What is the approach to diagnosing and treating lymphoma?

Diagnostic and Treatment Approach to Lymphoma

The definitive diagnosis of lymphoma requires an excisional lymph node biopsy providing adequate tissue for histopathological examination according to the WHO classification, with immunohistochemistry studies including CD20 for proper subtyping. 1

Diagnostic Workup

Initial Evaluation

• Surgical specimen/excisional lymph node biopsy is essential for diagnosis, providing enough material for fresh frozen and formalin-fixed samples 1
• Fine needle aspirations or core biopsies are inadequate for proper diagnosis and should only be used in rare emergency situations 1
• The histological report should follow the World Health Organization classification with appropriate immunohistochemistry 1

Staging Procedures

• Complete staging requires:
  • CT scan of thorax, abdomen, and pelvis 1
  • Bone marrow aspirate and biopsy 1
  • Complete blood count, LDH, uric acid, and screening for HIV and hepatitis B/C 1
• Ann Arbor staging system is used with mention of bulky disease 1
• For prognostic purposes:
  • International Prognostic Index (IPI) for large cell lymphomas 1
  • Follicular Lymphoma-specific International Prognostic Index (FLIPI) for follicular lymphomas 1

Special Considerations

• Diagnostic spinal tap with prophylactic cytarabine/methotrexate should be considered in high-risk patients (IPI>2) with bone marrow, testis, spine, or skull base involvement 1
• Protein electrophoresis is recommended for B-cell lymphomas 1
• Core needle biopsy with ultrasound guidance has 95% sensitivity when lymphoma is suspected based on clinical features 2

Treatment Approach

Follicular Lymphoma

• Limited Stage (I-II):

  • Radiotherapy is the treatment of choice with curative potential 1
  • Extended field irradiation is recommended 1
  • In selected patients with large tumor burden, systemic therapy may be used 1

• Advanced Stage (III-IV):

  • Treatment should be initiated upon symptoms (B-symptoms, hematopoietic impairments, bulky disease, or progression) 1
  • Primary chemotherapy options include:
    • Combination regimens: COP, CHOP
    • Single agents: fludarabine or chlorambucil
    • Addition of anti-CD20 antibodies (rituximab) to initial chemotherapy 1

Large Cell Non-Hodgkin's Lymphoma

• Treatment with curative intent:
  • R-CHOP (rituximab plus CHOP) given every 21 days for 8 cycles is the standard for CD20+ large-cell NHL of all stages 1
  • For T-cell lymphoma, CHOP remains the standard 1
  • Shortening the interval between CHOP cycles to two weeks with growth factor support may be considered 1
  • Dose reductions due to hematological toxicity should be avoided 1

Medication Considerations

• Rituximab is a CD20-directed cytolytic antibody indicated for various types of NHL 3
• Cyclophosphamide is effective alone in susceptible malignancies but more frequently used concurrently or sequentially with other antineoplastic drugs 4

Response Evaluation and Follow-up

Response Assessment

• Radiological tests should be performed:
  • After every 2-4 cycles of therapy 1
  • After completion of treatment 1
  • Whenever there are doubts about adequate response 1
• Patients with incomplete or lacking response should be evaluated for early salvage regimens 1

Follow-up Schedule

• History and physical examination:
  • Every 3 months for 2 years
  • Every 6 months for 3 more years
  • Then once a year with attention to transformation and secondary malignancies 1, 5
• Laboratory monitoring:
  • Blood count and LDH at 3,6,12, and 24 months
  • Then only as needed for evaluation of suspicious symptoms 1, 5
• Imaging surveillance:
  • Minimal adequate radiological examinations at 6,12, and 24 months after treatment 1, 5

Special Monitoring

• Thyroid function evaluation at 1,2, and 5 years in patients with neck irradiation 1, 5
• Women who received chest irradiation at premenopausal age should be screened for secondary breast cancers 1
• For patients who received rituximab, monitoring for hepatitis B reactivation for up to 2 years is recommended 5

Common Pitfalls and Caveats

• Avoid fine needle aspiration as the sole diagnostic approach for lymphoma 2, 6
• Supra- and infraclavicular lymph nodes are always suspicious of underlying malignancy and warrant prompt investigation 6
• Biopsy should be considered for any suspicious new or rapidly growing lesion to rule out transformation to aggressive lymphoma 5
• Long-term monitoring for radiation-related complications is essential, particularly thyroid dysfunction in patients who received neck irradiation 5
• Patients with lymphoma should receive pneumococcal vaccines and other age-appropriate vaccinations due to the immunosuppressive nature of the condition 7