What is lymphoma?

Definition of Lymphoma

Lymphoma is a heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer (NK) cells, with B-cell lymphomas representing 80-85% of cases in the United States, T-cell lymphomas accounting for 15-20%, and NK-cell lymphomas being rare. 1, 2

Main Types of Lymphoma

Lymphoma is broadly classified into two main categories:

1. Hodgkin Lymphoma (HL)

   • Characterized by Reed-Sternberg cells in an inflammatory background
   • Subtypes include:
     • Classical Hodgkin Lymphoma (CHL) - 95% of HL cases
       • Nodular sclerosis
       • Mixed cellularity
       • Lymphocyte-rich
       • Lymphocyte-depleted
     • Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)
   • Generally has better prognosis with cure rates of 80% or higher 2

2. Non-Hodgkin Lymphoma (NHL)

   • Over 90 subtypes according to WHO classification 2, 3
   • Major subtypes include:
     • Diffuse Large B-Cell Lymphoma (DLBCL) - most common, aggressive
     • Follicular Lymphoma (FL) - second most common, indolent
     • Mantle Cell Lymphoma (MCL) - approximately 6% of NHL cases
     • Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia (SLL/CLL)
     • MALT Lymphoma
     • Peripheral T-cell lymphomas
     • Cutaneous T-cell lymphomas 1, 2

Origin and Pathophysiology

Lymphomas arise from a clonal proliferation of lymphocytes at various stages of differentiation 4. The molecular basis involves:

• Genetic lesions and chromosomal translocations
• Abnormal expression of transcription factors
• Viral genomes (e.g., Epstein-Barr virus, HTLV-1)
• Abnormal expression of genes that inhibit apoptosis (e.g., bcl-2)
• Mutation or deletion of tumor suppressor genes (e.g., p53) 5

Clinical Presentation

Lymphoma typically presents as:

• Painless lymphadenopathy (most common)
• Systemic symptoms (B symptoms) in advanced disease:
  • Fever
  • Unexplained weight loss
  • Night sweats
• Organ-specific symptoms depending on site of involvement 2, 3

Diagnosis and Staging

Diagnosis requires:

• Excisional lymph node biopsy (preferred method)
• Immunohistochemistry to determine lymphoma type and subtype
• Flow cytometry
• Cytogenetic and molecular studies 2

Staging follows the Lugano classification system:

• Incorporates PET/CT imaging
• Evaluates disease extent and presence of systemic symptoms
• Guides treatment decisions 2, 3

Treatment Approaches

Treatment varies by lymphoma type, subtype, and stage:

• Hodgkin Lymphoma:

  • Combined modality therapy with chemotherapy (ABVD) and radiotherapy
  • Advanced disease: ABVD, Stanford V, or BEACOPP regimens 2, 3

• Non-Hodgkin Lymphoma:

  • Varies widely by subtype
  • DLBCL: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
  • Follicular Lymphoma: Rituximab-based regimens, with maintenance or consolidation therapy 1, 3
  • MCL: Rituximab plus high-dose cytarabine-containing regimens followed by autologous stem cell transplantation 1

Prognosis

Prognosis varies significantly by lymphoma type and subtype:

• Hodgkin Lymphoma: Generally favorable with cure rates of 80% or higher
• Indolent NHL (e.g., follicular lymphoma): Chronic disease with multiple recurrences
• Aggressive NHL (e.g., DLBCL): Potentially curable with appropriate therapy
• T-cell and NK-cell lymphomas: Generally less favorable outcomes 1, 2

Recent Advances

Novel therapies have improved outcomes:

• Monoclonal antibodies (e.g., rituximab for B-cell lymphomas)
• Antibody-drug conjugates (e.g., brentuximab vedotin)
• Bruton tyrosine kinase inhibitors (e.g., ibrutinib for MCL) 1, 2

Long-term follow-up is essential to monitor for late effects of treatment, including secondary malignancies and cardiovascular complications 2.