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Classical Hodgkin lymphoma is derived by malignant transformation of a mature B cell at the germinal center stage of differentiation and is characterized pathologically by multinucleated Hodgkin and Reed-Sternberg cells embedded in a mixed infiltrate of nonneoplastic cells. Hodgkin and Reed-Sternberg cells contain monoclonal immunoglobulin gene rearrangements but have lost most of the B-cell–specific expression program. Multiple signaling pathways and transcription factors are deregulated in Hodgkin lymphoma, and genetic lesions involving the JAK-STAT and nuclear factor-κB pathways are commonly identified. Epstein-Barr virus is an important environmental factor in the pathogenesis of Hodgkin lymphoma and also leads to activation of the nuclear factor-κB pathway. The inflammatory microenvironment promotes survival and allows escape of Hodgkin and Reed-Sternberg cells from immune attack. Morphologic and immunophenotypic features distinguish the four subtypes of classical Hodgkin lymphoma (accounting for 95 percent of cases) from nodular lymphocyte predominance Hodgkin lymphoma (accounting for 5 percent of cases). Hodgkin lymphoma spreads in a predictable, contiguous manner and is classified into four stages, I to IV. Classical Hodgkin lymphoma is treated with the intent to cure the disease in all stages, and long-term survival exceeds 85 percent. Doxorubicin-containing chemotherapy plays a major role in treatment of all stages of the disease, whereas radiotherapy is used selectively because of concerns for late toxicities. 18-Fluorodeoxyglucose positron emission tomography is a valuable diagnostic test for assessment of disease extent and response to treatment. High-dose therapy and autologous transplantation are effective in patients who have relapsed, and several new and effective biologic agents are available, including brentuximab vedotin (an anti-CD30 antibody–drug conjugate) as well as nivolumab and pembrolizumab (anti-PD-1–blocking antibodies). Concerns regarding late treatment effects guide therapy and followup decisions in Hodgkin lymphoma, which disproportionately affects adolescents and young adults. Major treatment challenges include the maintenance of high cure rates with fewer short-term and long-term complications, biomarker identification of the small refractory subgroup, and integration of biologic therapies into treatment paradigms.


Classical Hodgkin lymphoma (cHL) is a neoplasm of lymphoid tissue, in most cases derived from a germinal center B cell, defined by the presence of the malignant Hodgkin and Reed-Sternberg cells with a characteristic immunophenotype and appropriate cellular background*. cHL accounts for 95 percent of cases and contains four histologic subtypes distinguished on the basis of microscopic appearance and relative proportions of Hodgkin and Reed-Sternberg cells, lymphocytes, and fibrosis (nodular sclerosis, mixed cellularity, lymphocyte rich, and lymphocyte depleted; Table 8–1). Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) represents the other major category, which is distinguished by Hodgkin and Reed-Sternberg variants termed lymphocytic (L) and histiocytic cells (H) that, unlike cHL, express typical B-lineage markers.

TABLE 8–1.*Classification of Hodgkin Lymphoma

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