Mantle Cell Lymphomas
cell lymphoma (images) is in a category by itself. Although it is a diffuse proliferation of small lymphoid cells with relatively mature, condensed chromatin, it is distinguished from small lymphocytic lymphoma in several ways:
On the other hand, although mantle cell lymphoma follows a relatively aggressive course, its cell size and nuclear characteristics separate it from the somewhat more aggressive diffuse large-cell lymphomas.
- The infiltrate consists of monotonous sheets of small cells. In contrast to SLL, there are no prolymphocytes, paraimmunoblasts or proliferation centers (and unlike follicular lymphomas, there are no large centroblasts).
- The cells have angulated nuclei instead of rounded ones.
- Though usually diffuse, the low-power pattern is vaguely nodular in 30%-50% of cases. The nodularity may represent a selective infiltration and expansion of the mantle zones of pre-existing benign germinal centers by the lymphoma cells.
- There are often scattered histiocytes with eosinophilic, granular cytoplasm. These are neither tingible-body macrophages nor epithelioid histiocytes, although the distinction from the latter may be a fine one.
- Although like SLL the cells are reactive for CD5 and CD43, they are positive for FMC-7 but negative for CD23; and their surface immunoglobulin and CD20 expression is significantly stronger as measured by flow cytometry.
- Clinically mantle cell lymphoma is a more aggressive disease. Average survival is 4 years rather than 8-9 years. Like SLL, however, it is resistant to curative chemotherapy because of the relatively low proliferation rate.
- Most definitively, mantle cell lymphoma is characterized by a t(11;14) translocation involving the cyclin D1 gene.
Mantle cell lymphoma has previously been given a variety of labels: diffuse small-cleaved cell lymphoma, intermediate differentiation lymphoma, and centrocytic lymphoma. Despite all these names, it is not common (2%-10% of all non-Hodgkin's lymphomas). It primarily afflicts elderly men, who almost always present with advanced, Stage III or IV disease and, almost half the time, with B symptoms. Extranodal involvement is relatively common, including:
Over 75% of mantle cell lymphomas show a gene translocation, t(11;14). This rearranges the cyclin D1 gene (also called CCND1 or PRAD-1), which codes for the cyclin D1 protein. The rearrangement puts the gene under the control of the immunoglobulin gene promoter. This abnormality is only rarely (and perhaps never) seen in other B-cell lymphomas, except for some cases of multiple myeloma.
- spleen, often massively involved.
- liver, usually in the portal areas.
- bone marrow (80% of cases), with a variety of infiltrative patterns.
- less frequently (10%-30% of cases) the peripheral blood.
- less frequently the GI tract (20% of cases). This may take the form of "multiple lymphomatous polyposis" (image) in elderly men. Numerous polyps are found anywhere below the gastroesophageal junction, with the ileocecal region most commonly involved. Within the polyp the infiltrate usually spares the mucosa, so lymphoepithelial lesions as seen in maltomas are not present.
It is increasingly accepted as standard practice to assay any malignant proliferation of small, mature-appearing lymphoid cells for this genetic lesion, because the prognoses of mantle cell lymphoma and small lymphocytic lymphoma are so drastically different. In some cases morphologic distinction may be difficult; and occasional cases of small lymphocytic lymphoma have an atypical immunologic profile, being negative for CD23 and expressing bright CD20 and surface immunoglobulin.
Infrequently the cells of mantle cell lymphoma have a different appearance, including finer, powdery chromatin; more prominent nucleoli; more frequent mitotic figures; and variably larger nuclei. This variant, termed "blastoid", may be morphologically confused with lymphoblastic lymphoma, and some studies show that it is more aggressive than the usual type of mantle cell lymphoma.
No satisfactory treatment is available for mantle cell lymphoma. Neither low-intensity nor more aggressive chemotherapy produces median survival beyond 4 years or less. Autologous bone marrow transplantation has produced good response rates but not any definite improvement in overall survival.
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