Lymphoplasmacytic lymphoma diagnostic study of choice: Difference between revisions
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{{CMG}}; {{AE}}{{S.M.}} | {{CMG}}; {{AE}}{{S.M.}} | ||
== 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 [[bone marrow biopsy]] and [[serum]] [[protein]] analysis. | ||
== 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 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> | ||
====Diagnostic Criteria==== | ====Diagnostic Criteria:==== | ||
In September 26-30, 2002, in Athens, Greece,the Second International Workshop was held in which a diagnostic criteria for 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" /> | 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. | #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. | #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. | #*[[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 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 | #*[[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> | #*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. | #Intertrabecular pattern of [[bone marrow]] [[Infiltration (medical)|infiltration]]. | ||
#[[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+.<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> | #[[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> | ||
(3,4 are supportive of but not necessary for WM diagnosis). | (3,4 are supportive of but not necessary for WM diagnosis). | ||
*Another diagnostic Criteria for Waldenström Macroglobulinemia and | *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]]: | #[[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+, | #*[[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]]. | ||
#[[IgM MGUS]]: | #[[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. | #*[[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]]. | ||
#Smoldering Waldenström macroglobulinemia (also referred to as indolent or asymptomatic Waldenström macroglobulinemia): | #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 ≥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. | #*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. | ||
====Definitive Diagnostic Tests==== | ====Definitive Diagnostic Tests:==== | ||
*Genetic Testing. | *[[Genetic]] Testing. | ||
**ARIDA. | **ARIDA. | ||
**IG gene rearrangement. | **IG [[gene]] [[rearrangement]]. | ||
**CXCR4 5338X. | **[[CXCR4]] 5338X. | ||
**MYD88 L265P. | **[[MYD88]] L265P. | ||
*Immunophenotyping. | *[[Immunophenotyping]]. | ||
*Serum paraprotein. | *[[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 in the [[diagnosis]] of [[lymphoplasmacytic lymphoma]]. | ||
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> | 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> | ||
* A hypercellular bone marrow aspirate. | * A hypercellular [[bone marrow]] [[aspirate]]. | ||
* Lymphoplasmacytic infiltrate with characteristic immunophenotype. | * Lymphoplasmacytic infiltrate with characteristic [[immunophenotype]]. | ||
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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 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 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 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]]. | * Hypercellular and [[Infiltration (medical)|infiltrated]] with [[lymphoid]] and [[Plasmacytoid|plasmacytoid cells]]. | ||
* Dutcher bodies (PAS positive intra-nuclear vacuoles containing IgM monoclonal protein). | * Dutcher bodies ([[PAS stain|PAS]] positive intra-nuclear [[vacuoles]] containing [[IgM]] monoclonal protein). | ||
** Characteristic feature of lymphoplasmacytic lymphoma. | ** Characteristic feature of [[lymphoplasmacytic lymphoma]]. | ||
Three patterns of marrow involvement are described, as follows: | Three patterns of marrow involvement are described, as follows: | ||
* Lymphoplasmacytoid cells (lymphoplasmacytic and small lymphocytes) in a nodular pattern. | * Lymphoplasmacytoid cells (lymphoplasmacytic and small [[lymphocytes]]) in a [[nodular]] pattern. | ||
* Lymphoplasmacytic cells (small lymphocytes, mature plasma cells, mast cells) in an interstitial/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). | * 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 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 | *The [[paraprotein]] can be of any size. | ||
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> | [[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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===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 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 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> | ||
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Revision as of 18:43, 19 February 2019
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Lymphoplasmacytic lymphoma Microchapters |
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Differentiating Lymphoplasmacytic Lymphoma from other Diseases |
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Diagnosis |
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Treatment |
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Case Studies |
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Lymphoplasmacytic lymphoma diagnostic study of choice On the Web |
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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 biopsy and serum protein analysis.
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.[1][2]
Diagnostic Criteria:
In September 26-30, 2002, in Athens, Greece,the Second International Workshop was held in which a diagnostic criteria for Waldenstrom's Macroglobulinemia was proposed. According to this criteria, the following findings on performing bone marrow biopsy and serum protein analysis are confirmatory of Waldenström macroglobulinemia and exclude other small B cell lymphoid neoplasms with plasmacytic differentiation:[1]
- 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 by lymphoplasmacytoid lymphoma as defined by the Revised European-American Lymphoma classification and WHO criteria.[3] 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.[4]
- Intertrabecular pattern of bone marrow infiltration.
- 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+.[5][6][7]
(3,4 are supportive of but not necessary for WM diagnosis).
- Another diagnostic Criteria for Waldenström Macroglobulinemia and associated disorders is as follow:[8]
- 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 (also referred to as indolent or 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:
- Genetic Testing.
- ARIDA.
- IG gene rearrangement.
- CXCR4 5338X.
- MYD88 L265P.
- Immunophenotyping.
- Serum paraprotein.
Bone Marrow Aspirate:
A bone marrow aspirate is essential in the diagnosis of lymphoplasmacytic lymphoma.
Findings suggestive of lymphoplasmacytic lymphoma include:[9]
- A hypercellular bone marrow aspirate.
- Lymphoplasmacytic infiltrate with characteristic immunophenotype.
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Bone Marrow Biopsy:
A bone marrow biopsy may be helpful in the diagnosis of lymphoplasmacytic lymphoma. [9]
Findings on the biopsy suggestive of lymphoplasmacytic lymphoma include:[9]
- Hypercellular and infiltrated with lymphoid and plasmacytoid cells.
- Dutcher bodies (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
Serum protein electrophoresis is important for the diagnosis of lymphoplasmacytic lymphoma.
Findings on an electrophoresis diagnostic of lymphoplasmacytic lymphoma include:[10]
- Sharp, narrow spike of monoclonal IgM protein.
- Dense band of monoclonal IgM protein.
- The paraprotein can be of any size.
Serum immunofixation is important for the diagnosis of lymphoplasmacytic lymphoma. It helps in confirming the presence of a monoclonal protein, in addition to determining its type.[10]
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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 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.[11][12][13]
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References
- ↑ 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.
- ↑ 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.
- ↑ Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML; et al. (1994). "A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group". Blood. 84 (5): 1361–92. PMID 8068936.
- ↑ Remstein ED, Hanson CA, Kyle RA, Hodnefield JM, Kurtin PJ (2003). "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". Semin Oncol. 30 (2): 182–6. doi:10.1053/sonc.2003.50073. PMID 12720133.
- ↑ San Miguel JF, Vidriales MB, Ocio E, Mateo G, Sánchez-Guijo F, Sánchez ML; et al. (2003). "Immunophenotypic analysis of Waldenstrom's macroglobulinemia". Semin Oncol. 30 (2): 187–95. doi:10.1053/sonc.2003.50074. PMID 12720134.
- ↑ Owen RG, Barrans SL, Richards SJ, O'Connor SJ, Child JA, Parapia LA; et al. (2001). "Waldenström macroglobulinemia. Development of diagnostic criteria and identification of prognostic factors". Am J Clin Pathol. 116 (3): 420–8. doi:10.1309/4LCN-JMPG-5U71-UWQB. PMID 11554171.
- ↑ Konoplev S, Medeiros LJ, Bueso-Ramos CE, Jorgensen JL, Lin P (2005). "Immunophenotypic profile of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia". Am J Clin Pathol. 124 (3): 414–20. doi:10.1309/3G1X-DX0D-VHBN-VKB4. PMID 16191510.
- ↑ 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.
- ↑ 9.0 9.1 9.2 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.
- ↑ 10.0 10.1 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.