CD20 expression in plasma cell neoplasm and B-cell non-Hodgkin lymphoma with plasmacytic differentiation: insights into aberrant markers

WHO Classification of Tumours Editorial Board. Haematolymphoid tumours Internet. Lyon (France): International Agency for Research on Cancer; 2024 cited 2024/12/23. (WHO classification of tumours series, 5th ed.; vol. 11). Available from: https://tumourclassification.iarc.who.int/chapters/63.

Surveillance, Epidemiology, and End Results (SEER) Program. Cancer Stat Facts. National Cancer Institute. Available from: https://seer.cancer.gov/statfacts/ [Accessed 2024].

Sukpanichnant S. Malignancy of the lymph node: how general practitioners and pathologists can achieve a definitive diagnosis. Siriraj Medical Journal. 2022;74:604-17. Available from: https://he02.tci-thaijo.org/index.php/sirirajmedj/article/view/259166

Sukpanichnant S. Reflections on how to diagnose and classify lymphoma. Int J R Soc Thailand. 2023;15:66-83.

Sukpanichnant S. Transformation in malignant lymphoma: morphologic approach. Asian Archives of Pathology 2015;11:87-113.

Angela Dispenzieri; Monoclonal gammopathies of clinical significance. Hematology Am Soc Hematol Educ Program 2020; 2020:380-8.

Larson RS, Sukpanichnant S, Greer JP, Cousar JB, Collins RD. The spectrum of multiple myeloma: diagnostic and biological implications. Hum Pathol. 1997;28:1336-47.

Moreau P, Voillat L, Benboukher L, Mathiot C, Dumontet C, Robillard N, Hérault O, Garnache F, Garand R, Varoqueaux N, Avet-Loiseau H, Harousseau JL, Bataille R; IFM group. Rituximab in CD20 positive multiple myeloma. Leukemia. 2007 ;21:835-6.

National Comprehensive Cancer Network. B-Cell lymphomas. Version 3.2024. NCCN Clinical Practice Guidelines in Oncology. 2024. Available from: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf

National Comprehensive Cancer Network. Multiple Myeloma. Version 1.2025. NCCN Clinical Practice Guidelines in Oncology. 2024. Available from: https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf

Rajkumar SV. Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol. 2024;99:1802-24.

Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014 ; 15:e538-48.

Lin P. Plasma cell myeloma. Hematol Oncol Clin North Am. 2009 ;23:709-27.

Dogan A, Siegel D, Tran N, Fu A, Fowler J, Belani R, Landgren O. B-cell maturation antigen expression across hematologic cancers: a systematic literature review. Blood Cancer J. 2020;10:73.

Kloc D, Kurhajec S, Huniadi M, Sýkora J, Guman T, Šarišský M. SLAM Family Receptors in B Cell Chronic Lymphoproliferative Disorders. Int J Mol Sci. 2024;25:4014.

Frigyesi I, Adolfsson J, Ali M, Christophersen MK, Johnsson E, Turesson I, et al. Robust isolation of malignant plasma cells in multiple myeloma. Blood. 2014;123:1336-40.

Rolf N, Al-Attar A, Bunting S, Oak J. Pitfalls and Strategies for Flow Cytometry-based Post-Immunotherapy Disease Monitoring of Hematological Malignancies. ICCS Module #28. International Clinical Cytometry Society; 2024. Available from: https://www.cytometry.org/web/modules/Module_28.pdf [Accessed 2024].

Jiménez C, Garrote-de-Barros A, López-Portugués C, Hernández-Sánchez M, Díez P. Characterization of Human B Cell Hematological Malignancies Using Protein-Based Approaches. Int J Mol Sci. 2024;25:4644.

Olteanu H, Harrington AM, Hari P, Kroft SH. CD200 expression in plasma cell myeloma. Br J Haematol. 2011;153:408-11.

Soh KT, Wallace PK. Evaluation of measurable residual disease in multiple myeloma by multiparametric flow cytometry: Current paradigm, guidelines, and future applications. Int J Lab Hematol. 2021;43 Suppl 1:S43-53.

Cordone I, Amodeo R, Bellesi S, Bottan F, Buccisano F, De Propris MS, et. al. Consensus for Flow Cytometry Clinical Report on Multiple Myeloma: A Multicenter Harmonization Process Merging Laboratory Experience and Clinical Needs. Cancers (Basel). 2023;15:2060.

