Splenic marginal zone lymphoma (SMZL) is a lymphoma comprised of B-cells that replace the normal architecture of the white pulp of the spleen. The neoplastic cells are both small lymphocytes and larger, transformed blasts, and they invade the mantle zone of splenic follicles and erode the marginal zone, ultimately invading the red pulp of the spleen. Frequently, the bone marrow and splenic hilar lymph nodes are involved along with the peripheral blood. The neoplastic cells circulating in the peripheral blood are termed villious lymphocytes due to their characteristic appearance.

Synonyms

Under older classification systems, the following names were used:

Classification system	Name
Rappaport	well-differentiated lymphocytic lymphoma
Lukes-Collins	small lymphocytic lymphoma
Working Formulation	small lymphocytic lymphoma
FAB	splenic lymphoma with circulating villous lymphocytes

Cause

The cell of origin is postulated to be a post-germinal center B-cell with an unknown degree of differentiation.

Diagnosis

With splenic involvement a requirement for a diagnosis of SMZL, splenomegaly is seen in almost all patients, commonly without lymphadenopathy. Aside from the uniform involvement of the spleen, the bone marrow is frequently positive in patients with SMZL. Nodal and extranodal involvement are rare.

Circulating lymphoma cells are sometimes present in peripheral blood, and they occasionally show short villi at the poles of cells and plasmacytoid differentiation.

Autoimmune thrombocytopenia and anemia sometimes seen in patients with SMZL. Circulating villous lymphocytes are sometimes observed in peripheral blood samples. A monoclonal paraprotein is detected in a third of patients without hypergammaglobulinemia or hyperviscosity.

Reactive germinal centers in splenic white pulp are replaced by small neoplastic lymphocytes that efface the mantle zone and ultimately blend in with the marginal zone with occasional larger neoplastic cells that resemble blasts. The red pulp is always involved, with both nodules of larger neoplastic cells and sheets of the small neoplastic lymphocytes. Other features that may been seen include sinus invasion, epithelial histocytes, and plasmacytic differentiation of neoplastic cells.

Involved hilar lymph nodes adjacent to the spleen show an effaced architecture without preservation of the marginal zone seen in the spleen.

SMZL in bone marrow displays a nodular pattern with morphology similar to what is observed in the splenic hilar lymph nodes.

Molecular Findings

Immunophenotype

Antigen	Status
CD20	Positive
CD79a	Positive
CD5	Negative
CD10	Negative
CD23	Negative
CD43	Negative
cyclin D1	Negative

The relevant markers that define the immunophenotype for SMZL are shown in the table to the right. The lack of CD5 expression is helpful in the discrimination between SMZL and chronic lymphocytic leukemia/small lymphocytic lymphoma, and the lack of CD10 expression argues against follicular lymphoma. Mantle cell lymphoma is excluded due to the lack of CD5 and cyclin-D1 expression.

Genetics

Clonal rearrangements of the immunoglobulin genes (heavy and light chains) are frequently seen. The deletion 7q21-32 is seen in 40% of SMZL patients, and translocations of the CDK6 gene located at 7q21 have also been reported.

Epidemiology

Less than 1% of all lymphomas are splenic marginal zone lymphomas and it is postulated that SMZL may represent a large fraction of unclasssifiable CD5- chronic lymphocytic leukemias. The typical patient is over the age of 50, and gender preference has been described.

References