An approach for diagnosing plasma cell myeloma by three-color flow cytometry based on kappa/lambda ratios of CD38-gated CD138+ cells

Diagnostic Pathology

Toshiaki Hanafusa⁴  Motomu Tsuji¹  Yasuichiro Nishimura³  Hidema Tanaka²  Toshiyuki Ikemoto²  Yuki Masuda⁴  Uta Nishiwaki⁴  Ayami Takayama⁴  Takuji Miyoshi⁴  Toshikazu Akioka⁴  Kazuki Iwaki⁴  Yuji Hirata⁴  Taiji Yokote⁴  Shoko Nakayama⁴ 

[1] Division of Surgical Pathology, Osaka Medical College, Takatsuki City, Osaka, Japan;Central Clinical Laboratory, Osaka Medical College, Takatsuki City, Osaka, Japan;Division of Mathematics, Osaka Medical College, Takatsuki City, Osaka, Japan;First Department of Internal Medicine (I), Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka, 569-0801, Japan

关键词: CD38;    CD138;    kappa/lambda ratio;    Diagnosis;    Plasma cell myeloma;   

Others  :  807950
DOI  :  10.1186/1746-1596-7-131

 received in 2012-07-26, accepted in 2012-09-24,  发布年份 2012

【 摘 要 】

Background

World Health Organization (WHO) criteria are commonly used to diagnose plasma cell myeloma (PCM); however, these criteria are complex and require several laboratory parameters. For differentiating reactive plasmacytosis from clonal plasma cell (PC) neoplasms such as PCM, it is important to accurately determine the expression of cytoplasmic immunoglobulin light chains.

Methods

We retrospectively analyzed the records of 27 selected patients with PCM who underwent bone biopsies for confirmative diagnosis according to WHO criteria. Twenty-three controls were also investigated. In the present study, all the samples were analyzed using flow cytometry (FC) in the side scatter vs. CD38 histogram mode, and the CD38-gated PC population was identified. Bivariate histograms of CD138/kappa and CD138/lambda were assessed, and the ratios of dual-positive cells to the CD138⁺ PC population were calculated. The kappa/lambda ratio was defined as the ratio of CD138/kappa to CD138/lambda.

Results

PCM cells were distinguished from normal PCs using cutoff levels between 0.76 and 1.5, at a sensitivity of 96.3% and specificity of 95.7%.

Conclusions

Three-color FC analysis is simple to perform and inexpensive, with clinically relevant data obtained soon after the completion of FC measurements. The detection of the cytoplasmic kappa/lambda ratio of CD38-gated CD138⁺ PCs may be a useful tool in the diagnosis of PCM. To the best of our knowledge, this report represents the first diagnostic assessment of the cytoplasmic kappa/lambda ratio in CD38-gated CD138+ PCs using FC analysis. This method may help in more simple, efficient, rapid, and accurate diagnosis of PCM.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1568085959771735

