Hodgkin Lymphoma Classification—From Historical Concepts to Current Refinements

Abstract

The current classification of Hodgkin lymphoma (HL) is the result of an integrated approach that combines the evaluation of morphological patterns, immunophenotypic characteristics, molecular features, and clinical presentation. Evolving from its origins based solely on histological observation to the latest updates in the WHO 5th Edition, this system has become an essential tool for accurate diagnosis and personalized therapeutic strategies. Each subtype of classic HL (cHL)—nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted—exhibits distinctive pathological and clinical features, now better understood through multidisciplinary studies and international collaborations. HL also includes nodular lymphocyte-predominant HL (NLPHL), a distinct entity with unique morphologic, immunophenotypic, and clinical features. A hallmark morphological feature of cHL is the presence of Hodgkin and Reed-Sternberg (HRS) cells, large and often multinucleated cells derived from B lymphocytes that have lost their typical B-cell phenotype. Identifying these cells is critical for diagnosis and for differentiating HL from other hematologic malignancies. HL is characterized by the rarity of malignant cells, a high curability rate, and a rich immune cell microenvironment that is both shaped and exploited by the tumor. Understanding these core aspects paves the way for exploring the role of immunologic and genetic biomarkers in refining classification, enhancing diagnosis, improving prognostic assessment, and guiding therapy for patients with cHL.