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Cancer Health Center

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Childhood Hodgkin Lymphoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - General Information


Epstein-Barr virus and Hodgkin lymphoma

Epstein-Barr virus (EBV) has been implicated in the causation of Hodgkin lymphoma. A large proportion of patients with Hodgkin lymphoma have high EBV titers, suggesting that an enhanced activation of EBV may precede the development of Hodgkin lymphoma in some patients. EBV genetic material can be detected in Reed-Sternberg cells from some patients with Hodgkin lymphoma.

The incidence of EBV-associated Hodgkin lymphoma also shows the following distinct epidemiological features:

  • EBV positivity is most commonly observed in tumors with mixed-cellularity histology and is almost never seen in patients with lymphocyte-predominant histology.[12,13,14,15,16]
  • EBV positivity is more common in children younger than 10 years [12,16] compared with adolescents and young adults.[13,14]
  • The incidence of EBV tumor cell positivity for Hodgkin lymphoma in developed countries is 15% to 25% in adolescents and young adults.[15,16,17] There is a high incidence of mixed-cellularity histology in childhood Hodgkin lymphoma seen in developing countries, and these cases are generally EBV-positive (approximately 80%).[18]

EBV serologic status is not a prognostic factor for failure-free survival in pediatric and young adult Hodgkin lymphoma patients.[12,15,16,17,19] Patients with a prior history of serologically confirmed infectious mononucleosis have a fourfold increased risk of developing EBV-positive Hodgkin lymphoma; these patients are not at increased risk for EBV-negative Hodgkin lymphoma.[20]

Immunodeficiency and Hodgkin lymphoma

Among individuals with immunodeficiency, the risk of Hodgkin lymphoma is increased, although not as high as the risk of non-Hodgkin lymphoma.

Characteristics of Hodgkin lymphoma presenting in the context of immunodeficiency are as follows:

  • Hodgkin lymphoma usually occurs at a younger age and with histologies other than nodular sclerosing in patients with primary immunodeficiencies.[21]
  • The risk of Hodgkin lymphoma increases as much as 50-fold over the general population in patients with autoimmune lymphoproliferative syndrome.[22]
  • Although it is not an AIDS-defining malignancy, the incidence of Hodgkin lymphoma appears to be increased in HIV-infected individuals, including children.[23,24]

Clinical Presentation

The following presenting features of Hodgkin lymphoma result from direct or indirect effects of nodal or extranodal involvement and/or constitutional symptoms related to cytokine release from Reed-Sternberg cells.

  • Approximately 80% of patients present with painless adenopathy, most commonly involving the supraclavicular or cervical area.
  • Mediastinal disease is present in about 75% of adolescents and young adults and may be asymptomatic. In contrast, only about 35% of young children with Hodgkin lymphoma have mediastinal presentation, in part, reflecting the tendency of these patients to have either mixed cellularity or lymphocyte-predominant histology.
  • Approximately 20% of patients will have bulky adenopathy (maximum mediastinal diameter one-third of the chest diameter or greater and/or a node or nodal aggregate larger than 10 cm).
  • Based on data from large cooperative group cohorts, 80% to 85% of children and adolescents with Hodgkin lymphoma have involvement of lymph nodes and/or the spleen only (stages I-III).
  • The remaining 15% to 20% of patients will have noncontiguous extranodal involvement (stage IV). The most common sites of extranodal involvement are the lung, liver, bones, and bone marrow.[25,26]
  • Nonspecific constitutional symptoms including fatigue, anorexia, weight loss, pruritus, night sweats, and fever occur in approximately 25% of patients.[25,26]
  • Only three specific constitutional (B) symptoms have been correlated with prognosis-unexplained fever (temperature above 38.0°C orally), unexplained weight loss (10% of body weight within the 6 months preceding diagnosis), and drenching night sweats.[27]
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