Hodgkin’s lymphoma (HL) is a malignancy of mature B lymphocytes. It represents ~10% of all lymphomas diagnosed each year. The majority of HL diagnoses are classical HL (cHL), but there is a second subtype of HL, nodular lymphocyte predominant HL (NLPHL). While this diagnosis does resemble cHL morphologically in certain respects, there is some evidence that it is more related to the indolent B-cell NHLs biologically than it is to cHL. The majority of this chapter will be specific to cHL, with a discussion of NLPHL at the end.
Classical HL is one of the success stories of modern oncology. Until the advent of extended-field radiotherapy in the mid-twentieth century, it was a highly fatal disease of young people. Radiation therapy cured some patients with early stage disease, and the introduction of multi-agent chemotherapy in the 1970s resulted in further improved cure rates, both for patients with early and advanced stage disease. Cure rates now are >85%. The new challenge in the treatment of HL is late therapy-related toxicity, including a high rate of secondary malignancies and cardiovascular disease. Current clinical trials are aimed at minimizing this risk while preserving efficacy.
EPIDEMIOLOGY AND ETIOLOGY
HL is of B-cell origin. The incidence of HL appears fairly stable, with 8260 new cases diagnosed in 2017 in the United States. HL is more common in whites than in blacks and more common in males than in females. A bimodal distribution of age at diagnosis has been observed, with one peak incidence occurring in patients in their twenties and the other in those in their eighties. Some of the late age peak may be attributed to confusion among entities with similar appearance such as anaplastic large cell lymphoma and T-cell/histiocyte–rich B-cell lymphoma. There are four distinct subtypes of classical Hodgkin’s lymphoma (cHL) that are differentiated based on their histopathologic features (Table 105-1): nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted. Patients in the younger age groups diagnosed in the United States largely have the nodular sclerosing subtype of HL. Elderly patients, patients infected with HIV, and patients in Third World countries more commonly have mixed-cellularity HL or lymphocyte-depleted HL. Together, nodular sclerosis and mixed cellularity types account for nearly 95% of cases. Infection by HIV is a risk factor for developing HL. In addition, an association between infection by Epstein-Barr virus (EBV) and HL has been suggested. A monoclonal or oligoclonal proliferation of EBV-infected cells in 20–40% of the patients with HL has led to proposals for this virus having an etiologic role in HL. However, the matter is not settled definitively. Viral oncogenesis appears to play a greater role in HIV-related cHL: EBV can be detected in nearly all cases of HIV-associated cHL, compared to only one-third of cases of non-HIV-associated cHL. Reed-Sternberg (HRS) cells are the malignant cells in HL. HRS cells in HIV-associated cHL express the EBV-transforming protein latent membrane protein ...