Ishibashi M, Morita R, Tamura H. Immune Functions of Signaling Lymphocytic Activation Molecule Family Molecules in Multiple Myeloma. Cancers (Basel). 2021;13:279.

Hosen N, Ichihara H, Mugitani A, Aoyama Y, Fukuda Y, Kishida S, et al. CD48 as a novel molecular target for antibody therapy in multiple myeloma. Br J Haematol. 2012;156:213-24.

Clarke SE, Fuller KA, Erber WN. Chromosomal defects in multiple myeloma. Blood Rev. 2024;64:101168.

Hoyer JD, Hanson CA, Fonseca R, Greipp PR, Dewald GW, Kurtin PJ. The (11;14)(q13;q32) translocation in multiple myeloma. A morphologic and immunohistochemical study. Am J Clin Pathol. 2000;113:831-7.

Frye Naharro E, Peterson D, Yohe SL, Linden MA. Application and pitfalls of immunophenotyping in challenging plasma cell neoplasms: A case series. Hum Pathol. 2024;150:86-96.

An G, Xu Y, Shi L, Zou D, Deng S, Sui W, et al. t(11;14) multiple myeloma: a subtype associated with distinct immunological features, immunophenotypic characteristics but divergent outcome. Leuk Res. 2013;37:1251-7.

Miura D, Narita K, Kuzume A, Tabata R, Terao T, Tsushima T, et al. Clinical and prognostic impact of t(11;14)(q13;q32) translocation on patients with multiple myeloma. Blood. 2019;134(Suppl 1):s5507.

Robillard N, Avet-Loiseau H, Garand R, Moreau P, Pineau D, Rapp MJ, et al. CD20 is associated with a small mature plasma cell morphology and t(11;14) in multiple myeloma. Blood. 2003;102:1070-1.

Treon SP, Gustine J, Xu L, Manning RJ, Tsakmaklis N, Demos M, et al. MYD88 wild-type Waldenstrom Macroglobulinaemia: differential diagnosis, risk of histological transformation, and overall survival. Br J Haematol. 2018;180:374-80.

Jiménez C, Sebastián E, Chillón MC, Giraldo P, Mariano Hernández J, Escalante F, et al. MYD88 L265P is a marker highly characteristic of, but not restricted to, Waldenström's macroglobulinemia. Leukemia. 2013;27:1722-8.

Bassarova A, Trøen G, Spetalen S, Micci F, Tierens A, Delabie J. Lymphoplasmacytic lymphoma and marginal zone lymphoma in the bone marrow: paratrabecular involvement as an important distinguishing feature. Am J Clin Pathol. 2015;143:797-806.

Morice WG, Chen D, Kurtin PJ, Hanson CA, McPhail ED. Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenström's macroglobulinemia. Mod Pathol. 2009;22:807-16.

Ferreri AJ, Zucca E. Marginal-zone lymphoma. Crit Rev Oncol Hematol. 2007;63:245-56.

Hussaini M, Yeung C, Zhu X, Mirza AS, Pfeifer J, Hassan A. PRDM1 expression levels in marginal zone lymphoma and lymphoplasmacytic lymphoma. Int J Clin Exp Pathol. 2017;10:8610-8.

Tsuboi K, Iida S, Inagaki H, Kato M, Hayami Y, Hanamura I, et al. MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies. Leukemia. 2000;14:449-56.

Zhang LF, Zhang Y, Shui RH, Lu HF, Jiang WH, Cai X, et al. MNDA expression and its value in differential diagnosis of B-cell non-Hodgkin lymphomas: a comprehensive analysis of a large series of 1293 cases. Diagn Pathol. 2024;19:60.

Gupta N, Roychoudry S, Sticco KL, Hsu P, Zhang X, Sheikh-Fayyaz S. Study of the Utility of Myeloid Cell Nuclear Differentiation Antigen (MNDA) in the Diagnosis of Marginal Zone Lymphoma. Appl Immunohistochem Mol Morphol. 2023;31:217-23.

Wang Z, Cook JR. IRTA1 and MNDA Expression in Marginal Zone Lymphoma: Utility in Differential Diagnosis and Implications for Classification. Am J Clin Pathol. 2019;151:337-43.

