Vol 53, No 1 (2022)
Review article
Published online: 2021-10-06

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Atypical immunophenotype of chronic lymphocytic leukemia

Marta Urbaniak1, Elżbieta Iskierka-Jażdżewska21, Agata Majchrzak1, Tadeusz Robak12
Acta Haematol Pol 2022;53(1):48-52.

Abstract

Assessment of the immunophenotype plays a crucial role in the diagnostic process of chronic lymphocytic leukemia (CLL). The expression of CD5, CD19 and CD23 antigens with a concomitant reduction or lack of surface immunoglobulin expression as well as CD22 and CD79b antigens is the basic part of CLL diagnosis. A significant diagnostic challenge is atypical CLL with cells devoid of CD5 or CD23 antigens. The assessment of additional antigens in flow cytometry, especially the CD200 glycoprotein, may facilitate the process of differential diagnosis of atypical CLL from other B-cell lymphoproliferative neoplasms. The results of current studies analyzing the influence of atypical CLL on prognosis are inconclusive. The analysis of a large group of patients with atypical CLL is difficult because of the rare occurrence of CD5(–) or CD23(–) CLL and the misdiagnosis of this disease as other B-cell lymphoproliferative neoplasms. The following paper aims to show how important it is to include atypical CLL in the diagnostic process of this disease and to re-standardize the commonly used immunophenotypic scales for its diagnosis.

