University of Virginia Health System

Leukemic Phase of Splenic Lymphoma with Villous Lymphocytes
(SLVL)

 
(a) Splenic lymphoma with villous lymphocyte- Peripheral blood smear, Wright-Giemsa stain, 1000x

Description:

The morphologic appearance of the cells on a Wright-Giemsa stain of a peripheral blood smear is essentially diagnostic. The clonal cells are small, approximately the size of small cell B cell CLL cells or normall small peripheral blood lymphocytes, the cytoplasm is scant and grey to grey-blue in color, and the hairy projections of the cytoplasmic membrane are polar in contrast to hairy cell leukemia (HCL) cells in which the projections are circumferential. The nuclear chromatin is mature with variable clumping, and nucleoli are variably present. The number of clonal cells found in the peripheral blood is minimal as is the involvement of the bone marrow.

Immunophenotype:

The immunophenotype of the clonal B cells is characteristic, but not diagnostic: CD19+, FMC7+, CD11c+, CD5-, CD10-, and CD103-. This pattern distinguishes this disorder from HCL, B cell CLL and follicular lymphoma with peripheral blood involvement. The morphologic appearance of the cells with this immunophenotypic profile differentiates this entity from splenic marginal zone lymphoma and B or T cell prolymphocytic leukemia.

Cytogenetics:

No signature cytogenetic abnormality has been identified.

Clinical and Laboratory Manifestations:

The typical patient presents with splenomegaly, absence of peripheral lymphadenopathy, a variable pancytopenia, and minimal lymphocytosis. The course is indolent, and many patients will not require therapeutic intervention for many years.

Similar to B-CLL, a high incidence of autoimmune disorders is seen (up to 15%.) A rather unique feature is the high incidence, up to 25%, of monoclonal gammopathy, and most are IgM- not too surprising since normal marginal zone cells secrete predominantly IgM in response to antigen stimulation. An association with hepatitis C is well established along with an increased incidence of mixed cryoglobulinemia.

Differential Diagnosis:

Included are other indolent clonal lymphoproliferative disorders manifested by splenomegaly as a major clinical manifestation. These include: HCL, HCL-V, splenic marginal zone lymphoma, prolymphocytic leukemias, B and T cell subtypes, and a subset of B cell CLL and mantle cell lymphoma-leukemia. The clinical and laboratory findings, the morphologic appearance of the clonal cells by light microscopy on a Wright-Giemsa stained peripheral blood smear, and the immunophenotypic profile usually serves to differentiate among them. Whether splenic lymphomas with villous lymphocytes should be considered as a subset or the same entity as MZL is controversial. Even though the morphologic appearance of SLVL cells on a Wright-Giemsa stained peripheral blood smear is distinctly different, the immunophenotype is the same and clonal SLVL lymphocytes are sometimes seen in the peripheral blood in cases of splenic marginal zone lymphoma diagnosed by splenic pathology.

Splenomegaly and pancytopenia due to other disorders (e.g. intrinsic liver disease, occlusion of the portal or splenic vein, myelofibrosis with myeloid metaplasia, storage diseases) require other studies (e.g. MRI of liver and spleen with vascular phases, liver biopsy, bone marrow biopsy and aspiration) to make a correct diagnosis.

Prognosis:

Very good. Course is chronic with a median survival of 10 years or longer. Manifestations due to the splenomegaly usually resolve with splenectomy, and often for long periods, 10 years or longer. Response to regimens that are effective in B cell CLL is variable.

General References:

• Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. Pathology and genetics of tumours of hematopoietic and lymphoid tissues. Vol. 3 of World Health Organization classification of tumors, Lyon, France: IARC Press, 2001  
• Keren DF, McCoyd JP, Carey JL (eds). Flow cytometry in clinical diagnosis, 3rd ed. Chicago, ASCP Press, 2001
• Troussard N, Valensi F, Duchayne E, et al. Splenic lymphoma with villous lymphocytes: clinical presentation, biology and prognostic factors in a series of 100 patients. Br J Haematol 93: 731, 1996.
• Catovsky D, Matutes E. Splenic lymphoma with circulating villous lymphocytes/splenic marginal zone lymphoma. Semin Hematol 36:148, 1999.
• Shaye OS, Levine AM. Marginal zone lymphoma. J Natl Comprehensive Cancer Network 4(3):311, 2006

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