TRANSFORMATION OF MYCOSIS-FUNGOIDES - T-CELL RECEPTOR-BETA GENE ANALYSIS DEMONSTRATES A COMMON CLONAL ORIGIN FOR PLAQUE-TYPE MYCOSIS-FUNGOIDES AND CD30+ LARGE-CELL LYMPHOMA

it is well recognized that patients with classical mycosis fungoides (MF) may develop a large-cell lymphoma (LCL), a phenomenon known as ''transformation.'' An unresolved issue regarding the transformation of MF is whether MF and LCL represent two separate lymphomas or whether they are derived from the same T-cell clone. We report the clinicopathologic, immunophenotypic, and immunogenotypic analysis of MF and LCL in a white male. He developed a sh at age 51 that was diagnosed at age 56 as clinical stage IA patch/plaque MF. After topical nitrogen mustard and total skin electron beam therapy for progressive generalized CD3+CD4+ patch/plaque-lesions, he developed nodules of Ki-1+ (CD30+) T-LCL at age 72. Southern blot analysis of DNA digested with Bg/II or BamHI and probed with a T-cell receptor (TCR)-beta gene Jbeta1/Jbeta2 probe showed a single, identical rearranged band in both the MF and LCL skin lesions that had been obtained 4 years apart. Vbeta gene family - specific gene amplification assays demonstrated dominant Vbeta6 PCR products in both types of lesions. These PCR products and lesional cDNA exhibited a monoclonal pattern when amplified with consensus TCR-beta gene VDJ joint primers and electrophoresed under conditions that allowed the resolution of Small differences in size. Furthermore, sequence analysis of the Vbeta6 PCR products amplified from both the MF and LCL lesions showed an identical nucleotide sequence involving Vbeta6.4, Dbeta1.1, Jbeta1.2, and Cbeta1. These findings indicate that both the MF and the LCL in this patient arose from the same T-cell clone and that these diseases developed at a stage in the clone's differentiation subsequent to rearrangement of the TCR-beta gene.