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References

  1. National Cancer Institute. Surveillance epidemiology and end results cancer statistics review. 2016.
  2. Nabhan C, Rosen ST. Chronic lymphocytic leukemia: a clinical review. JAMA. 2014; 312(21): 2265–2276.
  3. Hallek M, Cheson BD, Catovsky D, et al. International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008; 111(12): 5446–5456.
  4. Muddasani R, Talwar N, Suarez-Londono JA, et al. Management of atypical chronic lymphocytic leukemia presenting with extreme leukocytosis. Clin Case Rep. 2020; 8(5): 877–882.
  5. Criel A, Verhoef G, Vlietinck R, et al. Further characterization of morphologically defined typical and atypical CLL: a clinical, immunophenotypic, cytogenetic and prognostic study on 390 cases. Br J Haematol. 1997; 97(2): 383–391.
  6. Matutes E, Oscier D, Garcia-Marco J, et al. Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients. Br J Haematol. 1996; 92(2): 382–388.
  7. Cuneo A, Balboni M, Piva N, et al. Atypical chronic lymphocytic leukaemia with t(11;14)(q13;q32): karyotype evolution and prolymphocytic transformation. Br J Haematol. 1995; 90(2): 409–416.
  8. Huh YO, Abruzzo LV, Rassidakis GZ, et al. The t(14;19)(q32;q13)-positive small B-cell leukaemia: a clinicopathologic and cytogenetic study of seven cases. Br J Haematol. 2007; 136(2): 220–228.
  9. Li Yi, Tong X, Huang L, et al. A new score including CD43 and CD180: increased diagnostic value for atypical chronic lymphocytic leukemia. Cancer Med. 2021; 10(13): 4387–4396.
  10. Jurisic V, Colovic N, Kraguljac N, et al. Analysis of CD23 antigen expression in B-chronic lymphocytic leukaemia and its correlation with clinical parameters. Med Oncol. 2008; 25(3): 315–322.
  11. Kriston C, Bödör C, Szenthe K, et al. Low CD23 expression correlates with high CD38 expression and the presence of trisomy 12 in CLL. Hematol Oncol. 2017; 35(1): 58–63.
  12. Köhnke T, Wittmann VK, Bücklein VL, et al. Diagnosis of CLL revisited: increased specificity by a modified five-marker scoring system including CD200. Br J Haematol. 2017; 179(3): 480–487.
  13. Matutes E, Owusu-Ankomah K, Morilla R, et al. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia. 1994; 8(10): 1640–1645.
  14. Moreau EJ, Matutes E, A'Hern RP, et al. Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody SN8 (CD79b). Am J Clin Pathol. 1997; 108(4): 378–382.
  15. Delia D, Bonati A, Giardini R, et al. Expression of the T1 (CD5, p67) surface antigen in B-CLL and B-NHL and its correlation with other B-cell differentiation markers. Hematol Oncol. 1986; 4(3): 237–248.
  16. Cartron G, Linassier C, Bremond JL, et al. CD5 negative B-cell chronic lymphocytic leukemia: clinical and biological features of 42 cases. Leuk Lymphoma. 1998; 31(1-2): 209–216.
  17. Efstathiou S, Tsioulos D, Zacharos I, et al. The prognostic role of CD5 negativity in B-cell chronic lymphocytic leukaemia: a case-control study. Haematologia (Budap). 2002; 32(3): 209–218.
  18. Romano C, Sellitto A, Chiurazzi F, et al. Clinical and phenotypic features of CD5-negative B cell chronic lymphoproliferative disease resembling chronic lymphocytic leukemia. Int J Hematol. 2015; 101(1): 67–74.
  19. Kurec AS, Threatte GA, Gottlieb AJ, et al. Immunophenotypic subclassification of chronic lymphocytic leukaemia (CLL). Br J Haematol. 1992; 81(1): 45–51.
  20. Friedman DR, Guadalupe E, Volkheimer A, et al. Clinical outcomes in chronic lymphocytic leukaemia associated with expression of CD5, a negative regulator of B-cell receptor signalling. Br J Haematol. 2018; 183(5): 747–754.
  21. Fournier S, Yang LP, Delespesse G, et al. The two CD23 isoforms display differential regulation in chronic lymphocytic leukaemia. Br J Haematol. 1995; 89(2): 373–379.
  22. Kilo MN, Dorfman DM. The utility of flow cytometric immunophenotypic analysis in the distinction of small lymphocytic lymphoma/chronic lymphocytic leukemia from mantle cell lymphoma. Am J Clin Pathol. 1996; 105(4): 451–457.
  23. Barna G, Reiniger L, Tátrai P, et al. The cut-off levels of CD23 expression in the differential diagnosis of MCL and CLL. Hematol Oncol. 2008; 26(3): 167–170.
  24. Dadmarz R, Cawley JC. Heterogeneity of CLL: high CD23 antigen and alpha IFN receptor expression are features of favourable disease and of cell activation. Br J Haematol. 1988; 68(3): 279–282.
  25. Lavabre-Bertrand T, Exbrayat C, Bourquard P, et al. CD23 antigen density is related to serum gamma globulin level, bone marrow reticulin pattern, and treatment in B chronic lymphocytic leukemia. Leuk Lymphoma. 1994; 13(1-2): 89–94.
  26. El Din Fouad NB, Ibrahim NY, Abdel Aziz RS, et al. CD200 expression in diagnostic and prognostic assessment of mature B cell lymphophoproliferative neoplasms. Asian Pac J Cancer Prev. 2018; 19(12): 3383–3392.
  27. Rahman K, Kumar P, Gupta R, et al. Role of CD200 in differential diagnosis of mature B-cell neoplasm. Int J Lab Hematol. 2017; 39(4): 384–391.
  28. Lesesve JF, Tardy S, Frotscher B, et al. Combination of CD160 and CD200 as a useful tool for differential diagnosis between chronic lymphocytic leukemia and other mature B-cell neoplasms. Int J Lab Hematol. 2015; 37(4): 486–494.
  29. D'Arena G, De Feo V, Pietrantuono G, et al. CD200 and chronic lymphocytic leukemia: biological and clinical relevance. Front Oncol. 2020; 10: 584427.
  30. D'Arena G, Vitale C, Rossi G, et al. CD200 included in a 4-marker modified Matutes score provides optimal sensitivity and specificity for the diagnosis of chronic lymphocytic leukaemia. Hematol Oncol. 2018 [Epub ahead of print].