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Lymphocytosis is defined as an absolute lymphocyte count exceeding 4 × 109/L, whereas lymphocytopenia is defined as a total lymphocyte count less than 1.0 × 109/L. Lymphocytosis can be categorized as either polyclonal or monoclonal. Monoclonal lymphocytosis reflects an underlying clonal lymphoid disease in which the numbers of lymphocytes are increased because of the acquisition of somatic mutations resulting in clonal expansion of a lymphocyte progenitor. This expansion can be stable, such as monoclonal B-cell lymphocytosis or a progressive malignancy such as acute lymphocytic leukemia, whereas polyclonal lymphocytosis is most commonly the result of stimulation or a 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 a 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

BNP, brain natriuretic peptide; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; CMV, cytomegalovirus; EBV, Epstein-Barr virus; GVHD, graft-versus-host disease; IFN-γ, interferon-gamma; Ig, immunoglobulin; IL, interleukin; LCK, lymphocyte-specific kinases; LGLL, large granular lymphocytic leukemia; MBL, monoclonal B-cell lymphocytosis; miRNA, microRNA; NK, natural killer; PPBL, persistent polyclonal B-cell lymphocytosis; TCR, T-cell receptor; UNC, uncoordinated; WHO, World Health Organization.



Lymphocytosis is defined as an absolute lymphocyte count exceeding 4 × 109/L, although somewhat higher threshold values (e.g., >5.0 × 109/L) 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). Tables 7–3 and 7–4 in Chapter 7, provide 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 (Chap. 82), large granular lymphocytes associated with large granular lymphocytic leukemia (Chap. 94), smudge cells associated with chronic lymphocytic leukemia (CLL; Chap. 92), or blasts of acute lymphocytic leukemia (Chap. 91). Chapter 73 provides a description of normal lymphocyte morphology.

Characterization of cell-surface markers is valuable in distinguishing primary lymphocytosis (leukemic) from secondary lymphocytosis (reactive). Improvements in flow cytometric techniques and reagents have allowed clinical laboratories to perform flow cytometric immunophenotyping to distinguish benign from neoplastic lymphoproliferative disease.1 Analysis for immunoglobulin or ...

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