What are the differences in biology, prognosis, and treatment approaches between Non-Hodgkin Lymphoma (NHL) and Hodgkin Lymphoma (HL)?

Key Differences Between Non-Hodgkin Lymphoma (NHL) and Hodgkin Lymphoma (HL)

Biology and Pathology

NHL and HL are fundamentally distinct lymphoid malignancies with different cellular origins, immunophenotypes, and biological behaviors that require completely different treatment approaches. 1

Cellular Characteristics

• HL is characterized by Reed-Sternberg cells (in classical HL) or lymphocyte-predominant "popcorn cells" (in nodular lymphocyte-predominant HL), which represent the malignant component surrounded by an inflammatory background 1
• NHL encompasses a diverse group of lymphoid neoplasms without Reed-Sternberg cells, representing direct malignant transformation of lymphocytes 2, 3
• Classical HL cells express CD15+/CD30+/CD20-, while nodular lymphocyte-predominant HL expresses CD15-/CD30-/CD20+ 1
• NHL cells typically express B-cell markers including CD20, making them targets for rituximab-based therapies 3

Disease Classification

• HL comprises only two main subtypes: Classical HL (95% of cases, with four histologic variants: nodular sclerosing, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted) and nodular lymphocyte-predominant HL 1
• NHL represents a heterogeneous collection of over 60 distinct lymphoid malignancies with widely varying biological behaviors, from indolent to highly aggressive 2, 3

Prognosis and Cure Rates

Hodgkin Lymphoma

• HL achieves permanent remission in 80-90% of patients with modern treatment strategies and is considered curable in the majority of cases 4, 1
• HL has a bimodal age distribution with peaks at 15-30 years and after age 55 1
• Early-stage favorable HL has excellent outcomes with combined modality therapy 1

Non-Hodgkin Lymphoma

• NHL prognosis varies dramatically by subtype, ranging from indolent diseases with median survivals exceeding 10 years to aggressive lymphomas requiring immediate intensive treatment 3
• Cure is only possible for a minority of patients with intermediate-grade NHL and a limited group with early-stage indolent disease 2
• Following relapse in low-grade NHL, up to 50% of patients die within five years, and salvage therapy rarely results in long-term survival 2
• Less than half of patients with intermediate-grade NHL achieve prolonged disease-free survival after relapse or failure of first-line treatment 2

Staging Approaches

Common Staging Elements

• Both HL and NHL use modified Ann Arbor staging with PET-CT formally incorporated for FDG-avid lymphomas 4
• Bone marrow biopsy is no longer routinely indicated for staging of HL and most diffuse large B-cell lymphomas when PET-CT is performed 4

Key Staging Differences

• B symptoms (fever, night sweats, weight loss) are formally incorporated into HL staging with A/B suffix designation, while this is not standard for NHL 4
• HL staging specifically evaluates contiguous lymph node spread patterns, reflecting its characteristic pattern of orderly progression through adjacent lymph node regions 1

Treatment Approaches

Hodgkin Lymphoma Treatment Strategy

• Early-stage favorable HL: 2 cycles of ABVD followed by 30 Gy involved-field radiotherapy 1
• Early-stage unfavorable HL: 4 cycles of ABVD followed by 30 Gy involved-field radiotherapy, or 2 cycles of BEACOPPescalated followed by 2 cycles of ABVD and 30 Gy radiotherapy for patients under 60 years 1
• Advanced-stage HL: 6-8 cycles of ABVD or 8 cycles of BEACOPPescalated for patients under 60 years, with radiotherapy limited to residual masses 1
• HL treatment is risk-adapted based on stage and clinical risk factors, with treatment intensity chosen accordingly 4
• For relapsed/refractory HL, high-dose chemotherapy followed by autologous stem cell transplantation is standard, with brentuximab vedotin for post-transplant failures 4, 1

Non-Hodgkin Lymphoma Treatment Strategy

• Low-grade NHL may follow "watch and wait" approach for asymptomatic patients 2
• Low-grade NHL typically receives single-agent alkylating therapy or CVP (cyclophosphamide, vincristine, prednisone) 2
• Intermediate-grade NHL receives CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as standard treatment 2
• Rituximab-based chemoimmunotherapy is standard for most B-cell NHL, given CD20 expression on malignant cells 3
• NHL treatment varies dramatically by specific subtype, with no unified approach across all NHL variants 3

Critical Treatment Distinction

• HL and NHL should never be treated interchangeably—excisional lymph node biopsy with expert hematopathology review is mandatory to distinguish these entities, as treatment approaches differ fundamentally 5
• The two diseases are biologically separate entities: molecular studies demonstrate that patients developing both HL and NHL at different time points typically have distinct clonal origins rather than transformation from a common clone 6

Response Assessment

PET-CT Utilization

• Both HL and NHL use PET-CT with the Deauville 5-point scale for response assessment in FDG-avid histologies 4, 1
• Interim PET after 2-4 cycles identifies poor-risk individuals in both diseases, though PET-guided treatment modification should be restricted to clinical trials 4, 1

Follow-up Differences

• HL requires specific monitoring for treatment-related late effects including thyroid dysfunction (TSH at 1,2, and 5+ years after neck irradiation), testosterone/estrogen levels in young patients, and screening for secondary malignancies and cardiovascular disease 4
• Routine surveillance scans are discouraged in both diseases unless clinical symptoms develop 4