Multicolor flow cytometry in the diagnosis of Waldenstrom macroglobulinemia

   Waldenstrom macroglobulinemia is a lymphoplasmacytic lymphoma, the morphological substrates of which are b‑lymphocytes, proplasmocytes, and plasma cells. The world Health Organization recommends multicolor flow cytometry with analysis of markers such as IgM, Cd19, Cd20, Cd22, Cd25, Cd10, Cd23, Cd103, Cd138, for diagnosing this disease. Based on international and our own experience, we recommend that tumor b‑lymphocytes and plasma cells be analyzed separately for the diagnosis of waldenstrom macroglobulinemia, since the immunophenotypic profile of these populations differs. In diagnostics, this approach provides a more complete understanding of various subpopulations contribution, and when monitoring minimal residual disease, it helps to detect the tumor clone, which after therapy is predominantly represented by plasma cells. we recommend using antibodies to surface and intracellular markers such as Cd138, Cd38, Cd19, Cd45, Cd20, Cd22, Cd27 cytκ, cytλ and cytIgM for immunophenotypic testing of waldenstrom macroglobulinemia.

1. Owen R.G., Treon S.P., Al­Katib A. et al. Clinicopathological definition of Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia. Semin Oncol 2003;30(2):110–5. DOI: 10.1053/sonc.2003.50082

2. Campo E., Swerdlow S.H., Harris N.L. et al. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood 2011;117(19):5019–32. DOI: 10.1182/blood­2011­01­293050

3. Alaggio R., Amador C., Anagnostopoulos I. et al. The 5^th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia 2022;36(7):1720–48. DOI: 10.1038/s41375­022­01620­2

4. Swerdlow S.H., Cook J.R., Sohani A.R. et al. Lymphoplasmacytic lymphoma. In: WHO classification of tumours of hematopoietic and lymphoid tissues. Eds.: S.H. Swerdlow, E. Campo, N.L. Harris et al. France: IARC, 2017. Pp. 232–235.

5. Tursz T., Brouet J.C., Flandrin G. et al. Clinical and pathologic features of Waldenström’s macroglobulinemia in seven patients with serum monoclonal IgG or IgA. Am J Med 1977;63(4):499–502. DOI: 10.1016/0002­9343(77)90193­0

6. Cao X., Medeiros L.J., Xia Y. et al. Clinicopathologic features and outcomes of lymphoplasmacytic lymphoma patients with monoclonal IgG or IgA paraprotein expression. Leuk Lymphoma 2016;57(5):1104–13. DOI: 10.3109/10428194.2015.1096357

7. Varettoni M., Boveri E., Zibellini S. et al. Clinical and molecular characteristics of lymphoplasmacytic lymphoma not associated with an IgM monoclonal protein: a multicentric study of the Rete Ematologica Lombarda (REL) network. Am J Hematol 2019;94(11):1193–9. DOI: 10.1002/ajh.25600

8. Castillo J.J., Itchaki G., Gustine J.N. et al. A matched case­control study comparing features, treatment and outcomes between patients with non­IgM lymphoplasmacytic lymphoma and Waldenström macroglobulinemia. Leuk Lymphoma 2020;61(6):1388–94. DOI: 10.1080/10428194.2020.1719100

9. Qiu L., Nwogbo O.V., Medeiros L.J. et al. Lymphoplasmacytic lymphoma with IgG or IgA paraprotein: a study of 29 cases including cases that can mimic plasma cell neoplasms. Hum Pathol 2022;130:47–57. DOI: 10.1016/j.humpath.2022.10.005

10. Kang J., Hong J.Y., Suh C. Clinical features and survival outcomes of patients with lymphoplasmacytic lymphoma, including non­IgM type, in Korea: a single­center experience. Blood Res 2018;53(3):189–97. DOI: 10.5045/br.2018.53.3.189

11. Waldenstrom J. Incipient myelomatosis or “essential” hyperglobulinemia with fibrinogenopenia – a new syndrome? Acta Med Scand 1944;3­4:216–22. DOI: 10.1111/j.0954­6820.1944.tb03955.x

12. Teras L.R., DeSantis C.E., Cerhan J.R. et al. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin 2016;66(6):443–59. DOI: 10.3322/caac.21357

13. Vos J.M., Minnema M.C., Wijermans P.W. et al. Guideline for diagnosis and treatment of Waldenström’s macroglobulinaemia. Neth J Med 2013;71(2):54–62.

