What laboratory, imaging, and biopsy tests are recommended for evaluating suspected lymphoma?

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Last updated: September 29, 2026 • View editorial policy

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Lymphoma Testing: Essential Diagnostic Workup

For suspected lymphoma, obtain an excisional or incisional lymph node biopsy (never fine-needle aspiration alone) with comprehensive immunophenotyping, followed by PET-CT imaging for staging in FDG-avid histologies, with bone marrow biopsy no longer routinely required for Hodgkin lymphoma or most diffuse large B-cell lymphomas. 1

Biopsy Requirements

The cornerstone of lymphoma diagnosis is adequate tissue sampling—fine-needle aspiration alone is inadequate for initial diagnosis. 2

Tissue Acquisition

  • Excisional or incisional biopsy is preferred to provide sufficient tissue for morphology, immunohistochemistry, and molecular studies 1
  • Core-needle biopsy can be considered when excisional biopsy is not feasible, but a nondiagnostic sample must be followed by excisional/incisional biopsy 1
  • In select circumstances where lymph nodes are inaccessible, a combination of core biopsy and FNA with appropriate ancillary techniques may suffice 2

Required Pathologic Studies

Essential immunophenotyping includes: 2

  • Paraffin panel: CD45, CD20, CD3, CD10, Ki-67, BCL2, BCL6, TdT
  • OR flow cytometry: kappa/lambda, CD45, CD20, CD3, CD5, CD19, CD10, TdT
  • Cytogenetics or FISH: t(8;14) or variants; MYC, IgH, BCL2, BCL6 rearrangements

The tissue must be reviewed by an experienced lymphoma pathologist, with additional paraffin-embedded or fresh-frozen tissue stored for future research when possible. 1

Imaging Studies

PET-CT has been formally incorporated into standard staging for FDG-avid lymphomas and represents the primary imaging modality. 1

Imaging Algorithm by Lymphoma Type

For FDG-avid lymphomas (Hodgkin lymphoma, diffuse large B-cell lymphoma, follicular lymphoma):

  • PET-CT is the standard imaging modality for staging and response assessment 1, 3
  • Covers chest, abdomen, pelvis, and neck regions 4

For variably FDG-avid lymphomas (marginal zone lymphoma):

  • PET-CT is an alternative to contrast-enhanced CT at baseline
  • May be used for response assessment if FDG-avid at baseline 3

For non-FDG-avid lymphomas (small lymphocytic lymphoma/chronic lymphocytic leukemia):

  • Contrast-enhanced CT exclusively at baseline and follow-up
  • PET-CT only if transformation to high-grade lymphoma is suspected 3

Essential imaging includes: 2

  • Chest/abdominal/pelvic CT with contrast of diagnostic quality
  • PET-CT scan (in selected cases based on histology)
  • Neck CT (useful in selected cases)

Laboratory Testing

Essential laboratory workup includes: 2

Blood Tests

  • Complete blood count with differential and platelets
  • Comprehensive metabolic panel
  • Lactate dehydrogenase (LDH)
  • Uric acid
  • HIV testing
  • Hepatitis B testing
  • Beta-2-microglobulin (useful in selected cases)

Bone Marrow Evaluation

A critical update from the Lugano classification: bone marrow biopsy is no longer indicated for routine staging of Hodgkin lymphoma and most diffuse large B-cell lymphomas. 1

  • PET-CT is adequate for determination of bone marrow involvement in Hodgkin lymphoma 1
  • Unilateral or bilateral bone marrow biopsy ± aspirate remains essential for other lymphoma subtypes 2
  • Biopsy may be needed in non-Hodgkin lymphomas where PET-CT cannot definitively rule out marrow involvement 3

CNS Evaluation (When Indicated)

For high-risk histologies or CNS symptoms: 1

  • Lumbar puncture with CSF cytology and flow cytometry
  • Brain MRI for leptomeningeal infiltration or mass lesions
  • CT for mass lesions

Clinical Assessment

Document the following clinical parameters: 1

  • B symptoms: Fevers >101°F (38.3°C), unexplained weight loss >10% in 6 months, drenching night sweats
  • Performance status
  • Comprehensive physical examination focusing on all node-bearing areas including Waldeyer's ring, liver and spleen size
  • Palpable lymphadenopathy characteristics

Additional Considerations

Pre-Treatment Assessment

  • MUGA scan or echocardiogram (if anthracycline-based chemotherapy planned) 2
  • Pregnancy testing in women of childbearing age
  • Discussion of fertility preservation and sperm banking

Common Pitfalls to Avoid

  1. Never rely on fine-needle aspiration alone for initial diagnosis—it provides inadequate tissue for comprehensive evaluation 2
  2. Avoid routine surveillance scans—these are discouraged per Lugano criteria 1
  3. Do not perform bone marrow biopsy routinely in Hodgkin lymphoma or most DLBCL—PET-CT is sufficient 1
  4. Avoid corticosteroids before biopsy—they can mask the histologic diagnosis of lymphoma 5

This algorithmic approach ensures accurate diagnosis and appropriate staging while avoiding unnecessary invasive procedures, directly impacting treatment selection and ultimately patient outcomes including mortality and quality of life.

References

2
Guideline

nccn clinical practice guidelines in oncology: non-hodgkin's lymphomas.

Journal of the National Comprehensive Cancer Network : JNCCN, 2010

4
Research

[Primary imaging diagnostics of lymphomas].

Radiologie (Heidelberg, Germany), 2025

5
Research

Lymphadenopathy: Evaluation and Differential Diagnosis.

American family physician, 2025

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