Chronic Lymphocytic Leukemia. Clinical Findings
A. Symptoms and Signs: Chronic lymphocytic leukemia is a disease of the elderly, with 90% of cases occurring after age 50 and a median age at presentation of 65. Many patients will be incidentally discovered to have lymphocytosis. Others present with fatigue or lymphadenopathy. On examination, 80% of patients will have lymphadenopathy and half will have enlargement of the liver or spleen.
A prognostically useful staging system has been developed as follows: stage 0, lymphocytosis only; stage I, lymphocytosis plus lymphadenopathy; stage II, organomegaly; stage III, anemia; stage IV, thrombocytopenia.
Chronic lymphocytic leukemia usually pursues an indolent course but occasionally will present as a rapidly progressive disease. These patients usually have larger, less mature-appearing lymphocytes and are said to have “prolymphocytic” leukemia. In 5–10% of cases, chronic lymphocytic leukemia may be complicated by autoimmune hemolytic anemia or autoimmune thrombocytopenia. In approximately 5% of cases, while the systemic disease remains stable, an isolated lymph node will be transformed into an aggressive large cell lymphoma (Richter’s syndrome).
B. Laboratory Findings: The hallmark of chronic lymphocytic leukemia is isolated lymphocytosis. The white blood count is usually greater than 20,000/mL and may be markedly elevated. Usually 75–98% of the circulating cells are lymphocytes. Lymphocytes appear small and “mature,” with condensed nuclear chromatin, and are morphologically indistinguishable from normal small lymphocytes. The hematocrit and platelet count are usually normal at presentation. The bone marrow is variably infiltrated with small lymphocytes. (See Supplemental Figures 13–28 and 13–29.) The malignant cells weakly express surface immunoglobulin, and the monoclonal nature of the cells can be demonstrated by the finding of a single light chain type on the surface. The immunophenotype of CLL is unique in that it co-expresses B lymphocyte lineage markers such as CD19 with the T lymphocyte marker CD5. Other B cell malignancies do not express CD5.
Hypogammaglobulinemia is present in half of cases and becomes more common with advanced disease. In some instances, a small amount of IgM paraprotein is present in the serum. Pathologic changes in lymph nodes are the same as in diffuse small cell lymphocytic lymphoma.