【 授权许可】

   
2012 Nakayama et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Swerdlow SH, Campo E, Harris NL, et al.: World Health Organization classification of tumors of haematopoietic and lymphoid tissue. Lyon, France: IARC Press; 2008:202-208.
• [2]Chang CC, Schur BC, Kampalath B, Lindholm P, Becker CG, Vesole DH: A novel multiparametric approach for analysis of cytoplasmic immunoglobulin light chains by flow cytometry. Mod Pathol 2001, 14:1015-1021.
• [3]Sobol RE, Dillman RO, Collins H, Griffiths JC, Green MR, Royston I: Applications and limitations of peripheral blood lymphocyte immunoglobulin light chain analysis in the evaluation of non-Hodgkins lymphoma. Cancer 1985, 56:2005-2010.
• [4]Hsu SM, Cossman J, Jaffe ES: Lymphocyte subsets in normal human lymphoid tissue. Am J Clin Pathol 1983, 80:21-30.
• [5]Witzig TE, Li CY, Tefferi A, Katzmann JA: Measurement of the intensity of cell surface antigen expression in B-cell chronic lymphocytic leukemia. Am J Clin Pathol 1994, 101:312-317.
• [6]Eckert F, Schmid L, Kradoler D, et al.: Bone-marrow plasmacytosis—an immunohistological study. Blut 1986, 53:11-19.
• [7]Pérez-Andrés M, Almeida J, Martín-Ayuso M, et al.: Clonal plasma cells from monoclonal gammopathy of undetermined significance, multiple myeloma and plasma cell leukemia show different expression profiles of molecules involved in the interaction with the immunological bone marrow microenvironment. Leukemia 2005, 19:449-455.
• [8]Dahl IM, Rasmussen T, Kauric G, Husebekk A: Differential expression of CD56 and CD44 in the evolution of extramedullary myeloma. Br J Haematol 2002, 116:273-277.
• [9]San Miguel JF, Gutiérrez NC, Mateo G, Orfao A: Conventional diagnostics in multiple myeloma. Eur J Cancer 2006, 42:1510-1519.
• [10]van Zaanen HC, Vet RJ, de Jong CM, von dem Borne AE, van Oers MH: A simple and sensitive method for determining plasma cell isotype and monoclonality in bone marrow using flow cytometry. Br J Haematol 1995, 91:55.
• [11]Harada H, Kawano MM, Huang N, et al.: Phenotypic difference of normal plasma cells from mature myeloma cells. Blood 1993, 81:2658-2663.
• [12]Leo R, Boeker M, Peest D, et al.: Multiparameter analyses of normal and malignant human plasma cells: CD38++, CD56+, CD54+, cIg + is the common phenotype of myeloma cells. Ann Hematol 1992, 64:132-139.
• [13]Witzig TE, Kimlinger TK, Greipp PR: Detection of peripheral blood myeloma cells by three-color flow cytometry. Curr Top Microbiol Immunol 1995, 194:3-8.
• [14]Weisberger J, Wu CD, Liu Z, Wong JY, Melamed MR, Darzynkiewicz Z, Gorczyca W: Differential diagnosis of malignant lymphomas and related disorders by specific pattern of expression of immunophenotypic markers revealed by multiparameter flow cytometry. Int J Oncol 2000, 17:1165-1177.
• [15]Almeida J, Orfao A, Ocqueteau M, et al.: High-sensitive immunophenotyping and DNA ploidy studies for the investigation of minimal residual disease in multiple myeloma. Br J Haematol 1999, 107:121-131.
• [16]Rawstron A, Barrans S, Blythe D, et al.: Distribution of myeloma plasma cells in peripheral blood and bone marrow correlates with CD56 expression. Br J Haematol 1999, 104:138-143.
• [17]Wijdenes J, Clement C, Klein B, et al.: CD138 (syndecan1) workshop panel reports. In Leukocyte Typing VI: White Cell Differentiation Antigens. Edited by Kishimoto T, Kikutani H, Borne AEG Vd. New York, NY: Garland Publishing; 1998:249-252.
• [18]Durie BG, Harousseau JL, Miguel JS, et al.: International uniform response criteria for multiple myeloma. Leukemia 2006, 20:1467-1473.
• [19]Rawstron AC, Orfao A, Beksac M, et al.: Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica 2008, 93:431-438.
• [20]Lin P, Owens R, Tricot G, Wilson CS: Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol 2004, 121:482-488.
• [21]Robillard N, Pellat-Deceunynck C, Bataille R: Phenotypic characterization of the human myeloma cell growth fraction. Blood 2005, 105:4845-4848.
• [22]Moreau P, Robillard N, Jégo G, et al.: Lack of CD27 in myeloma delineates different presentation and outcome. Br J Haematol 2006, 132:168-170.
• [23]de Tute RM, Jack AS, Child JA, Morgan GJ, Owen RG, Rawstron AC: A single-tube six-colour flow cytometry screening assay for the detection of minimal residual disease in myeloma. Leukemia 2007, 21:2046-2049.