Choong SHC, Chng WJ, De Mel S, Liu TC, Li BJ, Poon LMM, et al. Flow cytometric immunophenotyping distinguishes lymphoplasmacytic lymphoma from marginal zone lymphoma. Blood. 2019;134(Suppl 1):S5253.

National Comprehensive Cancer Network. Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma. Version 1.2025. NCCN Clinical Practice Guidelines in Oncology. 2024. Available from: https://www.nccn.org/professionals/physician_gls/pdf/waldenstroms.pdf

Braggio E, Dogan A, Keats JJ, Chng WJ, Huang G, Matthews JM, et al. Genomic analysis of marginal zone and lymphoplasmacytic lymphomas identified common and disease-specific abnormalities. Mod Pathol. 2012;25:651-60.

Sánchez-Beato M, Méndez M, Guirado M, Pedrosa L, Sequero S, Yanguas-Casás N, et al. A genetic profiling guideline to support diagnosis and clinical management of lymphomas. Clin Transl Oncol. 2024 ;26:1043-62.

Hamadeh F, MacNamara SP, Aguilera NS, Swerdlow SH, Cook JR. MYD88 L265P mutation analysis helps define nodal lymphoplasmacytic lymphoma. Mod Pathol. 2015;28:564-74.

Xu L, Hunter ZR, Yang G, Zhou Y, Cao Y, Liu X, et al. MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. Blood. 2013;121:2051-8.

Varettoni M, Arcaini L, Zibellini S, Boveri E, Rattotti S, Riboni R, et al. Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenström’s macroglobulinemia and related lymphoid neoplasms. Blood. 2013;121:2522-8.

Rosado FG, Morice WG, He R, Howard MT, Timm M, McPhail ED. Immunophenotypic features by multiparameter flow cytometry can help distinguish low grade B-cell lymphomas with plasmacytic differentiation from plasma cell proliferative disorders with an unrelated clonal B-cell process. Br J Haematol. 2015;169:368-76.

Carulli G, Cannizzo E, Zucca A, Buda G, Orciuolo E, Marini A, Petrini M. CD45 expression in low-grade B-cell non-Hodgkin's lymphomas. Leuk Res. 2008;32:263-7.

Ishikawa H, Tsuyama N, Mahmoud MS, Fujii R, Abroun S, Liu S, et al. CD19 expression and growth inhibition of tumours in human multiple myeloma. Leuk Lymphoma. 2002;43:613-6.

Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004;121:482-8.

Masir N, Marafioti T, Jones M, Natkunam Y, Rüdiger T, Hansmann ML, Mason DY. Loss of CD19 expression in B-cell neoplasms. Histopathology. 2006;48:239-46.

Dong HY, Browne P, Liu Z, Gangi M. PAX-5 is invariably expressed in B-cell lymphomas without plasma cell differentiation. Histopathology. 2008;53:278-87.

Zhang X, Lin Z, Kim I. Pax5 expression in non-Hodgkin's lymphomas and acute leukemias. J Korean Med Sci. 2003;18:804-8.

Lin P, Mahdavy M, Zhan F, Zhang HZ, Katz RL, Shaughnessy JD. Expression of PAX5 in CD20-positive multiple myeloma assessed by immunohistochemistry and oligonucleotide microarray. Mod Pathol. 2004;17:1217-22.

Falini B, Fizzotti M, Pucciarini A, Bigerna B, Marafioti T, Gambacorta M, et al. A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells. Blood. 2000 Mar 15;95:2084-92.

Natkunam Y, Warnke RA, Montgomery K, Falini B, van De Rijn M. Analysis of MUM1/IRF4 protein

expression using tissue microarrays and immunohistochemistry. Mod Pathol. 2001;14:686-94.

Broijl A, de Jong ACM, van Duin M, Sonneveld P, Kühnau J, van der Velden VHJ. VS38c and CD38-Multiepitope Antibodies Provide Highly Comparable Minimal Residual Disease Data in Patients With Multiple Myeloma. Am J Clin Pathol. 2022;157:494-7.

Turley H, Jones M, Erber W, Mayne K, de Waele M, Gatter K. VS38: a new monoclonal antibody for detecting plasma cell differentiation in routine sections. J Clin Pathol. 1994;47:418-22.

Hookway ES, Orosz Z, Uchihara Y, Grigoriadis A, Hassan AB, Oppermann U, Athanasou NA. Utility of VS38c in the diagnostic and prognostic assessment of osteosarcoma and other bone tumours/tumour-like lesions. Clin Sarcoma Res. 2017;7:17.

