Reed-Sternberg Cell: Survival in a Hostile Sea

In contrast to the non-Hodgkin's lymphomas, little is known regarding the origin, genetics, and function of the Reed-Sternberg cell of Hodgkin's disease. Unlike other cancers, the neoplastic cell of Hodgkin's disease, the Reed-Sternberg cell, is vastly outnumbered by a surrounding intense inflammatory infiltrate. How this rare neoplastic cell originates, persists, and disseminates in a presumably hostile cellular environment has remained a mystery. Understanding the biology of the Reed-Sternberg cell has been impeded by the rarity of the cell in tumor tissue. Herein, we describe how the application of single-cell genetic analysis has revealed a clonal and, possibly, germinal center B-cell origin of the Reed-Sternberg cell. By phenotype and function, Reed-Sternberg cells are highly interactive with their cellular microenvironment through cell-cell adhesion, expression of members of the tumor necrosis factor receptor superfamily, and elaboration of cytokines. Perhaps by their mimicry of immune system cells with antigen-presenting function, Reed-Sternberg cells mediate the unusual clinical and pathologic features of Hodgkin's disease: intense tissue inflammatory infiltrate, fibrosis, and constitutional symptoms.