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Multiparameter flow cytometry is necessary for detection, characterization and diagnostics of composite mature B-cell lymphoproliferative neoplasms

International Journal of Hematology volume 98, pages 589–596 (2013)Cite this article

Abstract

Composite mature B-cell lymphoproliferative neoplasms are rare entities characterized by the simultaneous presence of two or more distinctive B-cell derived monoclonal malignancies. This retrospective study used multiparametric flow cytometric analysis aimed at immunophenotypic profiling of composite mature B-cell lymphoproliferative neoplasms in a cohort of 413 subsequent patients with de novo leukemic B-cell chronic lymphoproliferative disorders diagnosed in our institution during a 30-month period. Biclonality was found in 16 (3.9 %) patients. The vast majority (88 %) of the cases had one of the clones phenotypically corresponding to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Only when composite cases were categorized by phenotype of the non-CLL/SLL malignant population did we find a statistically significant (P = 0.001) higher frequency of biclonality among cases with hairy cell leukemia (22 %). Biclonal cases had the overall B-cell membrane κ to λ ratio within the normal range (median, 1.9; reference interval 0.5–4.0), making recognition of malignancy somewhat challenging. Our analysis strategy was therefore based on the detection of aberrant B-cell phenotypes, with subsequent confirmation of the monoclonal nature of neoplastic clones with regards to light chain restriction analysis. Discrimination of the coexisting clones in biclonal cases was possible on the basis of the expression of other antigen(s) (63 %), light scatter properties (44 %), different surface light chain restriction (69 %) and/or pattern of expression (44 %). The most informative cell surface antigens proved to be CD22, CD20, surface IgM, and CD23. In conclusion, historic κ/λ ratio is not a reliable approach and is a poor measurement for the detection of composite lymphomas. More creative analysis techniques should be utilized for this purpose.

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Acknowledgments

This study was supported in part by grant from Croatian Ministry of Science, Education and Sports, Number 214-1081347-0355 (PI Drago Batinić).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Clinical Unit for Cellular Immunodiagnostics and In Vitro Procedures, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Kišpatićeva 12, 10000, Zagreb, Croatia

    Sanja Perković & Drago Batinić

  2. Division of Hematology, Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Kišpatićeva 12, 10000, Zagreb, Croatia

    Sandra Bašić-Kinda & Igor Aurer

  3. Department of Mathematics, Faculty of Natural Sciences, University of Zagreb, Bijenička cesta 30, 10000, Zagreb, Croatia

    Ivo Ugrina

  4. Department of Hematology, Rheumatology and Clinical Immunology, Clinical Hospital Centre Rijeka, Krešimirova 42, 51000, Rijeka, Croatia

    Antica Duletić-Načinović

  5. Department of Hematology, University Hospital Centre Split, Šoltanska 1, 21000, Split, Croatia

    Dominik Lozić

  6. Department of Physiology, School of Medicine, University of Zagreb, Šalata 3, 10000, Zagreb, Croatia

    Drago Batinić

Authors
  1. Sanja Perković
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  2. Sandra Bašić-Kinda
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  3. Igor Aurer
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  4. Ivo Ugrina
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  5. Antica Duletić-Načinović
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  6. Dominik Lozić
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  7. Drago Batinić
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Correspondence to Sanja Perković.

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Perković, S., Bašić-Kinda, S., Aurer, I. et al. Multiparameter flow cytometry is necessary for detection, characterization and diagnostics of composite mature B-cell lymphoproliferative neoplasms. Int J Hematol 98, 589–596 (2013). https://doi.org/10.1007/s12185-013-1432-7

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  • DOI: https://doi.org/10.1007/s12185-013-1432-7

Keywords

  • Flow cytometry
  • Composite lymphoma
  • Lymphoma, non-Hodgkin
  • Immunoglobulin light chains
  • Hematology