International Journal of Hematology

, Volume 98, Issue 5, pp 589–596 | Cite as

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

  • Sanja Perković
  • Sandra Bašić-Kinda
  • Igor Aurer
  • Ivo Ugrina
  • Antica Duletić-Načinović
  • Dominik Lozić
  • Drago Batinić
Original Article


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.


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


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Copyright information

© The Japanese Society of Hematology 2013

Authors and Affiliations

  • Sanja Perković
    • 1
  • Sandra Bašić-Kinda
    • 2
  • Igor Aurer
    • 2
  • Ivo Ugrina
    • 3
  • Antica Duletić-Načinović
    • 4
  • Dominik Lozić
    • 5
  • Drago Batinić
    • 1
    • 6
  1. 1.Clinical Unit for Cellular Immunodiagnostics and In Vitro Procedures, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, School of MedicineUniversity of ZagrebZagrebCroatia
  2. 2.Division of Hematology, Department of Internal Medicine, University Hospital Centre Zagreb, School of MedicineUniversity of ZagrebZagrebCroatia
  3. 3.Department of Mathematics, Faculty of Natural SciencesUniversity of ZagrebZagrebCroatia
  4. 4.Department of Hematology, Rheumatology and Clinical ImmunologyClinical Hospital Centre RijekaRijekaCroatia
  5. 5.Department of HematologyUniversity Hospital Centre SplitSplitCroatia
  6. 6.Department of Physiology, School of MedicineUniversity of ZagrebZagrebCroatia

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