What is the key difference between Hodgkin (HL) and non-Hodgkin lymphoma (NHL)?

Key Difference Between Hodgkin and Non-Hodgkin Lymphoma

The fundamental difference between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) is the presence of specific malignant cells: HL is defined by Reed-Sternberg cells (in classical HL) or lymphocyte-predominant "popcorn" cells (in nodular lymphocyte-predominant HL), while NHL lacks these characteristic cells and instead consists of various other malignant lymphoid cell types. 1, 2

Pathologic and Cellular Distinctions

Hodgkin Lymphoma Characteristics

• Classical Hodgkin lymphoma (CHL) is characterized by Reed-Sternberg cells embedded in an inflammatory background of non-malignant reactive cells, with the malignant cells representing only a small fraction of the total cellular population 1, 2
• Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) lacks Reed-Sternberg cells but contains lymphocyte-predominant (LP) cells, also called "popcorn cells," which constitute only 0.1-1% of cells within affected lymph nodes 3, 2

Immunophenotypic Profiles

The immunophenotype provides the most definitive diagnostic distinction:

Classical Hodgkin Lymphoma:

• CD30+ (positive)
• CD15+ (positive in majority)
• CD20+ (in less than 40% of cases)
• CD3- (negative)
• CD45- (negative) 1, 2

Nodular Lymphocyte-Predominant Hodgkin Lymphoma:

• CD20+ (positive)
• CD45+ (positive)
• CD15- (negative)
• CD30- (negative)
• CD3- (negative) 1, 3, 2

Non-Hodgkin Lymphoma:

• Variable immunophenotype depending on subtype (B-cell vs T-cell origin)
• Approximately 90% are B-cell lymphomas 4
• Does not contain Reed-Sternberg cells or lymphocyte-predominant cells 5

Clinical and Epidemiologic Differences

Prevalence and Distribution

• Hodgkin lymphoma accounts for approximately 5% of all lymphomas in Western countries, with CHL representing 95% of HL cases and NLPHL representing 5% 1, 2
• Non-Hodgkin lymphoma is far more common, with 55,000-60,000 new cases diagnosed annually in the United States (compared to approximately 9,000 HL cases) 4, 1

Age Distribution

• Hodgkin lymphoma demonstrates a characteristic bimodal age distribution with peaks at 15-30 years and after age 55 1, 2
• Non-Hodgkin lymphoma shows increasing incidence with age but lacks the distinctive bimodal pattern 4

Diagnostic Approach

Tissue Requirements

• Both require excisional lymph node biopsy for definitive diagnosis, as fine-needle aspiration alone is insufficient to assess architectural patterns and perform comprehensive immunophenotyping 1, 3
• 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) 1, 5

Critical Diagnostic Pitfall

• Reed-Sternberg-like cells can occasionally appear in B-cell NHL, creating diagnostic confusion 5
• The key distinguishing feature is the background cellular population: NHL shows a monomorphic background with CD20 positivity throughout, while HL shows a polymorphic inflammatory background with only scattered malignant cells 5

Prognosis and Treatment Implications

Hodgkin Lymphoma

• Now curable in at least 80% of patients with modern treatment 1, 2
• Treatment considerations often focus on minimizing long-term toxicity rather than improving cure rates, especially in early-stage disease 1, 2
• Standard treatment involves ABVD chemotherapy with or without radiotherapy, depending on stage and risk factors 2

Non-Hodgkin Lymphoma

• Prognosis varies dramatically by histologic subtype 4
• Low-grade lymphomas (e.g., follicular lymphoma) have long survival but are rarely cured 4
• Aggressive lymphomas (e.g., diffuse large B-cell lymphoma) are treated for cure with rituximab-based chemotherapy 4

Molecular and Genetic Considerations

• NLPHL demonstrates clonal B-cell origin with immunoglobulin heavy chain variable region (IGHV) gene rearrangements, confirming origin from a single transformed germinal center B-cell 3
• The relationship between HL and NHL is more complex than historically recognized, with composite lymphomas (both diagnoses in the same site) occurring more frequently than expected by chance, particularly NLPHL with large-cell B-cell lymphoma 6, 7
• This suggests that in some cases, HL may be clonally related to an underlying B-cell malignancy 7