Abstract
Background and Objective
Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder for which diagnosis is typically straightforward, based on bone marrow morphology and flow cytometry (FC) or immunohistochemistry. Nevertheless, variants present atypical expressions of cell surface markers, as is the case of CD5, for which the differential diagnosis can be more difficult. The aim of the current paper was to describe diagnosis of HCL with atypical CD5 expression, with an emphasis on FC.
Methods
The detailed diagnostic methodology for HCL with atypical CD5 expression is presented, including differential diagnosis from other lymphoproliferative diseases with similar pathologic features, by FC analysis of the bone marrow aspirate.
Results
Diagnosis of HCL by means of FC started by gating all events based on side scatter (SSC) versus CD45 and B lymphocytes were selected from the lymphocytes gate as CD45/CD19 positive. The gated cells were positive for CD25, CD11c, CD20, and CD103, while CD10 proved to be dim to negative. Moreover, cells positive for CD3, CD4, and CD8, the three pan-T markers, as well as CD19, showed a bright expression of CD5. The atypical CD5 expression is usually correlated with a negative prognosis and thus chemotherapy with cladribine should be initiated.
Conclusion
HCL is an indolent chronic lymphoproliferative disorder and diagnosis is usually straightforward. However, atypical expression of CD5 renders its differential diagnosis more difficult, but FC is a useful tool that allows an optimal classification of the disease and allows initiation of timely satisfactory therapy.
Similar content being viewed by others
References
Jasionowski TM, Hartung L, Greenwood JH, Perkins SL, Bahler DW. Analysis of CD10+ hairy cell leukemia. Am J Clin Pat. 2003;120(2):228–35.
Boyd SD, Natkunam Y, Allen JR, Warnke RA. Selective immunophenotyping for diagnosis of B-cell neoplasms: immunohistochemistry and flow cytometry strategies and results. Appl Immunohistochem Mol Morphol. 2013;21(2):116–31.
Bouroncle BA, Wiseman BK, Doan CA. Leukemic reticuloendotheliosis. Blood. 1958;13(7):609–30.
Isaacs A, Lindenmann J. Virus interference: I. The interferon. CA Cancer J Clin. 1988;38(5):280–90.
Dearden CE, Else M, Catovsky D. Long-term results for pentostatin and cladribine treatment of hairy cell leukemia. Leuk Lymphoma. 2011;52(Suppl 2):21–4.
Cross M, Dearden C. Hairy cell leukaemia. Curr Oncol Rep. 2020;22(5):42.
Maitre E, Cornet E, Troussard X. Hairy cell leukemia: 2020 update on diagnosis, risk stratification, and treatment. Am J Hematol. 2019;94(12):1413–22.
Stetler-Stevenson M, Tembhare PR. Diagnosis of hairy cell leukemia by flow cytometry. Leuk Lymphoma. 2011;52(Suppl 2):11–3.
Poret N, Fu Q, Guihard S, et al. CD38 in hairy cell leukemia is a marker of poor prognosis and a new target for therapy. Can Res. 2015;75(18):3902–11.
Troussard X, Cornet E. Hairy cell leukemia 2018: update on diagnosis, risk-stratification, and treatment. Am J Hematol. 2017;92(12):1382–90.
Tallman MS. Clinical features and diagnosis of hairy cell leukemia, UpToDate, 2023.
Maitre E, Cornet E, Salaün V, Kerneves P, Chèze S, Repesse Y, Damaj G, Troussard X. Immunophenotypic analysis of hairy cell leukemia (HCL) and hairy cell leukemia-like (HCL-like) disorders. Cancers. 2022;14:1050.
Böttcher S, Engelmann R, Grigore G, Fernandez PC, Caetano J, Flores-Montero J, Van der Velden VHJ, Novakova M, Philippé J, Ritgen M. Expert-independent classification of mature B-cell neoplasms using standardized flow cytometry: a multicentric study. Blood Adv. 2022;6:976–92.
Xi L, Arons E, Navarro W, Calvo KR, Stetler-Stevenson M, Raffeld M, Kreitman RJ. Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation. Blood. 2012;119(14):3330–2.
Javidiparsijani S, Choi YK, Arbini AA. A case of CD5 positive hairy cell leukemia with BRAF V600E mutation and lymph node involvement; unique case report and review of the literature. Blood. 2020;136(Supplement 1):17–8.
Hallek M, Al-Sawaf O. Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures. Am J Hematol. 2021;96(12):1679–705.
Soong D, Kumar P, Jatwani K, Park J, Dogan A, Taylor J. Hairy cell leukemia masquerading as CD5+ lymphoproliferative disease: the importance of BRAF V600E testing in diagnosis and treatment. JCO Prec Oncol. 2021;5:1035–9.
