Lymphocytosis

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List of terms related to Lymphocytosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Associate Editor-in-Chief: Shyam Patel [2]

Synonyms and keywords: Lymphocytosis; lymphocyte count raised (peripheral blood)

Overview

Lymphocytosis is an increase in the number or proportion of lymphocytes in the blood, usually detected when a complete blood count is routinely obtained. Lymphocytes are white blood cells that are derived from the common lymphoid progenitor, which arises from the hematopoietic stem cell. Lymphocytes include two broad categories: B cells and T cells. Both of these cell types arise from the bone marrow. B cells mature in the bone marrow, while T cells mature in the thymus. Lymphocytes normally represent 20 to 40% of circulating white blood cells. The absolute lymphocyte count can be directly measured by flow cytometry, or calculated by multiplying the total white blood cell (WBC) count by the percentage of lymphocytes found in the differential count. For example, if the total WBC count is 30,000 per microliter, and the %lymphocytes is 10%, the absolute lymphocyte count is 3,000 per microliter. In absolute lymphocytosis, the total lymphocyte count is elevated. In relative lymphocytosis, there is a higher proportion of lymphocytes amongst the white blood cells compared to other subsets of white blood cells, but a normal absolute number of lymphocytes. In adults, absolute lymphocytosis is present when the absolute lymphocyte count is greater than 4,000 per microliter, while relative lymphocytosis is present if the absolute lymphocyte count is normal but the differential percentage of lymphocytes is higher than 40%. Relative lymphocytosis is normal in children under age 2.

Lymphocytosis can be a feature of infection, particularly in children. In the elderly, lymphoproliferative disorders, including chronic lymphocytic leukemia and lymphomas, often present with lymphadenopathy and a lymphocytosis.

Historical Perspective

• Lymphocytosis was first described prior to the 1900s. Some of the first scientists who studied leukocytosis were Roemer and Gartner. However, there is limited published data from these scientists.

In 1906, lymphocytosis was further explored by W. Henwood Harvey, a British research from the Pharmacologic Laboratory of Cambridge.

In 1908, F.P Rous investigated mechanical factors that contribute to lymphocytosis. He noted that an increase in lymphocytosis could be produced by the flushing effect of lymph flow.. Rous noted that one could generate a increase in lymphocyte output via administration of pilocarpine.

In 1945, the first description of infectious lymphocytosis was reported. Birge and colleagues from the Raymond Blank Memorial Hospital for Children reported the case of a 4-year-od girl with earache who had a leukoocyte count of 34000 per microliter with 72% lymphocytes. These observations suggested that high lymphocyte count was associated with infection.

In 1946, Dr. Leo Meyer from King's County Hospital in Brooklyn, NY noted that the cellular basis for infectious mononucleosis was an increase in lymphocytes. He noted that mononuclear cells in infectious mononucleosis were usually young or abnormal lymphocytes.

Classification

• Lymphocytosis may be classified according to the cell type of origin:

• B cell lymphocytosis
• T cell lymphocytosis
• natural killer cell lymphocytosis

Pathophysiology

• The pathogenesis of lymphocytosis is characterized by either a reactive process (e.g. response to infection) or a primary malignant process (e.g. cancers like chronic lymphocytic leukemia. The underlying etiology include chronic antigen stimulation.
• The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
• On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
• On microscopic histopathological analysis, abundance of [lymphocytes] is characteristic findings of [lymphocytosis].

Causes

• Lymphocytosis may be caused by either a primary process (e.g. malignant proliferation) or a secondary process (e.g. response to an infection or inflammation).
• [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
• There are no established causes for [disease name].

Differential diagnosis of causes of lymphocytosis

Causes of absolute lymphocytosis include: acute viral infections, such as infectious mononucleosis (glandular fever), Epstein-Barr virus infection, and hepatitis; other acute infections such as pertussis and toxoplasmosis; chronic intracellular bacterial infections such as tuberculosis or brucellosis, or malignancy (or pre-malignant conditions).

Regarding clonal processes that cause lymphocytosis, two major causes include monoclonal B lymphocytosis and chronic lymphocytic leukemia.

Monoclonal B lymphocytosis is defined as the presence of less than 5000 clonal B cells per microliter in the peripheral blood. There are 3 categories of monoclonal B lymphocytosis: these include the CD5(+) subtype, CD5(-) subtype, and CLL-like. CLL-like monoclonal B lymphocytosis includes low-count (<500 B cells per microliter) and high-count (>500 B cells per microliter) subtypes.

Causes of relative lymphocytosis include: age less than 2 years; acute viral infections; connective tissue diseases, thyrotoxicosis, Addison's disease, and splenomegaly with splenic sequestration of granulocytes.

In alphabetical order.

• Acute infection
• Addison's Disease
• Adenovirus
• Brucellosis
• Ceftazidime
• Chickenpox
• Chronic and acute lymphocytic leukemia
• Chronic erythroleukemia
• Chronic myelogenous leukemia
• Cytomegalovirus
• Drug hypersensitivity
• Exertion
• Hairy Cell Leukemia
• Hepatitis viruses
• Herpes virus
• HIV
• Hyperthyroidism
• Immunocytoma
• Infectious mononucleosis
• Inflammatory Bowel Disease
• Measles
• Mumps
• Osteomyelofibrosis
• Pain
• Pergolide
• Pertussis
• Polycythemia
• Postoperative
• Rifaximin
• Sarcoidosis
• Stress
• Syphilis
• Toxoplasmosis
• Trauma
• Tuberculosis
• Varicella
• Viral pneumonia
• Waldenstrom's Syndrome

Epidemiology and Demographics

• The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
• In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

Age

• Patients of all age groups may develop [disease name].

• [Disease name] is more commonly observed among patients aged [age range] years old.
• [Disease name] is more commonly observed among [elderly patients/young patients/children].

Gender

• [Lymphocytosis] affects men and women equally.

• [Gender 1] are more commonly affected with [disease name] than [gender 2].
• The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

• There is no racial predilection for [disease name].

• [Disease name] usually affects individuals of the [race 1] race.
• [Race 2] individuals are less likely to develop [disease name].

Risk Factors

• Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis

• The majority of patients with [disease name] remain asymptomatic for [duration/years].
• Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
• If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
• Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
• Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].

Diagnosis

Diagnostic Criteria

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:

• [criterion 1]
• [criterion 2]
• [criterion 3]
• [criterion 4]

Symptoms

• [Disease name] is usually asymptomatic.
• Symptoms of [disease name] may include the following:

• [symptom 1]
• [symptom 2]
• [symptom 3]
• [symptom 4]
• [symptom 5]
• [symptom 6]

Physical Examination

• Patients with [disease name] usually appear [general appearance].
• Physical examination may be remarkable for:

• [finding 1]
• [finding 2]
• [finding 3]
• [finding 4]
• [finding 5]
• [finding 6]

Laboratory Findings

• There are no specific laboratory findings associated with [disease name].

• A [positive/negative] [test name] is diagnostic of [disease name].
• An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
• Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

Imaging Findings

• There are no imaging findings associated with [Lymphocytosis].

• [Imaging study 1] is the imaging modality of choice for [disease name].
• On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
• [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

• [Disease name] may also be diagnosed using [diagnostic study name].
• Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

• There is no treatment for [disease name]; the mainstay of therapy is supportive care.

• The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
• [Medical therapy 1] acts by [mechanism of action 1].
• Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

Surgery

• Surgery is the mainstay of therapy for [disease name].
• [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
• [Surgical procedure] can only be performed for patients with [disease stage] [disease name].

Prevention

• There are no primary preventive measures available for [disease name].

• Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

• Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].

References

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