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>
 
#[[Waldenström macroglobulinemia]]:
* [[Mayo Clinic|Mayo]] [[Stratification]] of [[Macroglobulinemia]] and [[RiskMetrics|Risk]]-[[Adapted process|Adapted]] [[Therapy]] (mSMART) [[Medical guideline|Guidelines]] 2016 for [[diagnosis]] of [[Waldenstrom macroglobulinemia]] and [[Association (statistics)|associated]] [[disorders]] are as follows:<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>
#*[[IgM]] monoclonal gammopathy (regardless of the size of the [[M protein]]) with >10% [[bone marrow]] lymphoplasmacytic [[Infiltration (medical)|infiltration]] (usually intertrabecular) by small [[lymphocytes]] that exhibit plasmacytoid or [[plasma cell]] [[differentiation]] and a typical [[immunophenotype]] (surface [[IgM]]+, [[CD5]]–, [[CD10]]–, [[CD19]]+, [[CD20]]+, [[CD23]]–) that satisfactorily excludes other [[lymphoproliferative disorders]], including [[chronic lymphocytic leukemia]] and [[mantle cell lymphoma]].
{| class="wikitable"
#[[IgM]] [[MGUS]]:
|+
#*[[Serum]] [[IgM monoclonal protein]] level <3 g/dL, [[bone marrow]] lymphoplasmacytic [[Infiltration (medical)|infiltration]] <10%, and no evidence of [[anemia]], constitutional [[symptoms]], [[hyperviscosity]], [[lymphadenopathy]], or [[hepatosplenomegaly]].
! colspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|mSMART guidelines 2016 for diagnosis of Waldenstrom macroglobulinemia and associated disorders}}
#Smoldering [[Waldenström macroglobulinemia]] (also referred to as indolent or [[asymptomatic]] [[Waldenström macroglobulinemia]]):
|-
#*Serum [[IgM monoclonal protein]] level ≥3 g/dL and/or [[bone marrow]] lymphoplasmacytic [[Infiltration (medical)|infiltration]] ≥10% and no evidence of end-organ damage, such as [[anemia]], constitutional symptoms, [[hyperviscosity]], [[lymphadenopathy]], or [[hepatosplenomegaly]], that can be attributed to a lymphoplasmacytic proliferative disorder.
|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Waldenström macroglobulinemia]]
|[[IgM]] [[monoclonal gammopathy]] (regardless of the [[Size consistency|size]] of the [[M protein]]) with >10% [[bone marrow]] lymphoplasmacytic [[Infiltration (medical)|infiltration]] (usually intertrabecular) by small [[lymphocytes]] that exhibit plasmacytoid or [[plasma cell]] [[differentiation]] and a [[Typical set|typical]] [[immunophenotype]] ([[Surface chemistry|surface]] [[IgM]]+, [[CD5]]–, [[CD10]]–, [[CD19]]+, [[CD20]]+, [[CD23]]–) that satisfactorily [[Exclusion criteria|excludes]] other [[lymphoproliferative disorders]], including [[chronic lymphocytic leukemia]] and [[mantle cell lymphoma]]
|-
|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[IgM]] [[MGUS]]
|[[Serum]] [[IgM monoclonal protein]] level <3 g/dL, [[bone marrow]] lymphoplasmacytic [[Infiltration (medical)|infiltration]] <10%, and no [[evidence]] of [[anemia]], constitutional [[symptoms]], [[hyperviscosity]], [[lymphadenopathy]], or [[hepatosplenomegaly]]
|-
|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Smoldering [[Waldenström macroglobulinemia]] (indolent /[[asymptomatic]] [[Waldenström macroglobulinemia]])
|[[Serum]] [[IgM monoclonal protein]] level ≥3 g/dL and/or [[bone marrow]] lymphoplasmacytic [[Infiltration (medical)|infiltration]] ≥10% and no [[evidence]] of [[End organ damage|end-organ damage]], such as [[anemia]], constitutional [[symptoms]], [[hyperviscosity]], [[lymphadenopathy]], or [[hepatosplenomegaly]], that can be [[Attribution (psychology)|attributed]] to a lymphoplasmacytic [[Proliferation|proliferative]] [[Disorder (medicine)|disorder]]
|}
 
