What is the work-up for lymphocytosis (elevated lymphocyte count)?

From the Guidelines

The workup for lymphocytosis should begin with a complete blood count with differential and peripheral blood smear to confirm the elevation in lymphocytes and assess their morphology, as sustained increase of peripheral blood lymphocytes ≥ 5 · 109 cells/l not explained by other clinical disorders is a key diagnostic criterion for chronic lymphocytic leukemia (CLL) 1.

Initial Evaluation

The initial evaluation should include:

• A thorough history and physical examination focusing on potential causes such as infections, medications, autoimmune disorders, and hematologic malignancies.
• Laboratory testing including a comprehensive metabolic panel, lactate dehydrogenase (LDH), bilirubin, serum protein electrophoresis, and Coombs test, as recommended for the initial evaluation of CLL 1.
• A chest X-ray to assess for any pulmonary involvement.
• Immunophenotyping to distinguish between reactive lymphocytosis and lymphoproliferative disorders, with a composite immunophenotype of CD5+, CD19+, CD20+ (low), CD23+, sIg low, CD79b low, FMC7– being characteristic of B-cell type CLL 1.

Further Testing

If a lymphoproliferative disorder is suspected, further testing may include:

• Bone marrow biopsy, which is not needed for diagnosis but is recommended before initiating therapy to evaluate unclear cytopenia 1.
• Cytogenetic studies, including fluorescent in situ hybridization (FISH) to detect cytogenetic abnormalities with apparent prognostic value 1.
• Molecular testing for detection of specific translocations, such as (t11;14), and staining for cyclin D1 to differentiate against mantle zone lymphoma 1.

Staging and Risk Assessment

The Binet staging system is generally used in Europe to separate patients into three groups of different prognosis, with the median survival at diagnosis varying between 1 and >10 years according to the initial stage of the disease 1.

• Patients with early disease are typically managed with a watch and wait strategy, with controls of blood cell counts and clinical examinations every 3 months 1.
• Patients with active disease, defined by rapid disease progression, should be treated as patients with advanced disease 1.

From the Research

Lymphocytosis Work-up

• Lymphocytosis is a condition characterized by an increased number of lymphocytes in the blood, which can be caused by various factors, including infections, autoimmune disorders, and lymphoproliferative diseases 2, 3.
• The work-up for lymphocytosis typically involves a combination of laboratory tests, including complete blood counts, blood smears, and immunophenotyping to determine the type and clonality of the lymphocytes 4, 5.
• The evaluation of lymphocytosis should also consider the patient's clinical presentation, medical history, and physical examination findings, such as lymphadenopathy or splenomegaly 2, 5.

Diagnostic Approach

• The diagnostic approach to lymphocytosis involves distinguishing between reactive and neoplastic causes, with reactive causes being more common 3, 4.
• Reactive lymphocytosis is often characterized by an increase in T-lymphocytes, particularly of the helper subset, and is typically seen in response to infections or other inflammatory conditions 2, 3.
• Neoplastic lymphocytosis, on the other hand, is characterized by a clonal proliferation of lymphocytes and is often associated with lymphoproliferative disorders, such as chronic lymphatic leukemia (CLL) 2, 5.

Laboratory Tests

• Laboratory tests, such as flow cytometry and immunohistochemistry, can help identify the type and clonality of the lymphocytes and distinguish between reactive and neoplastic causes 3, 4.
• The use of age and absolute lymphocyte count (ALC) thresholds can also help identify patients who require further evaluation and reduce the laboratory workload 4.
• Molecular analysis, such as PCR and next-generation sequencing, can also be used to detect clonal lymphoid populations and provide prognostic information 5, 6.