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Lymphocytosis is defined as an absolute lymphocyte count exceeding 4 × 109/L (4000/μL), whereas lymphocytopenia is defined as a total lymphocyte count less than 1.0 × 109/L (1000/μL). The causes of each are many and varied. Lymphocytosis can be categorized as either polyclonal or monoclonal. Monoclonal lymphocytosis generally reflects an underlying lymphoproliferative disease in which the numbers of lymphocytes are increased because of an intrinsic defect in the expanded lymphocyte population, whereas polyclonal lymphocytosis most commonly is secondary to stimulation or reaction to factors extrinsic to lymphocytes, generally infections and/or inflammation. Lymphocytopenia, on the other hand, typically reflects depletion of T cells, the most abundant lymphocyte subtype in the blood. The most common cause of such T-cell depletion is viral infection, such as infection with the human immunodeficiency virus, although other causes exist. This chapter outlines the conditions associated with abnormalities in the numbers of circulating lymphocytes in the blood. It also serves as a useful road map to other chapters in the book that describe in detail those conditions that commonly are associated with abnormalities in the absolute numbers of circulating lymphocytes.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: CLL, chronic lymphocytic leukemia; EBV, Epstein-Barr virus; HIV, human immunodeficiency virus; Ig, immunoglobulin; NK, natural killer; PPBL, persistent polyclonal B-cell lymphocytosis.


Lymphocytosis is defined as an absolute lymphocyte count exceeding 4 × 109/L (4000/μL), although somewhat higher threshold values (e.g., >5.0 × 109/L [>5000/μL]) are sometimes used. The normal absolute lymphocyte count is significantly higher in childhood. Chapter 2 describes the methods for determining the absolute lymphocyte count and the normal range for such counts in older children and adults (see Chap. 2, Tables 2–1 and 2–2). Chapter 6, Tables 6–3 and 6–4, provides the lymphocyte counts and lymphocyte subset counts in newborns and infants.

The blood film of patients with lymphocytosis should be evaluated for a predominance of reactive lymphocytes associated with infectious mononucleosis (see Chap. 84), large granular lymphocytes associated with large granular lymphocytic leukemia (see Chap. 96), smudge cells associated with chronic lymphocytic leukemia (CLL; see Chap. 94), or blasts of acute lymphocytic leukemia (see Chap. 93). Chapter 74 provides a description of normal lymphocyte morphology.

Characterization of cell surface markers is valuable in distinguishing primary lymphocytosis (leukemic) from secondary lymphocytosis (reactive). New improvements in flow cytometric techniques and reagents have allowed clinical laboratories to perform flow cytometric immunophenotyping to distinguish benign from neoplastic lymphoproliferative disease (see Chap. 15). Analysis for immunoglobulin or T-cell receptor gene rearrangement also may provide evidence for monoclonal B-cell or T-cell proliferation, respectively.1

Primary Lymphocytosis

Primary lymphocytosis defines conditions associated with an increase in the absolute number of lymphocytes secondary to an intrinsic defect in the expanded lymphocyte ...

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