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Essentials of Diagnosis
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Most patients are asymptomatic at presentation
B-cell lymphocytosis with CD19 expression > 5000/mcL (5.0 × 109/L)
Mature morphologic appearance of lymphocytes
Coexpression of CD19, CD5
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General Considerations
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A clonal malignancy of B lymphocytes
The course is usually indolent, with slowly progressive accumulation of long-lived small lymphocytes that are immunoincompetent
Results in immunosuppression, bone marrow failure, and organ infiltration with lymphocytes
Immunodeficiency also related to inadequate antibody production by abnormal B cells
In severe disease, B lymphocytes may cause damage by direct tissue infiltration
Prognostically a useful staging system (Rai system)
Stage 0, lymphocytosis only
Stage I, lymphocytosis plus lymphadenopathy
Stage II, organomegaly (spleen, liver)
Stage III, anemia
Stage IV, thrombocytopenia
Information about CLL is evolving rapidly, with new biological findings and new treatment options; outcomes are improving significantly
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Incidentally discovered lymphocytosis in many patients
Fatigue
Diffuse lymphadenopathy in 80%
Hepatomegaly or splenomegaly in 50%
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Differential Diagnosis
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Atypical lymphocytosis due to bacterial or viral infection or pertussis
Lymphoma in its leukemic stage, especially mantle cell lymphoma
Hairy cell leukemia
Waldenström macroglobulinemia
Monoclonal B-cell lymphocytosis (MBL) characterized by < 5000/mcL (5.0 × 109/L) B-cells is considered a precursor to B-CLL
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White blood cell count is usually > 20,000/mcL (20 × 109/L) and may be markedly abnormal (elevated to several hundred thousand)
Differential: usually 75–98% of circulating cells are lymphocytes
Hematocrit and platelet count usually normal at presentation
On peripheral smear, lymphocytes are usually morphologically indistinguishable from normal lymphocytes
Larger and more immature cells are found in prolymphocytic leukemia (PLL)
CLL is diagnosed by coexpression of B-lymphocyte lineage marker CD19 with T-lymphocyte marker CD5
CLL is distinguished from mantle cell lymphoma by
High expression of CD38 or ZAP-70 is correlated with more aggressive course
Fluorescence in-situ hybridization (FISH) assesses genomic changes
Hypogammaglobulinemia is found in half of CLL patients, becomes more common with advanced disease
Serum protein electrophoresis: IgM paraprotein may be present
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Diagnostic Procedures
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