14. Wang H., Chen Y., Li F. et al. Temporal and geographic variations of Waldenstrom macroglobulinemia incidence: a large population­based study. Cancer 2012;118(15):3793–800. DOI: 10.1002/cncr.26627

15. Groves F.D., Travis L.B., Devesa S.S. et al. Waldenström’s macroglobulinemia: incidence patterns in the United States, 1988–1994. Cancer 1998;82(6):1078–81.

16. Krajny M., Pruzanski W. Waldenström’s macroglobulinemia : review of 45 cases. Can Med Assoc J 1976;114(10):899–900, 902, 905.

17. Sekhar J., Sanfilippo K., Zhang Q. et al. Waldenström macroglobulinemia : a Surveillance, Epidemiology, and End Results database review from 1988 to 2005. Leuk Lymphoma 2012;53(8):1625–6. DOI: 10.3109/10428194.2012.656103

18. Cho J.H., Shim J.H., Yoon S.E. et al. Real­world data on the survival outcome of patients with newly diagnosed Waldenström macroglobulinemia. Korean J Intern Med 2021;36(3):668–78. DOI: 10.3904/kjim.2019.367

19. Kaseb H., Gonzalez­Mosquera L.F., Parsi M., Mewawalla P. Lymphoplasmacytic Lymphoma. 2023. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025–.

20. Morel P., Duhamel A., Gobbi P. et al. International prognostic scoring system for Waldenstrom macroglobulinemia. Blood 2009;113(18):4163–70. DOI: 10.1182/blood­2008­08­174961

21. Kyle R.A., Treon S.P., Alexanian R. et al. Prognostic markers and criteria to initiate therapy in Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia. Semin Oncol 2003;30(2):116–20. DOI: 10.1053/sonc.2003.50038

22. Paiva B., Montes M.C., García­-Sanz R. et al. Multiparameter flow cytometry for the identification of the Waldenström’s clone in IgM­ MGUS and Waldenström’s Macroglobulinemia: new criteria for differential diagnosis and risk stratification. Leukemia 2014;28(1):166–73. DOI: 10.1038/leu.2013.124

23. Kyle R.A., Therneau T.M., Rajkumar S.V. et al. Long­term follow-up of IgM monoclonal gammopathy of undetermined significance. Semin Oncol 2003;30(2):169–71. DOI: 10.1053/sonc.2003.50062

24. Kyle R.A., Benson J.T., Larson D.R. et al. Progression in smoldering Waldenstrom macroglobulinemia: long­term results. Blood 2012;119(19):4462–6. DOI: 10.1182/blood­2011­10­384768

25. Fraumeni J.F., Wertelecki W., Blattner W.A. et al. Varied manifestations of a familial lymphoproliferative disorder. Am J Med 1975;59(1):145–51. DOI: 10.1016/0002­9343(75)90333­2

26. Blattner W.A., Garber J.E., Mann D.L. et al. Waldenström’s macroglobulinemia and autoimmune disease in a family. Ann Intern Med 1980;93(6):830–2. DOI: 10.7326/0003­4819­93­6­830

27. Kyle R.A., Garton J.P. The spectrum of IgM monoclonal gammopathy in 430 cases. Mayo Clin Proc 1987;62(8):719–31. DOI: 10.1016/s0025­6196(12)65225­2

