Splenic marginal-zone lymphoma (SMZL, splenic lymphoma with villous lymphocytes)

Definition

There is prominent splenic involvement with minimal involvement of the liver, blood and bone marrow. Small lymphocytes replace the splenic white pulp germinal centres, efface the follicle mantle and merge with a peripheral (marginal) zone of larger cells. Splenic hilar nodes and bone marrow are often involved. Villous lymphocytes may be found in the peripheral blood.

Synonyms

Epidemiology

Rare, less than 1% of all lymphoid neoplasms, but accounts for many CD5-negative chronic lymphoid leukaemias.

Macroscopic appearances

Splenic weight may be mildly or massively increased. The cut surface shows a multimicronodular pattern, with nodules less than 0.5 cm in diameter. Splenic hilar lymph nodes are commonly enlarged. The liver may be involved but usually not peripheral lymph nodes.

Histopathology

The distribution of the neoplastic cells varies. Most cases show the classical appearance in which the white pulp shows neoplastic nodules with a centre compsoed of small lymphocytes surrounded by a an outer zone of larger pale cells. This is accompanied by variable red pulp inifiltration. In a minority of cases, the red pulp infiltrate predominates. In some cases, a diffuse infiltrate effaces the splenic architecture.

The infiltrating cells are medium sized and resemble monocytoid B cells; they have abundant pale cytoplasm, clear cell borders and nuclei with are oval or slightly irregular. Larger immunoblasts / centroblasts are seen but usually constitute a small proportion of the population. Follicles may be reactive in appearance or show a Castleman-like onion-bulb pattern. In some cases, there is a lymphoplasmacytic component is present involving the marginal zones, germinal centres as well as infiltrating the mantle zones. The red pulp is always involved with both small nodules of the larger cells and sheets of small lymphocytes. epithelioid histiocytes may be present. Plasmacytic differentiation may occur, rarely with clusters of plasma cell in the centres of the white pulp follicles. There may be a focal pseudo-angiomatous pattern, as is seen in hairy cell leukaemia.

The lymph nodes of the splenic hilum are infiltrated by monocytoid cells, varying from a perifollicular arrangement (although the formation of a marginal zone is less distinct) to homogenisation. If there is a plasmacytoid component in the spleen, this is also seen in the lymph nodes. Sinuses are dilated.

Liver and bone marrow involvement are common1. The marrow infiltrate is nodular and interstitial. Villous lymphocyte leukaemia appears to represent a leukaemic phase of splenic marginal zone lymphoma.

One case of SMZL associated with micronodular T-cell rich B-cell lymphoma in the red pulp has been reported6.

Immunohistochemistry

The profile is that of mature B-cells and is not specific to SMZL.

†: fresh frozen tissue only

Monotypic immunoglobulins are demonstrable in those cases with plasmacytoid differentiation1. CD3, CD5 and CD43 stain only the T cell component, which is present in the red pulp and in periarteriolar sheets, but may sometimes infiltrate the marginal zones in large numbers1.

Cytogenetics

There is no unique genetic lesion7. The most common abnormalities in splenic lymphoma with villous lymphocytes involve 7q, usually at q21-22. This is immediately upstream of the CDK6 gene, which controls entry to the S phase of the cell cycle, suggesting that deregulation of CDK6 contributes to the pathogenesis of SMZL5. Immunoglobulin and bcl-6 mutations occur.

Differential diagnosis

• Other low grade non-Hodgkin's lymphomas: immunophenotypes

• A multimicronodular pattern may be observed in a range of small B-cell lymphomas, including follicular lymphoma and mantle cell lymphoma4, with the exception of hairy cell leukaemia.

• lymphoplasmacytoid differentiation may cause a resemblance to lymphoplasmacytic lymphoma.

Prognosis

The clinical course is indolent. 7q deletion with unmutated immunoglobulins may be associated with a worse prognosis8. About 10% of cases undergo transformation to large B-cell lymphoma3.

References

World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

1 J-P D van Huyen et al. Splenic marginal zone lymphoma with or without plasmacytic differentiation. Am J Surg Pathol 2000;24:1581-1592.

2 Wotherspoon AC, Hasserjian RP. Immunophenotyping in the differential diagnosis of histologically low grade B cell lymphomas. Current Diagnostic Pathology 2000;6:55-63.

3 Camacho, F. I., Mollejo, M., Mateo, M. S. Progression to large B-cell lymphoma in splenic marginal zone lymphoma: a description of a series of 12 cases. Am J Surg Pathol 2001;25:1268-1276.

4 Piris, M. A., Mollejo, M., Campo, E., Menarguez, J., Flores, T., Isaacson, P. G. A marginal zone pattern may be found in different varieties of non- Hodgkin's lymphoma: the morphology and immunohistology of splenic involvement by B-cell lymphomas simulating splenic marginal zone lymphoma. Histopathology 1998;33:230-9.

5 Leoncini, L., Lazzi, S., Bellan, C. and Tosi, P. Cell kinetics and cell cycle regulation in lymphomas. J Clin Pathol 2002;55:648-55.

6 Wang SA, Olson N, Zukerberg L, et al. Splenic Marginal Zone Lymphoma With Micronodular T-Cell Rich B-Cell Lymphoma. Am J Surg Pathol 2006; 30:128-132

7 Papadaki T, Stamatopoulos K, Belessi C, et al. Splenic marginal-zone lymphoma: one or more entities? A histologic, immunohistochemical, and molecular study of 42 cases. Am J Surg Pathol 2007; 31:438-46

8 Algara P, Mateo MS, Sanchez-Beato M, et al. Analysis of the IgV(H) somatic mutations in splenic marginal zone lymphoma defines a group of unmutated cases with frequent 7q deletion and adverse clinical course. Blood 2002; 99:1299-304 FULL TEXT

9 Papadaki T, Stamatopoulos K, Belessi C, et al. Splenic marginal-zone lymphoma: one or more entities? A histologic, immunohistochemical, and molecular study of 42 cases. Am J Surg Pathol 2007; 31:438-46

This page last revised 20.6.2007.

©SMUHT/PW Bishop