From the Guidelines
The workup for lymphocytosis should begin with a thorough history and physical examination, followed by a complete blood count with differential to confirm the elevated lymphocyte count, and initial laboratory tests should include peripheral blood smear examination, comprehensive metabolic panel, and lactate dehydrogenase levels, as recommended by the most recent guidelines 1. The initial step in evaluating lymphocytosis is to determine if the cause is reactive or neoplastic.
- A complete blood count with differential is essential to confirm the elevated lymphocyte count (>4,000 cells/μL in adults) and to assess for any cytopenias.
- Peripheral blood smear examination can help identify characteristic morphologic features of certain lymphoproliferative disorders, such as smudge cells in chronic lymphocytic leukemia (CLL) 1.
- Comprehensive metabolic panel and lactate dehydrogenase levels can help assess for any organ dysfunction or lymphoma-related metabolic abnormalities. If reactive causes like viral infections aren't evident, further testing should include:
- Flow cytometry to distinguish between reactive and neoplastic lymphocytosis, and to identify specific lymphocyte subsets and clonality 1.
- Specific tests for common infectious causes, such as EBV serology, CMV PCR, HIV testing, and hepatitis panel. For suspected chronic lymphocytic leukemia or other lymphoproliferative disorders, additional studies may include:
- Immunophenotyping to confirm the diagnosis and to assess for specific surface markers 1.
- FISH analysis for chromosomal abnormalities, such as del(13q14) or trisomy 12, which can help prognosticate and guide treatment decisions.
- Bone marrow biopsy to assess for bone marrow involvement and to guide treatment decisions.
- CT scans to evaluate lymphadenopathy and organomegaly, particularly in patients with suspected lymphoma or CLL 1. The workup should be tailored to the patient's age, as lymphocytosis in children is commonly reactive to infections, while in older adults it more frequently indicates a hematologic malignancy.
- In children, a thorough infectious disease workup should be performed, including tests for common viral and bacterial infections.
- In older adults, a more comprehensive workup, including flow cytometry, immunophenotyping, and imaging studies, should be considered to rule out hematologic malignancies. This stepwise approach helps differentiate between benign reactive lymphocytosis and more serious conditions requiring specific treatment, and is supported by the most recent guidelines 1.
From the Research
Workup for Lymphocytosis
The workup for lymphocytosis involves a thorough clinical review, including:
- A thorough history
- Examination
- Appropriate preliminary investigations, such as:
- Blood tests
- Blood film examination 2
- The majority of patients with chronic lymphocytic leukemia (CLL) present incidentally due to a lymphocytosis found on routine blood tests 2
Diagnostic Evaluation
Effective evaluation of leukocytosis, which includes lymphocytosis, requires:
- An attentive history
- Careful physical examination
- Meticulous review of the complete blood count and peripheral blood smear
- Judicious application of laboratory and radiologic testing
- Thoughtful analysis 3
- Definitive diagnosis may require:
- Bone marrow aspiration and biopsy
- Imaging studies
- Specialized molecular tests 3
Distinguishing Malignant from Benign Leukocytosis
Distinguishing malignant from benign leukocytosis is a critical step in the care of a patient, which initiates a vastly different decision tree, and involves:
- Confirmation of the complete blood cell count and the WBC differential
- Examination of the PB smear
- Separation of the leukocytosis into a myeloid versus a lymphoid process
- Distinguishing a reactive lymphoid proliferation from a lymphoproliferative disorder requires examination of lymphocyte morphology 4
Further Testing
Further testing, such as:
- Flow cytometry
- Molecular studies
- Bone marrow examination, may be necessary to confirm and characterize lymphoproliferative disorders 4