What is the recommended workup and treatment approach for lymphoma?

Workup for Lymphoma

The diagnostic workup for lymphoma requires an excisional lymph node biopsy for definitive diagnosis, followed by comprehensive staging with contrast-enhanced CT of neck/chest/abdomen, PET-CT when available, bone marrow biopsy (if PET-CT unavailable), complete blood count, blood chemistry including LDH, and mandatory screening for HIV, hepatitis B, and hepatitis C. 1

Diagnostic Approach

Tissue Diagnosis

• Obtain an excisional lymph node biopsy or surgical specimen providing adequate tissue for both formalin-fixed and fresh frozen samples 1, 2
• Core biopsies should only be used when easily accessible lymph nodes are unavailable (e.g., retroperitoneal locations) or in rare emergency situations requiring immediate treatment 1, 2
• Fine-needle aspirations are insufficient for reliable primary diagnosis and should be avoided 1
• The histological report must follow WHO classification with immunohistochemistry including CD20 expression 1, 2

Critical pitfall: For Hodgkin lymphoma, HRS cells stain positive for CD30 and CD15, occasionally positive for CD20, and negative for CD45 1. For follicular lymphoma, histological grading requires assessment of centroblasts per high-power field, with grade 3B treated as aggressive lymphoma while grades 1,2, and 3A are managed as indolent disease 1

Clinical Assessment

• Document complete medical history including B symptoms (fever >38°C, drenching night sweats, unexplained weight loss >10% over 6 months) 1
• Record disease-related symptoms including fatigue, pruritus, and alcohol-induced pain 1
• Perform thorough physical examination documenting all lymph node regions 1, 2

Staging Workup

Imaging Studies

• Chest X-ray is mandatory 1
• Contrast-enhanced CT scan of neck, chest, and abdomen is required 1, 2
• Baseline whole-body PET-CT should be performed when available and is mandatory to confirm localized stage I/II disease before radiotherapy 1
• PET-CT is recommended for routine staging in follicular lymphoma as it improves accuracy for nodal and extranodal sites 1

Bone Marrow Assessment

• Bone marrow biopsy is no longer indicated if PET-CT is performed due to high sensitivity of PET-CT for bone marrow involvement 1
• Bone marrow aspirate and biopsy of at least 20 mm length must be obtained if PET-CT is unavailable 1

Laboratory Studies

• Complete blood count with differential 1, 2
• Erythrocyte sedimentation rate (ESR) 1
• Blood chemistry including:
  • Lactate dehydrogenase (LDH) 1, 2
  • Beta-2-microglobulin (B2M) 1
  • Alkaline phosphatase (AP) 1
  • Liver enzymes and albumin 1
  • C-reactive protein (CRP) 1
  • Uric acid 1, 2
  • Immunoglobulin levels 1

Mandatory Infectious Disease Screening

• Hepatitis B virus (HBV) screening is compulsory 1, 2
• Hepatitis C virus (HCV) screening is compulsory 1, 2
• HIV screening is compulsory 1, 2

Pretreatment Evaluations

• Electrocardiography (ECG) 1, 2
• Echocardiography for cardiac function assessment 1, 2
• Pulmonary function testing 1, 2
• Reproductive counseling for patients of reproductive age with consideration of sperm banking, oocyte collection, or ovarian tissue cryopreservation before treatment 1, 2
• Serum pregnancy test in female patients of reproductive age 1

Special Considerations

• Diagnostic lumbar puncture with prophylactic intrathecal chemotherapy (cytarabine and/or methotrexate) should be considered in high-risk patients with more than two adverse IPI parameters, especially with bone marrow, testicular, spinal, or skull base involvement 1
• Consultation with ear, nose, and throat specialist including fibreoptic nasolaryngoscopy if PET-CT unavailable at initial staging 1

Risk Stratification

Staging Classification

• Use Ann Arbor classification system with documentation of bulky disease (>6 cm) when applicable 1, 2
• Patients are allocated to limited, intermediate, or advanced stage categories based on staging results and clinical risk factors 1

Prognostic Indices

• International Prognostic Index (IPI) should be established for large B-cell lymphomas 1, 2
• Follicular Lymphoma International Prognostic Index (FLIPI) should be calculated for follicular lymphoma 1, 2

Important caveat: Store additional biopsy material (fresh frozen and paraffin fixed) when possible for future molecular analyses, though gene expression profiling and clinicogenetic risk scores remain investigational 1