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 rash 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 J beta 1/J beta 2 probe showed a single, identical rearranged band in both the MF and LCL skin lesions that had been obtained 4 years apart. V beta gene family--specific gene amplification assays demonstrated dominant V beta 6 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 V beta 6 PCR products amplified from both the MF and LCL lesions showed an identical nucleotide sequence involving V beta 6.4, D beta 1.1, J beta 1.2, and C beta 1. 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.
Wood
G S
GS
Department of Dermatology, Case Western Reserve University, Cleveland, Ohio.
Bahler
D W
DW
Hoppe
R T
RT
Warnke
R A
RA
Sklar
J L
JL
Levy
R
R
D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D001483:Base Sequence; D015139:Blotting, Southern; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D017730:Ki-1 Antigen; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009182:Mycosis Fungoides / Q000473:pathology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D012878:Skin Neoplasms / Q000473:pathology*
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D017730:Ki-1 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta