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