28. Renier G., Ifrah N., Chevailler A. et al. Four brothers with Waldenstrom’s macroglobulinemia. Cancer 1989;64(7):1554–9. DOI: 10.1002/1097­0142(19891001)64:7<1554::aid-cncr2820640734>3.0.co;2­3

29. Taleb N., Tohme A., Abi Jirgiss D. et al. Familial macroglobulinemia in a Lebanese family with two sisters presenting Waldenström’s disease. Acta Oncol 1991;30(6):703–5. DOI: 10.3109/02841869109092443

30. Treon S.P., Hunter Z.R., Aggarwal A. et al. Characterization of familial Waldenstrom’s macroglobulinemia. Ann Oncol 2006;17(3):488–94. DOI: 10.1093/annonc/mdj111

31. Seligmann M. A genetic predisposition to Waldenström’s macroglobulinaemia. Acta Med Scand Suppl 1966;445:140–6. DOI: 10.1111/j.0954­6820.1966.tb02353.x

32. Björnsson O.G., Arnason A., Gudmunosson S. et al. Macroglobulinaemia in an Icelandic family. Acta Med Scand 1978;203(4):283–8. DOI: 10.1111/j.0954­6820.1978.tb14874.x

33. Steingrímsson V., Lund S.H., Turesson I. et al. Population­-based study on the impact of the familial form of Waldenström macroglobulinemia on overall survival. Blood 2015;125(13):2174–5. DOI: 10.1182/blood­2015­01­622068

34. Kristinsson S.Y., Björkholm M., Goldin L.R. et al. Risk of lymphoproliferative disorders among first­degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population­based study in Sweden. Blood 2008;112(8):3052–6. DOI: 10.1182/blood­2008­06­162768

35. Sahota S.S., Forconi F., Ottensmeier C.H. et al. Typical Waldenstrom macroglobulinemia is derived from a B­cell arrested after cessation of somatic mutation but prior to isotype switch events. Blood 2002;100(4):1505–7.

36. Walsh S.H., Laurell A., Sundström G. et al. Lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia derives from an extensively hypermutated B cell that lacks ongoing somatic hypermutation. Leuk Res 2005;29(7):729–34. DOI: 10.1016/j.leukres.2004.12.008

37. Sahota S.S., Babbage G., Weston­Bell N.J. CD27 in defining memory B­-cell origins in Waldenström’s macroglobulinemia. Clin Lymphoma Myeloma 2009;9(1):33–5. DOI: 10.3816/CLM.2009.n.007

38. Remstein E.D., Hanson C.A., Kyle R.A. et al. 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 2003;30(2):182–6. DOI: 10.1053/sonc.2003.50073

39. Lemal R., Poulain S., Ledoux­Pilon A. et al. Mast cell density and its clinical relevance in Waldenström’s macroglobulinemia. EJHaem 2022;3(2):371–8. DOI: 10.1002/jha2.378

40. Ho A.W., Hatjiharissi E., Ciccarelli B.T. et al. CD27­CD70 interactions in the pathogenesis of Waldenstrom macroglobulinemia. Blood 2008;112(12):4683–9. DOI: 10.1182/blood­2007­04­084525

41. Pasricha S.R., Juneja S.K., Westerman D.A. et al. Bone­marrow plasma cell burden correlates with IgM paraprotein concentration in Waldenstrom macroglobulinaemia. J Clin Pathol 2011;64(6):520–3. DOI: 10.1136/jcp.2010.088591

42. Morice W.G., Chen D., Kurtin P.J. et al. Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenström’s macroglobulinemia. Mod Pathol 2009;22(6):807–16. DOI: 10.1038/modpathol.2009.34

43. Barakat F.H., Medeiros L.J., Wei E.X. et al. Residual monotypic plasma cells in patients with Waldenstrom macroglobulinemia after therapy. Am J Clin Pathol 2011;135(3):365–73. DOI: 10.1309/AJCP15YFULCZHZVH