Coupland SE, Hellmich M, Auw-Haedrich C, Lee WR, Anagnostopoulos I, Stein H. Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases. Br J Ophthalmol. 2005;89:352-9.

Xu Y, Mao X, Que Y, Xu M, Li C, Almeida VDF, et al. The exploration of B cell maturation antigen expression in plasma cell dyscrasias beyond multiple myeloma. BMC Cancer. 2023;23:123.

Dong N, Zhang H, Song J, Mammadova J, Shah B, Saeed H, et al. B-cell maturation antigen expression and clinical features of plasmablastic lymphoma. EJHaem. 2024;5:285-9.

Khattar P, Pichardo J, Jungbluth A, Gao Q, Smith EL, Roshal M, et al. B-cell maturation antigen is exclusively expressed in a wide range of B-cell and plasma cell neoplasm and is a potential therapeutic target for BCMA directed therapies. Blood. 2017;130(Suppl 1):S2755.

Vardanyan S, Meid K, Udd KA, Wang J, Li M, Sanchez E, et al. Serum levels of B-cell maturation antigen are elevated in Waldenström's macroglobulinemia patients and correlate with disease status and conventional M-protein and IgM levels. Blood. 2015;126:1778.

Chiraphapphaiboon W, Luangwattananun P, Chieochansin T, Samutpradit D, Hengswat P, Areesawangkit P, et al. Identification of HLA-restricted Cytotoxic T Lymphocyte Epitopes of B Cell Maturation Antigen as Promising Peptide Vaccine Candidates for Preventive and Therapeutic Strategies in Multiple Myeloma. Advanced Therapeutics. 2023;6:2300208.

Mason DY, Cordell JL, Brown MH, Borst J, Jones M, Pulford K, et al. CD79a: a novel marker for B-cell neoplasms in routinely processed tissue samples. Blood. 1995;86:1453-9.

Tanaka T, Ichimura K, Sato Y, Takata K, Morito T, Tamura M, et al. Frequent downregulation or loss of CD79a expression in plasma cell myelomas: potential clue for diagnosis. Pathol Int. 2009;59:804-8.

Hussaini M, Yeung C, Zhu X, Mirza AS, Pfeifer J, Hassan A. PRDM1 expression levels in marginal zone lymphoma and lymphoplasmacytic lymphoma. Int J Clin Exp Pathol. 2017;10:8610-8.

Zhang L, Nakhla H, Balos L, Deeb G, Sands A, Liu W, et al. Anaplastic plasma cell myeloma with features mimicking angiosarcoma: a case report. Am J Clin Pathol. 2015;144(Suppl 2):S118.

Gustmann C, Altmannsberger M, Osborn M, Griesser H, Feller AC. Cytokeratin expression and vimentin content in large cell anaplastic lymphomas and other non-Hodgkin's lymphomas. Am J Pathol. 1991;138:1413-22.

Douds JJ, Long DJ, Kim AS, Li S. Diagnostic and prognostic significance of CD200 expression and its stability in plasma cell myeloma. J Clin Pathol. 2014;67:792-6.

Alapat D, Coviello-Malle J, Owens R, Qu P, Barlogie B, Shaughnessy JD, Lorsbach RB. Diagnostic usefulness and prognostic impact of CD200 expression in lymphoid malignancies and plasma cell myeloma. Am J Clin Pathol. 2012;137:93-100.

Challagundla P, Medeiros LJ, Kanagal-Shamanna R, Miranda RN, Jorgensen JL. Differential expression of CD200 in B-cell neoplasms by flow cytometry can assist in diagnosis, subclassification, and bone marrow staging. Am J Clin Pathol. 2014;142:837-44.

Shim H, Ha JH, Lee H, Sohn JY, Kim HJ, Eom HS, Kong SY. Expression of myeloid antigen in neoplastic plasma cells is related to adverse prognosis in patients with multiple myeloma. Biomed Res Int. 2014;2014:893243.

Raimbault A, Machherndl-Spandl S, Itzykson R, Clauser S, Chapuis N, Mathis S, et al. CD13 expression in B cell malignancies is a hallmark of plasmacytic differentiation. Br J Haematol. 2019;184:625-33.

