Mantle cell lymphoma, MCL


A neoplasm of monomorphous B-cells resembling centrocytes. They are thought to be pre-germinal centre B lymphocytes that home to primary lymphoid follicles and to the mantel zones of secondary follicles. Neoplastic follicles are lacking.


Mantle zone lymphoma, lymphocytic lymphoma of intermediate grade of differentiation. This entity was previously known as centrocytic lymphoma. It is now recognised that the neoplastic cells are more closely related to mantle cells than to follicle centre centrocytes.


3-10% of non-Hodgkin lymphomas. Occurs in middle aged to elderly (median 60 years) with a male predominance of at least 2:115.

Clinical features

Presentation is with lymphadenopathy (90%), splenomegaly (55%, frequently massive), hepatomegaly (35%), bone marrow involvement (75%) or blood involvement (25%), involvement of the gastrointestinal tract (15%) in the form of multiple lymphomatous polyposis or Waldeyer's ring (10%)3. More than 25% of cases are associated with a leukaemic component; a marked lymphocytosis may resemble prolymphocytic leukaemia. Most patients present with stage III or IV disease.



The architecture may be diffuse or nodular, with or without residual germinal centres, or in a mantle zone growth pattern. Follicular dendritic cells may be present in loose or tight aggregates. The neoplastic cells are small to medium sized with irregular nuclei, fine chromatin, small inconspicuous nucleoli and pale indistinct scant cytoplasm, resembling centrocytes. Blastic cells (cells resemble centroblasts, immunoblasts or paraimmunoblasts) are rare or absent. However, at relapse, some cases show enlarged nuclei as seen in the "blastoid variant" of MCL. Hyalinised vessels are common. Scattered epithelioid histiocytes may give a "starry sky" appearance. Non-neoplastic plasma cells may be present.


Cyclin D1 negative patients have significantly better prognosis, suggesting that these patients probably have other low-grade lymphomas resembling mantle cell lymphoma3.




usually positive15













negative15 or weakly positive





Cyclin D1

70% to 100% of cases1,2, 16/1815




negative: rare aberrant expression may occur14



SIgM and SIgD


a4b7 homing receptor

positive in gastrointestinal cases




CD21 and CD35 demonstrate loose meshworks of FDCs.


Differential diagnosis


Mantle cell lymphoma has the worst 5-year survival (11%) among all lymphoma types2 and a median survival of only 3 to 4 years3. A more aggressive course is associated with:


Transformation to typical large cell lymphoma does not occur.


World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

Wotherspoon AC, Hasserjian RP. Immunophenotyping in the differential diagnosis of histologically low grade B cell lymphomas Current Diagnostic Pathology 2000;6:55-63.

1 de Boer, C. J. van Krieken, J. H. Schuuring, E. Kluin, P. M. Bcl-1/cyclin D1 in malignant lymphoma. Ann Oncol 1997;8(suppl2):109-17.

2 Chan, J. K., Miller, K. D., Munson, P., Isaacson, P. G. Immunostaining for cyclin D1 and the diagnosis of mantle cell lymphoma: is there a reliable method? Histopathology 1999;34:266-268.

3 Swerdlow, S. H., Williams, M. E. From centrocytic to mantle cell lymphoma: a clinicopathologic and molecular review of 3 decades. Human Pathol 2002;33;7-20.

4 Zoldan, M. C., Inghirami, G., Masuda, Y. et al. Large-cell variants of mantle cell lymphoma: cytologic characteristics and p53 anomalies may predict poor outcome. Br J Haematol 1996;93:475-86.

5 Bea, S., Ribas, M., Hernandez, J. M. et al. Increased number of chromosomal imbalances and high-level DNA amplifications in mantle cell lymphoma are associated with blastoid variants. Blood 1999;93:4365-74.

6 Bernard, M., Gressin, R., Lefrere, F. et al. Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype. Leukemia 2001;15:1785-91.

7 Swerdlow, S. H., Zukerberg, L. R., Yang, W. I., Harris, N. L., Williams, M. E. The morphologic spectrum of non-Hodgkin's lymphomas with BCL1/cyclin D1 gene rearrangements. Am J Surg Pathol 1996;20:627-40.

8 Yatabe, Y., Suzuki, R., Matsuno, Y. et al. Morphological spectrum of cyclin D1-positive mantle cell lymphoma: study of 168 cases. Pathol Int 2001;51:747-61.

9 Anagnostopoulos, I., , Foss, H. D., Hummel, M., Trenn, G., Stein, H. Extranodal mantle cell lymphoma mimicking marginal zone cell lymphoma. Histopathology 201;29:561-5.

10 Jones D. Dismantling the germinal center: comparing the processes of transformation, regression and fragmentation of the lymphoid follicle. Advances in Anatomic Pathology 2002;9:129-138.

11 Wong, K.F., So, C.C. and Chan, J.K. Nucleolated variant of mantle cell lymphoma with leukemic manifestations mimicking prolymphocytic leukemia. Am J Clin Pathol 2002;117:246-51.

12 Leoncini, L., Lazzi, S., Bellan, C. and Tosi, P. Cell kinetics and cell cycle regulation in lymphomas. J Clin Pathol 2002;55:648-55.

13 Ott, G., J. Kalla, et al. (1997). "Blastoid variants of mantle cell lymphoma: frequent bcl-1 rearrangements at the major translocation cluster region and tetraploid chromosome clones." Blood 89(4): 1421-9.

14 Camacho, F. I., J. F. Garcia, et al. (2004). "Aberrant Bcl6 protein expression in mantle cell lymphoma." Am J Surg Pathol 28(8): 1051-6.

15 Parrens M, Belaud-Rotureau MA, Fitoussi O, et al. Blastoid and common variants of mantle cell lymphoma exhibit distinct immunophenotypic and interphase FISH features. Histopathology 2006; 48:353-62

16 Young KH, Chan WC, Fu K, et al. Mantle Cell Lymphoma With Plasma Cell Differentiation. Am J Surg Pathol 2006; 30:954-961

17 Schlette E, Bueso-Ramos C, Giles F, et al. Mature B-cell leukemias with more than 55% prolymphocytes. A heterogeneous group that includes an unusual variant of mantle cell lymphoma. Am J Clin Pathol 2001; 115:571-81


This page last revised 17.11.2006.

©SMUHT/PW Bishop