Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a CD5⁺ mature B-cell lymphoma of small- to medium-sized lymphocytes with irregular (indented) nuclei characterized by BCL1 (cyclin D1) expression and translocation t(11;14)(q13;q32), leading to rearrangement between CCND1 gene coding for the cyclin D1 and IGH gene [1–6]. MCL has a distinct immunophenotypic profile: CD5⁺/CD20⁺/CD23^–/BCL1⁺/SOX11⁺. MCL is characterized by disseminated disease, with most patients presenting with stage III or IV disease, lymphadenopathy, hepatosplenomegaly, and bone marrow (BM) and blood involvement. The gastrointestinal tract is frequently involved (most often in the form of microscopic infiltrate, but occasionally also in the form of lymphomatous polyposis). BM involvement is observed in 50–80%, hepatosplenomegaly in 30–60%, B-symptoms in 50%, and extranodal involvement in 20% of patients [7–10]. Very rare cases of MCL have been reported to lack BCL1 (cyclin D1) expression and CCND1 rearrangement; those cases have the molecular prolife typical for MCL, are positive for SOX11 and CD5, and in 55% carry CCND2 translocations [11,12]. According to the 2016 WHO classification, there are two major variants of MCL: classic MCL, which affects the lymph nodes and extranodal sites, and leukemic non-nodal MCL (L-NN-MCL), which involves the BM, blood, and spleen [1]. Cases with a lack of B-symptoms, white blood cell count <30 × 10⁹/L, Ki-67 in non-BM tissue <30%, non-blastoid/pleomorphic histomorphology, spleen <20 cm, lymph node diameter <3 cm, absence of TP53 or NOTCH1/2 mutations, and absence of 17p deletion or MYC translocation have been termed smoldering MCL [6].