Lymphoma Overview
Lymphoma is a heterogeneous group of malignant neoplasms originating from lymphocytes in the lymph nodes and lymphatic system, divided into two main categories: Hodgkin lymphoma and non-Hodgkin lymphoma, with the majority being highly treatable and often curable with modern therapies. 1
Classification and Epidemiology
Hodgkin Lymphoma
- Classical Hodgkin lymphoma (CHL) accounts for the majority of cases in Western countries and is characterized by Reed-Sternberg cells in an inflammatory background 1
- Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) lacks Reed-Sternberg cells but contains lymphocyte-predominant cells (popcorn cells) 1
- Bimodal age distribution with peaks between 15-30 years and again after age 55 years 1
- Approximately 9,050 new cases diagnosed annually in the United States with 1,150 deaths 1
- Now curable in at least 80% of patients, representing one of oncology's greatest success stories 1
Non-Hodgkin Lymphoma
- B-cell lymphomas constitute 80-85% of all NHL cases, with T-cell lymphomas representing 15-20% and NK-cell lymphomas being rare 1
- Approximately 70,800 new cases diagnosed annually in the United States 1
- The most common subtypes are diffuse large B-cell lymphoma (31%) and follicular lymphoma (22%), together accounting for over 50% of all NHL cases in the United States 1
- Other significant subtypes include small lymphocytic lymphoma/chronic lymphocytic leukemia (6%), mantle cell lymphoma (6%), peripheral T-cell lymphoma (6%), and MALT lymphoma (5%) 1
Clinical Presentation
Common Features
- Painless lymphadenopathy is the most typical presenting symptom 2
- B symptoms (fever, unexplained weight loss >10%, drenching night sweats) indicate more advanced disease 1, 2
- Splenomegaly and bone marrow involvement are common, particularly in indolent lymphomas 3
- Extranodal involvement occurs but is less common in most subtypes 3
Hodgkin-Specific Features
- Most patients diagnosed between ages 15-30 years, with second peak after age 55 1
- Often presents with mediastinal adenopathy 1
Non-Hodgkin-Specific Features
- Median age at diagnosis is 72 years for chronic lymphocytic leukemia, with 70% diagnosed after age 65 1
- Follicular lymphoma patients are often asymptomatic despite advanced stage disease 3
- Constitutional symptoms are uncommon in indolent lymphomas unless transformation occurs 3
Diagnosis and Staging
Diagnostic Approach
- Open lymph node biopsy is preferred over needle biopsy to provide adequate tissue for grade assessment and transformation evaluation 2, 3
- Immunohistochemical staining is essential for subtype classification 1, 3
- For follicular lymphoma: positive staining for CD19, CD20, CD10, and monoclonal immunoglobulin, with bcl-2 protein expression 3
- Genetic features detected by cytogenetics or FISH are increasingly important, including the t(14;18) translocation in follicular lymphoma 1, 3
Staging Systems
- Hodgkin lymphoma uses the Ann Arbor staging system with three prognostic groups: early-stage favorable (stage I-II without unfavorable factors), early-stage unfavorable (stage I-II with unfavorable factors), and advanced-stage (stage III-IV) 1
- Unfavorable factors include bulky mediastinal disease (mediastinal mass ratio >0.33), bulky disease >10 cm, B symptoms, ESR >50, and >3 nodal sites 1
- The International Prognostic Score (IPS) predicts prognosis for advanced-stage Hodgkin lymphoma 1
- The Lugano classification system incorporates PET/CT imaging for staging lymphoma 2
Treatment Principles
Hodgkin Lymphoma
- Chemotherapy or combined modality therapy is standard initial treatment, followed by PET/CT restaging using the Deauville 5-point scale 1
- Brentuximab vedotin (CD30-directed antibody-drug conjugate) shows encouraging results for relapsed or refractory disease 1
- Long-term follow-up is essential due to potential late treatment effects 1
Non-Hodgkin Lymphoma
- Rituximab-based chemoimmunotherapy (R-CHOP) is standard for diffuse large B-cell lymphoma 2
- Observation remains appropriate for asymptomatic patients with low-bulk follicular lymphoma and no cytopenias, as early treatment shows no overall survival advantage 3
- For follicular lymphoma requiring treatment: chemoimmunotherapy with rituximab maintenance improves outcomes 1, 3
- Mantle cell lymphoma: rituximab-based chemoimmunotherapy followed by high-dose therapy and autologous stem cell rescue for advanced-stage disease 1
- Ibrutinib (Bruton tyrosine kinase inhibitor) approved for relapsed or refractory mantle cell lymphoma 1
Chronic Lymphocytic Leukemia
- FCR (fludarabine, cyclophosphamide, rituximab) represents standard of care in younger or fit patients 1
- Older patients with comorbidities may not tolerate myelosuppressive regimens and require alternative approaches 1
- Poor-risk cytogenetic abnormalities [del(17p), del(11q)] and unmutated IGHV gene predict inferior outcomes even with chemoimmunotherapy 1
Prognosis
Hodgkin Lymphoma
- 5-year survival rates have improved dramatically, with cure rates exceeding 80% 1
- Represents one of the most successful treatment advances in oncology over the past four decades 1
Non-Hodgkin Lymphoma
- Prognosis varies significantly by subtype 1
- Indolent lymphomas (follicular, marginal zone) are generally incurable but have prolonged survival with modern therapies 3
- Aggressive lymphomas (diffuse large B-cell) are potentially curable with intensive chemoimmunotherapy, with 40-80% cure rates depending on stage 4
- Follicular Lymphoma International Prognostic Index (FLIPI) uses five factors: age >60, hemoglobin <12 g/dL, elevated LDH, stage III/IV, >4 nodal areas 3
Important Considerations
Risk Factors
- Tobacco use and obesity are major modifiable risk factors 2
- Genetic, infectious (EBV), and inflammatory etiologies contribute to lymphoma development 1, 2
Surveillance and Prevention
- Patients need routine surveillance for complications, relapse, and age-appropriate cancer screenings 2
- 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine (at least 8 weeks later) plus age-appropriate vaccinations are essential due to immunosuppression 2
- Household contacts should maintain current immunizations 2