44. De Tute R.M., Rawstron A.C., Owen R.G. Immunoglobulin M concentration in Waldenström macroglobulinemia: correlation with bone marrow B cells and plasma cells. Clin Lymphoma Myeloma Leuk 2013;13(2):211–3. DOI: 10.1016/j.clml.2013.02.018

45. Kyrtsonis M.C., Levidou G., Korkolopoulou P. et al. CD138 expression helps distinguishing Waldenström’s macroglobulinemia (WM) from splenic marginal zone lymphoma (SMZL). Clin Lymphoma Myeloma Leuk 2011;11(1):99–102. DOI: 10.3816/CLML.2011.n.019

46. Pérez­Escurza O., Flores­Montero J., Óskarsson J.Þ. et al. Immunophenotypic assessment of clonal plasma cells and B­-cells in bone marrow and blood in the diagnostic classification of early stage monoclonal gammopathies: an iSTOPMM study. Blood Cancer J 2023;13(1):182. DOI: 10.1038/s41408­023­00944­1

47. Lin P., Medeiros L.J. Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia: an evolving concept. Adv Anat Pathol 2005;12(5):246–55. DOI: 10.1097/01.pap.0000184176.65919.17

48. Treon S.P., Xu L., Yang G. et al. MYD88 L265P somatic mutation in Waldenström’s macroglobulinemia. N Engl J Med 2012;367(9):826–33. DOI: 10.1056/NEJMoa1200710

49. Jiménez C., Sebastián E., Chillón M.C. et al. MYD88 L265P is a marker highly characteristic of, but not restricted to, Waldenström’s macroglobulinemia. Leukemia 2013;27(8):1722–8. DOI: 10.1038/leu.2013.62

50. Varettoni M., Arcaini L., Zibellini S. et al. Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom’s macroglobulinemia and related lymphoid neoplasms. Blood 2013;121(13):2522–8. DOI: 10.1182/blood­2012­09­457101

51. Poulain S., Roumier C., Decambron A. et al. MYD88 L265P mutation in Waldenstrom macroglobulinemia. Blood 2013;121(22):4504–11. DOI: 10.1182/blood­2012­06­436329

52. Xu L., Hunter Z.R., Yang G. et al. MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B­cell lymphoproliferative disorders using conventional and quantitative allele­specific polymerase chain reaction [published correction appears in Blood 2013;121(26):5259]. Blood 2013;121(11):2051–8. DOI: 10.1182/blood­2012­09­454355

53. Ondrejka S.L., Lin J.J., Warden D.W. et al. MYD88 L265P somatic mutation: its usefulness in the differential diagnosis of bone marrow involvement by B­cell lymphoproliferative disorders. Am J Clin Pathol 2013;140(3):387–94. DOI: 10.1309/AJCP10ZCLFZGYZIP

54. Ansell S.M., Hodge L.S., Secreto F.J. et al. Activation of TAK1 by MYD88 L265P drives malignant B­cell Growth in non-Hodgkin lymphoma. Blood Cancer J 2014;4(2):e183. DOI: 10.1038/bcj.2014.4

55. Rodriguez S., Celay J., Goicoechea I. et al. Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma. Sci Adv 2022;8(3):eabl4644. DOI: 10.1126/sciadv.abl4644

56. Willenbacher W., Willenbacher E., Brunner A. et al. Improved accuracy of discrimination between IgM multiple myeloma and Waldenström macroglobulinaemia by testing for MYD88 L265P mutations. Br J Haematol 2013;161(6):902–4. DOI: 10.1111/bjh.12313

57. Schmidt J., Federmann B., Schindler N. et al. MYD88 L265P and CXCR4 mutations in lymphoplasmacytic lymphoma identify cases with high disease activity. Br J Haematol 2015;169(6):795–803. DOI: 10.1111/bjh.13361

58. Martinez­Lopez A., Curiel­Olmo S., Mollejo M. et al. MYD88 (L265P) somatic mutation in marginal zone B­cell lymphoma. Am J Surg Pathol 2015;39(5):644–51. DOI: 10.1097/PAS.0000000000000411

