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% of cases, Reed-Sternberg cells of classic Hodgkin disease (HD) are derived from B cells of germinal center origin. Attempts to determine the cellular nature of the remaining cases have so far failed. To clarify whether they are 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-gamma) genes by single copy polymerase chain reaction. Monoclonally rearranged TCR-gamma genes were detectable in 2 of the 13 classic HD cases with T-cell 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 also studied for rearrangements of immunoglobulin genes. Six of the 8 T-cell marker-positive cases harbored clonal immunoglobulin gene rearrangements. The 2 cases without rearranged immunoglobulin genes were those that contained clonal TCR-gamma rearrangements and lacked expression of the B-cell-specific activator protein. From these findings we conclude that cases of classic 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%) originated from B cells, indicating that the T-cell antigens expressed by HRS cells are, in contrast to those expressed in non-Hodgkin lymphoma, not lineage specific.
Seitz
V
V
Institute of Pathology, Consultation and Reference Center for Lymph Node Pathology and Haematopathology, University Hospital Benjamin Franklin, Free University Berlin, Germany.
Hummel
M
M
Marafioti
T
T
Anagnostopoulos
I
I
Assaf
C
C
Stein
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006689:Hodgkin Disease / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology; D016539:Reed-Sternberg Cells / Q000276:immunology*
D016692:Receptors, Antigen, T-Cell, gamma-delta