====Definitive Diagnostic Tests====
*[[Genetic]] [[Testing]]:
**ARIDA
**[[Immunoglobulin|IG]] [[gene]] [[rearrangement]]
**[[CXCR4]] 5338X
**[[MYD88]] L265P
*[[Immunophenotyping]]
*[[Serum]] [[paraprotein]]


====Definitive Diagnostic Tests:====
*[[Genetic]] Testing.
**ARIDA.
**IG [[gene]] [[rearrangement]].
**[[CXCR4]] 5338X.
**[[MYD88]] L265P.
*[[Immunophenotyping]].
*[[Serum]] [[paraprotein]].
===Bone Marrow Aspirate:===
===Bone Marrow Aspirate:===
A [[Bone marrow aspiration|bone marrow aspirate]] is essential in the [[diagnosis]] of [[lymphoplasmacytic lymphoma]].
* A [[Bone marrow aspiration|bone marrow aspirate]] is [[Essential medicines|essential]] in the [[diagnosis]] of [[lymphoplasmacytic lymphoma]]
 
* Findings [[Suggestion|suggestive]] of [[lymphoplasmacytic lymphoma]] include:<ref name="pmid18555588">{{cite journal| author=Leleu X, Roccaro AM, Moreau AS, Dupire S, Robu D, Gay J et al.| title=Waldenstrom macroglobulinemia. | journal=Cancer Lett | year= 2008 | volume= 270 | issue= 1 | pages= 95-107 | pmid=18555588 | doi=10.1016/j.canlet.2008.04.040 | pmc=3133633 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18555588  }} </ref>
Findings suggestive of [[lymphoplasmacytic lymphoma]] include:<ref name="pmid18555588">{{cite journal| author=Leleu X, Roccaro AM, Moreau AS, Dupire S, Robu D, Gay J et al.| title=Waldenstrom macroglobulinemia. | journal=Cancer Lett | year= 2008 | volume= 270 | issue= 1 | pages= 95-107 | pmid=18555588 | doi=10.1016/j.canlet.2008.04.040 | pmc=3133633 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18555588  }} </ref>
** Hypercellular [[bone marrow]] [[aspirate]]
* A hypercellular [[bone marrow]] [[aspirate]].
**[[Lymphoplasmacytic lymphoma|Lymphoplasmacytic]] [[Infiltration (medical)|infiltrate]] with [[Characteristic function (probability theory)|characteristic]] [[immunophenotype]]
* Lymphoplasmacytic infiltrate with characteristic [[immunophenotype]].


