Mantle cell lymphoma is a distinct subtype of non-Hodgkin lymphoma with a pathognomonic chromosomal translocation t(11;14), leading to constitutive cyclin D1 overexpression. The clinical presentation usually is characterized by widespread disease, occurring more often in male patients older than age 60 years. Despite high initial response rates, early relapses occur frequently after conventional chemotherapy, resulting in a median survival time of only 3–5 years. However, 10% to 15% of patients present with a more indolent, chronic course. Dose-intensified treatment regimens containing cytarabine, rituximab, and autologous stem cell transplantation can achieve long-term remissions in patients fit enough to tolerate such aggressive therapy. For the majority of older adult patients, rituximab maintenance therapy can result in prolonged survival. Targeted approaches, including proteasome inhibitors, immunomodulatory drugs, and inhibitors of the B-cell receptor pathway, have proven highly efficacious in patients with relapsed disease and should be implemented in a multimodal treatment plan.
Acronyms and Abbreviations
ASCT, autologous stem cell transplantation; ATM, ataxia- telangiectasia mutant; BR, bendamustine and rituximab; BTK, Bruton tyrosine kinase; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; CLL, chronic lymphocytic leukemia; DHAP, dexamethasone, high-dose cytarabine, and cisplatinum; LDH, lactate dehydrogenase; MCL, mantle cell lymphoma; MIPI, Mantle Cell Lymphoma International Prognostic Index; mTOR, mammalian target of rapamycin; MTX, methotrexate; NF-κB, nuclear factor kappa B; PI3K, phosphoinositol 3'-kinase; PFS, progression-free survival; R- CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CVP, rituximab, cyclophosphamide, vincristine, and prednisone; R-hyperCVAD, rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone; sIg, secretory immunoglobulin; TBI, total-body irradiation.
DEFINITION AND HISTOLOGY
Mantle cell lymphoma (MCL) was originally named centrocytic lymphoma or subsumed under the term intermediate lymphocytic lymphoma. In 1992, the term mantle cell lymphoma was adopted for this entity because of morphologic and immunophenotypic similarities of the malignant T cells to lymphocytes of the mantle zone of germinal centers.1 In 1994, the term mantle cell lymphoma was incorporated into the revised European-American classification of the International Lymphoma Study Group and remains a distinctive lymphoma subtype in the World Health Organization classification of malignant lymphoid disorders2,3 (Chaps. 89 and 95).
Based on cytology, the classical form is characterized by small- to intermediate-size cells with irregular, cleaved nuclei; dense chromatin; and indistinct nucleoli. A leukemic nonmodal variant, resembling chronic lymphocytic leukemia (CLL), associated with missing SOX-11 expression, may be associated with a more indolent course.3,4 In contrast, the blastoid cell variant, including a blastic and a pleomorphic phenotype, displays a more aggressive clinical course.3
Histologically, MCL most frequently displays a diffuse infiltration of the lymph nodes; less commonly a nodular pattern; and, rarely, a mantle zone pattern, the last of which may represent an earlier phase of the disease.5 The immunophenotype of the cells resembles the lymphocytes in the mantle zone of normal germinal follicles and is characterized by coexpression of B-cell antigens (CD19+, CD20+, ...