What is lymphoma and how is it managed?

Lymphoma: Understanding and Management

Lymphoma is a cancer that originates from lymphocytes and primarily affects the lymphatic system, with two main types: Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL), each requiring distinct treatment approaches based on histology, staging, and risk factors. 1

Types of Lymphoma

Hodgkin Lymphoma (HL)

• Accounts for approximately 10-15% of all lymphoma cases 1, 2
• Characterized by the presence of Reed-Sternberg cells in an inflammatory background 3
• Subtypes include:
  • Classical HL (95% of cases): Nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted 3
  • Nodular lymphocyte-predominant HL (5% of cases): Characterized by "popcorn cells" 1
• Most patients are diagnosed between 15-30 years of age, with another peak in adults ≥55 years 3
• Highly curable with at least 80% of patients achieving long-term remission 3

Non-Hodgkin Lymphoma (NHL)

• Accounts for approximately 85-90% of all lymphoma cases 1, 4
• Heterogeneous group with over 90 subtypes 1
• Origin:
  • B-cell (80-85% of cases): DLBCL, follicular lymphoma, mantle cell lymphoma, etc.
  • T-cell (15-20% of cases)
  • NK-cell (rare)
• Clinical course varies widely from indolent to highly aggressive 3, 2

Clinical Presentation

• Most common presentation: Painless lymphadenopathy 4
• Systemic symptoms (B symptoms):
  • Fever >38°C
  • Unexplained weight loss >10% of body weight in 6 months
  • Drenching night sweats
• Other presentations may include:
  • Mediastinal mass (especially in HL)
  • Extranodal disease
  • Splenomegaly
  • Bone marrow involvement with cytopenias
  • Organ-specific symptoms based on site of involvement

Diagnosis

• Excisional lymph node biopsy is the gold standard for diagnosis 1
  • Core needle biopsy may be adequate in some cases but excisional is preferred
  • Fine needle aspiration is inadequate for initial diagnosis
• Immunohistochemistry is essential to determine lymphoma type and subtype 1
• Staging workup should include:
  • PET/CT scan (particularly important for early-stage disease) 3
  • Bone marrow biopsy for advanced stages
  • Laboratory tests: CBC, LDH, beta2-microglobulin, liver/kidney function 3
  • HIV and hepatitis B/C screening 3

Staging

• Lugano classification system (updated Ann Arbor) incorporating PET/CT imaging 1, 4
  • Stage I: Single lymph node region or single extralymphatic site
  • Stage II: Two or more lymph node regions on the same side of the diaphragm
  • Stage III: Lymph node regions on both sides of the diaphragm
  • Stage IV: Disseminated extralymphatic involvement
• Prognostic indices:
  • HL: International Prognostic Score (IPS)
  • Follicular lymphoma: FLIPI or FLIPI-2 3
  • DLBCL: International Prognostic Index (IPI)

Treatment Approach

Hodgkin Lymphoma

1. Early-stage favorable disease:

   • Combined modality therapy: 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by 20-30 Gy involved-field radiotherapy 3, 1

2. Early-stage unfavorable disease:

   • 4 cycles of ABVD followed by involved-field radiotherapy 3
   • Alternative: Stanford V regimen followed by radiotherapy 3

3. Advanced-stage disease:

   • 6 cycles of ABVD 3
   • Alternative: BEACOPP regimen for high-risk patients 4
   • PET-guided approach with interim PET after 2 cycles to guide subsequent therapy 3

4. Relapsed/refractory disease:

   • High-dose chemotherapy with autologous stem cell transplantation 3, 1
   • Brentuximab vedotin (CD30-directed antibody-drug conjugate) 1
   • Checkpoint inhibitors (nivolumab, pembrolizumab)

Non-Hodgkin Lymphoma

1. Indolent B-cell lymphomas (e.g., follicular lymphoma):

   • Asymptomatic, low tumor burden: Watch and wait strategy 3
   • Symptomatic or high tumor burden:
     • Rituximab plus chemotherapy (R-CHOP, R-CVP, or BR) 3, 5
     • Rituximab maintenance for responding patients 3

2. Aggressive B-cell lymphomas (e.g., DLBCL):

   • R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for 6 cycles 3, 5, 6
   • CNS prophylaxis for high-risk patients 7
   • Consolidative radiation for bulky disease

3. Mantle cell lymphoma:

   • Younger patients: Intensive induction (including cytarabine) followed by autologous stem cell transplantation 3
   • Older patients: Less intensive chemoimmunotherapy regimens 3
   • Maintenance therapy with rituximab 3

4. Relapsed/refractory disease:

   • Salvage chemotherapy followed by high-dose therapy and autologous stem cell transplantation
   • Targeted therapies (ibrutinib, idelalisib, venetoclax) 3
   • CAR-T cell therapy for eligible patients 8

Long-term Follow-up

• Regular surveillance to monitor for:
  • Disease recurrence
  • Secondary malignancies (especially after radiation therapy)
  • Cardiovascular complications (particularly after anthracycline-based chemotherapy)
  • Endocrine dysfunction
  • Pulmonary toxicity (especially after bleomycin)
• Immunization recommendations:
  • Pneumococcal vaccines (13-valent followed by 23-valent) 4
  • Annual influenza vaccination
  • Age-appropriate vaccinations

Pitfalls and Caveats

• Avoid misdiagnosis by ensuring adequate tissue sampling through excisional biopsy rather than fine needle aspiration
• Do not initiate treatment without complete staging evaluation
• Monitor for treatment toxicities, particularly:
  • Bleomycin-induced pulmonary toxicity
  • Anthracycline-induced cardiotoxicity
  • Increased risk of secondary malignancies
• Recognize that interim PET results must be interpreted using standardized criteria (Deauville score) 3
• Consider clinical trials for eligible patients, especially those with relapsed/refractory disease 3

Lymphoma management has evolved significantly with improved diagnostic techniques and novel therapies, resulting in better outcomes and survival rates, particularly for Hodgkin lymphoma where cure rates exceed 80% 3.