{|
{|
|
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[[File:Wm bm aspirate.png|thumb|250px|none| Bone marrow aspirate. Lymphocytes with lymphoplasmacytoid appearance (arrows).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3894394_br-48-300-g001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=91 Source: D'Angelo G. et al, Laboratorio di Chimica-Clinica, Ematologia e Microbiologia (Ematologia/Coagulazione), Azienda Ospedaliera "S. Antonio Abate" di Gallarate, Varese, Italy.]]]
[[File:Wm bm aspirate.png|thumb|250px|none| [[Bone marrow]] [[aspirate]]. [[Lymphocytes]] with [[Lymphoplasmacytic lymphoma|lymphoplasmacytic]] appearance (arrows).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3894394_br-48-300-g001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=91 Source: D'Angelo G. et al, Laboratorio di Chimica-Clinica, Ematologia e Microbiologia (Ematologia/Coagulazione), Azienda Ospedaliera "S. Antonio Abate" di Gallarate, Varese, Italy.]]]
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=== Bone Marrow Biopsy: ===
=== Bone Marrow Biopsy: ===
A [[bone marrow biopsy]] may be helpful in the diagnosis of [[lymphoplasmacytic lymphoma]]. <ref name="pmid18555588">{{cite journal| author=Leleu X, Roccaro AM, Moreau AS, Dupire S, Robu D, Gay J et al.| title=Waldenstrom macroglobulinemia. | journal=Cancer Lett | year= 2008 | volume= 270 | issue= 1 | pages= 95-107 | pmid=18555588 | doi=10.1016/j.canlet.2008.04.040 | pmc=3133633 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18555588  }} </ref>
*A [[bone marrow biopsy]] may be [[Help desk|helpful]] in the [[diagnosis]] of [[lymphoplasmacytic lymphoma]] <ref name="pmid18555588">{{cite journal| author=Leleu X, Roccaro AM, Moreau AS, Dupire S, Robu D, Gay J et al.| title=Waldenstrom macroglobulinemia. | journal=Cancer Lett | year= 2008 | volume= 270 | issue= 1 | pages= 95-107 | pmid=18555588 | doi=10.1016/j.canlet.2008.04.040 | pmc=3133633 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18555588  }} </ref>
*Findings on the [[biopsy]] [[Suggestion|suggestive]] of [[lymphoplasmacytic lymphoma]] include:<ref name="pmid18555588">{{cite journal| author=Leleu X, Roccaro AM, Moreau AS, Dupire S, Robu D, Gay J et al.| title=Waldenstrom macroglobulinemia. | journal=Cancer Lett | year= 2008 | volume= 270 | issue= 1 | pages= 95-107 | pmid=18555588 | doi=10.1016/j.canlet.2008.04.040 | pmc=3133633 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18555588  }} </ref>
**Hypercellular and [[Infiltration (medical)|infiltrated]] with [[lymphoid]] and [[Plasmacytoid|plasmacytoid cells]]
**Dutcher [[Body|bodies]] ([[PAS stain|PAS]] positive intra-nuclear [[vacuoles]] containing [[IgM]] [[monoclonal]] [[protein]])
***[[Characteristic function (probability theory)|Characteristic]] [[Features (pattern recognition)|feature]] of [[lymphoplasmacytic lymphoma]]
*Three [[Pattern|patterns]] of [[Bone marrow|marrow]] involvement are described, as follows:
**Lymphoplasmacytoid [[Cells (biology)|cells]] (lymphoplasmacytic and small [[lymphocytes]]) in a [[nodular]] [[pattern]]
**[[Lymphoplasmacytic lymphoma|Lymphoplasmacytic]] [[Cells (biology)|cells]] (small [[lymphocytes]], mature [[plasma cells]], [[mast cells]]) in an [[interstitial]]/[[nodular]] [[pattern]]
**A polymorphous [[Infiltration (medical)|infiltrate]] (small [[lymphocytes]], [[plasma cells]], [[plasmacytoid]] [[Cells (biology)|cells]], [[Immunoblast|immunoblasts]] with [[mitotic]] figures)


Findings on the biopsy suggestive of [[lymphoplasmacytic lymphoma]] include:<ref name="pmid18555588">{{cite journal| author=Leleu X, Roccaro AM, Moreau AS, Dupire S, Robu D, Gay J et al.| title=Waldenstrom macroglobulinemia. | journal=Cancer Lett | year= 2008 | volume= 270 | issue= 1 | pages= 95-107 | pmid=18555588 | doi=10.1016/j.canlet.2008.04.040 | pmc=3133633 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18555588  }} </ref>
* Hypercellular and [[Infiltration (medical)|infiltrated]] with [[lymphoid]] and [[Plasmacytoid|plasmacytoid cells]].
* Dutcher bodies ([[PAS stain|PAS]] positive intra-nuclear [[vacuoles]] containing [[IgM]] monoclonal protein).
** Characteristic feature of [[lymphoplasmacytic lymphoma]].
Three patterns of marrow involvement are described, as follows:
* Lymphoplasmacytoid cells (lymphoplasmacytic and small [[lymphocytes]]) in a [[nodular]] pattern.
* Lymphoplasmacytic cells (small [[lymphocytes]], mature [[plasma cells]], [[mast cells]]) in an [[interstitial]]/[[nodular]] pattern.
* A polymorphous infiltrate (small [[lymphocytes]], [[plasma cells]], plasmacytoid cells, immunoblasts with mitotic figures).
===Electrophoresis and Immunofixation===
===Electrophoresis and Immunofixation===
[[Serum protein electrophoresis]] is important for the diagnosis of [[lymphoplasmacytic lymphoma]].
*[[Serum protein electrophoresis]] is important for the [[diagnosis]] of [[lymphoplasmacytic lymphoma]]
 
