Laboratory Tests for Lymphadenopathy Evaluation
The recommended laboratory workup for a patient presenting with lymphadenopathy should include a complete blood count with differential, peripheral blood smear, comprehensive metabolic panel, lactate dehydrogenase (LDH), and targeted infectious disease testing based on clinical presentation.
Initial Laboratory Evaluation
- Complete blood count (CBC) with differential to evaluate for cytopenias, abnormal cell populations, lymphocytosis, or eosinophilia 1
- Peripheral blood smear review to identify abnormal cells suggestive of hematologic malignancy 1, 2
- Comprehensive metabolic panel including liver and renal function tests 1
- Lactate dehydrogenase (LDH) as a marker for hemolysis or malignancy 1, 3
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to assess for inflammatory conditions 4
Infectious Disease Workup
- Bacterial cultures if infection is suspected, particularly for cervical lymphadenopathy 1
- Viral studies including EBV, CMV, HIV, and hepatitis testing when clinically indicated 1, 2
- Tuberculosis testing (PPD or interferon-gamma release assay) when granulomatous disease is suspected 1, 4
- Specific serologies based on travel history or exposures (e.g., Brucella, fungal infections) 1
Additional Testing Based on Clinical Presentation
- Serum protein electrophoresis and immunofixation if paraproteinemia is suspected 3, 2
- Direct antiglobulin test (DAT) and haptoglobin if hemolysis is suspected 1
- Thyroid function tests if thyroid dysfunction is suspected 3
- Flow cytometry of peripheral blood for immunophenotyping if lymphoproliferative disorder is suspected 1, 2
- β2-microglobulin as a prognostic marker for certain hematologic malignancies 3
Imaging Studies
- CT scan of the chest, abdomen, and pelvis with contrast to document organomegaly and/or extent of lymphadenopathy 1
- Ultrasound for initial evaluation of superficial lymphadenopathy 2, 5
- PET/CT if transformation to aggressive lymphoma is suspected 1
Advanced Testing When Indicated
- Bone marrow aspiration and biopsy with immunohistochemistry if abnormal cells are found in peripheral blood or if myeloproliferative/lymphoproliferative disorder is suspected 1, 2
- Lymph node biopsy (fine-needle aspiration, core needle, or excisional) for persistent unexplained lymphadenopathy or when malignancy is suspected 4, 6
- Molecular testing for MYD88 mutation in cases of suspected Waldenström macroglobulinemia 1
Special Considerations
- For patients with supraclavicular, epitrochlear, or iliac lymphadenopathy, which are always abnormal, a more aggressive workup including early biopsy should be considered 6
- Avoid administering corticosteroids before obtaining a definitive diagnosis, as they can mask histologic findings of lymphoma 4, 6
- For lymphadenopathy persisting beyond 4 weeks or accompanied by systemic symptoms (fever, night sweats, weight loss), more extensive laboratory testing and imaging are warranted 4
Common Pitfalls to Avoid
- Delaying bone marrow evaluation in patients with concerning peripheral blood findings 2
- Overlooking the need for HIV testing in patients with unexplained lymphadenopathy 1
- Failing to consider medication-induced lymphadenopathy in the differential diagnosis 6
- Administering empiric antibiotics without appropriate cultures in cases where malignancy is a concern 4