CLONALITY IN NODULAR LYMPHOCYTE-PREDOMINANT HODGKINS-DISEASE

Background There is general agreement that lymphocytic and histiocytic (L&H) cells, the variants of Reed-Sternberg cells in nodular lymphocy te-predominant Hodgkin's disease, belong to the B-cell lineage. Howeve r, the clonality of L&H cells remains controversial. Methods We used c omplementarity-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 nodula r lymphocyte-predominant Hodgkin's disease. The heavy-chain CDR3 of ea ch cell was amplified by the polymerase chain reaction, The products w ere analyzed by gel electrophoresis, and representative amplification products from each patient were sequenced. Results L&H cells whose hea vy-chain CDR3 was related, indicating the presence of a clonal populat ion, were detected in all five patients and were the dominant populati on in three. In four of the five patients, members of the clone were f ound in different nodules in the tissue section, different tissue bloc ks from the same tumor, or different lymph nodes from the same patient . The CDR3 sequences in each clone frequently contained nucleotide sub stitutions indicative of intraclonal mutation. Conclusions Clonal popu lations of L&H cells occur in nodular lymphocyte-predominant Hodgkin's disease. Intraclonal variation in nucleotide sequences suggests that hypermutation of the heavy-chain CDR3 continues to occur among the clo nal progeny. (C) 1997, Massachusetts Medical Society.