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  • The neoplasm of lymphoid tissue in most cases is derived from germinal center B cells, defined by the presence of the Reed-Sternberg cells or its mononuclear variant Hodgkin cells with a characteristic immunophenotype and appropriate cellular background.

  • The Reed-Sternberg and Hodgkin cell, the neoplastic cells defining Hodgkin disease, are considered of B-cell origin based on their clonal immunoglobulin gene rearrangements.

  • Classic Hodgkin disease accounts for 95% of cases and contains four histologic subtypes that are distinguished on the basis of microscopic appearance and relative proportions of Reed-Sternberg cells, lymphocytes, and fibrosis: nodular sclerosis, mixed cellularity, lymphocyte-depleted, or lymphocyte-rich Hodgkin disease. A fifth subtype, nodular lymphocyte predominance has been added to the four classic histologic types (Table 59–1).



  • In 2014 in the United Stated, there were 9190 cases of Hodgkin lymphoma.

  • Incidence rate is influenced by socioeconomic and environmental factors.

  • There is a bimodal age distribution, with a peak between ages 15 to 34 and in those older than age 60 years (Figure 59–1).

  • Nodular sclerosis subtype predominates in young adults.

  • Mixed cellularity subtype predominates in older ages.

  • Presence of the Epstein-Barr virus (EBV) in Reed-Sternberg and Hodgkin cells is more common in less-developed countries and in pediatric and older adult cases.

  • Role for EBV in etiology is suggested by evidence that serologically confirmed mononucleosis confers a threefold risk for Hodgkin disease in young adults.

  • Increased risk among siblings and close relatives suggests genetic factors may contribute to disease susceptibility.


The graph depicts the incidence of Hodgkin lymphoma as a function of age among American males and females, 2000 to 2011. (Data from the Surveillance, Epidemiology, and End Results (SEER) Program ( Research Data (1973–2011), National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2014, based on the November 2013 submission; 2014. Source: Williams Hematology, 9th ed, Chap. 97, Fig. 97–1.)


  • Reed-Sternberg cells are relatively large cells that typically have bilobed nuclei with prominent eosinophilic nucleoli separated by a clear space from a thickened nuclear membrane (Figure 59–2).

  • Reed-Sternberg cells express CD30 in virtually all and CD15 in the majority of cases of classic Hodgkin lymphoma (Figure 59–3).

  • Reed-Sternberg cells represent monoclonal outgrowths of germinal center B cells that have incurred extensive somatic mutations, most likely in the course of the immune response to antigen.

  • Mononuclear Reed-Sternberg cell variants, referred to as Hodgkin cells, have similar nuclear characteristics and ...

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