Detection of clonal T-cell receptor gamma-chain gene rearrangements in Reed-Sternberg cells of classic Hodgkin disease

Recent molecular single-cell studies have shown that in approximately 95% o f cases, Reed-Sternberg cells of classic Hodgkin disease (HD) are derived f rom B cells of germinal center origin, Attempts to determine the cellular n ature of the remaining cases have so far failed, To clarify whether they ar e derived from T cells, this study examined 791 single CD30(+) Hodgkin and Reed-Sternberg (HRS) cells from 13 T-cell marker-positive cases and from 6 cases with null-cell phenotype for rearranged T-cell receptor-gamma (TCR-ga mma) genes by single copy polymerase chain reaction. Monoclonally rearrange d TCR-gamma genes were detectable in 2 of the 13 classic HD cases with T-ce ll marker-positive HRS cells, with none detectable in the null-cell cases, Eight of the T-cell marker-positive cases and all 6 null-cell cases were al so studied for rearrangements of immunoglobulin genes. Six of the 8 T-cell marker-positive cases harbored clonal immunoglobulin gene rearrangements. T he 2 cases without rearranged immunoglobulin genes were those that containe d clonal TCR-gamma rearrangements and lacked expression of the B-cell-speci fic activator protein. From these findings we conclude that cases of classi c HD with T-cell-derived HRS cells definitely exist, although their overall incidence at 1% to 2% is very low. Even within the T-cell marker-positive cases only a minority (15%) were derived from T cells. The majority (85%) o riginated from B cells, indicating that the T-cell antigens expressed by HR S cells are, in contrast to those expressed in non-Hodgkin lymphoma, not li neage specific. (C) 2000 by The American Society of Hematology.