Polyclonal rearrangement of the T-cell antigen receptor genes in Hodgkin's disease: implications for diagnosis.

Distinction between Hodgkin's disease and peripheral T-cell lymphoma can be difficult, based on routine morphologic and immunohistologic stains. To assess the utility of Southern blot analysis, we investigated the genes for the beta (T beta) and gamma (T gamma) chains of the T-cell antigen receptor and immunoglobin heavy and light chains in 15 unselected cases of Hodgkin's disease. Following digestion with the restriction enzyme EcoRI, the intensity of the germline band corresponding to the first constant region of T beta was reduced when compared with the intensity of the second constant region germline band, a pattern consistent with polyclonal rearrangement of this gene. Hybridization of EcoRI-digested DNA with a probe recognizing the joining regions of T gamma revealed multiple rearranged bands corresponding to the known limited recombinatorial possibilities of this gene. Clonal rearrangement of T beta and T gamma was never demonstrated, although the banding pattern seen with T gamma could easily be misinterpreted as such. The findings in Hodgkin's disease were identical to those obtained in hyperplastic lymph nodes, normal thymuses, and normal peripheral blood enriched for T-cells. We then examined the status of T-cell receptor and immunoglobulin genes in six cases that could not be definitely classified as either Hodgkin's disease or T-cell lymphoma by either morphology or immunohistology. Clonal T-cell receptor gene rearrangement was found in three cases, supporting the diagnosis of T-cell lymphoma. Our study confirms the polyclonal lineage of the major fraction of T-cells and B-cells in Hodgkin's disease, a finding that may have diagnostic importance.