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  • Neoplasm of lymphoid tissue in most cases 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 its clonal immunoglobulin gene rearrangements.

  • Classic Hodgkin disease accounts for 95 percent 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 (see Table 59–1).



  • In 2009 in the United Stated, there were 8510 cases of Hodgkin lymphoma.

  • Incidence rate is influenced by socioeconomic and environmental factors.

  • Bimodal age distribution: peak between ages 15 to 34 and in those older than age 60 years.

  • Nodular sclerosis predominates in young adults.

  • Mixed cellularity 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.


  • 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 (see Fig. 59–1).

  • 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 may represent Reed-Sternberg cells cut in a plane that shows only one lobe of the nucleus.

  • Nearly all Hodgkin and Reed-Sternberg cells have rearranged and somatically mutated immunoglobulin VH genes (IgHV).

  • It is possible that Hodgkin and Reed-Sternberg cells originate from a preapoptotic germinal center B cell with unfavorable mutations that has escaped negative selection.

  • Karyotypes are usually hyperdiploid with structural abnormalities but without pathognomonic chromosomal aberrations.

  • Reed-Sternberg cells secrete a variety of cytokines and chemokines that may be responsible for the recruitment of nonmalignant cells that comprise the bulk of the cells in the tumor population.

  • Hodgkin and Reed-Sternberg cells show a global loss of their B-cell phenotype, retaining only B-cell features ...

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