Epstein-Barr virus-negative Hodgkin's lymphoma after mycosis fungoides: Molecular evidence for distinct clonal origin

The association of mycosis fungoides (MF) and Hodgkin's lymphoma is a relat ively frequent occurrence, but the potential clonal relationship of the two neoplasms is still controversial. We report a case of a patient with a his tory of MF in Clinical Stage 1A who developed retroperitoneal lymphadenopat hy 9 years after the initial diagnosis of MF. A bone marrow biopsy obtained at this time showed nodular involvement by a mixed cellular infiltrate wit h large, atypical cells consistent with Hodgkin and Reed-Sternberg (RS) cel ls. These atypical cells were positive for CD30 and CD15 and did not expres s B- or T-cell markers. In addition, they lacked evidence of infection by E pstein-Barr virus, both by immunohistochemical staining for latent membrane protein 1 and by in situ hybridization for EBER1/2 The background populati on consisted mainly of small T cells without morphological or phenotypical signs of malignancy. Review of the skin biopsy obtained 9 years before show ed the typical features of MF. Polymerase chain reaction analysis of the T- cell receptor gamma -gene confirmed the presence of a clonal T-cell rearran gement in the skin specimen. The bone marrow biopsy, however, showed a poly clonal pattern both for the T-cell receptor gamma -gene, as well as for imm unoglobulin heavy chain genes. Isolation of RS cells stained for CD30 was p erformed by laser capture microdissection. Polymerase chain reaction analys is of several groups of RS cells showed a reproducible biallelic rearrangem ent of IgH genes, which was confirmed by cloning and sequencing of polymera se chain reaction products. To our knowledge, this is the first case in whi ch a distinct clonal origin of MF and Hodgkin's lymphoma arising in the sam e patient is clearly demonstrated, based on molecular analysis of microdiss ected RS cells.