What is the initial approach to managing lymphoma?

Initial Approach to Managing Lymphoma

The definitive diagnosis of lymphoma requires an excisional or incisional lymph node biopsy, as fine-needle aspiration alone is inadequate for initial diagnosis. 1 This is the critical first step in the management of any suspected lymphoma case.

Diagnostic Workup

Biopsy

• Excisional biopsy is the preferred method for lymphoma diagnosis due to its high diagnostic accuracy 1
• Incisional biopsy is an acceptable alternative when complete excision is not feasible 1
• Core needle biopsy should only be used when excisional or incisional biopsy is not possible (e.g., retroperitoneal nodes) 1
• The specimen should be sent fresh and intact, never immersed unsectioned in fixative 1

Pathology Assessment

• Immunohistochemistry is essential for proper classification
• Minimum panel should include CD45, CD20, and CD3 1
• Additional markers for B-cell lymphomas: CD10, BCL2, BCL6, Ki-67, CD138, kappa/lambda 1
• For Hodgkin lymphoma: CD3, CD15, CD20, CD30, CD45, CD79a, and PAX5 1

Staging Workup

Imaging Studies

1. PET-CT scan from skull base to mid-thigh 1
2. Contrast-enhanced CT of the neck, chest, abdomen, and pelvis 1
3. Chest X-ray in cases with large mediastinal mass 1

Laboratory Tests

• Complete blood count with differential and platelets
• Lactate dehydrogenase (LDH)
• Comprehensive metabolic panel
• Uric acid
• Hepatitis B and C testing
• HIV testing 1

Additional Assessments

• Bone marrow biopsy (may be omitted if PET scan is negative or shows homogeneous bone marrow uptake) 1
• Lumbar puncture with cytology and flow cytometry for high-risk patients 1
• Gastrointestinal endoscopy in rare limited stages I/II 2

Staging and Risk Stratification

Staging is performed according to the Ann Arbor classification system:

Stage	Description
I	One lymph node region or localized involvement of a single extralymphatic organ
II	Two or more lymph node regions on the same side of the diaphragm
III	Lymph node regions on both sides of the diaphragm
IV	Diffuse or disseminated involvement of one or more extralymphatic organs

2, 1

Risk assessment tools:

• International Prognostic Index (IPI) for most lymphomas 1
• Follicular Lymphoma International Prognostic Index (FLIPI) for follicular lymphoma 1
• Simplified MIPI risk factor for mantle cell lymphoma 2

Treatment Approach

Non-Hodgkin Lymphoma

• Follicular Lymphoma (indolent):

  • Limited stage (I/II): Radiotherapy (involved or extended field, 30-40 Gy) has curative potential 1
  • Advanced stage: Observation for asymptomatic patients; rituximab plus chemotherapy (R-CHOP, R-CVP, R-bendamustine) when treatment is needed 1

• Diffuse Large B-Cell Lymphoma (aggressive):

  • First-line therapy: Rituximab plus chemotherapy (R-CHOP) 1, 3

• Mantle Cell Lymphoma:

  • Combination regimens such as R-CHOP or R-bendamustine 2, 1

Hodgkin Lymphoma

• Combined chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) 3
• Alternative regimens: Stanford V or BEACOPP with radiotherapy 3
• Bleomycin dosing: 0.25 to 0.50 units/kg (10 to 20 units/m²) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly 4
• Doxorubicin dosing: 40 to 75 mg/m² given intravenously every 21 to 28 days as part of combination therapy 5

Follow-up and Monitoring

• PET-CT after 2-4 cycles and at completion of therapy 1
• Physical examination every 3 months for the first year, every 6 months for 2-3 more years, and then annually 2, 1
• Laboratory tests (CBC, LDH) at 3,6,12, and 24 months, then as needed 2, 1
• CT imaging at 6,12, and 24 months after treatment 2, 1
• Repeat bone marrow biopsy at the end of treatment if initially involved 1

Special Considerations

• Hepatitis B reactivation: Test all patients before anti-CD20 therapy; prophylaxis may be needed 1, 6
• Tumor lysis syndrome: Take precautions in patients with high tumor burden 1
• Fertility preservation: Discuss before starting treatment 1
• Vaccination: Patients should receive pneumococcal vaccines and age-appropriate vaccinations due to immunosuppression 3
• Cardiotoxicity monitoring: Regular assessment of left ventricular ejection fraction for patients receiving anthracyclines 5

Common Pitfalls to Avoid

1. Inadequate biopsy: Fine-needle aspirations are inappropriate for initial diagnosis and should only be used in emergency situations 2, 1
2. Improper tissue handling: Never immerse unsectioned lymph node in fixative 1
3. Incomplete staging: Thorough staging is essential as treatment substantially depends on disease stage 2
4. Overlooking hepatitis B status: Failure to screen for hepatitis B before rituximab therapy can lead to reactivation 6
5. Exceeding safe cumulative doses: Total doses of bleomycin over 400 units should be given with great caution due to pulmonary toxicity risk 4