What is the approach and workup for a patient with suspected lymphoma?

Lymphoma Workup and Approach

An excisional lymph node biopsy is the mandatory first step for suspected lymphoma, 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

Initial Tissue Diagnosis

Biopsy Requirements

• Excisional lymph node biopsy is the gold standard and must provide sufficient tissue for both fresh frozen and formalin-fixed samples to enable complete immunophenotypic and molecular analysis 1, 2
• Core needle biopsies should only be performed when lymph nodes are surgically inaccessible or when surgical approach poses excessive risk 1
• Fine needle aspiration is inadequate for proper lymphoma diagnosis and should only be used in rare emergency situations requiring immediate treatment 1, 2
• Immediate processing by an experienced pathology laboratory with full diagnostic capabilities (immunophenotypic and molecular) is essential 1

Pathological Evaluation

• Diagnosis must follow World Health Organization (WHO) classification 1
• For Hodgkin lymphoma: Hodgkin and Reed-Sternberg (HRS) cells staining positive for CD30 and CD15, occasionally CD20-positive, but CD45-negative are disease-defining 1
• For diffuse large B-cell lymphoma: morphological diagnosis must be confirmed by immunophenotypic investigations, with assessment of MYC and BCL2 rearrangement by FISH recommended 1

Mandatory Laboratory Studies

Core Blood Work

• Complete blood count with differential and platelets to evaluate bone marrow involvement and cytopenias 1, 2, 3
• Comprehensive metabolic panel including liver enzymes, albumin, and renal function 1, 2, 3
• Lactate dehydrogenase (LDH) as a critical prognostic marker and component of International Prognostic Index 1, 2, 3
• Erythrocyte sedimentation rate (ESR) for Hodgkin lymphoma specifically 1, 2
• C-reactive protein (CRP) and alkaline phosphatase (AP) 1, 2
• Uric acid as part of tumor lysis syndrome panel, especially before treatment initiation 1, 2, 3

Mandatory Viral Screening

• Hepatitis B (HBV), hepatitis C (HCV), and HIV screening are compulsory before initiating therapy due to reactivation risk with immunosuppressive treatment, particularly anti-CD20 antibodies 1, 2, 3

Additional Laboratory Tests

• Protein electrophoresis is recommended to evaluate for paraproteinemia 1, 3
• β2-microglobulin serves as an important prognostic marker, especially in follicular lymphoma 3

Imaging Studies

Required Imaging

• Chest X-ray followed by contrast-enhanced CT scan of neck, chest, abdomen, and pelvis is mandatory 1, 2
• Baseline whole-body PET-CT is the gold standard for staging and should be performed according to recommendations for staging and response assessment in lymphoma 1, 2
• If contrast-enhanced CT is not performed before PET-CT, a full diagnostic high-dose contrast-enhanced CT should be carried out when necessary in combination with PET-CT 1

Special Imaging Considerations

• For suspected CNS involvement: MRI is the modality of choice, with diagnostic lumbar puncture considered in high-risk patients 1, 2
• For suspected gastrointestinal involvement: gastrointestinal endoscopy should be performed 2

Bone Marrow Assessment

Given the high sensitivity of PET-CT for bone marrow involvement, bone marrow biopsy is no longer indicated in patients undergoing PET-CT evaluation 1, 2

However, bone marrow biopsy with aspirate must be performed if:

• PET-CT is not available 1, 2
• PET-CT is negative but results would change prognosis and treatment, particularly when shortened immunochemotherapy cycles are proposed 1

Pre-Treatment Evaluations

Cardiac and Pulmonary Assessment

• Electrocardiography (ECG) and echocardiography to assess left ventricular ejection fraction (LVEF) are required before anthracycline-based treatment 1, 2, 3
• Pulmonary function tests are mandatory 1, 2

Reproductive Considerations

• Reproductive counseling for patients of reproductive age 1, 2
• Serum pregnancy test for female patients of reproductive age 1, 2

Additional Evaluations

• For Hodgkin lymphoma: consultation with ear, nose, and throat specialist including fibreoptic nasolaryngoscopy if PET-CT is unavailable at initial staging 1
• For male patients: evaluation for testicular involvement 2

Staging and Risk Stratification

Staging System

• Staging is performed according to the Ann Arbor classification system with patients allocated to limited, intermediate, or advanced stage categories 1, 2
• Medical history must document B symptoms (fever >38°C, drenching night sweats, unexplained weight loss >10% over 6 months) and disease-related symptoms including fatigue, pruritus, and alcohol-induced pain 1

Prognostic Scoring

• For diffuse large B-cell lymphoma: International Prognostic Index (IPI) and age-adjusted IPI (aa-IPI) must be calculated 1
• For follicular lymphoma: Follicular Lymphoma-specific International Prognostic Index (FLIPI) should be determined 1, 2

Special Considerations for Elderly Patients

• Comprehensive geriatric assessment (CGA) is recommended to guide treatment choice in elderly patients 1
• Cardiac assessment (LVEF) is required for patients treated with curative intent 1

Common Pitfalls to Avoid

• Never rely on fine needle aspiration alone as it provides insufficient material for proper subtyping and molecular analysis 1, 2
• Do not skip viral screening, as hepatitis B reactivation can be fatal during rituximab-based therapy 1, 3
• Avoid performing bone marrow biopsy when PET-CT is available and shows advanced-stage disease, as it adds no diagnostic value 1, 2
• Do not proceed with treatment without baseline cardiac assessment in patients receiving anthracycline-based regimens 1, 3