Roncador G, Puñet-Ortiz J, Maestre L, Rodríguez-Lobato LG, Jiménez S, Reyes-García AI, García-González Á, et al. CD229 (Ly9) a Novel Biomarker for B-Cell Malignancies and Multiple Myeloma. Cancers (Basel). 2022;14:2154.

la Torre A, Reece D, Crump M, Atenafu EG, Chen C, Prica A, Kukreti V. Light Chain Amyloidosis (AL) Associated With B Cell Lymphoma a Single Center Experience. Clin Lymphoma Myeloma Leuk. 2021;21:e946-e59.

Sukpanichnant S, Pinijvechagarn M, Poungvarin N. MYD88 L265P mutation status in small B-cell lymphoma with plasmacytic differentiation and extensive amyloid deposition. Journal of Hematology and Transfusion Medicine. 2020;30:369-78.

Treasure J, Lane A, Jones DB, Wright DH. CD43 expression in B cell lymphoma. J Clin Pathol. 1992;45:1018-22.

Andriko JA, Swerdlow SH, Aguilera NI, Abbondanzo SL. Is lymphoplasmacytic lymphoma/immunocytoma a distinct entity? A clinicopathologic study of 20 cases. Am J Surg Pathol. 2001;25:742-51.

Ning X, Wei X, Chen B, Li Z, Zheng Z, Yi Z, et al. CD43 is an adverse prognostic factor in newly diagnosed multiple myeloma. Leuk Lymphoma. 2022;63:2573-8.

Falini B, Agostinelli C, Bigerna B, Pucciarini A, Pacini R, Tabarrini A, et al. IRTA1 is selectively expressed in nodal and extranodal marginal zone lymphomas. Histopathology. 2012;61(5):930-41.

Falini B, Tiacci E, Pucciarini A, Bigerna B, Kurth J, Hatzivassiliou G, et al. Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT). Blood. 2003;102:3684-92.

Ikeda J, Kohara M, Tsuruta Y, Nojima S, Tahara S, Ohshima K, et al. Immunohistochemical analysis of the novel marginal zone B-cell marker IRTA1 in malignant lymphoma. Human Pathology. 2017;59:70-79.

Phikulsod P, Sukpanichnant S, Kunacheewa C, Chieochansin T, Junking M, Yenchitsomanus P-T. High prevalence of Wilms tumor 1 expression in multiple myeloma and plasmacytoma: A cohort of 142 Asian patients’ samples. Pathol Oncol Res 2023;29:1610844.

Drakos E, Rassidakis GZ, Tsioli P, Lai R, Jones D, Medeiros LJ. Differential expression of WT1 gene product in non-Hodgkin lymphomas. Appl Immunohistochem Mol Morphol. 2005;13:132-7.

Miranda RN, Briggs RC, Shults K, Kinney MC, Jensen RA, Cousar JB. Immunocytochemical analysis of MNDA in tissue sections and sorted normal bone marrow cells documents expression only in maturing normal and neoplastic myelomonocytic cells and a subset of normal and neoplastic B lymphocytes. Hum Pathol. 1999;30:1040-9.

Donnellan R, Chetty R. Cyclin D1 and human neoplasia. Mol Pathol. 1998;51:1-7.

Mozos A, Royo C, Hartmann E, De Jong D, Baró C, Valera A, et al. SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype. Haematologica. 2009;94:1555-62.

Padhi S, Varghese RG, Ramdas A. Cyclin D1 expression in multiple myeloma by immunohistochemistry: Case series of 14 patients and literature review. Indian J Med Paediatr Oncol. 2013;34:283-91.

Mansoor A, Akbari M, Auer I, Lai R. Cyclin D1 and t(11;14)-positive B-cell neoplasms resembling marginal zone B-cell lymphoma: a morphological variant of mantle cell lymphoma. Human Pathology. 2007;38:797-802.

Ribera-Cortada I, Martinez D, Amador V, Royo C, Navarro A, Beà S, et al. Plasma cell and terminal B-cell differentiation in mantle cell lymphoma mainly occur in the SOX11-negative subtype. Modern Pathology. 2015;28:1435-47.

Chen YH, Gao J, Fan G, Peterson LC. Nuclear expression of SOX11 is highly associated with mantle cell lymphoma but is independent of t(11;14)(q13;q32) in non-mantle cell B-cell neoplasms. Mod Pathol. 2010;23:105-12.