What is the appropriate workup and treatment for a patient suspected of having Non-Hodgkin Lymphoma (NHL)?

Workup and Treatment for Non-Hodgkin Lymphoma (NHL)

The appropriate workup for suspected NHL requires a comprehensive tissue biopsy, complete physical examination, laboratory studies including CBC, LDH, and hepatitis testing, and CT imaging of chest/abdomen/pelvis with contrast, followed by bone marrow biopsy to establish diagnosis and staging. 1

Diagnostic Workup

Essential Initial Evaluation

• Tissue acquisition: Excisional or incisional lymph node biopsy is mandatory for reliable diagnosis 1

  • Core needle biopsies should only be performed for difficult-to-access nodes (e.g., retroperitoneal)
  • Fine-needle aspirations are inadequate for diagnosis

• Physical examination:

  • Thorough examination of all node-bearing areas
  • Assessment of liver and spleen size
  • Documentation of performance status and symptoms 1

• Laboratory studies:

  • Complete blood count (CBC)
  • Serum lactate dehydrogenase (LDH)
  • Comprehensive metabolic panel
  • Hepatitis B testing (HBsAg and HBcAb) - mandatory before anti-CD20 therapy 1
  • Hepatitis C testing in high-risk patients and those with splenic marginal zone lymphoma 1
  • Protein electrophoresis for B-cell lymphomas 1

• Imaging:

  • CT chest/abdomen/pelvis with oral and IV contrast (unless renal insufficiency) 1
  • PET-CT is highly sensitive for most NHL subtypes and superior for detecting nodal and extranodal involvement 2

Additional Essential Workup

• Bone marrow biopsy with or without aspirate:

  • Required for all NHL patients except those with SLL/CLL with clonal lymphocytosis identified by flow cytometry 1
  • Bilateral cores recommended for potentially early-stage indolent lymphoma (stage I or II) 1
  • Particularly important for aggressive subtypes like primary cutaneous DLBCL, leg-type 1

• Cardiac assessment:

  • MUGA scan or echocardiogram when anthracycline-containing regimens are planned 1

Optional Procedures (Based on NHL Subtype)

• β-microglobulin
• Head CT or brain MRI
• Lumbar puncture for cerebrospinal fluid analysis (especially for MCL and DLBCL) 1
• Endoscopic ultrasound for gastric MALT lymphoma 1
• Discussion of fertility issues and sperm banking when appropriate 1

Staging and Risk Assessment

Ann Arbor Staging System 1, 2

• Stage I: Single lymphatic region or localized involvement of single extralymphatic organ
• Stage II: Two or more lymphatic regions on same side of diaphragm
• Stage III: Lymphatic regions on both sides of diaphragm
• Stage IV: Diffuse or disseminated involvement of one or more extralymphatic organs

Risk Assessment

• International Prognostic Index (IPI) should be calculated for prognostic purposes 1
• For follicular lymphoma, the Follicular Lymphoma International Prognostic Index (FLIPI) should be used 2

Treatment Approach

Diffuse Large B-Cell Lymphoma (DLBCL)

• First-line therapy: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) given every 14 or 21 days for 6-8 cycles is the standard treatment 1

  • For limited-stage disease: 6 cycles of R-CHOP followed by involved-field radiation therapy
  • For extensive disease: 6-8 cycles of R-CHOP

• Relapsed/Refractory Disease:

  • Salvage regimens (R-DHAP, R-ESHAP, R-ICE) followed by high-dose therapy with stem cell support in responsive patients under age 65 1
  • Additional involved-field radiation may be used for limited-stage relapse 1

Follicular Lymphoma

• Limited-stage disease: Radiation therapy 3
• Advanced-stage disease requiring treatment:
  • Rituximab plus chemotherapy (R-CHOP, R-CVP, R-bendamustine) 2, 4
  • Bendamustine dose: 90-120 mg/m² IV on days 1 and 2 of a 21-28 day cycle 4

T-Cell Lymphomas

• CHOP remains the standard treatment 1

Response Evaluation and Follow-up

Response Assessment

• CT imaging after 2-4 cycles and at completion of therapy 1
• PET-CT is valuable for response assessment, particularly for aggressive lymphomas 1
• Repeat bone marrow biopsy at end of treatment if initially involved 1

Follow-up Schedule

• Physical examination: Every 3 months for first year, every 6 months for 2 more years, then annually 1
• Laboratory tests: CBC and LDH at 3,6,12, and 24 months, then as needed 1
• Imaging: CT scans at 6,12, and 24 months after treatment 1
• Thyroid function: Evaluate at 1,2, and 5 years in patients who received neck irradiation 1
• Breast cancer screening: For women who received chest irradiation at premenopausal age, especially <25 years 1

Special Considerations

• Hepatitis B reactivation: Test all patients before anti-CD20 therapy; prophylaxis may be needed 1
• CNS prophylaxis: Consider for high-risk patients (IPI>2) with involvement of bone marrow, testis, spine, or skull base 1
• Tumor lysis syndrome: Take precautions in patients with high tumor burden 1
• Fertility preservation: Should be discussed before starting treatment 2

Remember that NHL represents a heterogeneous group of diseases, and treatment approaches must be tailored based on histologic subtype, stage, and patient factors. Early consultation with a hematologist/oncologist is essential for optimal management.