59. Hunter Z.R., Xu L., Yang G. et al. The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-­like CXCR4 mutations, and small somatic deletions associated with B­cell lymphomagenesis. Blood 2014;123(11):1637–46. DOI: 10.1182/blood­2013­09­525808

60. Poulain S., Roumier C., Venet­Caillault A. et al. Genomic landscape of CXCR4 mutations in Waldenström Macroglobulinemia. Clin Cancer Res 2016;22(6):1480–8. DOI: 10.1158/1078­0432.CCR­15­0646

61. Treon S.P., Cao Y., Xu L. et al. Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia. Blood 2014;123(18):2791–6. DOI: 10.1182/blood­2014­01­550905

62. Orfao A., Almeida J., Sanchez M.L. et al. Immunophenotypic diagnosis of leukemic B­cell chronic lymphoproliferative disorders other than chronic lymphocytic leukemia. In: Chronic Lymphocytic Leukemia. Contemporary Hematology. Ed.: Faguet G.B. Humana Press, Totowa, NJ. 2004. Pp. 173–190.

63. Seegmiller A.C., Hsi E.D., Craig F.E. The current role of clinical flow cytometry in the evaluation of mature B­cell neoplasms. Cytometry B Clin Cytom 2019;96(1):20–9. DOI: 10.1002/cyto.b.21756

64. Stetler­Stevenson M., Braylan R.C. Flow cytometric analysis of lymphomas and lymphoproliferative disorders. Semin Hematol 2001;38(2):111–23.

65. Brooimans R.A., Kraan J., van Putten W. et al. Flow cytometric differential of leukocyte populations in normal bone marrow: influence of peripheral blood contamination. Cytometry B Clin Cytom 2009;76(1):18–26. DOI: 10.1002/cyto.b.20439

66. Dogliotti I., Jiménez C., Varettoni M. et al. Diagnostics in Waldenström’s macroglobulinemia: a consensus statement of the European Consortium for Waldenström’s Macroglobulinemia. Leukemia 2023;37(2):388–95. DOI: 10.1038/s41375­022­01762­3

67. Banchereau J., Rousset F. Human B lymphocytes: phenotype, proliferation, and differentiation. Adv Immunol 1992;52:125–262. DOI: 10.1016/s0065­2776(08)60876­7

68. Shrimpton J.K. Plasma cell differentiation in the B­cell malignancy Waldenström macroglobulinemia. University of Leeds, 2019. 338 p.

69. Van Lochem E.G., van der Velden V.H., Wind H.K. et al. Immunophenotypic differentiation patterns of normal hematopoiesis in human bone marrow: reference patterns for age­related changes and disease­induced shifts. Cytometry B Clin Cytom 2004;60(1):1–13. DOI: 10.1002/cyto.b.20008

70. Perez­-Andres M., Paiva B., Nieto W.G. et al. Human peripheral blood B­cell compartments: a crossroad in B­cell traffic. Cytometry B Clin Cytom 2010;78(Suppl 1):S47–60. DOI: 10.1002/cyto.b.20547

71. Mizuta S., Yamane N., Mononobe S. et al. VS38 staining contributes to a novel gating strategy in flow cytometry for small B cell lymphoma, especially in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Cytometry B Clin Cytom 2022;102(1):50–61. DOI: 10.1002/cyto.b.22000

72. Caraux A., Klein B., Paiva B. et al. Circulating human B and plasma cells. Age­associated changes in counts and detailed characterization of circulating normal CD138− and CD138+ plasma cells. Haematologica 2010;95(6):1016–20. DOI: 10.3324/haematol.2009.018689

73. Klein U., Rajewsky K., Küppers R. Human immunoglobulin (Ig) M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J Exp Med 1998;188(9):1679–89. DOI: 10.1084/jem.188.9.1679

