What lab tests and workup are necessary for a comprehensive diagnosis of lymphoma?

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Lymphoma Laboratory Workup

A comprehensive lymphoma workup requires complete blood count with differential, lactate dehydrogenase, comprehensive metabolic panel, hepatitis B and C screening, HIV testing, beta-2-microglobulin, uric acid, and bone marrow biopsy (except in Hodgkin lymphoma when PET-CT is performed). 1, 2

Essential Core Laboratory Tests

  • Complete blood count (CBC) with differential and platelets evaluates for cytopenias, leukocytosis, abnormal lymphocyte populations, and potential bone marrow involvement 1, 2

  • Serum lactate dehydrogenase (LDH) is the single most important serologic prognostic marker, reflecting tumor burden and cell turnover, and is a critical component of the International Prognostic Index 1, 2

  • Comprehensive metabolic panel including electrolytes, renal function (creatinine, BUN), and liver function tests (AST, ALT, alkaline phosphatase, bilirubin, albumin) assesses organ function and potential disease involvement 1, 2

  • Uric acid is essential for assessing tumor lysis syndrome risk, particularly critical before initiating treatment in high tumor burden cases 3, 1, 2

Mandatory Infectious Disease Screening

  • Hepatitis B testing (HBsAg, anti-HBc, anti-HBs) is required before initiating anti-CD20 monoclonal antibody therapy (rituximab) due to the risk of potentially fatal hepatitis B reactivation 3, 1, 2

  • Hepatitis C screening is particularly important for high-risk patients and those with splenic marginal zone lymphoma 3, 1, 2

  • HIV serology is mandatory as HIV status affects prognosis and treatment selection 3, 2

Additional Prognostic Markers

  • Beta-2-microglobulin is an important prognostic marker, especially in follicular lymphoma where it is incorporated into the revised FLIPI 2 scoring system 3, 1, 2

  • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are required for Hodgkin lymphoma staging and risk stratification 3

  • Protein electrophoresis is recommended for B-cell lymphomas to detect monoclonal proteins and evaluate for potential paraproteinemia 1, 2

Bone Marrow Evaluation

  • Bone marrow aspirate and biopsy are essential for staging in most lymphomas, with involvement occurring in 39% of low-grade, 36% of intermediate-grade, and 18% of high-grade lymphomas 3, 1

  • Bone marrow biopsy is no longer indicated in Hodgkin lymphoma when PET-CT is performed, as PET-CT has higher sensitivity for detecting bone marrow involvement 3, 4

  • For non-Hodgkin lymphomas, bone marrow biopsy remains important even with PET-CT imaging 4

Tissue-Based Immunophenotyping

  • Flow cytometry on peripheral blood or bone marrow is essential for determining lymphoma subtype and clonality 1

  • The initial immunophenotyping panel should include pan-B cell markers (CD19, CD20, CD22) and pan-T cell markers (CD3, CD5) 1

  • Tissue specimens require a minimal mandatory antibody panel including CD45, CD20, and CD3 2

Subtype-Specific Testing

Follicular Lymphoma

  • Beta-2-microglobulin, diameter of largest lymph node measurement, and hemoglobin level are incorporated into FLIPI 2 prognostic scoring 3

Gastric MALT Lymphoma

  • Helicobacter pylori testing by histochemistry or urea breath test is mandatory 3
  • FISH analysis or PCR for t(11;18) detection identifies patients unlikely to respond to antibiotic therapy 3

Hodgkin Lymphoma

  • ESR is specifically required for risk stratification 3

Pre-Treatment Cardiac and Pulmonary Assessment

  • Electrocardiography (ECG) and echocardiography or MUGA scan are required before anthracycline-based chemotherapy regimens to assess left ventricular ejection fraction 3, 1

  • Pulmonary function tests should be performed before treatment initiation, particularly when bleomycin-containing regimens are planned 3

Special Circumstances

  • Lumbar puncture with cerebrospinal fluid analysis (cell count, flow cytometry, cytology) should be performed in high-risk patients with suspected CNS involvement 1, 2

  • Tumor lysis syndrome panel (LDH, uric acid, potassium, phosphorus, calcium) is especially important in pediatric patients and those with high tumor burden before initiating treatment 1

  • Coagulation studies (PT, PTT, fibrinogen) assess for disseminated intravascular coagulation in aggressive lymphomas 1

Critical Pitfalls to Avoid

  • Fine-needle aspiration is inappropriate for reliable lymphoma diagnosis; excisional or core needle biopsy providing adequate tissue is strongly preferred for accurate diagnosis and immunohistochemistry 3, 2, 5

  • Hepatitis B reactivation can be fatal during rituximab therapy if not identified and managed prophylactically with antiviral therapy 2

  • Relying on inadequate tissue samples from core biopsies may miss heterogeneity in follicular lymphoma grading; re-biopsy may be required 3

  • Bone marrow biopsy must still be performed if PET-CT is not available for staging 3

References

1
Guideline

Essential Components of a Detailed Blood Workup for Lymphoma

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

2
Guideline

Laboratory Tests for Lymphoma Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

3
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

4
Guideline

Lymphoma Screening and Staging Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

5
Research

Lymphoma: Diagnosis and Treatment.

American family physician, 2020

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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