*Findings on an [[electrophoresis]] [[diagnostic]] of [[lymphoplasmacytic lymphoma]] include:<ref name="pmid1872571">{{cite journal| author=Riches PG, Sheldon J, Smith AM, Hobbs JR| title=Overestimation of monoclonal immunoglobulin by immunochemical methods. | journal=Ann Clin Biochem | year= 1991 | volume= 28 ( Pt 3) | issue=  | pages= 253-9 | pmid=1872571 | doi=10.1177/000456329102800310 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1872571  }} </ref>
Findings on an [[electrophoresis]] diagnostic of [[lymphoplasmacytic lymphoma]] include:<ref name="pmid1872571">{{cite journal| author=Riches PG, Sheldon J, Smith AM, Hobbs JR| title=Overestimation of monoclonal immunoglobulin by immunochemical methods. | journal=Ann Clin Biochem | year= 1991 | volume= 28 ( Pt 3) | issue=  | pages= 253-9 | pmid=1872571 | doi=10.1177/000456329102800310 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1872571  }} </ref>
**Sharp, narrow [[Spike sorting|spike]] of [[monoclonal]] [[IgM]] [[protein]]
*Sharp, narrow spike of monoclonal [[IgM]] protein.
**[[Dense]] band of [[monoclonal]] [[IgM]] [[protein]]
*Dense band of monoclonal [[IgM]] protein.
**The [[paraprotein]] can be of any [[Size consistency|size]]
*The [[paraprotein]] can be of any size.
*[[Serum]] [[immunofixation]] is important for the [[diagnosis]] of [[lymphoplasmacytic lymphoma]]. It helps in [[Confirmatory factor analysis|confirming]] the [[Presenting symptom|presence]] of a [[Monoclonal|monoclonal protein]], in [[Addition reaction|addition]] to determining its type<ref name="pmid1872571">{{cite journal| author=Riches PG, Sheldon J, Smith AM, Hobbs JR| title=Overestimation of monoclonal immunoglobulin by immunochemical methods. | journal=Ann Clin Biochem | year= 1991 | volume= 28 ( Pt 3) | issue=  | pages= 253-9 | pmid=1872571 | doi=10.1177/000456329102800310 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1872571  }} </ref>
 
[[Serum]] [[immunofixation]] is important for the diagnosis of [[lymphoplasmacytic lymphoma]]. It helps in confirming the presence of a [[Monoclonal|monoclonal protein]], in addition to determining its type.<ref name="pmid1872571">{{cite journal| author=Riches PG, Sheldon J, Smith AM, Hobbs JR| title=Overestimation of monoclonal immunoglobulin by immunochemical methods. | journal=Ann Clin Biochem | year= 1991 | volume= 28 ( Pt 3) | issue=  | pages= 253-9 | pmid=1872571 | doi=10.1177/000456329102800310 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1872571  }} </ref>


