What laboratory tests are used to rule out lymphoma (lymphatic system cancer) in children?

Laboratory Testing to Rule Out Lymphoma in Children

The essential laboratory workup to rule out lymphoma in children includes a complete blood count (CBC) with differential and platelets, lactate dehydrogenase (LDH), and a comprehensive metabolic panel, followed by tissue biopsy with immunophenotyping if lymphoma is suspected based on clinical presentation and initial labs. 1

Initial Laboratory Studies

Core Blood Tests

• CBC with differential and platelets is the foundational screening test to identify cytopenias, abnormal white blood cell counts, or circulating blasts that may suggest lymphoma 1
• Peripheral blood smear evaluation should be performed to assess cell morphology and identify dysplastic changes or abnormal lymphocytes 2
• Lactate dehydrogenase (LDH) is elevated in many lymphomas and serves as both a diagnostic marker and prognostic indicator 1
• Comprehensive metabolic panel including liver function tests, calcium, phosphorus, potassium, and uric acid to assess for tumor lysis syndrome and organ involvement 1

Additional Screening Labs

• Beta-2-microglobulin can be useful as it is often elevated in lymphoproliferative disorders 1
• Uric acid measurement is important given the risk of tumor lysis syndrome in aggressive lymphomas 1
• Erythrocyte sedimentation rate (ESR) may be elevated in Hodgkin lymphoma specifically 1

Important Clinical Context

When Lymphoma is Suspected

If clinical presentation (painless lymphadenopathy, B symptoms, mediastinal mass) and initial labs suggest lymphoma, tissue diagnosis via excisional or incisional lymph node biopsy is mandatory - fine needle aspiration alone is insufficient for initial diagnosis 1, 3

• Chest X-ray should be obtained to rule out mediastinal masses, which are common in T-cell lymphoblastic lymphoma 1
• PET/CT scan is recommended if lymphoblastic lymphoma is specifically suspected based on clinical features 1

Critical Distinction: Lymphoma vs. Leukemia

The distinction between lymphoblastic lymphoma and acute lymphoblastic leukemia (ALL) is primarily based on the degree of bone marrow involvement, not just peripheral blood findings 1. If initial labs show significant abnormalities:

• Bone marrow aspirate and biopsy with flow cytometry, cytogenetics, and molecular testing should be performed when acute lymphoblastic leukemia or lymphoblastic lymphoma is suspected 1
• This distinction matters because lymphoblastic lymphoma with <25% bone marrow blasts is treated differently than ALL with ≥25% marrow involvement 4

Common Pitfalls to Avoid

Screening vs. Diagnostic Testing

• Routine CBC screening is NOT recommended for early detection of lymphoma in asymptomatic children, even those with genetic predisposition syndromes like ataxia-telangiectasia 1
• Laboratory testing should be symptom-driven - prompted by clinical findings such as persistent lymphadenopathy, unexplained fevers, night sweats, weight loss, or abnormal physical examination 1

Inadequate Tissue Sampling

• Core needle biopsy or fine needle aspiration alone is generally insufficient for initial lymphoma diagnosis, though may be acceptable in specific circumstances when combined with comprehensive immunophenotyping 1
• An excisional lymph node biopsy provides adequate tissue for morphology, immunohistochemistry, flow cytometry, cytogenetics, and molecular studies required for accurate subtyping 1, 3

Required Immunophenotyping Panel

When tissue is obtained, the following studies are essential 1:

• Immunohistochemistry panel: CD20, CD3, CD5, CD10, BCL2, BCL6, cyclin D1, CD21, CD23, CD30, CD15, CD45, CD79a, PAX5
• Flow cytometry: kappa/lambda light chains, CD19, CD20, CD5, CD23, CD10
• Molecular analysis: antigen receptor gene rearrangements (immunoglobulin and T-cell receptor)
• Cytogenetics/FISH: to detect specific translocations like t(14;18), BCL6 rearrangements, MYC rearrangements

Risk-Stratified Approach

High-Risk Presentations Requiring Immediate Workup

Children presenting with the following require urgent comprehensive evaluation 1:

• Mediastinal mass on chest X-ray
• Significant lymphadenopathy (>2cm, firm, non-tender, progressive)
• B symptoms (fever >38°C, drenching night sweats, >10% weight loss)
• Cytopenias on CBC
• Markedly elevated LDH

Additional Testing for Specific Scenarios

• DIC panel (D-dimer, fibrinogen, PT, PTT) if Burkitt lymphoma suspected given high tumor burden 1
• Hepatitis B and C testing before initiating immunotherapy or chemotherapy due to reactivation risk 1
• Pregnancy testing in females of childbearing age if chemotherapy is anticipated 1
• HIV testing in appropriate clinical contexts as immunodeficiency increases lymphoma risk 1