Brunangelo Falini

Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells?

Primary mediastinal large B-cell lymphomas (LBCLs) constitute a unique subtype of diffuse LBCLs, with distinct clinical, immunophenotypic, and morphologic features. These lymphomas are thought to originate from the thymus, and it has been hypothesized that they derive from a population of B lymphocytes normally present in the thymic medulla. Most diffuse LBCLs harbor somatic mutations in their immunoglobulin genes, suggesting that they have been exposed to the germinal center. To investigate the possible relationship of mediastinal LBCLs to germinal center B cells, we analyzed the expression of bcl-6 and CD10 in 19 mediastinal LBCLs, using an immunoperoxidase technique on formalin-fixed tissue. We found that 19 of 19 (100%) mediastinal LBCLs were bcl-6+ and 6 of 19 (32%) mediastinal LBCLs were CD10+. Because mediastinal LBCLs usually lack BCL-6 gene rearrangement or mutations, expression of bcl-6 and CD10 in these tumors tends to support a germinal center derivation.

The Reed-Sternberg Cell and the CD30 Antigen

The tumour cells of Hodgkin’s disease (HD), called Reed-Sternberg and Hodgkin cells (H-RS cells) are, in conjunction with an admixture of non-malignant cells of various types, pathognomonic for HD. In most cases, the H-RS cells account for less than 5% and in some cases for less than 1% of the total tumour mass. In classical cases, the H-RS cells are large cells with bi-lobed or poly-lobed nuclei so that the cells appear binucleated or multinucleated. It is possible that, in some cases, bona fide multinucleation does actually occur. The nuclear membrane is thick and sharply defined, and there is a very large, variously shaped, acidophilic central nucleolus surrounded by a clear halo. In the most typical example of the H-RS cell, the two nuclear lobes face each other. The non-malignant counterpart of these cells is still a matter of debate. In most cases they react with the lymphoid surface markers CD30 (Schwab et al., 1982; Stein et al., 1985) and CD70 and in some cases with CDw75, CD3, T-cell receptor s chain (TcRs) (Dallenbach and Stein, 1989), J-chain (Stein et al., 1986) and CD20. These data, as well as the detection of immunoglobulin and T-cell receptor (TcR) rearrangements by Southern blot in some instances (Herbst et al., 1989), provide evidence for a lymphoid origin of these tumour cells. In particular, Dallenbach and Stein (1989) were able to detect TcRs on the H-RS cells of 24 of 65 cases and CD20 on the H-RS cells of 12 of 65 cases. Recently, support of these data came from Tamaru et al. (1994) who reported that in 67% of HD cases with B-cell-antigen positive H-RS cells, clonal VDJ rearrangements of the immunoglobulin heavy chain (IgH) gene were detectable; no VDJ rearrangements were detected in cases with T-cell antigen-positive H-RS cells.