78 Lymphocytosis and Lymphocytopenia

Question 1

Lymphocytosis is defined as an absolute lymphocyte count exceeding

Answer 1

4 × 10 9 /L

Question 2

TRUE OR FALSE

The normal absolute lymphocyte count is significantly higher in childhood

Answer 2

TRUE

The normal absolute lymphocyte count is significantly higher in childhood

Question 3

Blood film association

Reactive lymphocytes:
Large granular lymphocytes:
Smudge cells:
Blasts:

Answer 3

Blood film association

Reactive lymphocytes: infectious mononucleosis
Large granular lymphocytes: large granular lymphocytic leukemia
Smudge cells: chronic lymphocytic leukemia
Blasts: acute lymphocytic leukemia

Question 4

Patients with ______________________ leukemia may have only transient lymphocytosis that is induced by stress or exercise.

Answer 4

Large granular lymphocytic leukemia

Question 5

A syndrome in patients who have expanded populations of monoclonal B cells without other associated clinical signs or symptoms

Answer 5

Monoclonal B-Cell Lymphocytosis

Question 6

Defined as the expansion of a monoclonal population of B cells with an absolute B-cell count of less than 5.0 × 10 9 /L in the absence of organomegaly, lymphadenopathy, extramedullary involvement, and cytopenias

Answer 6

Monoclonal B-Cell Lymphocytosis

Question 7

Absolute B cell count of Low-count MBL/ screening MBL

Answer 7

<0.5 × 10 9 /L

Question 8

Absolute B cell count of High-count MBL/clinical MBL

Answer 8

≥0.5 × 10 9 /L

Question 9

TRUE OR FALSE

Individuals with known high-count MBL should not be considered suitable for blood donation

Answer 9

TRUE

Individuals with known high-count MBL should not be considered suitable for blood donation, and whether this applies to low-count MBL is a matter of investigation.

Both has risk for infection and not eligible for stem-cell donation

Question 10

TRUE OR FALSE

Low-count MBL require routine followup by a hematologist because of the progression of low-count MBL to high-count MBL and CLL.

Answer 10

FALSE

Low-count MBL does not require routine followup by a hematologist because the progression of low-count MBL to high-count MBL and CLL is negligibe

Question 11

TRUE OR FALSE

High-count MBL is biologically indistinguishable from CLL. High-count MBL is characterized by having a higher risk of infection, development of nonhematologic cancer, and progression to CLL compared with low-count MBL.

Answer 11

TRUE

High-count MBL is biologically indistinguishable from CLL. High-count MBL is characterized by having a higher risk of infection, development of nonhematologic cancer, and progression to CLL compared with low-count MBL.

Question 12

The risk of progression requiring CLL-specific treatment among individuals with high-count MBL

Answer 12

1%–2% per year

Question 13

Patients with high-count MBL are at an increased risk of developing a nonhematologic cancer (breast, lung, and gastrointestinal tract) by a factor of

Answer 13

2

Question 14

Individuals with high-count MBL should be followed with a physical examination and complete blood count with differential counts by a hematologist every _______ months, and monitored for progression to CLL

Answer 14

6–12 months

Question 15

A chronic, moderate increase in absolute lymphocyte counts (>4 × 10 9 /L) without evidence for infection or other conditions that can increase the lymphocyte count

Answer 15

Persistent Polyclonal Lymphocytosis of B Lymphocytes

Question 16

Mostly affects middle-aged women who often are human leukocyte antigen DR7–positive and is associated with smoking.

Answer 16

Persistent Polyclonal Lymphocytosis of B Lymphocytes

Question 17

Characteristic of lymphocytes in Persistent Polyclonal Lymphocytosis

Answer 17

• CD27+ IgM+IgD+ B cells
• Binucleated lymphocytes
• Increased IgM serum levels

Question 18

Specific morphologic features predictive of Persistent Polyclonal Lymphocytosis of B Lymphocytes

Answer 18

Basophilic vacuolated cytoplasm and monocytoid changes

Question 19

Conditions associated with an increase in the absolute number of lymphocytes secondary to a physiologic or pathophysiologic response to infection, toxins, cytokines, or unknown factors.

Answer 19

SECONDARY (REACTIVE) LYMPHOCYTOSIS

Question 20

The most common cause reactive lymphocytosis

Answer 20

Infectious Mononucleosis

Question 21

In cases of mononucleosis secondary to infection with Epstein-Barr virus (EBV), the atypical lymphocytes commonly consist of polyclonal populations of

Answer 21

CD8+ T cells, γ/δ T cells, and CD16+CD56+ NK cells

Question 22

A disorder that occurs in children usually between the ages of 2 and 10 years characterized by an increase in blood lymphocytes, often to 20–30 × 10 9 /L and occasionally as high as 100 × 10 9 /L

Answer 22

Acute infection lymphocytosis

• Lymph node enlargement and splenomegaly do not occur
• Patient’s serum usually is negative for heterophile antibodies
• Caused by cytomegalovirus, coxsackievirus B2

Question 23

Characteristic of the lymphocytes in cases of pertussis

Answer 23

Lymphocytes have cleaved nuclei

Question 24

Pathophysiology of lymphocytosis in pertussis

Answer 24

Lymphocytosis in pertussis is polyclonal with a normal T:B lymphocyte ratio and primarily results from failure of lymphocytes to leave the blood because of pertussis toxin

Question 25

Result from expansions of NK cells, CD8+ T cells, or, more rarely, CD4+ T cells

Answer 25

Large granular lymphocytosis (LGL)

Question 26

The lymphocytosis in LGL is secondary to ______________NK cells and is termed NK lymphocytosis

Answer 26

CD3–CD16+CD56+ NK cells

Question 27

LGLL is a heterogeneous disorder characterized by an increase in the number of blood large granular lymphocytes between 2 and 20 × 10 9 /L for more than ____________ without a clearly identified cause

Answer 27

Six months

Question 28

Most notable mutation in T-LGLL and NK-LGLL

Answer 28

STAT3 and STAT5B

Question 29

STAT3 or STAT5B Less common and are associated with a more aggressive disease.

