What is the initial approach to diagnosing and treating lymphoma?

Initial Approach to Diagnosing and Treating Lymphoma

The initial approach to lymphoma diagnosis must begin with an excisional or incisional lymph node biopsy, as fine needle aspirations are inappropriate for establishing a reliable diagnosis. 1, 2 Following biopsy confirmation, comprehensive staging with CT imaging and bone marrow assessment is essential for determining appropriate treatment strategy.

Diagnostic Approach

Tissue Biopsy

• Surgical specimen/excisional lymph node biopsy is mandatory 1, 2
  • Core biopsies should only be performed when lymph nodes are not easily accessible (e.g., retroperitoneal disease)
  • Fine needle aspirations are inadequate and should be avoided
  • Immediate processing by an experienced pathology institute is crucial

Pathologic Evaluation

• Histological report should classify according to World Health Organization (WHO) classification
• For follicular lymphoma, grading is based on number of blasts/high power field:
  • Grade 1: ≤5 blasts/high power field
  • Grade 2: 6-15 blasts/high power field
  • Grade 3A: >15 blasts with intermingled centrocytes
  • Grade 3B: >15 blasts with pure sheets of blasts (treated as aggressive lymphoma) 1
• Review by an expert hematopathologist is recommended, especially for grade 3 follicular lymphoma

Initial Laboratory Workup

• Complete blood count
• Comprehensive metabolic panel
• Lactate dehydrogenase (LDH) and uric acid
• β2-microglobulin (for prognostic assessment)
• Hepatitis B and C screening
• HIV testing 2
• Protein electrophoresis for B-cell lymphomas

Staging and Risk Assessment

Imaging Studies

• CT scan of neck, thorax, abdomen, and pelvis with contrast 1, 2
• PET-CT is recommended for:
  • Confirming localized stage I/II disease before radiotherapy
  • Identifying areas suspicious for transformation
  • Baseline for response assessment 1, 2

Bone Marrow Assessment

• Bone marrow aspirate and biopsy required for complete staging 1, 2
• Bilateral cores recommended for potentially early-stage indolent lymphoma 2

Staging Classification

• Ann Arbor classification system:
  • Stage I: Single lymph node region or localized involvement of single extralymphatic site
  • Stage II: Two or more lymph node regions on same side of diaphragm
  • Stage III: Lymph node regions on both sides of diaphragm
  • Stage IV: Diffuse or disseminated extralymphatic organ involvement 1, 2

Prognostic Assessment

• Follicular Lymphoma International Prognostic Index (FLIPI) for follicular lymphoma 1, 2
  • Includes: age >60 years, hemoglobin <12 g/dL, elevated LDH, advanced stage III/IV, >4 involved nodal areas
• International Prognostic Index (IPI) for aggressive lymphomas 2

Treatment Approach

Early Stage Disease (I-II)

• For follicular lymphoma: Radiotherapy (involved or extended field, 30-40 Gy) with curative potential 1
• For large cell lymphomas: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) for 6-8 cycles 2, 3

Advanced Stage Disease (III-IV)

• For follicular lymphoma:
  • Observation may be appropriate for asymptomatic patients (watch and wait) 1
  • Initiate treatment for symptomatic disease (B-symptoms, hematopoietic impairment, bulky disease, or progression) 1
  • When treatment is needed: Rituximab plus chemotherapy (R-CHOP, R-CVP, R-bendamustine) 1, 2
• For aggressive lymphomas (DLBCL, grade 3B follicular lymphoma):
  • R-CHOP given every 14 or 21 days for 6-8 cycles 2, 3

Response Assessment

• PET-CT after 2-4 cycles and at completion of therapy 1, 2
• Repeat bone marrow biopsy at end of treatment if initially involved 2

Follow-up and Surveillance

• Physical examination:
  • Every 3 months for first year
  • Every 6 months for 2 more years
  • Then annually 1, 2
• Laboratory tests (CBC, LDH) at 3,6,12, and 24 months, then as needed 1, 2
• CT imaging at 6,12, and 24 months after treatment 1, 2

Common Pitfalls and Special Considerations

• Biopsy pitfalls: Inadequate sampling with core biopsies may miss heterogeneity in follicular lymphoma grading 1
• Hepatitis B reactivation: Test all patients before anti-CD20 therapy; prophylaxis may be needed 2, 4
• Transformation risk: Approximately 30% of indolent lymphomas may transform to aggressive histology 2
• Vaccination: Patients should receive pneumococcal vaccines and other age-appropriate vaccinations due to immunosuppression 3
• Secondary malignancies: Increased risk with anthracycline-based regimens; monitor for development 5
• Fertility preservation: Should be discussed before starting treatment 2

By following this structured approach to diagnosis and treatment, clinicians can optimize outcomes for patients with lymphoma while minimizing treatment-related morbidity and mortality.