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#Intertrabecular pattern of [[bone marrow]] [[Infiltration (medical)|infiltration]].
#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>
#[[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>
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| colspan="3" |Presence of [[IgM]] monoclonal [[gammopathy]] of any concentration on [[serum]] protein analysis.
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| 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]].
|[[Proliferation]] centers (pathognomonic of [[CLL]]/[[SLL]]) and paler-appearing marginal zone type [[differentiation]] (seen in marginal zone lymphoma) are absent.
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|[[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]].
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|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" />
|
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|-
| colspan="3" |Intertrabecular pattern of [[bone marrow]] [[Infiltration (medical)|infiltration]].
|
|
|-
| 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" />
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|}
(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 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>
*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>

Revision as of 16:51, 20 February 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 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]

  1. Presence of IgM monoclonal gammopathy of any concentration on serum protein analysis.
  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.
  3. Intertrabecular pattern of bone marrow infiltration.
  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+.[5][6][7]
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]
  1. Waldenström macroglobulinemia:
  2. IgM MGUS:
  3. Smoldering Waldenström macroglobulinemia (also referred to as indolent or asymptomatic Waldenström macroglobulinemia):

Definitive Diagnostic Tests:

Bone Marrow Aspirate:

A bone marrow aspirate is essential in the diagnosis of lymphoplasmacytic lymphoma.

Findings suggestive of lymphoplasmacytic lymphoma include:[9]

Bone marrow aspirate. Lymphocytes with lymphoplasmacytoid appearance (arrows).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:

A bone marrow biopsy may be helpful in the diagnosis of lymphoplasmacytic lymphoma. [9]

Findings on the biopsy suggestive of lymphoplasmacytic lymphoma include:[9]

Three patterns of marrow involvement are described, as follows:

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]

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.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:

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]

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). 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. 3.0 3.1 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.
  4. 4.0 4.1 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.
  5. 5.0 5.1 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.
  6. 6.0 6.1 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.
  7. 7.0 7.1 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.
  8. 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. 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. 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.
  11. 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.
  12. 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.
  13. 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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