What is the initial workup for a patient suspected of having lymphoma?

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Last updated: August 13, 2025View editorial policy

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Initial Workup for Suspected Lymphoma

The initial workup for a patient suspected of having lymphoma should include an excisional lymph node biopsy, complete physical examination, comprehensive laboratory studies, and contrast-enhanced CT scan of the chest, abdomen, and pelvis. 1

Diagnostic Procedures

Biopsy

  • Excisional lymph node biopsy is mandatory for accurate diagnosis 1
    • Core biopsies should only be performed when lymph nodes are not easily accessible (e.g., retroperitoneal masses)
    • Fine-needle aspiration is inadequate and inappropriate for reliable diagnosis
    • Review by an expert hematopathologist is essential

Immunophenotypic Analysis

  • Essential for differentiating lymphoma subtypes 1
  • Can be performed using:
    • Flow cytometry
    • Immunohistochemistry
  • Initial panel should include Pan-B and Pan-T-cell antigens 1
  • Additional markers based on morphology and clinical features

Cytogenetic/Molecular Analysis

  • May be necessary to identify characteristic chromosomal translocations 1
  • Helps establish clonality in certain cases

Physical Examination

  • Thorough examination with particular attention to:
    • All lymph node-bearing areas
    • Liver and spleen size
    • Performance status assessment
    • Evaluation for B symptoms (fever, night sweats, weight loss)

Laboratory Studies

Essential Laboratory Tests

  • Complete blood count (CBC) with differential 1
  • Comprehensive metabolic panel 1
  • Serum lactate dehydrogenase (LDH) 1
  • Hepatitis B testing (HBsAg and HBcAb) 1
    • Critical before initiating anti-CD20 monoclonal antibody therapy
  • HIV testing 1
  • Uric acid level 1

Additional Laboratory Tests

  • β2-microglobulin (important prognostic marker) 1
  • Hepatitis C testing (especially for splenic marginal zone lymphoma) 1

Imaging Studies

Essential Imaging

  • CT scan of chest, abdomen, and pelvis with oral and intravenous contrast 1
  • PET-CT scan (improves accuracy of staging for nodal and extranodal sites) 1
    • Particularly important to confirm localized stage I/II disease

Additional Imaging

  • Chest radiograph (recommended for patients with large mediastinal mass) 1
  • Endoscopic ultrasound (for gastric MALT lymphoma) 1
  • Brain MRI (if CNS involvement is suspected) 1

Bone Marrow Assessment

  • Bone marrow biopsy with or without aspirate 1
    • May be deferred in certain circumstances
    • Not required in Hodgkin lymphoma if PET scan is negative or shows homogenous bone marrow uptake 1

Cardiac Assessment

  • Evaluation of ejection fraction (MUGA scan or echocardiogram) 1
    • Recommended when anthracycline-containing regimens are planned

Additional Considerations

  • Pulmonary function tests (including DLCO) 1
    • Recommended for patients who will receive bleomycin-based chemotherapy
  • Lumbar puncture 1
    • Consider in high-risk cases (blastoid variant, elevated LDH, impaired performance status) or with neurological symptoms
  • Pregnancy test for women of childbearing age 1
  • Discussion of fertility preservation options 1

Common Pitfalls to Avoid

  • Relying on fine-needle aspiration for diagnosis
  • Inadequate pathology review (always seek expert hematopathology consultation)
  • Incomplete staging before treatment decisions
  • Failure to test for hepatitis B status before rituximab therapy
  • Missing extranodal disease due to insufficient imaging

By following this comprehensive diagnostic approach, clinicians can accurately diagnose and stage lymphoma, which is essential for determining the appropriate treatment strategy and improving patient outcomes.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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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