The cytomorphology and immunophenotype of mantle-cell lymphoma


Authors: D. Starostka 1;  D. Koláček 1;  P. Mikula 1;  M. Tichý 2,3
Authors‘ workplace: Oddělení klinické hematologie, Nemocnice s poliklinikou Havířov, p. o. 1;  Ústav klinické a molekulární patologie, Lékařská fakulta UP v Olomouci 2;  CGB laboratoř, a. s. 3
Published in: Transfuze Hematol. dnes,21, 2015, No. 4, p. 173-183.
Category: Comprehensive Reports, Original Papers, Case Reports

Overview

 

Introduction:
Mantle-cell lymphoma (MCL) is a rare lymphoid neoplasm of B-cell origin characterized by over-expres-sion of cyclin D1 and it is usually associated with the chromosomal translocation t(11; 14). MCL may exhibit classical morphology or one of 4 morphological variants (small-cell, pleomorphic, blastoid and marginal zone lymphoma-like). The immunophenotype is characterized by the high expression of pan-B-cell markers - CD19, CD20, CD22, CD79, surface membrane immunoglobulins IgM, IgD including their light chains and CD5 antigen. The intranuclear expres-sion of cyclin D1 is specific for MCL. The surface membrane marker FMC7 is usually positive; CD43, CD38, bcl-2 and transcription factor SOX11 are regularly positive as well. The antigens CD23, CD10, CD11c, CD103, CD200 and bcl-6 are typically negative in MCL.

Methods:
16 cases of newly diagnosed MCL were included in the study (samples included peripheral blood, bone marrow, lymph nodes and cerebrospinal fluid). The cytomorphology evaluation was done on samples of peripheral blood and bone marrow smears, lymph node imprints and cerebrospinal fluid cytospins using classical panoptic staining. This determined the cytomorphological subtype of MCL. The immunophenotype was then detected by flow cytometric analysis using the FACS Canto II flow cytometer (manufactured by Becton-Dickinson). Multiparameter analysis of surface membrane antigen expression included detecting positivity or negativity of CD19, CD20, CD22, CD79b, surface membrane light chains kappa and lambda, CD23, FMC7, CD5, CD10, CD25, CD35, CD38, CD11c, CD103 and CD200; the signal intensity of each CD marker expression (mean fluorescence intensity, MFI) was also measured by using a diagnostic panel of monoclonal antibodies.

Results:
The study included 11 men and 5 women with a median age of 70 years. Cytomorphological features included 7 cases of classic MCL and 9 cases of variant types (4 small-cell, 3 pleomorphic, 1 blastoid, 1 „marginal zone lymphoma-like” form). Surface membrane cell markers CD19, CD20, CD22 and CD79b were constantly positive with high expression (the highest being CD20). Surface membrane light chains kappa and lambda expression were observed alternately in one half the cases (with prevalent lambda light chain intensity expression). The expression of CD5 was mostly high; two cases were CD5-negative. FMC7 was positive in 10 cases with variable expression of intensity. Variable expression of CD25 was observed and CD35 was positive in three-quarters of all patients, CD38 was positive in the majority of cases (high intensity of expression). CD23, CD11c and CD103 were negative, CD43 was also mostly negative. One CD10 positive case and two CD200 positive cases were found in our study. The variability of expression intensity was common even for CD markers with the highest intensity of expression.

Conclusions:
Assessment of the immunocytological profile is one of the main components of MCL diagnosis. The cytomorphological and immunophenotypical variability of MCL is high. Accurate differential diagnosis of MCL, chronic lymphocytic leukaemia, marginal zone lymphoma and some cases of B-prolymphocytic leukaemia is necessary. The immunophenotypical panel used in our study is appropriate to diagnose most MCL cases.

Key words:
mantle-cell lymphoma, cytology, immunophenotype


Sources

1. Swerdlow SH, Campo E, Lee Harris N, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Fourth Edition. IARC: Lyon 2008.

2. Kačírková P, Campr V, Karban J, Mikulenková D. Hematoonkologický atlas krve a kostní dřeně. Grada Publishing, a. s. Praha. 2007.

3. Dreyling M, Kluin-Nelemans HC, Bea S, et al. Update on the molecular pathogenesis and clinical treatment of mantle cell lymphoma: report of the 11th annual conference of the European Mantle Cell Lymphoma Network. Leuk Lymphoma 2013; 54: 699–707.

4. Richard P, Vassallo J, Valmary S, Missoury R, Delsol G, Brousset P. „In situ-like“ mantle cell lymphoma: a report of two cases. J Clin Pathol 2006; 59: 995–996.

5. Craig FE, Foon KA. Flow cytometric immunophenotyping for hematologic neoplasms. Blood 2008; 111: 3941–3967.

6. Mozos A, Royo C, Hartmann E, De Jong D, Baró C, Valera A. SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype. Haematologica 2009; 94: 1555–1562.

7. Rubio-Moscardo F, Climent J, Siebert R, et al. Mantle cell lymphoma genotypes identified with CGH to BAC microarrays define a leukemic subgroup of disease and predict patient outcome. Blood 2005; 105: 4445–4454.

8. Starostka D, Mikula P. Možnosti diagnostiky CD5-pozitivních B-lymfoproliferací. Onkologie 2014; 8(3): 102–106.

9. Hardy RR. B-1 B Cell Development. J Immunol 2006; 177: 2749–2754.

10. Sen R, Gupta S, Gill M, Kohli R, Gupta V, Verma R. Blastoid variant of mantle cell lymphoma – a rare case report. Am J Med Case Rep 2014; 2: 161–163.

