The tumor cells in nodular lymphocyte-predominant Hodgkin disease are clonally related to the large cell lymphoma occurring in the same individual - Direct demonstration by single cell analysis

Large cell lymphoma (LCL) sometimes occurs concurrently or subsequently inp atients with nodular lymphocyte-predominant Hodgkin disease (NLPHD). Althou gh there is evidence of a clonal relationship between LCL and NLPHD, there has been no direct demonstration that the lymphocytic and histiocytic (L&H) cells in NLPHD are related to the tumor cells in LCL. We identified 2 case s of NLPHD with an associated LCL. Single L&H cells, the Reed-Sternberg cel l variants in NLPHD, were isolated from immunostained tissue sections by mi cromanipulation, and the immunoglobulin heavy chain gene (IgH) complementar ity determining region (CDR) III of the cells was amplified by the polymera se chain reaction (PCR). The products were compared with those obtained fro m microdissected LCL cells using polyacrylamide gel electrophoresis and nuc leotide sequencing. The IgH CDRIII sequences from the L&H cells were relate d to each other, but also showed nucleotide substitutions, consistent with a germinal center origin. The sequences from the L&H cells also were relate d to those from the corresponding LCL cells. We have provided direct eviden ce through sequence analysis of the IgH CDRIII that the L&H cells are clona lly related to the corresponding LCL arising in 2 cases of NLPHD.