74. Tangye S.G., Liu Y.J., Aversa G. et al. Identification of functional human splenic memory B cells by expression of CD148 and CD27. J Exp Med 1998;188(9):1691–703. DOI: 10.1084/jem.188.9.1691

75. Radbruch A., Muehlinghaus G., Luger E.O. et al. Competence and competition: the challenge of becoming a long­lived plasma cell. Nat Rev Immunol 2006;6(10):741–50. DOI: 10.1038/nri1886

76. O’Connell F.P., Pinkus J.L., Pinkus G.S. CD138 (syndecan­1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms. Am J Clin Pathol 2004;121(2):254–63. DOI: 10.1309/617D­WB5G­NFWX­HW4L

77. Costes V., Magen V., Legouffe E. et al. The Mi15 monoclonal antibody (anti­syndecan­1) is a reliable marker for quantifying plasma cells in paraffin­embedded bone marrow biopsy specimens. Hum Pathol 1999;30(12):1405–11. DOI: 10.1016/s0046­8177(99)90160­0

78. Jung J., Choe J., Li L., Choi Y.S. Regulation of CD27 expression in the course of germinal center B cell differentiation: the pivotal role of IL­10. Eur J Immunol 2000;30(8):2437–43. DOI: 10.1002/1521­4141(2000)30:8<2437::AID-IMMU2437>3.0.CO;2­M

79. Mei H.E., Wirries I., Frölich D. et al. A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow. Blood 2015;125(11):1739–48. DOI: 10.1182/blood­2014­02­555169

80. Arumugakani G., Stephenson S.J., Newton D.J. et al. Early emergence of CD19­-negative human antibody­secreting cells at the plasmablast to plasma cell transition. J Immunol 2017;198(12):4618–28. DOI: 10.4049/jimmunol.1501761

81. Flores-­Montero J., de Tute R., Paiva B. et al. Immunophenotype of normal vs. myeloma plasma cells: toward antibody panel specifications for MRD detection in multiple myeloma. Cytometry B Clin Cytom 2016;90(1):61–72. DOI: 10.1002/cyto.b.21265

82. Shaheen S.P., Talwalkar S.S., Lin P., Medeiros L.J. Waldenström macroglobulinemia : a review of the entity and its differential diagnosis. Adv Anat Pathol 2012;19(1):11–27. DOI: 10.1097/PAP.0b013e31824019d0

83. Growková K., Kryukova E., Kufová Z. et al. Waldenström’s macroglobulinemia: two malignant clones in a monoclonal disease? Molecular background and clinical reflection. Eur J Haematol 2017;99(6):469–78. DOI: 10.1111/ejh.12959

84. Diagnostic algorithms and treatment protocols for blood system disorders : in 2 volumes. Ed.: E.N. Parovichnikova. Vol. 2. Moscow: Praktika, 2024. Pp. 174–202.

85. Gong J.Z., Lagoo A.S., Peters D. et al. Value of CD23 determination by flow cytometry in differentiating mantle cell lymphoma from chronic lymphocytic leukemia/small lymphocytic lymphoma. Am J Clin Pathol 2001;116(6):893–7. DOI: 10.1309/UQ4N­M5KL­0ANY­YD3G

86. Palumbo G.A., Parrinello N., Fargione G. et al. CD200 expression may help in differential diagnosis between mantle cell lymphoma and B­cell chronic lymphocytic leukemia. Leuk Res 2009;33(9):1212–6. DOI: 10.1016/j.leukres.2009.01.017

87. Xu Y., McKenna R.W., Kroft S.H. Assessment of CD10 in the diagnosis of small B­cell lymphomas: a multiparameter flow cytometric study. Am J Clin Pathol 2002;117(2):291–300. DOI: 10.1309/T88X­71U4­WC0R­2531

88. Lau H., Nagy A., Atwater S.K. et al. An integrated flow cytometry analysis of 286 mature B cell neoplasms identifies CD13 as a useful marker for diagnostic subtyping. Int J Lab Hematol 2018;40(6):715–20. DOI: 10.1111/ijlh.12909

