What are the steps to diagnose lymphoma?

How to Test for Lymphoma

Obtain an excisional lymph node biopsy as the first and most critical diagnostic step, followed by comprehensive staging with PET-CT imaging, complete laboratory evaluation including viral screening, and bone marrow assessment if PET-CT is unavailable. 1, 2

Tissue Diagnosis: The Foundation

Excisional lymph node biopsy is mandatory and provides the definitive diagnosis. 3, 1, 2 This surgical specimen must provide sufficient material for both formalin-fixed samples and fresh frozen tissue storage for molecular characterization. 3, 1

When Core Biopsy is Acceptable

• Core needle biopsies should only be performed when lymph nodes are not easily accessible or in rare patients requiring emergency treatment. 3, 1, 2
• Core needle biopsy has 95% sensitivity with ultrasound guidance and may be preferred over fine needle aspiration if lymphoma is suspected based on clinical features (92% vs 74% sensitivity). 4

What to Avoid

• Never use fine needle aspiration as the primary diagnostic approach except in emergency situations requiring immediate treatment. 3, 2
• Avoid open biopsy as the initial diagnostic approach due to higher complication risk. 4

Pathology Requirements

• Minimal immunohistochemistry must include CD45, CD20, and CD3. 3
• The histological report must follow the World Health Organization classification. 3, 1, 2

Laboratory Studies: Comprehensive Baseline Assessment

Mandatory Blood Tests

• Complete blood count with platelets and differential 1, 2
• Blood chemistry profile including lactate dehydrogenase (LDH), C-reactive protein, alkaline phosphatase, liver enzymes, albumin, uric acid, and renal function tests 1, 2
• Erythrocyte sedimentation rate 1

Viral Screening (Non-Negotiable)

• Mandatory screening for hepatitis B, hepatitis C, and HIV must be performed in all patients. 3, 1, 2

Tumor Lysis Syndrome Panel

• Serum LDH, uric acid, potassium, phosphates, and calcium 1, 2
• This is particularly important in patients with high tumor burden. 3

Additional Studies

• Protein electrophoresis is recommended. 3

Imaging Studies: Defining Disease Extent

Primary Imaging

• Contrast-enhanced CT scan of neck, chest, abdomen, and pelvis is required. 3, 1, 2
• Baseline whole-body PET-CT scan is strongly recommended for staging, confirming localized disease, identifying areas with high standardized uptake values suspected of transformation, and serving as baseline for response assessment. 3, 1, 2

PET-CT Advantages

• PET scanning better delineates disease extent and is essential for evaluating treatment response according to revised criteria. 3
• PET-CT has high sensitivity for bone marrow involvement. 1

Bone Marrow Assessment: When and Why

Bone marrow biopsy is no longer indicated in patients undergoing PET-CT evaluation due to the high sensitivity of PET-CT for bone marrow involvement. 1 However, bone marrow aspirate and biopsy must be performed if PET-CT is not available. 3, 1, 2

Site-Specific Evaluations

CNS Involvement

• Diagnostic lumbar puncture for cerebrospinal fluid analysis should be considered in high-risk patients. 3
• CT/MRI scan of the head with contrast if CNS involvement is suspected. 1, 2

Other Sites

• Gastrointestinal endoscopy for suspected GI involvement 1, 2
• Testicular evaluation for male patients 1, 2

Pre-Treatment Assessments

Cardiac and Pulmonary Function

• Electrocardiography and echocardiography to assess left ventricular ejection fraction 3, 1
• Pulmonary function tests 1
• Performance status assessment 3

Reproductive Considerations

• Reproductive counseling for all patients of reproductive age 1
• Serum pregnancy test for female patients of reproductive age 1

Staging and Risk Stratification

Staging System

• Use the Ann Arbor classification system to establish stage. 3, 1, 2
• Patients should be allocated to limited, intermediate, or advanced stage categories. 1

Prognostic Indices

• Calculate International Prognostic Index (IPI) and age-adjusted IPI for diffuse large B-cell lymphoma. 3
• Determine Follicular Lymphoma-specific International Prognostic Index (FLIPI) for follicular lymphoma. 3, 1, 2

Common Pitfalls to Avoid

• Never start corticosteroids before obtaining tissue diagnosis, as they can mask the histologic diagnosis of lymphoma. 5
• Do not rely on fine needle aspiration alone for initial diagnosis. 3, 2
• Do not skip viral screening—hepatitis B reactivation during treatment can be fatal. 3, 1, 2
• Ensure adequate tissue is obtained; insufficient material compromises molecular characterization. 3, 1