Mantle cell lymphoma is neoplasm derived from B cells that normally occupy the mantle zone surrounding the lymphoid follicle. Mantle cell lymphomas account for about 8% of non-Hodgkin lymphomas. They contain a characteristic cytogenetic abnormality, t(11;14)(q13;q32), that results in the overexpression of cyclin D1 (1).
Patients with mantle cell lymphoma are typically older white men. The disease usually (90%) presents in advanced stage (III or IV) and very often includes extranodal involvement of the bone marrow (80%), gastrointestinal tract (80% histologically involved, 25% symptomatic), and liver, in addition to lymphadenopathy and enlarged spleen and nodal tissue in Waldeyer's ring. The peripheral blood may show lymphocytosis but clonal abnormal cells are detectable by flow cytometry even when lymphocytosis is absent. B symptoms are present in 20%. Cells overexpressing cyclin D1 are detected in asymptomatic normal people rarely (5%–8%), but it is not clear that their presence presages the development of lymphoma. Involvement of the gastrointestinal tract may produce multiple lymphomatous polyposis.
The natural history of the disease is variable. About 15% of patients may have an indolent clinical course. In the extreme, a patient may not manifest progressive disease over many years of follow-up without treatment. However, the majority of patients show disease progression within the first 1 or 2 months of diagnosis. About 10% of patients show extremely rapid disease progression and follow a downhill course in a few months. The usual patient responds to chemotherapy but complete remissions are seldom durable and the median survival is 3–5 years (2).
PATHOLOGY AND GENETIC FEATURES
Mantle cell lymphomas are not graded according the WHO Classification of Lymphoid Tumors but classical variants and highly aggressive variants (blastoid and pleomorphic) are recognized. The classical form involves vaguely nodular sheets of small to intermediate size lymphoid cells often with a notched nuclear contour. The overexpression of cyclin D1 is a hallmark and is usually associated with the characteristic t(11;14)(q13;q32) translocation juxtaposing the cyclin D1 gene with the immunoglobulin heavy chain gene. Rare mantle cell lymphomas do not overexpress cyclin D1; these tend to overexpress cyclin D2 or D3. An unusual translocation of cyclin D2 to the immunoglobulin kappa light-chain gene [t(2:12)(p12;p13)] has been observed in some cases. The pattern of gene expression in these unusual variants mimics the pattern seen in cyclin D1-overexpressing tumors (3).
The malignant cell of mantle cell lymphoma expresses surface immunoglobulin (IgM and IgD) intensely, CD20, and CD5, but not CD10 or BCL6. Cyclin D1 and BCL-2 are expressed in the cytoplasm and are thought to be key to tumorigenesis. Cyclin D1 expression interferes with the G1 checkpoint (controlled by RB, the retinoblastoma protein, p27kip) at which the cell takes inventory and assesses its ability to enter DNA synthesis. BCL-2 prevents the programmed cell death that would normally occur in cells ...