THE INTERRELATIONSHIP BETWEEN HODGKINS-DISEASE AND NON-HODGKINS-LYMPHOMAS

Background: While Hodgkin's disease (HD) and the non-Hodgkin's lymphom as (NHLs) have long been regarded as distinct disease entities, recent observations suggest a closer association. The analysis of cases in w hich both diseases are present in the same anatomic site (composite ly mphomas), or in separate sites (simultaneous or sequential HD and NHL) , indicates that this phenomenon occurs more frequently than would be expected by chance alone. Design: We reviewed our experience with comp osite, simultaneous, and sequential cases of HD and NHL, including bot h nodular lymphocyte-predominant HD (NLPHD) and the other (so-called ' usual') subtypes of HD. Cases analyzed included 43 cases of NLPHD and large-cell lymphoma (LCL); 14 cases of NHL following HD; 12 cases of c omposite lymphoma; 2 cases of simultaneous HD and NHL involving differ ent sites; 8 cases of chronic lymphocytic leukemia (CLL) with Reed-Ste rnberg (RS) cells; and 22 cases of HD following NHL. Immunophenotypic analysis of both components (HD & NHL) was performed when possible. In addition, in situ hybridization for Epstein-Barr virus (EBV) EBER1 mR NA was performed in 35 cases of usual HD associated with NHL. Results: The most common form of composite lymphoma was coexistent NLPHD with LCL of B-cell immunophenotype. With the abnormal cells of NLPHD also b eing of B-cell lineage, this finding suggests the existence of a clona l relationship between the two components. The association of nodular sclerosis or mixed cellularity HD and NHL was less common but still si gnificant. The vast majority of the NHL associated with HD were of B-c ell origin, most commonly follicular lymphomas. EBV was identified mor e frequently in the NHL of composite NHL + HD (4/12 cases; 33%) than t he other patient groups studied (2/23; 9%). Moreover, in 4/5 composite lymphomas both the HD and NHL component were EBV-positive, suggesting an origin from a common EBV-infected progenitor cell. Conclusion: The se findings suggest that, at least in some cases, HD may be clonally r elated to an underlying B-cell malignancy, and that the Reed-Sternberg cell may be an altered B lymphocyte. A process that may have a differ ent pathogenesis is the late occurrence of aggressive, usually EBV-neg ative (12/14 cases), B-cell NHL in patients successfully treated for H D. Such tumors may be related to an underlying and persistent immunode ficiency in these patients, and may be of similar pathogenesis to the Burkitt-like lymphomas associated with HIV-infection.