Mantle Cell Lymphoma
(Previous terms: centrocytic lymphoma, lymphocytic lymphoma of
intermediate differentiation, mantle zone lymphoma [1-3])
Introduction: Mantle cell lymphoma (MCL) is a rare type of lymphoma (5-10% of all malignant lymphomas [1, 2]). The normal cellular counterpart is a B cell found in small numbers in the mantle zone of lymphoid follicles (see diagram below) [1, 4]. MCL was originally classified as a low-grade lymphoma, but recent reports of outcome indicate that most cases behave as an intermediate-grade lymphoma. It has neither the long survival of low-grade tumors nor the response to aggressive chemotherapy of high-grade tumors. One exception is the infrequent "mantle zone" variant, which may have a more indolent course [1, 2].
Clinical features: These tumors present in older adults with a median age of 65 (range 39-86); males predominate 2.3:1. (Patients with the blastic type (see below) are younger (median age 40) compared to the others ). Disease is often at an advanced stage (III or IV) at presentation, and lymph node masses may be >10 cm in diameter. Extranodal disease is common (76%) and may involve bone marrow, spleen, liver, the gastrointestinal tract, peripheral blood, and Waldeyer's ring [1, 2]. Therapy varies with extent of disease from radiation alone for limited disease to multiagent chemotherapy ± local radiation for more aggressive disease. In one study, the overall median survival of 600 patients was 36 mo . In another study of 80 patients, median survival was 43 months with all dead by 9 y . Poor performance status was a bad prognostic feature, but age, stage, number of extranodal sites, and serum LDH did not predict patient outcome. Histologically, an increased mitotic rate >2/high power field, blastic transformation, and peripheral blood involvement at onset predicted a poor outcome .
Histologic changes: This tumor is difficult to diagnose histologically. Furthermore, four types have been described (see figure). Cells are small- to medium-sized lymphocytes with irregularly-shaped nuclei, small nucleoli, and scant cytoplasm. The frequency of each type varies somewhat with the series . Immunologic and molecular features distinguish this lymphoma from others. Cells express the pan-T-cell antigen CD5, surface IgM and IgD, and pan-B-cell antigens CD 19, CD 20, and CD 22.
Figure: Each of the circles below illustrates a subtype of MCL. Mantle zone: This pattern resembles a normal node with lymphoid follicles, germinal centers, and parafollicular zones. Only the dark-blue mantle zone (arrow) is composed of neoplastic cells. Nodular: Ill-defined, nodular follicles of neoplastic cells blend with non-neoplastic, parafollicular cells. Germinal centers are absent. Diffuse: Small neoplastic lymphocytes replace the node. Blastic: Enlarged neoplastic lymphocytes replace the node.
Molecular changes: A chromosomal translocation t(11;14) involves the bcl-1 locus (chromosome 11) and the immunoglobulin heavy chain locus (chromosome 14). The translocation causes overexpression of the PRAD-1 gene that encodes cyclin D1, a promoter of progression of the cell cycle . The relation of this expression to disease is not known . The translocation can be detected in only about 1/2 of cases, but the overproduction of cyclin D1 is a more constant diagnostic feature .
The photo shows effacement of the nodal architecture by diffuse MCL. The capsule is to the right.
At higher magnification, one residual normal germinal center remained in the whole section. Thus, in this case, the diffuse neoplastic infiltrate may be considered as an expanded mantle zone. Note that the cells in the germinal center, which are not neoplastic, bear no resemblance to the small lymphocytes of the tumor.
Conclusions: This lymphoma responds to chemotherapy but usually recurs within 2 years . It is classified as an intermediate-grade lymphoma. New therapeutic approaches are needed to extend survival or to cure. A protocol involving myoablative therapy and treatment with radiolabeled-anti-B-cell antibody followed by bone marrow reconstitution is being tested .
1. Argatoff L, Connors J, Klasa R, Horsman D, Gascoyne R. Mantle cell lymphoma: a clinicopathologic study of 80 cases. Blood 1997; 89:2067-2078.
2. Fisher R. Mantle-cell lymphoma: classification and therapeutic implications. Ann Oncol 1996; 7 (Suppl. 6):S35-S39.
3. Meusers P, Hense J, Brittinger G. Mantle cell lymphoma: diagnostic criteria, clinical aspects and therapeutic problems. Leukemia 1997; 11 (Suppl. 2):S60-S64.
4. Majlis A, Pugh W, Rodriguez M, Benedict W, Cabanillas F. Mantle cell lymphoma: correlation of clinical outcome and biologic features with three histologic variants. J Clin Oncol 1997; 15:1664-1671.
5. Press O, Eary J, Appelbaum F, Martin P, Badger C, Nelp W, Glenn S, et al. Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. N Engl J Med 1993; 329:1219-1224.
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