What laboratory tests should be ordered to evaluate abnormal lymph nodes?

Laboratory Evaluation of Abnormal Lymph Nodes

Order a complete blood count with differential, comprehensive metabolic panel including liver and renal function, lactate dehydrogenase, and HIV/hepatitis B/hepatitis C serology as your initial laboratory workup for any patient presenting with abnormal lymphadenopathy. 1, 2

Initial Essential Laboratory Tests

Complete Blood Count (CBC) with Differential

• Evaluate for cytopenias, lymphocytosis, eosinophilia, or abnormal cell populations that suggest hematologic malignancy 1, 2
• Request a peripheral blood smear review to identify atypical lymphocytes, blasts, or other abnormal cells 1
• If abnormal cells are detected, proceed immediately to flow cytometry of peripheral blood for immunophenotyping 1

Comprehensive Metabolic Panel

• Obtain liver function tests (AST, ALT, alkaline phosphatase, bilirubin) and renal function (creatinine, BUN) to assess organ involvement and establish baseline before potential chemotherapy 3, 1
• Measure serum calcium, as hypercalcemia occurs in certain T-cell lymphomas, particularly adult T-cell leukemia/lymphoma 3, 2
• Include electrolytes to detect metabolic derangements 1

Lactate Dehydrogenase (LDH)

• This is a critical prognostic marker; levels >2× normal are particularly significant in aggressive lymphoma subtypes 3, 2
• Elevated LDH suggests hemolysis or malignancy 1

Infectious Disease Serology

• HIV, hepatitis B, and hepatitis C testing are mandatory for all patients with lymphadenopathy 1, 2
• These infections can cause lymphadenopathy directly or increase risk of certain lymphomas 1

Additional Testing Based on Clinical Context

Inflammatory Markers

• C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) help assess systemic inflammation and differentiate infectious from malignant causes 4, 1

Tuberculosis Screening

• PPD or interferon-gamma release assay (IGRA) when granulomatous disease is suspected, particularly in endemic areas or high-risk populations 1

Specialized Hematologic Testing

• Serum protein electrophoresis and immunofixation if paraproteinemia is suspected (monoclonal gammopathy, lymphoplasmacytic lymphoma) 1
• Direct antiglobulin test (DAT) and haptoglobin if hemolysis is suspected 1
• Uric acid to assess tumor lysis risk, especially before initiating treatment 2

Flow Cytometry Panels

• For B-cell lymphomas: minimum panel includes CD19, CD20, CD23, and surface immunoglobulin light chains (kappa/lambda) to assess clonality 2
• Additional B-cell markers: CD5, CD10, BCL2, BCL6 for specific subtype classification 2
• For T-cell lymphomas: minimum panel includes CD2, CD3, CD4, CD5, CD7, CD8, and CD25 3, 2

HTLV-I Serology

• Required when adult T-cell leukemia/lymphoma is suspected, particularly in endemic regions 3

Critical Timing and Sequencing

Immediate Laboratory Workup (Day 1-2)

• CBC with differential, CMP, LDH, and infectious serology should be obtained at initial presentation 4, 1
• Do not delay these tests awaiting imaging or biopsy results 4

If Peripheral Blood Shows Abnormalities

• Proceed immediately to flow cytometry and consider bone marrow aspiration and biopsy 1, 2
• Molecular testing (FISH, cytogenetics) becomes essential for risk stratification and treatment selection 2

Before Tissue Biopsy

• Complete the basic laboratory panel to guide the pathologist and inform biopsy site selection 4, 1
• Abnormal laboratory values may indicate systemic disease requiring bone marrow evaluation rather than lymph node biopsy alone 1

Common Pitfalls to Avoid

Do not rely solely on fine-needle aspiration cytology without core tissue or excisional biopsy - lymphoma diagnosis requires architectural assessment that FNA cannot provide 3, 4

Never delay bone marrow evaluation when peripheral blood shows concerning findings - this represents a critical missed opportunity for early diagnosis 1

Avoid overlooking HIV testing in patients with unexplained lymphadenopathy - HIV status fundamentally changes the differential diagnosis and management approach 1

Do not dismiss normal initial laboratory values as excluding malignancy - lymphoma can present with entirely normal blood work, and tissue diagnosis remains essential 5

Never start empiric antibiotics or corticosteroids before obtaining tissue diagnosis - corticosteroids can mask the histologic diagnosis of lymphoma, and antibiotics may delay recognition of underlying malignancy 5