Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Matutes E, Owusu-Ankomah K, Morilla R, Garcia Marco J, Houlihan A, Que TH, Catovsky D. The immunological profile of B-cell disorders: a proposal of a scoring system for the diagnosis of CLL. Leukemia. 1994;8(10):1640–5.

    PubMed  CAS  Google Scholar 

  2. Montserrat E. Chronic lymphoproliferative disorders. Curr Opin Oncol. 1997;9(1):34–41.

    Article  PubMed  CAS  Google Scholar 

  3. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: International agency for research on cancer (IARC); 2008.

    Google Scholar 

  4. Sklar J, Cleary ML, Thielemans K, Garlow J, Warnke R, Levy R. Biclonal B-cell lymphoma. New Engl J Med. 1984;311(1):20–7.

    Article  PubMed  CAS  Google Scholar 

  5. Fend F, Quintanilla-Martinez L, Kumar S, Beaty MW, Blom L, Sorbara L, et al. Composite low grade B-cell lymphomas with two immunophenotypically distinct cell populations are true biclonal lymphomas. A molecular analysis using laser capture microdissection. Am J Pathol. 1999;154(6):1857–66.

    Article  PubMed  CAS  Google Scholar 

  6. Gonzalez-Campos J, Rios-Herranz E, De Blas-Orlando JM, Martin-Noya A, Parody-Ruiz-Berdejo R, Rodriguez-Fernandez JM. Chronic lymphocytic leukemia with two cellular populations: a biphenotypic or biclonal disease. Ann Haematol. 1997;74:243–6.

    Article  CAS  Google Scholar 

  7. Sanchez ML, Almeida J, Gonzalez D, Gonzalez M, Garcia-Marcos MA, Balanzategui A, et al. Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone. Blood. 2003;102(8):2994–3002.

    Article  PubMed  CAS  Google Scholar 

  8. Gine E, Bosch F, Villamor N, Rozman N, Colomer D, Lopez-Guillermo A, et al. Simultaneous diagnosis of hairy cell leukemia and chronic lymphocytic leukemia/small lymphocytic lymphoma: a frequent association? Leukemia. 2002;16(8):1454–9.

    Article  PubMed  CAS  Google Scholar 

  9. Demurtas A, Aliberti S, Bonello L, Di Celle PF, Cavaliere C, Barreca A, et al. Usefulness of multiparametric flow cytometry in detecting composite lymphoma: a study of 17 cases in a 12-year period. Am J Clin Pathol. 2011;135(4):541–55.

    Article  PubMed  Google Scholar 

  10. Hsi ED, Hoeltge G, Tubbs RR. Biclonal chronic lymphocytic leukemia. Am J Clin Pathol. 2000;113(6):798–804.

    Article  PubMed  CAS  Google Scholar 

  11. Dennis KL, Wallentine SL, Vanveldhuizen PJ, Persons DL, Mathur SC. Biclonal post-transplant B-cell lymphoma: report of the case with two distinct cell populations, XX, t(14;18) and XY, t(11;14). Cancer Genet Cytogenet. 2007;173(2):150–3.

    Article  PubMed  CAS  Google Scholar 

  12. Zamo A, Zanotti R, Lestani M, Ott G, Katzenberger T, Scarpa A, et al. Molecular characterization of composite mantle cell and follicular lymphoma. Virchows Arch. 2006;448(5):639–43.

    Article  PubMed  Google Scholar 

  13. Deville JP, Heimann P, El Housni H, Boutriaux M, Jeronnez A, Remmelink M, et al. Biclonal low grade B-cell lymphoma confirmed by both flow cytometry and karyotypic analysis, in spite of a normal kappa/lambda Ig light chain ratio. Am J Hematol. 2007;82(6):473–80.

    Article  Google Scholar 

  14. Roulett MR, Martinez D, Ma L, Flowler MH, McPhail ED, Judkins A, et al. Coexisting follicular and mantle cell lymphoma with each having an in situ component: a novel, curious and complex consultation case of coincidental, composite, colonizing lymphoma. Am J Clin Pathol. 2010;133(4):584–91.

    Article  Google Scholar 

  15. Ilgenfritz RB, Le Tourneau A, Arborio M, Molina TJ, Diebold J, Damotte D, et al. Composite mantle cell and follicular lymphoma. A case report. Hum Pathol. 2009;40(2):259–63.

    Article  PubMed  Google Scholar 

  16. Lefebrve C, Fabre B, Vettier C, Rabin L, Florin A, Wang J, et al. Composite splenic marginal zone lymphoma and mantle cell lymphoma arising from 2 independent B-cell clones. Hum Pathol. 2007;38(4):660–7.

    Article  Google Scholar 

  17. Sanchez ML, Almeida J, Lopez A, Sayagues JM, Rasillo A, Sarasquete EA, et al. Heterogeneity of neoplastic cells in B-cell chronic lymphoproliferative disorders: biclonality versus intraclonal evolution of a single tumor cell clone. Haematologica. 2006;91(3):331–9.

    PubMed  CAS  Google Scholar 

Download references

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.

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandra Bašić-Kinda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Igor Aurer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ivo Ugrina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antica Duletić-Načinović
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dominik Lozić
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Drago Batinić
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sanja Perković.

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

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

Keywords

Search

Navigation