Hodgkin's vs Non-Hodgkin's Lymphoma: Key Differences
The fundamental distinction between Hodgkin's and non-Hodgkin's lymphoma is pathologic: Hodgkin's lymphoma is defined by the presence of Reed-Sternberg cells (in classical HL) or lymphocyte-predominant "popcorn" cells (in nodular lymphocyte-predominant HL), while non-Hodgkin's lymphoma lacks these characteristic cells and consists of various other malignant lymphoid cell types. 1
Epidemiology and Incidence
Age Distribution:
- Hodgkin's lymphoma demonstrates a characteristic bimodal age distribution with peaks at 15-30 years and after age 55, making it particularly common in young adults aged 20-40 years 2, 1
- Non-Hodgkin's lymphoma incidence increases progressively with age, from 0.3/100,000 per year in ages 35-39 to 26.6/100,000 per year in ages 80-84 2
Relative Frequency:
- Hodgkin's lymphoma accounts for approximately 5% of all lymphomas in Western countries, with a crude incidence of 2.3 cases/100,000/year in the European Union 2, 1
- Non-Hodgkin's lymphoma is far more common, with a crude incidence of 3-4/100,000/year for large cell lymphoma alone, and B-cell lymphomas constituting approximately 80-90% of all NHL cases 2, 3
Histologic and Cellular Characteristics
Hodgkin's Lymphoma:
- Classical HL (95% of cases) is characterized by Reed-Sternberg cells embedded in an inflammatory background, with malignant cells representing only a small fraction of the total cellular population 2, 1
- Immunophenotype: HRS cells stain consistently positive for CD30 and CD15, occasionally positive for CD20, and negative for CD45 2
- Nodular lymphocyte-predominant HL (5% of cases) contains LP cells ("popcorn cells") that are CD20+, CD45+, but lack CD15 and CD30 2
Non-Hodgkin's Lymphoma:
- NHL represents a highly heterogeneous group with multiple subtypes, lacking Reed-Sternberg cells 1, 3
- B-cell lymphomas account for 80-90% of NHL, with follicular lymphoma and diffuse large B-cell lymphoma being the most common entities 3
- T-cell lymphomas represent 15-20% of cases, while NK-cell lymphomas are rare 2
Diagnostic Approach
Biopsy Requirements:
- Both HL and NHL require excisional lymph node biopsy for definitive diagnosis, as fine-needle aspiration alone is insufficient 2, 1, 4
- The specimen must provide enough material for fresh frozen and formalin-fixed samples to allow comprehensive immunohistochemistry, flow cytometry, and molecular studies 2
Immunohistochemistry:
- Immunohistochemistry is highly recommended and often essential to distinguish between HL and NHL, particularly when Reed-Sternberg-like cells appear in NHL (a rare diagnostic pitfall) 2, 1
- For classical HL: CD30+, CD15+ (majority); CD3-, CD45-; CD20+ (<40%) 2
- For NLPHL: CD20+, CD45+; CD3-, CD15-, CD30- 2
Staging and Risk Assessment
Common Elements:
- Both use the Ann Arbor staging classification system 2
- Both require assessment of B symptoms (fever, drenching night sweats, unexplained weight loss >10% over 6 months) 2
- PET-CT is the gold standard for staging FDG-avid lymphomas in both diseases 2, 4
Hodgkin's-Specific Risk Stratification:
- Patients are allocated to three categories: limited, intermediate, and advanced stages based on EORTC/LYSA or GHSG definitions 2
- Given the high sensitivity of PET-CT for bone marrow involvement, bone marrow biopsy is no longer indicated in HL patients undergoing PET-CT evaluation 2
- ESR is a key prognostic factor in HL staging 2
Non-Hodgkin's-Specific Risk Stratification:
- The International Prognostic Index (IPI) is used to define prognostic subgroups in NHL 2, 3
- Bone marrow biopsy is required in stage IB, IIB, and stage III-IV NHL 2
- Risk assessment varies significantly by NHL subtype (follicular vs. DLBCL vs. others) 3
Treatment Approaches
Hodgkin's Lymphoma:
- Hodgkin's lymphoma is now curable in at least 80% of patients with modern treatment 1
- Standard treatment for early-stage favorable HL is combined modality therapy with ABVD x 2-4 cycles or Stanford V x 8 weeks plus involved-field radiotherapy 2
- Treatment considerations often focus on minimizing long-term toxicity rather than improving cure rates, especially in early-stage disease 1
- Bleomycin is FDA-approved for use in Hodgkin's disease as part of combination regimens 5
Non-Hodgkin's Lymphoma:
- Treatment is highly dependent on histologic subtype and stage 3
- For CD20+ large-cell NHL, CHOP combined with rituximab every 21 days for usually 8 cycles is the current standard 2
- Rituximab is FDA-approved for multiple NHL subtypes including relapsed/refractory low-grade or follicular B-cell NHL, previously untreated follicular NHL, and diffuse large B-cell NHL in combination with CHOP 6
- For follicular lymphoma with early-stage disease, radiation therapy is generally used, whereas stage III-IV disease requires chemotherapy, immunotherapy, or radioimmunotherapy 3
- High-dose therapy with stem cell support is the treatment of choice for chemosensitive relapsed aggressive lymphomas 3
Prognosis
Hodgkin's Lymphoma:
- Mortality rate is 0.4 cases/100,000/year in the European Union 2
- Cure rates exceed 80% with modern therapy 1
- Long-term survivors face risks of treatment-related complications including secondary malignancies 7
Non-Hodgkin's Lymphoma:
- Prognosis varies dramatically by subtype 3
- Follicular lymphoma patients generally experience long survival, but only a minority are cured 3
- Diffuse large B-cell lymphoma has better cure potential with aggressive treatment, but disease relapse remains a significant problem 3
Critical Diagnostic Pitfalls
Common Errors to Avoid:
- Never rely on fine-needle aspiration alone for initial diagnosis of either lymphoma type 1, 4
- Do not fail to perform comprehensive immunophenotyping, as this is essential for distinguishing HL from NHL and for NHL subtype classification 2, 1
- Do not skip baseline PET-CT before therapy in FDG-avid lymphomas, as this compromises accurate response assessment 4
- Be aware that Reed-Sternberg-like cells can rarely appear in NHL, making immunohistochemistry critical for accurate diagnosis 1