Salem DA, Scott D, McCoy CS, Liewehr DJ, Venzon DJ, Arons E, Kreitman RJ, Stetler-Stevenson M, Yuan CM. Differential expression of CD43, CD81, and CD200 in classic versus variant hairy cell leukemia. Cytom Part B. 2019;96B:275–82.
Szczepański T, van der Velden VH, van Dongen JJ. Flow-cytometric immunophenotyping of normal and malignant lymphocytes. Clin Chem Lab Med. 2006;44(7):775–96.
Shao H, Calvo KR, Grönborg M, Tembhare PR, Kreitman RJ, Stetler-Stevenson M, Yuan CM. Distinguishing hairy cell leukemia variant from hairy cell leukemia: development and validation of diagnostic criteria. Leuk Res. 2013;37(4):401–9.
Vittoria L, Bozzi F, Capone I, Carniti C, Lorenzini D, Gobbo M, Bolli N, Aiello A. A rare biclonal Hairy Cell Leukemia disclosed by an integrated diagnostic approach: a case report. Cytom B Clin Cytom. 2021;100(6):692–4.
Mahdi T, Rajab A, Padmore R, Porwit A. Characteristics of lymphoproliferative disorders with more than one aberrant cell population as detected by 10-color flow cytometry. Cytom B Clin Cytom. 2018;94(2):230–8.
Maitre E, Cornet E, Salaün V, Kerneves P, Chèze S, Repesse Y, Damaj G, Troussard X. Immunophenotypic analysis of hairy cell leukemia (HCL) and hairy cell leukemia-like (HCL-like) disorders. Cancers (Basel). 2022;14(4):1050.
Robak T. Hairy-cell leukemia variant: recent view on diagnosis, biology and treatment. Cancer Treat Rev. 2011;37(1):3–10.
Venkataraman G, Aguhar C, Kreitman RJ, Yuan CM, Stetler-Stevenson M. Characteristic CD103 and CD123 expression pattern defines hairy cell leukemia: usefulness of CD123 and CD103 in the diagnosis of mature B-cell lymphoproliferative disorders. Am J Clin Pathol. 2011;136(4):625–30.
Cessna MH, Hartung L, Tripp S, Perkins SL, Bahler DW. Hairy cell leukemia variant: fact or fiction. Am J Clin Pathol. 2005;123(1):132–8.
Mendez-Hernandez A, Moturi K, Hanson V, Andritsos LA. Hairy cell leukemia: where are we in 2023? Curr Oncol Rep. 2023. https://doi.org/10.1007/s11912-023-01419-z.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
Diana Cenariu, Mihai Cenariu, Jon Thor Bergthorsson, and Victor Greiff are financed by an international collaborative grant of the European Economic Space between Romania, Iceland, and Norway 2014–2021 (Grant no 21-COP-0034). Diana Cenariu also received funding from a grant of the National Research Ministry of Romania - PN-III-P4-ID-PCE-2020-1118.
Conflict of interest
Diana Cenariu, Ioana Rus, Jon Thor Bergthorsson, Ravnit Grewal, Mihai Cenariu, Victor Greiff, Bogdan Tigu, Delia Dima, Mihnea Zdrenghea, Cristina Selicean, Bobe Petrushev, Jonathan Fromm, Carmen-Mariana Aanei, and Ciprian Tomuleasa declare that they have no conflicts of interest.
Availability of data and material
Data supporting the results reported in the article can be found at Medfuture Research Center for Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Ethics approval
The study was approved by the Ethics committee of the Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.
Consent to participate
Informed written consent was obtained from the patient included in the study.
Consent for publication
Not applicable.
Code availability
Not applicable.
Author contributions
Diana Cenariu, Bogdan Tigu, Cristina Selicean, Mihnea Zdrenghea, Bobe Petrushev, and Mihai Cenariu prepared the samples and performed the flow cytometry analysis; Ioana Rus, Delia Dima, and Ciprian Tomuleasa performed clinical examination of the patient, collected the bone marrow sample, and established the final diagnosis and treatment. Jon Thor Bergthorsson, Victor Greiff, Ravnit Grewal, and Jonathan Fromm provided valuable input on bone marrow analysis methodology, evaluated the results and participated in the preparation of the Discussion section, Diana Cenariu, Ioana Rus, and Mihai Cenariu drafted the manuscript; Carmen-Mariana Aanei and Ciprian Tomuleasa reviewed the whole manuscript and established its final form.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Cenariu, D., Rus, I., Bergthorsson, J.T. et al. Flow Cytometry of CD5-Positive Hairy Cell Leukemia. Mol Diagn Ther 27, 593–599 (2023). https://doi.org/10.1007/s40291-023-00658-x
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40291-023-00658-x