89. Rawstron A.C., Orfao A., Beksac M. et al. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica 2008;93(3):431–8. DOI: 10.3324/haematol.11080

90. Konoplev S., Medeiros L.J., Bueso­Ramos C.E. et al. Immunophenotypic profile of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Am J Clin Pathol 2005;124(3):414–20. DOI: 10.1309/3G1X­DX0D­VHBN­VKB4

91. San Miguel J.F., Vidriales M.B., Ocio E. et al. Immunophenotypic analysis of Waldenstrom’s macroglobulinemia. Semin Oncol 2003;30(2):187–95. DOI: 10.1053/sonc.2003.50074

92. Paulus A., Chitta K.S., Wallace P.K. et al. Immunophenotyping of Waldenströms macroglobulinemia cell lines reveals distinct patterns of surface antigen expression: potential biological and therapeutic implications. PLoS One 2015;10(4):e0122338. DOI: 10.1371/journal.pone.0122338

93. Hodge L.S., Novak A.J., Grote D.M. et al. Establishment and characterization of a novel Waldenstrom macroglobulinemia cell line, MWCL­1. Blood 2011;117(19):e190–7. DOI: 10.1182/blood­2010­12­326868

94. Kriangkum J., Taylor B.J., Treon S.P. et al. Clonotypic IgM V/D/J sequence analysis in Waldenstrom macroglobulinemia suggests an unusual B­cell origin and an expansion of polyclonal B cells in peripheral blood. Blood 2004;104(7):2134–42. DOI: 10.1182/blood­2003­11­4024

95. Babbage G., Townsend M., Zojer N. et al. IgM­expressing Waldenstrom’s macroglobulinemia tumor cells reveal a potential for isotype switch events in vivo. Leukemia 2007;21(4):827–30. DOI: 10.1038/sj.leu.2404538

96. García­-Sanz R., Hunter Z.R., Poulain S. et al. New developments in the diagnosis and characterization of Waldenström’s macroglobulinemia. Expert Rev Hematol 2023;16(11):835–47. DOI: 10.1080/17474086.2023.2270779

97. Seegmiller A.C., Xu Y., McKenna R.W. et al. Immunophenotypic differentiation between neoplastic plasma cells in mature B­-cell lymphoma vs plasma cell myeloma. Am J Clin Pathol 2007;127(2):176–81. DOI: 10.1309/5EL22BH45PHUPM8P

98. Hunter Z.R., Branagan A.R., Manning R. et al. CD5, CD10, and CD23 expression in Waldenstrom’s macroglobulinemia. Clin Lymphoma 2005;5(4):246–9. DOI: 10.3816/clm.2005.n.008

99. Pangalis G.A., Kyrtsonis M.C., Kontopidou F.N. et al. Differential diagnosis of Waldenstrom’s macroglobulinemia and other B-­cell disorders. Clin Lymphoma 2005;5(4):235–40. DOI: 10.3816/clm.2005.n.006

100. Paiva B., Corchete L.A., Vidriales M.B. et al. The cellular origin and malignant transformation of Waldenström macroglobulinemia. Blood 2015;125(15):2370–80. DOI: 10.1182/blood­2014­09­602565

101. Marti G.E., Rawstron A.C., Ghia P. et al. Diagnostic criteria for monoclonal B­-cell lymphocytosis. Br J Haematol 2005;130(3): 325–32. DOI: 10.1111/j.1365­2141.2005.05550.x

102. Rosado F.G., Morice W.G., He R. et al. Immunophenotypic features by multiparameter flow cytometry can help distinguish low grade B­cell lymphomas with plasmacytic differentiation from plasma cell proliferative disorders with an unrelated clonal B-­cell process. Br J Haematol 2015;169(3):368–76. DOI: 10.1111/bjh.13303