What is the initial diagnostic and treatment approach for a patient with lymphoma presenting with B symptoms?

Diagnostic and Treatment Approach for Lymphoma with B Symptoms

For patients with lymphoma presenting with B symptoms, the initial diagnostic approach requires an excisional lymph node biopsy followed by comprehensive staging, with treatment determined by lymphoma subtype, stage, and risk factors. 1

Initial Diagnostic Workup

Biopsy

• Surgical excisional/incisional lymph node biopsy is mandatory for accurate diagnosis 2, 1
• Fine-needle aspirations or core biopsies are inappropriate and should only be used in rare cases requiring emergency treatment or when nodes are difficult to access (e.g., retroperitoneal) 2, 1
• Immediate processing by an experienced pathology institute is essential 1
• Fresh-frozen material should be preserved for additional molecular analysis 1

Laboratory Tests

• Complete blood count with differential
• Complete blood chemistry including:
  • Lactate dehydrogenase (LDH)
  • Uric acid
  • β2-microglobulin
  • Liver enzymes
  • Albumin
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP)
• Serum protein electrophoresis
• Screening tests for HIV, hepatitis B and C 2, 1

Imaging Studies

• Contrast-enhanced CT scan of neck, chest, abdomen, and pelvis
• Whole-body PET-CT scan (preferred) from base of skull to mid-thigh 2, 1
• PET-CT is particularly important for patients with B symptoms as it helps identify disease extent and has prognostic value 1

Bone Marrow Assessment

• Bone marrow biopsy is indicated if PET-CT is not available
• Not necessary if PET-CT is performed and negative for bone marrow involvement 2

Staging and Risk Assessment

Ann Arbor Staging System

• 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 1

Risk Assessment Tools

• For follicular lymphoma: Follicular Lymphoma-specific International Prognostic Index (FLIPI) 2
• For other lymphomas: International Prognostic Index (IPI) 1
• B symptoms (fever >38°C, drenching night sweats, unexplained weight loss >10% over 6 months) indicate more advanced disease 2

Treatment Approach

Follicular Lymphoma

1. Limited Stage (I-II):

   • Radiotherapy (involved or extended field, 30-40 Gy) with curative potential 2
   • Consider systemic therapy before radiation for large tumor burden 2

2. Advanced Stage (III-IV) with B symptoms:

   • Rituximab plus chemotherapy (R-CHOP, R-CVP, R-bendamustine) 2, 1, 3
   • Treatment should be initiated promptly in patients with B symptoms 2
   • Single-agent therapy (fludarabine, bendamustine, chlorambucil) for patients with contraindications to more intensive regimens 2

Hodgkin Lymphoma

1. Early Stage:

   • Combined-modality therapy with abbreviated chemotherapy followed by involved-field radiation 4

2. Advanced Stage or with B symptoms:

   • More prolonged course of combination chemotherapy:
     • ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)
     • Stanford V regimen
     • BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) 5, 4
   • Radiation therapy used selectively 4

Diffuse Large B-Cell Lymphoma (DLBCL)

• R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is standard therapy 3, 5
• Treatment should be initiated promptly in patients with B symptoms

Response Evaluation and Follow-up

Response Assessment

• PET-CT after 2-3 cycles of therapy and at completion of treatment 2, 1
• Persistent PET positivity identifies patients with adverse prognosis 1
• Patients with incomplete response should be evaluated for early salvage regimens 2

Follow-up Schedule

• History and physical examination every 3 months for 2 years, every 6 months for 3 additional years, then annually 2, 1
• Blood count and LDH at 3,6,12, and 24 months, then as needed 2, 1
• Radiological examinations at 6,12, and 24 months after treatment 2, 1
• Monitor for transformation, especially if LDH rises, single site grows disproportionately, or new B symptoms develop 1

Important Considerations

• B symptoms (fever, night sweats, weight loss) indicate more aggressive disease and typically require prompt treatment initiation 2
• PET-CT has higher sensitivity for detecting disease in advanced stages (100% for stage III-IV) compared to early stages (42.3% for stage I-II) 6
• Patients with lymphoma should receive pneumococcal vaccination (13-valent followed by 23-valent) and other age-appropriate vaccinations due to immunosuppression 5
• Treatment toxicities include neuropathy, cardiotoxicity, and secondary cancers, which should be considered in treatment selection 5