Is Hodgkin's disease an infectious disease?

Several lines of evidence question the concept of Hodgkin's disease (HD) starting as a true malignant disorder of the lymphatic system: (i) In early stages HD exerts pronounced clinical and biological features of an atypic immune response. (ii) Despite extensive investigations, the Hodgkin/Reed-Sternberg (H/RS) cells have not been unequivocally determined as the definite malignant cell population in HD. (iii) The epidemiological pattern of HD strongly resembles that of an infectious disease. (iv) About 50% of HD cases can be linked to infection with Epstein-Barr virus. Hodgkin's disease in early stages might thus be understood as the unsuccessful attempt of the organism to eliminate a cell expressing a putative (cellular or viral) target antigen. A stepwise transformation of this antigen-carrying cell, possibly triggered by an inherent genetic instability, might then lead to outgrowth of a malignant cell clone in late stages of the disease.