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[[File:Serum immunofixation electrophoresis.png|thumb|250px|none| Serum immunofixation electrophoresis. (A) There is a slightly dense band with IgM, kappa antisera, suggestive of monoclonal gammopathy (B) After the treatment, a dense band with IgM was disappeared.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3102879_jkms-26-824-g002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=41 Source: Kim YL. et al, Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea.]]]
[[File:Serum immunofixation electrophoresis.png|thumb|250px|none| Serum [[immunofixation]] electrophoresis. (A) There is a slightly dense band with [[IgM]], kappa [[antisera]], suggestive of [[Monoclonal gammopathy|monoclonal]] gammopathy (B) After the treatment, a dense band with [[IgM]] was disappeared.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3102879_jkms-26-824-g002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=41 Source: Kim YL. et al, Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea.]]]
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===CSF flow cytometry, protein electrophoresis and immunofixation for diagnosis of Bing-Neel syndrome:===
===CSF flow cytometry, protein electrophoresis and immunofixation for diagnosis of Bing-Neel syndrome:===
For diagnosing [[Bing-Neel syndrome]], after [[lumbar puncture]], [[CSF]] [[flow cytometry]] is done which shows a [[Lambda (anatomy)|lambda]] [[light chain]]-restricted population of [[B-cells]] consistent with a [[CD5]]+ [[CD10]]+ [[B-cell lymphoma]]. Furthermore, [[protein electrophoresis]] and [[immunofixation]] should be done for the detection and [[classification]] of a monoclonal protein as well as [[molecular]] diagnostic testing for [[immunoglobulin]] gene rearrangement and [[mutated]] [[MYD88]].<ref name="pmid30228918">{{cite journal| author=O'Neil DS, Francescone MA, Khan K, Bachir A, O'Connor OA, Sawas A| title=A Case of Bing-Neel Syndrome Successfully Treated with Ibrutinib. | journal=Case Rep Hematol | year= 2018 | volume= 2018 | issue=  | pages= 8573105 | pmid=30228918 | doi=10.1155/2018/8573105 | pmc=6136466 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30228918  }} </ref><ref name="pmid27758817">{{cite journal| author=Minnema MC, Kimby E, D'Sa S, Fornecker LM, Poulain S, Snijders TJ et al.| title=Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome. | journal=Haematologica | year= 2017 | volume= 102 | issue= 1 | pages= 43-51 | pmid=27758817 | doi=10.3324/haematol.2016.147728 | pmc=5210231 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27758817  }} </ref><ref name="pmid30279255">{{cite journal| author=Tallant A, Selig D, Wanko SO, Roswarski J| title=First-line ibrutinib for Bing-Neel syndrome. | journal=BMJ Case Rep | year= 2018 | volume= 2018 | issue=  | pages=  | pmid=30279255 | doi=10.1136/bcr-2018-226102 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30279255  }} </ref>
*For [[Diagnosis|diagnosing]] [[Bing-Neel syndrome]], after [[lumbar puncture]], [[CSF]] [[flow cytometry]] is [[done]] which shows a [[Lambda (anatomy)|lambda]] [[light chain]]-[[Restriction|restricted]] [[population]] of [[B-cells]] consistent with a [[CD5]]+ [[CD10]]+ [[B-cell lymphoma]]
*Furthermore, [[protein electrophoresis]] and [[immunofixation]] should be [[done]] for the [[Detection theory|detection]] and [[classification]] of a [[monoclonal]] [[protein]] as well as [[molecular]] [[diagnostic testing]] for [[immunoglobulin]] [[gene]] [[rearrangement]] and [[mutated]] [[MYD88]]<ref name="pmid30228918">{{cite journal| author=O'Neil DS, Francescone MA, Khan K, Bachir A, O'Connor OA, Sawas A| title=A Case of Bing-Neel Syndrome Successfully Treated with Ibrutinib. | journal=Case Rep Hematol | year= 2018 | volume= 2018 | issue=  | pages= 8573105 | pmid=30228918 | doi=10.1155/2018/8573105 | pmc=6136466 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30228918  }} </ref><ref name="pmid27758817">{{cite journal| author=Minnema MC, Kimby E, D'Sa S, Fornecker LM, Poulain S, Snijders TJ et al.| title=Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome. | journal=Haematologica | year= 2017 | volume= 102 | issue= 1 | pages= 43-51 | pmid=27758817 | doi=10.3324/haematol.2016.147728 | pmc=5210231 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27758817  }} </ref><ref name="pmid30279255">{{cite journal| author=Tallant A, Selig D, Wanko SO, Roswarski J| title=First-line ibrutinib for Bing-Neel syndrome. | journal=BMJ Case Rep | year= 2018 | volume= 2018 | issue=  | pages=  | pmid=30279255 | doi=10.1136/bcr-2018-226102 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30279255  }} </ref>


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[[File:Brain biopsy.png|thumb|250px|none| Stereostactic brain biopsy showing diffuse infiltration of atypical plasmacytoid lymphocytes into the dural fibrous tissue (A) Hematoxylin & eosin (original magnification ×200); (B) Positive immunohistochemical staining for CD20 (original magnification ×40). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2694623_jkms-22-1079-g002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=29 Source: Kim HD. et al, Department of Internal Medicine, Yeoungnam University College of Medicine, Daegu, Korea.]]]
[[File:Brain biopsy gif.gif|thumb|250px|none| Stereotactic brain [[biopsy]] showing diffuse infiltration of atypical plasmacytoid [[lymphocytes]] into the dural [[fibrous tissue]] (A) [[Hematoxylin and eosin stain|Hematoxylin]] & eosin (original magnification ×200); (B) Positive [[immunohistochemical]] staining for [[CD20]] (original magnification ×40). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2694623_jkms-22-1079-g002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=29 Source: Kim HD. et al, Department of Internal Medicine, Yeoungnam University College of Medicine, Daegu, Korea.]]]
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[[File:Csf plasmacytoid cells.png|thumb|250px|none| Plasmacytoid cells found on cytospin of the cerebrospinal fluid confirming cellular infiltration of the central nervous system.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC4837273_CRIHEM2016-3931709.004&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=71 Source: Halperin D. et al, Whipps Cross Hospital, London E11 1NR, UK.]]]
[[File:Csf plasmacytoid cells.png|thumb|250px|none| Plasmacytoid cells found on cytospin of the cerebrospinal fluid confirming cellular infiltration of the central nervous system.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC4837273_CRIHEM2016-3931709.004&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=71 Source: Halperin D. et al, Whipps Cross Hospital, London E11 1NR, UK.]]]
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[[Category:Disease]]
[[Category:Blood]]
[[Category:Hematology]]

