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The Reed-Sternberg cell and the pathogenesis of Hodgkin lymphoma

Authors
Jon C Aster, MD
Olga Pozdnyakova, MD
Section Editor
Arnold S Freedman, MD
Deputy Editor
Alan G Rosmarin, MD

INTRODUCTION

Hodgkin lymphoma (HL, formerly called Hodgkin's disease) is a neoplasm characterized by the presence of clonal malignant Hodgkin/Reed-Sternberg (HRS) cells (picture 1 and picture 2) in a reactive cellular background comprised of variable numbers of granulocytes, macrophages, plasma cells, and lymphocytes. Historically, HRS cells have been enigmatic and difficult to study, as they often constitute less than 1 percent of the cells in involved tissues. The central pathogenic issues in HL are: the origin of HRS cells, the identity of the events underlying the transformation of HRS cells, and the nature of the signals that produce the intense, characteristic tissue response.

The mystery of the origin of HRS cells was ultimately solved by elegant molecular studies that relied on single cell micromanipulation of HRS cells, coupled with amplification of RNA and genomic DNA by the polymerase chain reaction (PCR). These techniques established a B cell origin for HRS cells in the vast majority of cases of HL [1,2], and led to the identification of recurrent molecular abnormalities in HRS cells [3-6].

The Hodgkin/Reed-Sternberg cell and the pathobiology of classical HL will be reviewed here. The role of Epstein-Barr virus infection in the development of HL is discussed separately. (See "The role of Epstein-Barr virus in Hodgkin lymphoma", section on 'Association with infectious mononucleosis and EBV'.)

CLASSICAL VERSUS NON-CLASSICAL DISEASE

One complication when discussing the nature of Hodgkin/Reed-Sternberg (HRS) cells is heterogeneity within the diagnostic category of Hodgkin lymphoma (HL). HL is currently divided into two broad groups [7]:

Classical HL, which includes the nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depletion subtypes.

                    

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