What is Hodgkin's lymphoma?

Hodgkin Lymphoma: Definition and Classification

Hodgkin lymphoma (HL) is an uncommon malignancy involving lymph nodes and the lymphatic system, characterized by the presence of specific malignant cells in an inflammatory background, with high cure rates exceeding 80% with appropriate treatment. 1

Types of Hodgkin Lymphoma

Hodgkin lymphoma is divided into two main types:

1. Classical Hodgkin Lymphoma (CHL) - 95% of cases in Western countries

   • Characterized by Reed-Sternberg cells in an inflammatory background
   • Subtypes include:
     • Nodular sclerosis
     • Mixed cellularity
     • Lymphocyte-depleted
     • Lymphocyte-rich

2. Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) - 5% of cases

   • Lacks Reed-Sternberg cells
   • Characterized by lymphocyte-predominant cells (sometimes called "popcorn cells")

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Epidemiology

• Most patients are diagnosed between 15-30 years of age
• Second peak occurs in adults aged 55 years or older
• Bimodal age distribution is characteristic
• In 2020, an estimated 8,480 new cases and 970 deaths in the United States
• Incidence in Western countries is approximately 2-3 per 100,000 per year

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Pathophysiology

• CHL is derived mainly from monoclonal, preapoptotic B cells
• Reed-Sternberg cells (the malignant cells in CHL) carry rearranged, somatically mutated immunoglobulin heavy chains
• These cells escape apoptosis through various mechanisms including mutations and aberrant signaling pathways
• The malignant cells represent only 0.1-1% of the entire cell population in the affected tissue
• The remaining cells consist of a heterogeneous mixture of lymphocytes, histiocytes, eosinophils, plasma cells, and fibroblasts

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Clinical Presentation

• Most patients (>60%) present with asymptomatic enlarged lymph nodes
• Common sites of involvement:
  • Cervical lymph nodes
  • Supraclavicular lymph nodes
  • Mediastinal lymph nodes
• Less common:
  • Sub-diaphragmatic presentations
  • Bone marrow involvement
  • Hepatic involvement
• Systemic symptoms (B symptoms) occur in approximately 35% of cases:
  • Fever
  • Night sweats
  • Weight loss

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Diagnosis

• Diagnosis always requires a lymph node biopsy
• Immunophenotyping helps distinguish between CHL and NLPHL:
  • CHL: CD15+/CD30+/CD20-
  • NLPHL: CD15-/CD30-/CD20+
• Staging is based on the Ann Arbor staging system or its Cotswolds modification
• Staging workup includes:
  • Physical examination
  • CT scans of chest and abdomen
  • Bone marrow biopsy
  • PET/CT scan (plays a central role in staging and response assessment)

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Prognosis and Risk Stratification

• Overall 5-year relative survival rate is 94-97%

• Patients are typically classified into three risk groups:

  1. Early-stage favorable (stage I-II with no unfavorable factors)
  2. Early-stage unfavorable (stage I-II with unfavorable factors)
  3. Advanced-stage disease (stage III-IV)

• Unfavorable factors for early-stage disease include:

  • Large mediastinal mass
  • Multiple nodal sites (>3)
  • B symptoms
  • Elevated ESR (≥50)

• For advanced disease, the International Prognostic Score (IPS) helps determine prognosis based on seven adverse factors:

  • Age ≥45 years
  • Male gender
  • Stage IV disease
  • Albumin <4 g/dL
  • Hemoglobin <10.5 g/dL
  • Leukocytosis
  • Lymphocytopenia

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Treatment Approach

• Early-stage favorable HL: Two cycles of ABVD chemotherapy followed by 30 Gy involved-field radiotherapy
• Early-stage unfavorable HL: Combined modality therapy with more intensive chemotherapy
• Advanced-stage HL: Longer course of chemotherapy (typically ABVD or BEACOPP)
• Relapsed/refractory disease: High-dose chemotherapy with autologous stem cell transplantation
• Newer agents such as brentuximab vedotin (CD30-directed antibody-drug conjugate) and anti-PD-1 antibodies are being incorporated into treatment regimens

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Long-term Follow-up

• Long-term follow-up is essential after completion of treatment
• Potential late effects of treatment remain an important consideration
• Monitoring for secondary malignancies and cardiovascular complications is necessary

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Important Clinical Considerations

• PET/CT is crucial for response assessment using the Deauville criteria (5-point scale)
• HL typically spreads by contiguity within the lymphatic tissue network
• Late extension to adjacent and distant viscera may occur
• Clinical trials are encouraged for all patients with HL, especially those with relapsed or refractory disease

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