Splenic marginal zone lymphoma (SMZL) is a lymphoma that infiltrates the marginal and mantle zones of splenic follicles [1–3]. The disease probably arises in a splenic marginal zone B cell that may or may not have encountered an antigen . Analysis of immunoglobulin (Ig) genes shows that around a third of cases have no or low level of IGHV mutations whilst two-thirds show mutations of IGHV supporting a post-germinal centre memory B-cell origin in the latter cases. Ongoing Ig gene mutations occur .
Another designation used in the past was splenic lymphoma with villous lymphocytes, which represents a morphological subset of SMZL characterized by circulating lymphoma cells with fine cytoplasmic projections.
Patients present with splenomegaly, minimal peripheral lymphadenopathy, lymphocytosis and cytopenias that are often related to hypersplenism, autoantibodies and/or bone marrow infiltration. Some patients present with an isolated lymphocytosis and develop splenomegaly during the disease course. In some patients, the disease is associated with hepatitis C infection, this association being observed particularly around the Mediterranean area and in Japan . Transformation to diffuse large B-cell lymphoma occurs in about 10% of cases.
Haematological and pathological features
The peripheral blood may be normal or there may be a moderate lymphocytosis with the lymphoma cells either being small lymphocytes with no distinguishing features or ‘villous’ lymphocytes; the latter have fine cytoplasmic projections, sometimes at one or both poles of the cell (Figures 10.1 and 10.2). In some cases, the cells have pale, relatively abundant cytoplasm thus resembling monocytoid cells. Chromatin is condensed and sometimes there are small nucleoli. There may also be circulating plasmacytoid lymphocytes. Pancytopenia may be present as a result of splenomegaly and hypersplenism. When high grade transformation occurs, this may be evident in the peripheral blood (Figure 10.3). A paraprotein is present in about one-third of patients but the concentration is low. It may be IgM or IgG.
Peripheral blood film of a patient with splenic marginal zone lymphoma (SMZL) (splenic lymphoma with villous lymphocytes) showing rouleaux and two villous lymphocytes; one of the lymphocytes has a detectable Golgi zone. Romanowsky stain, ×100 objective.
Peripheral blood film of a patient with SMZL (splenic lymphoma with villous lymphocytes) showing two nucleolated lymphocytes, one of which has villi at both poles of the cell. Romanowsky stain, ×100 objective.
Peripheral blood film of a patient with high grade transformation showing four large highly atypical cells, one with vacuolation and nuclear lobulation and one with a large vesicular nucleolus, in addition to one small neoplastic cell. Romanowsky stain, ×100 objective.