The interrelationship between Hodgkin's disease and non-Hodgkin's lymphomas

While Hodgkin's disease (HD) and the non-Hodgkin's lymphomas (NHLs) have long been regarded as distinct disease entities, recent observations suggest a closer association. The analysis of cases in which both diseases are present in the same anatomic site (composite lymphomas), or in separate sites (simultaneous or sequential HD and NHL), indicates that this phenomenon occurs more frequently than would be expected by chance alone.

We reviewed our experience with composite, simultaneous, and sequential cases of HD and NHL, including both 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 composite lymphoma; 2 cases of simultaneous HD and NHL involving different sites; 8 cases of chronic lymphocytic leukemia (CLL) with Reed-Sternberg (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 mRNA was performed in 35 cases of usual HD associated with NHL.

The most common form of composite lymphoma was coexistent NLPHD with LCL of B-cell immunophenotype. With the abnormal cells of NLPHD also being of B-cell lineage, this finding suggests the existence of a clonal relationship between the two components. The association of nodular sclerosis or mixed cellularity HD and NHL was less common but still significant. The vast majority of the NHL associated with HD were of B-cell origin, most commonly follicular lymphomas. EBV was identified more frequently in the NHL of composite NHL + HD (4/12 cases; 33%) than the 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.

These findings suggest that, at least in some cases, HD may be clonally related to an underlying B-cell malignancy, and that the Reed-Sternberg cell may be an altered B lymphocyte. A process that may have a different pathogenesis is the late occurrence of aggressive, usually EBV-negative (12/14 cases), B-cell NHL in patients successfully treated for HD. Such tumors may be related to an underlying and persistent immunodeficiency in these patients, and may be of similar pathogenesis to the Burkitt-like lymphomas associated with HIV-infection.