Clonality in Nodular Lymphocyte-Predominant Hodgkin's Disease

Abstract

Background There is general agreement that lym- phocytic and histiocytic (L&H) cells, the variants of Reed–Sternberg cells in nodular lymphocyte-predom- inant Hodgkin’s disease, belong to the B-cell lineage. However, the clonality of L&H cells remains contro- versial. Methods We used complementarity-determining region 3 (CDR3) of the immunoglobulin heavy-chain gene as a clonal marker to study individual L&H cells isolated by micromanipulation from tissue sections of five patients with nodular lymphocyte-predomi- nant Hodgkin’s disease. The heavy-chain CDR3 of each cell was amplified by the polymerase chain reaction. The products were analyzed by gel electrophoresis, and representative amplification products from each patient were sequenced. Results L&H cells whose heavy-chain CDR3 was related, indicating the presence of a clonal popula- tion, were detected in all five patients and were the dominant population in three. In four of the five pa- tients, members of the clone were found in different nodules in the tissue section, different tissue blocks from the same tumor, or different lymph nodes from the same patient. The CDR3 sequences in each clone frequently contained nucleotide substitutions indica- tive of intraclonal mutation. Conclusions Clonal populations of L&H cells oc- cur in nodular lymphocyte-predominant Hodgkin’s disease. Intraclonal variation in nucleotide sequenc- es suggests that hypermutation of the heavy-chain CDR3 continues to occur among the clonal progeny.