Hodgkin and Non-Hodgkin Lymphoma Diagnosis and Treatment

Pathologic and Cellular Distinctions

The National Comprehensive Cancer Network recommends that Hodgkin lymphoma (HL) 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 lymphoma (NHL) lacks these characteristic cells and instead consists of various other malignant lymphoid cell types 1, 2, 3
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, 3
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 4, 3

The National Comprehensive Cancer Network states that Hodgkin lymphoma accounts for approximately 5% of all lymphomas in Western countries, with CHL representing 95% of HL cases and NLPHL representing 5% 2, 5, 3
Hodgkin lymphoma demonstrates a characteristic bimodal age distribution with peaks at 15-30 years and after age 55 1, 3

The National Comprehensive Cancer Network recommends that both HL and NHL require excisional lymph node biopsy for definitive diagnosis, as fine-needle aspiration alone is insufficient to assess architectural patterns and perform comprehensive immunophenotyping 2, 5, 4
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) 5

The National Comprehensive Cancer Network states that Hodgkin lymphoma is now curable in at least 80% of patients with modern treatment 1, 3
Treatment considerations often focus on minimizing long-term toxicity rather than improving cure rates, especially in early-stage disease 2, 3
Standard treatment involves ABVD chemotherapy with or without radiotherapy, depending on stage and risk factors 3

Nodular lymphocyte-predominant Hodgkin lymphoma (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 4

Reed‑Sternberg cells are mandatory for the diagnosis of classical Hodgkin lymphoma, which represents approximately 95 % of all Hodgkin lymphoma cases. 6
A complete excisional lymph‑node biopsy is required for definitive diagnosis; fine‑needle aspiration alone cannot reliably identify Reed‑Sternberg cells or the characteristic nodular architecture. 6

Reed‑Sternberg cells constitute only about 0.1 %–1 % of the total cellular population within an involved lymph node, existing amid a heterogeneous inflammatory infiltrate of lymphocytes, histiocytes, eosinophils, plasma cells, and fibroblasts. 6, 7, 8

Classical Hodgkin lymphoma cells characteristically express CD15 and CD30 while lacking CD20 (CD15⁺/CD30⁺/CD20⁻). 6, 7, 8
Lymphocyte‑predominant Hodgkin lymphoma (≈5 % of Hodgkin lymphoma cases) shows the opposite pattern, with CD15⁻/CD30⁻/CD20⁺ “popcorn” cells. 6

More than 60 % of patients initially present with enlarged cervical lymph nodes. 6, 7, 8