11. Jares P, Campo E. Advances in the understanding of mantle cell lymphoma. Br J Haematol 2008; 142(2): 149–165.

12. Räty R, Franssila K, Jansson SE, Joensuu H, Wartiovaara-Kautto U, Elonen E. Predictive factors for blastoid transformation in the common variant of mantle cell lymphoma. Eur J Cancer 2003; 39(3): 321-329.

13. Pittaluga S, Verhoef G, Criel A, et al. Prognostic significance of bone marrow trephine and peripheral blood smears in 55 patients with mantle-cell lymphoma. Leuk Lymphoma 1996, 21: 115–125.

14. Bosch F, Lopez-Guillermo A, Campo E, et al. Mantle cell lymphoma: presenting features, response to therapy and prognostic factors. Cancer 1998, 82: 567–575.

15. Schlette E, Lai R, Onciu M, Doherty D, Bueso-Ramos C, Medeiros J. Leukemic mantle cell lymphoma: clinical and pathologic spectrum of twenty-three cases. Mod Pathol 2001; 14(11): 1133–1140.

16. Gao J, Peterson L, Nelson B, Goolsby C, Chen YH. Immunophenotypic variations in mantle cell lymphoma. Am J Clin Pathol 2009; 132(5): 699–706.

17. Liu Z, Dong HY, Gorczyca W, et al. CD5- mantle cell lymphoma. Am J Clin Pathol 2002; 118: 216–224.

18. Seok Y, Kim J, Choi JR, et al. CD5-negative blastoid variant mantle cell lymphoma with complex CCND1/IGH and MYC aberrations. Ann Lab Med 2012; 32: 95–98.

19. Hashimoto Y, Omura H, Tanaka T, Hino N, Nakamoto S. CD5-negative mantle cell lymphoma resembling extranodal marginal zone lymphoma of MALT: a case report. J Clin Exp Hematopathol 2012; 52: 185–191.

20. Ahmad E, Garcia D, Davis BH. Clinical utility of CD23 and FMC7 antigen coexistent expression in B-cell lymphoproliferative disorder subclassification. Cytometry 2002; 50: 1–7.

21. Garcia DP, Rooney MT, Ahmad E, et al. Diagnostic usefulness of CD23 and FMC7 antigen expression patterns in B-cell lymphoma classification. Am J Clin Pathol 2001; 115: 258–265.

22. Gong JZ, Lagoo AS, Peters D, et al. Value of CD23 determination by flow cytometry in differentiating mantle cell lymphoma from chronic lymphocytic leukemia/small lymphocytic lymphoma. Am J Clin Pathol 2001; 116: 893–897.

23. Zanetto U, Dong H, Huang Y, et al. Mantle cell lymphoma with aberrant expression of CD10. Histopathology 2008; 53: 20–29.

24. Dong HY, Gorczyca W, Liu Z, et al. B-cell lymphomas with coexpression of CD5 and CD10. Am J Clin Pathol 2003; 119: 218–230.

25. Morice WG, Hodnefield JM, Kurtin PJ, et al. An unusual case of leukemic mantle cell lymphoma with a blastoid component, showing loss of CD5 and aberrant expression of CD10. Am J Clin Pathol 2004; 122: 122–127.

26. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Döhner H. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) updating the National Cancer Institute-Working Group (NCI-WG) 1996 guidelines. Blood 2008; 11: 5446–5456.

27. Krober A, Seiler T, Benner A, et al. V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood 2002; 100: 1410–1416.

28. Matutes E, Owusu-Ankomah K, Morilla R, Garcia Marco J, Houlihan A, Que TH. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia 1994; 8: 1640–1645.

29. Alapat D, Coviello-Malle J, Owens R, et al. Diagnostic usefulness and prognostic impact of CD200 expression in lymphoid malignancies and plasma cell myeloma. Am J Clin Pathol 2012; 137(1): 93–100.

30. Palumbo GA, Parrinello N, Fargione G, et al. CD200 expression may help in differential diagnosis between mantle cell lymphoma and B-cell chronic lymphocytic leukemia. Leuk Res 2009; 33: 1212–1216.

31. Spacek M, Karban J, Radek M, etal. CD200 expression improves differential diagnosis between chronic lymphocytic leukemia and mantle cell lymphoma. Blood 2014; 124(21): abstrakt 5637.

32. Dorfman DM, Shahsafaei A. CD200 (OX-2 membrane glycoprotein) expression in B cell-derived neoplasms. Am J Clin Pathol 2010; 134: 726–733.

33. Matutes E, Oscier D, Montalban C, et al. Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria. Leukemia 2008; 22: 487–495.

34. Baseggio L, Traverse-Glehen A, Petinataud F, Callet-Bauchu E, Berger F, Ffrench M. CD5 expression identifies a subset of splenic marginal zone lymphomas with higher lymphocytosis: a clinico-pathological, cytogenetic and molecular study of 24 cases. Haematologica 2010; 95: 604–612.

35. Yatabe Y, Suzuki R, Tobinai K, et al. Significance of cyclin D1 overexpression for the diagnosis of mantle cell lymphoma: a clinicopathologic comparison of cyclin D1-positive MCL and cyclin D1-negative MCL-like B-cell lymphoma. Blood 2000; 95(7): 2253–2261.

36. Zhou DM, Chen G, Zheng XW, Zhu WF, Chen BZ. Clinicopathologic features of 112 cases with mantle cell lymphoma. Cancer Biol Med 2015; 12(1): 46–52.

37. Juskevicius D, Ruiz C, Dirnhofer S, Tzankov A. Clinical, morphologic, phenotypic, and genetic evidence of cyclin D1-positive diffuse large B-cell lymphomas with CYCLIN D1 gene rearrangements. Am J Surg Pathol 2014; 38(5): 719–727.

Labels
Haematology Internal medicine Clinical oncology
Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account