What is the recommended workup and management for a patient with suspected non‑Hodgkin lymphoma?

Workup and Management of Suspected Non-Hodgkin Lymphoma

For suspected NHL, obtain an excisional lymph node biopsy (or core biopsy if excisional is not feasible) with immunohistochemistry including CD20 to establish diagnosis, followed by comprehensive staging with CT imaging, bone marrow biopsy, and laboratory assessment including LDH to guide risk-stratified treatment. 1

Diagnostic Approach

Tissue Acquisition

• Excisional lymph node biopsy is the gold standard, providing adequate tissue for both fresh frozen and formalin-fixed samples 1
• Core needle biopsy is acceptable when excisional biopsy is not feasible, particularly in patients requiring emergency treatment or those unsuitable for curative therapy 1
• Fine-needle aspiration is insufficient except in rare circumstances when combined with immunohistochemistry and interpreted by an expert hematopathologist 1
• Immediate processing by an experienced pathology institute must be ensured 1

Required Immunohistochemistry

• CD20 immunohistochemistry is mandatory to confirm B-cell lineage and guide rituximab eligibility 1
• The histological report must provide diagnosis according to WHO classification 1

Staging Workup

Imaging Studies

• CT scan of neck, chest, abdomen, and pelvis is required for all patients amenable to curative therapy 1
• Chest X-ray (posterior-anterior and lateral) is recommended as baseline 1
• PET-CT is not routinely recommended for NHL staging, but may be helpful to confirm localized disease when radiotherapy is considered 1

Laboratory Assessment

• Complete blood count with differential and platelets 1
• Serum LDH is essential for prognostic assessment via the International Prognostic Index (IPI), though normal LDH does not exclude NHL 1, 2
• Comprehensive metabolic panel including liver and renal function tests, albumin, and uric acid 1
• Screening for HIV, hepatitis B, and hepatitis C is required before initiating therapy 1
• Protein electrophoresis is recommended for B-cell lymphomas 1

Bone Marrow Evaluation

• Bone marrow aspirate and biopsy are required for patients amenable to curative therapy 1
• May be omitted in terminally ill patients with confirmed advanced-stage disease and normal peripheral blood counts 1

CNS Prophylaxis Consideration

• Diagnostic lumbar puncture with immediate prophylactic intrathecal chemotherapy (cytarabine or methotrexate) should be performed in high-risk patients 1
• High-risk features include: IPI score >2, bone marrow involvement, testicular involvement, spinal involvement, or skull base involvement 1

Risk Stratification

International Prognostic Index (IPI)

• Calculate IPI score using five factors: age >60 years, Ann Arbor stage III-IV, ECOG performance status ≥2, elevated LDH (>1× upper limit of normal), and >1 extranodal site 2
• Four risk groups: Low (0-1 factors), Low-Intermediate (2 factors), High-Intermediate (3 factors), High (4-5 factors) 2

Clinical Assessment

• Document B symptoms: unexplained fever >38°C, drenching night sweats, or weight loss >10% within 6 months 1
• Assess for alcohol intolerance, pruritus, fatigue, and performance status 1
• Physical examination must include all lymphoid regions, spleen, and liver 1
• Identify bulky disease (masses requiring specific notation for treatment planning) 1

Management by Histologic Subtype

Diffuse Large B-Cell Lymphoma (Most Common Aggressive NHL)

• R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) every 21 days for 8 cycles is the standard for CD20-positive disease at all stages 1, 3
• Consider shortening cycle interval to 14 days with growth factor support 1
• Avoid dose reductions for hematological toxicity; use prophylactic growth factors for febrile neutropenia in curative-intent treatment 1

T-Cell Lymphomas

• CHOP without rituximab remains standard, as these are CD20-negative 1

Follicular Lymphoma (Indolent NHL)

• "Watch and wait" is appropriate for asymptomatic patients regardless of age 1
• For symptomatic advanced-stage disease: bendamustine plus rituximab (dose-reduced to 70 mg/m² for 4 cycles in elderly/frail patients versus 90 mg/m² for 6 cycles in fit patients) 1

Response Evaluation

Interim Assessment

• Perform radiological evaluation after 2-4 cycles of chemotherapy 1
• Repeat initially abnormal bone marrow biopsy or lumbar puncture at end of treatment 1

End-of-Treatment Assessment

• Imaging after final cycle of chemotherapy (with or without radiotherapy) 1
• Patients with incomplete response should be evaluated for early salvage regimens 1

Follow-Up Surveillance

Clinical Monitoring

• Every 3 months for first year, then every 6 months for years 2-3, then annually 1
• Focus on detecting secondary malignancies and long-term treatment toxicities 1

Laboratory Monitoring

• Blood count and LDH at 3,6,12, and 24 months, then only as clinically indicated 1

Imaging Surveillance

• CT scans at 6,12, and 24 months post-treatment 1
• Routine PET surveillance is not recommended 1

Special Considerations

• TSH monitoring at 1,2, and 5 years for patients who received neck irradiation 1
• Breast cancer screening (clinical examination and mammography after age 40-50) for women who received chest irradiation at premenopausal age, especially <25 years 1

Critical Pitfalls to Avoid

• Do not rely on fine-needle aspiration alone—inadequate tissue prevents accurate subtyping and immunophenotyping 1
• Do not assume normal LDH excludes NHL—early-stage and low-grade lymphomas frequently present with normal LDH 2
• Do not perform extensive staging procedures once advanced-stage disease is confirmed if they will not change management 1
• Do not reduce chemotherapy doses for hematological toxicity in curative-intent treatment—use growth factor support instead 1
• Do not omit CNS evaluation in high-risk patients (IPI >2, bone marrow/testicular/CNS involvement) 1