Latest revision as of 14:44, 29 October 2019

Lymphoplasmacytic lymphoma Microchapters

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

Overview

The diagnosis of lymphoplasmacytic lymphoma is based on bone marrow aspiration and biopsy and serum protein analysis studies such as immunohistochemistry, flow cytometry and cytogenetics to distinguish LPL from other types of B-cell lymphomas. CSF flow cytometry, protein electrophoresis and immunofixation is done for the diagnosis of Bing-Neel syndrome (a late, but severe, rare complication).

Diagnostic Study of Choice

Diagnostic Criteria:

Diagnostic criteria presented in second International Workshop, Greece, 2002

Diagnostic criteria presented in second International Workshop, Greece, 2002
1:Presence of IgM monoclonal gammopathy of any concentration on serum protein analysis Necessary criteria
2:A bone marrow biopsy demonstrating more than 10% infiltration by small lymphocytes, plasmacytoid lymphocytes, and plasma cells, (with variable numbers of admixed immunoblasts), with an intertrabecular pattern consistent with lymphoplasmacytic lymphoma Proliferation centers (pathognomonic of CLL/SLL) and paler-appearing marginal zone type differentiation (seen in marginal zone lymphoma) are absent Necessary criteria
IgM concentration widely varies in WM, and it is not possible to define a concentration that reliably distinguishes WM from other lymphoproliferative disorders. Hence, a diagnosis of WM can be made irrespective of IgM concentration if there is an evidence of bone marrow infiltration by lymphoplasmacytoid lymphoma as defined by the Revised European-American Lymphoma classification and WHO criteria. This is a tumor of small lymphocytes showing evidence of plasmacytoid or plasma cell differentiation.
A recent study found that, in 39% of patients, the bone marrow aspirate contained a spectrum of small lymphocytes, plasmacytoid lymphocytes, and plasma cells; in 39% of patients, there was a predominance of small lymphocytes with fewer plasmacytoid lymphocytes or plasma cells, and 22% of the patients contained a mixture of small lymphocytes and plasma cells, with rare plasmacytoid cells. Mast cells were increased in 26% of patients.
3:Intertrabecular pattern of bone marrow infiltration Supportive criteria
4:Immunophenotype of the lymphoplasmacytic infiltrate consistent with Waldenstrom's macroglobulinemia. This includes: IgM+, CD5-, CD10-, CD11c-, CD19+, CD20+, CD22+, CD23-, CD25+, CD27+, FMC7+, CD103- and CD138+ Supportive criteria

mSMART guidelines for diagnosis of Waldenstrom macroglobulinemia and associated disorders

mSMART guidelines 2016 for diagnosis of Waldenstrom macroglobulinemia and associated disorders
Waldenström macroglobulinemia IgM monoclonal gammopathy (regardless of the size of the M protein) with >10% bone marrow lymphoplasmacytic infiltration (usually intertrabecular) by small lymphocytes that exhibit plasmacytoid or plasma cell differentiation and a typical immunophenotype (surface IgM+, CD5–, CD10–, CD19+, CD20+, CD23–) that satisfactorily excludes other lymphoproliferative disorders, including chronic lymphocytic leukemia and mantle cell lymphoma
IgM MGUS Serum IgM monoclonal protein level <3 g/dL, bone marrow lymphoplasmacytic infiltration <10%, and no evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly
Smoldering Waldenström macroglobulinemia (indolent /asymptomatic Waldenström macroglobulinemia) Serum IgM monoclonal protein level ≥3 g/dL and/or bone marrow lymphoplasmacytic infiltration ≥10% and no evidence of end-organ damage, such as anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly, that can be attributed to a lymphoplasmacytic proliferative disorder

Definitive Diagnostic Tests

Bone Marrow Aspirate:

Bone marrow aspirate. Lymphocytes with lymphoplasmacytic appearance (arrows).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3894394_br-48-300-g001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=91 Source: D'Angelo G. et al, Laboratorio di Chimica-Clinica, Ematologia e Microbiologia (Ematologia/Coagulazione), Azienda Ospedaliera "S. Antonio Abate" di Gallarate, Varese, Italy.
]

Bone Marrow Biopsy:

