Hodgkin's disease in 1987—is history repeating itself?

Abstract

The history of Hodgkin's disease (HD) has been long and controversial (Hodgkin, 1832;Kaplan, 1980), but has remained a source of interest and fascination to pathologists and clinicians alike, with each succeeding generation of medical researchers adding their thoughts and investigations to the already voluminous literature on the disease. While I do not intend to comprehensively review the history of research on HD, as this has been well documented by others (e.g. Taylor, 1978), it is important to point out that the controversy over the putative malignant nature of H D has waxed and waned over its 150-year history (Sternberg, 1898;Reed, 1902), and has not been entirely laid to rest today. Although most contemporary authorities on HD have reached a consensus opinion in recent years that the disease is a malignant lymphoma, there still exists little objective evidence for this conclusion based on the standard parameters defining malignancy, including chromosomal abnormalities in the putative malignant cells, and the demonstration that such cell populations are monoclonal or at least oligoclonal. The curious polymorphic histopathologic lesion of H D remains a conundrum to those trying to argue that a malignant lymphoma can often exhibit less than 1 per cent putative tumour cells (i.e. RSC and variants) and still qualify as a member of the family of neoplasms that includes the Non-Hodgkins lymphomas (NHL). The well-known occurrence of RSC in a wide variety of benign conditions such as infectious mononucleosis is not reassuring.Over the years the study of H D has matured, roughly in parallel with the rest ofmedical science, and there has been the tendency to apply new technologies to this disease as they have been developed (Ford et al., 1987). For example, cell culture techniques have been widely applied to in vitro studies for many years now (Kadin and Asbury, 1973;Kaplan and Gartner, 1977), and immunological markers were utilized in HD shortly after their description (Braylan et al., 1974;Kay and Kadin, 1975). These studies for the first time began to approach the immunophenotypic characterization of the cellular constituents of the H D lesion on something more than a morphologic basis. The conclusions from these early phenotypic studies tended to favour a histiocytic cell as the progenitor of the RSC, which was regarded as the malignant cell, and the remaining heterogeneous cell types as being reactive. With the advent of monoclonal antibodies (MAb), a plethora of studies using a wide range of MAb reagents thought to be specific for a given cell lineage were employed (Poppema et al., 1982;Stein et al., 1982a). Although the predictions that MAb would provide the ultimate answer to the nature of the RSC and its mononuclear variant Hodgkin cell (HC) were encouraging, it soon became clear that they were overly optimistic. Instead of clarifying the situation, many of the studies turned out to be more ambiguous than could have been imagined. While providing detailed phenotypic information on many of the cell types in th...