Splenic marginal zone lymphoma

Synonyms
This disease was classified under the following names per older classification systems:

ICD-O Code
9689/3

Definition
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.

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.

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

Clinical Presentation
With splenic involvement a sine qua non for SMZL, splenomegaly is seen in almost all patients, commonly without lymphadenopathy.

Laboratory Findings
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.

Sites of Involvement
Aside from the uniform involvement of the spleen, the bone marrow is frequently positive in patients with SMZL. Nodal and extranodal involvement are rare.

Spleen
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.

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

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

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

Immunophenotype
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.