At a Glance

Chronic lymphocytic leukemia is the most common leukemia in adults in the Western world. Patients are often asymptomatic and are found to have a lymphocytosis on a routine complete blood count (CBC), a CBC being performed pre-operatively, or a CBC performed on admission to the hospital. At the time of diagnosis, patients often have a normal hemoglobin and a normal platelet count and have a variably elevated white blood cell count with an absolute lymphocytosis (lymphocyte count >5.0×10 9/liter). Review of a peripheral blood smear will usually show “smudge cells” (nonintact white blood cells) and a population of small to medium-sized lymphocytes with a nucleus with a characteristic mature, clumped chromatin pattern, which has occasionally been described as looking like a soccer ball.

Chronic lymphocyte leukemia and small lymphocyte leukemia differ only in where the bulk of the disease is found.

In the case of chronic lymphocytic leukemia, the disease is initially seen as predominantly in the peripheral blood in the bone marrow, and, in the case of small lymphocytic lymphoma, the bulk of the disease is extramedullary (outside the bone marrow) in the lymph nodes or as a mass.

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What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Flow cytometric immunophenotyping on a peripheral blood sample is the definitive way to make the diagnosis of chronic lymphocytic leukemia. The lymphocytes have a characteristic immunophenotype: monoclonal B cells that co-express CD5 and CD23 and are usually negative for FMC 7. Clinical staging systems have been used to measure extent of disease with a more extensive disease associated with a worse prognosis.

New prognostic features have become increasingly important, particularly in early-stage disease. Adverse prognostic features have included expression of CD38 and/or ZAP 70 on the neoplastic B cells identified by flow cytometry. Recently, cytogenetic abnormalities identified by fluorescent in situ hybridization studies have provided prognostic information with del(11q22-23), del(17p), and del(6q) associated with a worse outcome and del(13q14.3) associated with more favorable outcome.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Patients are often asymptomatic and have no physical findings at the time of diagnosis. If a bone marrow examination is performed, patients almost always have involvement. In later stages of the disease, patients may have cytopenias, lymphadenopathy, and hepatosplenomegaly.

What Lab Results Are Absolutely Confirmatory?

Viral infections may cause a lymphocytosis. The lymphocytes on a peripheral blood smear usually have a spectrum of sizes and shapes, with a moderate to abundant amount of cytoplasm, which characteristically molds around the adjacent red cells and are described as reactive lymphocytes or atypical lymphocytes.

Mantle cell lymphoma may present with a lymphocytosis with a lymphocyte morphology that might suggest chronic lymphocytic leukemia. Flow cytometric immunophenotyping is helpful in distinguishing between chronic lymphocytic leukemia and Mantle cell lymphoma. The immunophenotype of a Mantle cell lymphoma is typically monoclonal B cells that are CD5 positive (like chronic lymphocytic leukemia), but, in contrast to chronic lymphocytic leukemia, the lymphocytes are negative for CD23 and positive for FMC7.

Peripheralization of lymphoma, such as follicular lymphoma (usually in later stages) or marginal zone lymphoma (particularly splenic lymphoma with villous lymphocytes), may show a lymphocytosis. Usually, the morphology of the lymphocytes is different from that seen in chronic lymphocytic leukemia, and flow cytometric immunophenotyping is helpful in distinguishing between chronic lymphocytic leukemia and other neoplastic lymphocytosis.

If the absolute lymphocyte count is less than 5.0×10 9/L with a chronic lymphocytic leukemia phenotype and no evidence of extramedullary involvement, then the classification of monoclonal B cell lymphocytosis (likened to monoclonal gammopathy of unknown significance) may be used.