Answer 29

STAT5B

Question 30

LGLL and chronic NK lymphocytosis are considered indolent diseases with a median survival of ______years

Answer 30

9–10 years

Question 31

**Neutropenia** and association with **rheumatoid arthritis** is more associated with ______ LGLL

Answer 31

T-LGLL

Question 32

LGL has been observed in 20% of allogeneic hematopoietic cell transplant recipients for a variety of malignancies, with a median onset of _____ days from transplant

Answer 32

312 days

Question 33

Patients with NK lymphocytosis frequently have recurrent cutaneous lesions, such as:

Answer 33

Livedoid vasculopathy, urticarial vasculitis, or complex recurrent aphthous stomatitis

Question 34

Drugs associated with lymphocytosis when used for chronic myelogenous leukemia and CLL

Answer 34

Dasatinib and ibrutinib

Question 35

TRUE OR FALSE Some studies suggest that lymphocytosis after dasatinib is associated with a favorable response in chronic myelogenous leukemia.

Answer 35

TRUE Some studies suggest that lymphocytosis after dasatinib is associated with a favorable response in chronic myelogenous leukemia.

Question 36

TRUE OR FALSE The prolonged lymphocytosis in CLL taking Ibrutinib likely represents a persistent quiescent clone and is not associated with a risk of relapse

Answer 36

TRUE The prolonged lymphocytosis in CLL taking Ibrutinib likely represents a persistent quiescent clone and is not associated with a risk of relapse ## Footnote This resolves within 8 months in most patient

Question 37

Two phases of stress lymphocytosis after catecholamine administration:

Answer 37

A quick (<30 min) mobilization of lymphocytes, followed by an increase in granulocyte numbers with decreasing lymphocyte numbers

Question 38

Delayed hypersensitivity reactions to insect bites, especially__________, may be associated with a large granular lymphocytic lymphocytosis and adenopathy.

Answer 38

Mosquitos

Question 39

Neoplastic disease that may have a **polyclonal T-cell lymphocytosis** thought to be secondary to the aberrant release of hormones by the neoplastic epithelium.

Answer 39

Malignant thymoma

Question 40

Lymphocytopenia is defined as a total lymphocyte count less than

Answer 40

1.0 × 10 9 /L ## Footnote But some consider the lower limit of normal to be 1.5 × 10 9 /L

Question 41

Approximately 80% of normal adult blood lymphocytes are ______lymphocytes and nearly two-thirds of blood T lymphocytes are ____________T lymphocytes

Answer 41

T lymphocytes CD4+ (helper) T lymphocytes

Question 42

Average absolute number of T lymphocytes in normal adult blood

Answer 42

1.9 × 10 9 /L ranging from 1.0–2.3 × 10 9 /L

Question 43

Average absolute number of CD4+ T lymphocytes

Answer 43

1.1 × 10 9 /L ranging from 7.2–14 × 10 8 /L

Question 44

Average absolute number of CD8+ T lymphocytes

Answer 44

6.5 × 10 8 /L ranging from 3.8–9.7 × 10 8 /L

Question 45

Condition with associated **lymphopenia** because of **premature destruction of T cells** secondary to a defect in the lymphocyte cytoskeleton

Answer 45

Wiskott-Aldrich syndrome

Question 46

Ethnic groups that have lower CD4+ T-cell counts in the absence of other identified factors

Answer 46

Ethiopians and Chukotka natives

Question 47

The most common infectious disease associated with lymphopenia

Answer 47

AIDS caused by HIV ## Footnote Destruction and/or clearance of CD4+ T cells infected with HIV-1 or HIV-2

Question 48

TRUE OR FALSE Lymphopenia is considered a surrogate marker for sepsis-induced immunosuppression and identifies a subpopulation of patients at a higher risk of death

Answer 48

TRUE Lymphopenia is considered a surrogate marker for sepsis-induced immunosuppression and identifies a subpopulation of patients at a higher risk of death

Question 49

Presence of_________ antibodies was independently associated with disease activity and lupus nephritis

Answer 49

Antilymphocyte antibodies

Question 50

TRUE OR FALSE Lymphocytopenia remains a strong predictor of all-cause or cardiovascular mortality

Answer 50

TRUE Lymphocytopenia remains a strong predictor of all-cause or cardiovascular mortality

Question 51

Deficiency of this mineral leads to a significant decrease in the development of B cells in the bone marrow.

Answer 51

Zinc

Question 52

Defined by the WHO as a CD4+ T-lymphocyte count less than 0.3 × 10 9 /L on two separate occasions in patients without serologic or virologic evidence of HIV-1 or HIV-2 infection or any other cause of immunodeficiency.

Answer 52

Idiopathic CD4+ T lymphocytopenia (ICL) ## Footnote Unlike in HIV infection, the decrease in the CD4 cell counts of patients with ICL is generally **slow**.

Question 53

A mutation in the ______ gene led to an immunodeficiency syndrome manifesting as an absence of B cells, agammaglobulinemia, and infections highlighting the importance of zinc in B-cell development

Answer 53

ZIP7 gene