Electrophoresis and Immunofixation

Serum immunofixation electrophoresis. (A) There is a slightly dense band with IgM, kappa antisera, suggestive of monoclonal gammopathy (B) After the treatment, a dense band with IgM was disappeared.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3102879_jkms-26-824-g002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=41 Source: Kim YL. et al, Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea.
]

CSF flow cytometry, protein electrophoresis and immunofixation for diagnosis of Bing-Neel syndrome:

Stereotactic brain biopsy showing diffuse infiltration of atypical plasmacytoid lymphocytes into the dural fibrous tissue (A) Hematoxylin & eosin (original magnification ×200); (B) Positive immunohistochemical staining for CD20 (original magnification ×40). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2694623_jkms-22-1079-g002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=29 Source: Kim HD. et al, Department of Internal Medicine, Yeoungnam University College of Medicine, Daegu, Korea.
]
Plasmacytoid cells found on cytospin of the cerebrospinal fluid confirming cellular infiltration of the central nervous system.Source: Halperin D. et al, Whipps Cross Hospital, London E11 1NR, UK.

References

  1. ↑ 1.0 1.1 Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP (2005). "Diagnosis and management of Waldenstrom's macroglobulinemia". J Clin Oncol. 23 (7): 1564–77. doi:10.1200/JCO.2005.03.144. PMID 15735132.
  2. ↑ Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R; et al. (2016). "The 2016 revision of the World Health Organization classification of lymphoid neoplasms". Blood. 127 (20): 2375–90. doi:10.1182/blood-2016-01-643569. PMC 4874220. PMID 26980727.
  3. ↑ Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML; et al. (2003). "Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia". Semin Oncol. 30 (2): 110–5. doi:10.1053/sonc.2003.50082. PMID 12720118.
  4. ↑ Ansell, Stephen M.; Kyle, Robert A.; Reeder, Craig B.; Fonseca, Rafael; Mikhael, Joseph R.; Morice, William G.; Bergsagel, P. Leif; Buadi, Francis K.; Colgan, Joseph P.; Dingli, David; Dispenzieri, Angela; Greipp, Philip R.; Habermann, Thomas M.; Hayman, Suzanne R.; Inwards, David J.; Johnston, Patrick B.; Kumar, Shaji K.; Lacy, Martha Q.; Lust, John A.; Markovic, Svetomir N.; Micallef, Ivana N.M.; Nowakowski, Grzegorz S.; Porrata, Luis F.; Roy, Vivek; Russell, Stephen J.; Short, Kristen E. Detweiler; Stewart, A. Keith; Thompson, Carrie A.; Witzig, Thomas E.; Zeldenrust, Steven R.; Dalton, Robert J.; Rajkumar, S. Vincent; Gertz, Morie A. (2010). "Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines". Mayo Clinic Proceedings. 85 (9): 824–833. doi:10.4065/mcp.2010.0304. ISSN 0025-6196.
  5. ↑ 5.0 5.1 5.2 Leleu X, Roccaro AM, Moreau AS, Dupire S, Robu D, Gay J; et al. (2008). "Waldenstrom macroglobulinemia". Cancer Lett. 270 (1): 95–107. doi:10.1016/j.canlet.2008.04.040. PMC 3133633. PMID 18555588.
  6. ↑ 6.0 6.1 Riches PG, Sheldon J, Smith AM, Hobbs JR (1991). "Overestimation of monoclonal immunoglobulin by immunochemical methods". Ann Clin Biochem. 28 ( Pt 3): 253–9. doi:10.1177/000456329102800310. PMID 1872571.
  7. ↑ O'Neil DS, Francescone MA, Khan K, Bachir A, O'Connor OA, Sawas A (2018). "A Case of Bing-Neel Syndrome Successfully Treated with Ibrutinib". Case Rep Hematol. 2018: 8573105. doi:10.1155/2018/8573105. PMC 6136466. PMID 30228918.
  8. ↑ Minnema MC, Kimby E, D'Sa S, Fornecker LM, Poulain S, Snijders TJ; et al. (2017). "Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome". Haematologica. 102 (1): 43–51. doi:10.3324/haematol.2016.147728. PMC 5210231. PMID 27758817.
  9. ↑ Tallant A, Selig D, Wanko SO, Roswarski J (2018). "First-line ibrutinib for Bing-Neel syndrome". BMJ Case Rep. 2018. doi:10.1136/bcr-2018-226102. PMID 30279255.

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