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A 68-year-old man who has been in good health presents with the recent onset of marked fatigue and shortness of breath. He gives no history of an increased frequency of infections, nor any bleeding tendency, and has no family history of hematologic disorders. Examination is remarkable for pallor and the presence of multiple firm, freely movable, nontender nodes in the neck, axilla, and groin. The spleen and liver are not palpable.

CBC: Hematocrit/hemoglobin - 18%/6 g/dL

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MCV - 88 fL MCH - 33 pg MCHC - 36 g/dL
WBC count - 20,500/μL


Neutrophils - 18%

Lymphocytes - 80%

Monocytes - 1%

Eosinophils - 1%

Platelet count - 30,000/μL

Reticulocyte count/index - 14%/3

Coombs test - positive


  • What abnormalities are apparent from the CBC?

  • What further laboratory tests should be obtained?

The most common lymphoproliferative disorder in Western countries is B-cell chronic lymphocytic leukemia (CLL). At the same time, there are a number of other lymphoproliferative disorders that present with a leukemic component and need to be differentiated from CLL. Understanding and diagnosing the various lymphoproliferative disorders requires familiarity with the normal lymphocyte subsets, which are described in Chapters 20 and 21.


B-cell CLL typically has a long course, and therefore is considered the least "malignant" of the lymphoproliferative disorders. B-cell CLL is almost entirely a disease of older adults (median age 65-68 years, with 90% over 40 years of age). CLL demonstrates major genetic and environmental influences in different populations. In the United States, the incidence among white populations is 5 and 2.5/100,000 for males and females, respectively. By contrast, B-cell CLL is a very infrequent disease in Asians, including longstanding US immigrants. Recent studies have explored the interaction between genetic factors and hitherto undefined environmental factors in the initiation of the CLL B-cell clonal expansion. In European populations, the nature of genes from the variable heavy chain (IgVH) selected during the process of recombination of the variable (V), diversity (D), and joining (J) regions of the immunoglobulin genes in CLL clones have clearly shown differences from polyclonal cells in specific IgVH frequencies.

The major clinical manifestation of CLL is an increase in the number of circulating lymphocytes. The patient with CLL may also have varying degrees of lymphadenopathy, ranging from little at all to massive involvement. With the increasing availability of lymphocyte marker studies, CLL is being diagnosed earlier and in younger patients. In fact, small collections of clonal B cells with the characteristic surface markers of B-cell CLL (CD19, CD20, and CD5 positive) can be found in otherwise normal individuals with normal blood counts (<5000 lymphocytes/μL) in 3% to 4% of individuals over age 40 and in 5.1% older than 60. The frequency of small populations of circulating monoclonal CLL B ...

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