University of Virginia Health System

Leukemic Phase of Splenic Marginal Zone Lymphoma
(SMZL)

 
Leukemic phase of splenic marginal zone lymphoma (SMZL)- Peripheral blood smear, Wright-Giemsa stain, 1000x

Description:

The clonal cells are larger by 1½-2 times than normal small peripheral blood lymphocytes and those in B-CLL, and have more abundant grey to light blue cytoplasm. The nuclei are round, oval or slightly irregular and the nuclear chromatin is mature with variable clumping, and prominent nucleoli are frequently present. The cell size and nuclear to cytoplasmic ratio are similar to those seen in the large granular lymphocytic syndrome, but lack the cytoplasmic azurophilic granules.

Immunophenotype:

A diagnostic phenotype has not been identified. The clonal cells are CD19+, CD20+, and FMC7+, but are CD5-, CD10-, CD23-, and CD103-. This profile, however, distinguishes this subtype from splenomegalic B cell CLL and mantle cell leukemia-lymphoma, hairy cell leukemia (HCL), and leukemic phase of follicular lymphoma, but does not differentiate from splenic lymphoma with villous lymphocytes; the morphologic appearance of villous lymphocytes, on a Wright-Giemsa stain, however, is quite distinct, and serves to differentiate between these 2 types of low grade splenomegalic lymphomas.

Clinical and Laboratory Manifestations:

The leukemic phase of marginal zone B cell lymphoma is seen mostly in patients who present with splenomegaly, absence of lymphadenopathy, and a variable pancytopenia. The incidence of peripheral blood involvement in this splenic marginal zone lymphoma (SMZL) is up to 70%. Autoimmune disorders are common, up to 15%, similar to B cell CLL. A rather unique feature is the high incidence of monoclonal gammopathy, up to 25%, and most are IgM, a not too surprising finding since normal marginal zone B cells secrete predominantly IgM. An association with hepatitis C infection has been well documented as has an increased incidence of mixed cryoglobulinemia.

Differential Diagnosis:

A  differentiation among the various low grade splenomegalic lymphomas can usually be made based on the morphology of the clonal cells on a Wright-Giemsa stained peripheral blood smear and the immunophenotypic profile. There is controversy as to whether splenic marginal zone B cell lymphoma (MZL) and splenic lymphoma with villous lymphocytes (SLVL) are the same or two separate entities, even though the morphology of the clonal cells are distinctly different. Findings favoring a single entity are the same immunophenotype, the finding of circulating clonal villous lymphocytes in cases of splenic marginal zone lymphoma based on the pathologic findings in the spleen, and the almost identical clinical manifestations and clinical course of the two diseases. Nevertheless, it is important to recognize the distinct morphologic differences between the two entities for diagnostic purposes.

Other causes of splenomegaly and pancytopenia (e.g. intrinsic liver disease, portal or splenic vein occlusion, 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 indolent. If the major clinical manifestations are due to splenomegaly, splenectomy alone often results in resolution of the manifestations for long periods of time, up to 10 years or longer. Response to the various therapeutic modalities 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
• Catovsky D, Matutes E. Splenic lymphoma with 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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