Abstract
We report a unique case of composite hairy cell leukemia (HCL) and monoclonal B-cell lymphocytosis with chronic lymphocytic leukemia (CLL) phenotype evaluated comprehensively through cell sorting and deep sequencing. The patient presented with decreased exercise tolerance and complete blood count revealed neutropenia, monocytopenia, and thrombocytopenia. The peripheral blood film was suggestive of HCL. However, a bone marrow evaluation was suspicious for composite HCL and CLL. Flow cytometry not only confirmed monoclonal kappa light chain restricted HCL and CLL populations, but also identified a kappa restricted population with co-expression of bright CD20, bright CD22, and CD11c without CD25 or CD103. Each population was isolated by cell sorting and subsequent B-cell receptor gene rearrangement analysis showed distinct rearrangements in each population. Likewise, next-generation sequencing (NGS) showed distinct mutation patterns in each of the monoclonal B-cell populations. The HCL clone harbored the signature BRAF V600E mutation, the CLL clone harbored an RB1 (L343fs*6) mutation, and the third clone was essentially negative for either mutation. In HCL, the BRAF V600E has been found in hematopoietic stem cells, raising the possibility of a common stem cell origin for composite HCL/CLL. However, our findings suggest a process of independent clonal development of multiple neoplastic B-cell populations in composite lymphoma, likely occurring somewhere after the common lymphoid progenitor stage.
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References
Küppers R, Dührsen U, Hansmann ML (2014) Pathogenesis, diagnosis, and treatment of composite lymphomas. Lancet Oncol 15:e435–e446. https://doi.org/10.1016/S1470-2045(14)70153-6
Fend F, Quintanilla-Martinez L, Kumar S, Beaty MW, Blum L, Sorbara L, Jaffe ES, Raffeld M (1999) Composite low grade B-cell lymphomas with two immunophenotypically distinct cell populations are true biclonal lymphomas. Am J Pathol 154:1857–1866. https://doi.org/10.1016/S0002-9440(10)65443-0
Giné E, Bosch F, Villamor N, Rozman M, Colomer D, López-Guillermo A, Campo E, Montserrat E, Pi Sunyer A (2002) Simultaneous diagnosis of hairy cell leukemia and chronic lymphocytic leukemia/small lymphocytic lymphoma: a frequent association? Leukemia 16:1454–1459. https://doi.org/10.1038/sj.leu.2402553
Sokol L, Agosti SJ (2004) Simultaneous manifestation of chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL). Am J Hematol 75:107–109. https://doi.org/10.1002/ajh.10459
Brown SA, Phillips J, Ahsan G, Slater NGP (1998) Coexistent hairy cell leukaemia and chronic lymphocytic leukaemia coexistent hairy cell leukaemia and chronic lymphocytic leukaemia. Leuk Lymphoma 30:203–209. https://doi.org/10.3109/10428199809050945
Kikushige Y, Ishikawa F, Miyamoto T, Shima T, Urata S, Yoshimoto G, Mori Y, Iino T, Yamauchi T, Eto T, Niiro H, Iwasaki H, Takenaka K, Akashi K (2011) Self-renewing hematopoietic stem cell is the primary target in pathogenesis of human chronic lymphocytic leukemia. Cancer Cell 20:246–259. https://doi.org/10.1016/j.ccr.2011.06.029
Chung SS, Kim E, Park JH, Chung YR, Lito P, Teruya-Feldstein J, Hu W, Beguelin W, Monette S, Duy C, Rampal R, Telis L, Patel M, Kim MK, Huberman K, Bouvier N, Berger MF, Melnick AM, Rosen N, Tallman MS, Park CY, Abdel-Wahab O (2014) Hematopoietic stem cell origin of BRAFV600E mutations in hairy cell leukemia. Sci Transl Med 6:238ra71. https://doi.org/10.1126/scitranslmed.3008004
Liptrot S, O’Brien D, Langabeer SE, Quinn F, Mackarel A, Elder P, Vandenberghe E, Hayden PJ (2013) An immunophenotypic and molecular diagnosis of composite hairy cell leukaemia and chronic lymphocytic leukaemia. Med Oncol 30:692. https://doi.org/10.1007/s12032-013-0692-7
Cavalli M, Ilari C, Del Giudice I, Marinelli M, Della Starza I, De Propris M, De Novi L, Nunes V, Cafforio L, Raponi S, Mancini F, Mauro F, Tiacci E, Falini B, Guarini A, Foà R (2016) A case of concomitant chronic lymphocytic leukaemia and hairy cell leukaemia evaluated for IGHV-D-J rearrangements and BRAF-V600E mutation: lack of evidence for a common origin. Br J Haematol 174:329–331. https://doi.org/10.1111/bjh.13770
Garrido P, Jiménez P, Sánchez C, Valero F, Balanzategui A, Almagro M, López P, De Pablos JM, Navarro P, Cabrera A, González M, Jurado M, Ruiz-Cabello F (2011) Molecular and flow cytometry characterization during the follow-up of three simultaneous lymphoproliferative disorders: hairy cell leukemia, monoclonal B-cell lymphocytosis, and CD4 ++/CD8 +/−dim T-large granular lymphocytosis—a case report. Clin Cytom 80B:195–200. https://doi.org/10.1002/cyto.b.20579
Kampmeier P, Spielberger R, Dickstein J, Mick R, Golomb H, Vardiman JW (1994) Increased incidence of second neoplasms in patients treated with interferon alpha 2b for hairy cell leukemia: a clinicopathologic assessment. Blood 83:2931–2938
Kurzrock R, Strom S, Estey E, O’Brien S, Keating M, Jiang H, Adams T, Talpaz M (1997) Second cancer risk in hairy cell leukemia: analysis of 350 patients. J Clin Oncol 15:1803–1810. https://doi.org/10.1200/JCO.1997.15.5.1803
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The authors would like to thank the UWCCC Flow Cytometry Shared Service for the performance of cell sorting.
Funding
This project was supported by grant P30 CA014520 from the National Cancer Institute and 1S10RR025483-01 from the National Institute of Health Shared Instrument Grant.
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Supplementary table 1
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Supplementary Fig 1
The complete results of clonality analysis from unsorted population (a), PH (b), P3(c) and PC (d). The unique peaks in each population are highlighted by red circles. (GIF 3339 kb)
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Zhang, R., Accola, M.A., Johnson, J.C. et al. Clonality and mutational profiling of a case of composite hairy cell leukemia and chronic lymphocytic leukemia. J Hematopathol 10, 81–86 (2017). https://doi.org/10.1007/s12308-017-0301-3
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DOI: https://doi.org/10.1007/s12308-017-0301-3