What are the diagnostic steps for lymphoma?

Diagnostic Approach for Lymphoma

The diagnosis of lymphoma requires an excisional lymph node biopsy as the gold standard, followed by comprehensive staging with PET-CT imaging, complete laboratory evaluation including viral screening, and bone marrow assessment (though bone marrow biopsy can be omitted in Hodgkin lymphoma when PET-CT is available). 1, 2

Tissue Diagnosis

Excisional lymph node biopsy is mandatory and provides sufficient material for both fresh frozen and formalin-fixed samples for complete pathologic analysis. 3, 1

• Core needle biopsy should only be used when excisional biopsy is anatomically not feasible or in rare patients requiring emergency treatment 3, 1
• Fine needle aspiration is inappropriate for primary diagnosis and should be avoided 3
• The specimen must be processed immediately by an experienced pathology institute to ensure adequate quality 3
• Minimal immunohistochemistry must include CD45, CD20, and CD3 for diffuse large B-cell lymphoma 3
• For Hodgkin lymphoma, HRS cells stain positive for CD30 and CD15, occasionally positive for CD20, and negative for CD45 3

Clinical Assessment

Document specific B symptoms, which include: 3, 1, 2

• Fever >38°C (not from infection)
• Drenching night sweats
• Unexplained weight loss >10% over 6 months

Additional disease-related symptoms to record: 3, 2

• Fatigue
• Pruritus
• Alcohol-induced pain (particularly in Hodgkin lymphoma)

Perform thorough physical examination of all lymphoid regions with special attention to hepatosplenomegaly and abdominal masses 1

Document performance status as it impacts treatment decisions and prognosis 1

Laboratory Evaluation

Mandatory baseline laboratory studies include: 3, 1, 2

• Complete blood count with differential to assess for cytopenias or abnormal cell populations 3, 1, 2
• Comprehensive metabolic panel including liver and renal function tests 3, 1, 2
• Lactate dehydrogenase (LDH) as a marker of tumor burden and for prognostic purposes 3, 1, 2
• Uric acid levels 3, 1
• Erythrocyte sedimentation rate (ESR) for Hodgkin lymphoma 3
• C-reactive protein (CRP), alkaline phosphatase (AP), liver enzymes, and albumin for Hodgkin lymphoma 3

Viral screening is compulsory before initiating therapy, particularly rituximab: 3, 1, 2

• Hepatitis B virus (HBV)
• Hepatitis C virus (HCV)
• Human immunodeficiency virus (HIV)

Protein electrophoresis is recommended for diffuse large B-cell lymphoma 3

Imaging Studies

PET-CT scan from skull base to mid-thigh is essential for initial staging and should be performed as baseline imaging. 3, 1, 2

If PET-CT is not immediately available: 3, 1, 2

• Chest X-ray is mandatory 3
• Contrast-enhanced CT scan of neck, chest, abdomen, and pelvis is required 3, 1

Bone Marrow Assessment

For Hodgkin lymphoma: 3, 2

• Bone marrow biopsy is no longer indicated when PET-CT is available due to high sensitivity for bone marrow involvement
• Bone marrow biopsy must be performed if PET-CT is not available

For non-Hodgkin lymphoma: 3, 1, 2

• Bone marrow aspirate and biopsy remain mandatory for complete staging
• May be omitted only if PET-CT demonstrates multifocal skeletal lesions 1

Staging and Risk Stratification

Apply Ann Arbor staging system for all lymphoma subtypes. 3, 1, 2

Calculate appropriate prognostic indices based on lymphoma subtype: 1, 2

• International Prognostic Index (IPI) or age-adjusted IPI (aa-IPI) for diffuse large B-cell lymphoma 3, 1
• Follicular Lymphoma International Prognostic Index (FLIPI) for follicular lymphoma 3, 1
• Document presence of bulky disease 3

Pretreatment Assessments

Before initiating chemotherapy, obtain: 3, 2

• Electrocardiography (ECG) 3, 2
• Echocardiography to assess left ventricular ejection fraction before anthracycline-based therapy 3, 2
• Pulmonary function testing before bleomycin-containing regimens 3, 2
• Serum pregnancy test in female patients of reproductive age 3
• Reproductive counseling with consideration of sperm banking, oocyte collection, or ovarian tissue cryopreservation for patients of reproductive age 3

Special Considerations

For high-risk patients with diffuse large B-cell lymphoma, consider diagnostic spinal tap to evaluate for CNS involvement 3

For patients with high tumor load, administer prednisone 100 mg orally for several days as "prephase" treatment to prevent tumor lysis syndrome 3