What is the workup for diffuse large B cell lymphoma?

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Last updated: December 20, 2025View editorial policy

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Workup for Diffuse Large B-Cell Lymphoma

The workup for diffuse large B-cell lymphoma requires tissue diagnosis with immunohistochemistry, comprehensive staging with CT imaging and bone marrow biopsy, PET/CT scanning, laboratory assessment including LDH and viral screening, and risk stratification using the International Prognostic Index. 1

Tissue Diagnosis

Obtain an excisional lymph node biopsy or adequate tissue specimen to provide sufficient material for comprehensive pathological evaluation. 1

  • Core needle biopsies may be acceptable only in patients requiring emergency treatment where surgical biopsy is not feasible. 1
  • Mandatory immunohistochemistry panel must include CD45, CD20, and CD3 to confirm B-cell lineage and CD20 positivity, which is essential for rituximab eligibility. 1
  • Fresh frozen tissue collection for molecular characterization is recommended, though gene expression profiling remains investigational and does not currently influence treatment decisions. 1
  • The pathology report must provide diagnosis according to current WHO classification. 1

Important caveat: While cell-of-origin classification (germinal center-like versus activated B-cell-like subtypes) has prognostic significance, immunohistochemical determination shows contradictory results and poor reproducibility—do not base routine clinical decisions on these results outside clinical trials. 2

Laboratory Assessment

Complete the following baseline laboratory studies: 1

  • Complete blood count
  • Comprehensive metabolic panel including lactate dehydrogenase (LDH) and uric acid (critical for IPI calculation and tumor lysis risk assessment)
  • HIV, hepatitis B, and hepatitis C screening (mandatory given treatment implications and increased lymphoma aggressiveness with HIV) 1, 3
  • Protein electrophoresis (recommended) 1

Imaging Studies

CT scan of chest, abdomen, and pelvis is required as minimum staging imaging. 1

PET/CT scanning is strongly recommended for superior disease delineation and essential for accurate post-treatment response assessment according to revised response criteria. 1, 3

  • PET/CT provides better extent-of-disease assessment than CT alone 1
  • Post-treatment PET is highly recommended to define complete remission 1
  • Do not use routine surveillance PET scans during follow-up—this is not recommended 1

Bone Marrow Evaluation

Perform bone marrow aspirate and biopsy in all patients amenable to curative therapy. 1

  • This is required for complete staging according to Ann Arbor classification 1
  • Repeat bone marrow assessment at end of treatment only if initially involved 1

CNS Risk Assessment

Consider diagnostic lumbar puncture with CSF analysis in high-risk patients. 1

High-risk features warranting CNS evaluation include: 3

  • Multiple extranodal sites (≥2)
  • Testicular involvement
  • Renal/adrenal involvement
  • HIV-positive status
  • Elevated LDH with extranodal disease

Functional Assessment

Evaluate performance status and cardiac function before treatment: 1

  • Document ECOG or Karnofsky performance status
  • Assess left ventricular ejection fraction (LVEF) given planned anthracycline therapy 1
  • This is critical for determining treatment intensity and eligibility for dose-intensive approaches

Risk Stratification

Calculate the International Prognostic Index (IPI) and age-adjusted IPI (aa-IPI) using: 1

  • Age >60 years
  • Elevated LDH
  • ECOG performance status ≥2
  • Ann Arbor stage III or IV
  • 1 extranodal site

Apply Ann Arbor staging system (stages I-IV based on lymph node regions and extranodal involvement). 1

The IPI score directly influences treatment strategy selection and intensity, with higher scores indicating need for more aggressive approaches. 1

Special Considerations

For suspected primary mediastinal large B-cell lymphoma, recognize this as a distinct entity where R-CHOP may not be the definitive treatment and radiotherapy remains controversial. 1

In cases with high tumor burden, assess for tumor lysis syndrome risk and plan prophylaxis with hydration, allopurinol or rasburicase, and electrolyte monitoring before initiating treatment. 3

Common pitfall: Avoid dose reductions of chemotherapy due to hematological toxicity—maintain dose intensity and use prophylactic growth factors instead. 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Diffuse Large B-Cell Lymphoma Prognosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Diagnosis and Treatment of Diffuse Large B-Cell Lymphoma

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 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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