Lymphomatoid papulosis and associated cutaneous lymphoproliferative disorders exhibit a common clonal origin

Abstract

Determination of the clonal relationship among multiple lymphoproliferative disorders occurring in individual patients has been hampered by dependence on molecular biologic techniques that require analysis of advanced lesions containing high tumor clone densities to isolate dominant, clonal antigen-receptor gene rearrangements. Polymerase chain reaction/denaturing gradient gel electrophoresis (PCR/DGGE) involves the amplification of T-cell receptor (TCR)-γ gene rearrangements followed by their electrophoresis in denaturing gradient gels. This method detects dominant TCR-γ gene rearrangements at tumor clone densities as low as 0.1%, making this assay suitable for analysis of early as well as late lesions. Using this approach, we analyzed skin lesions of lymphomatoid papulosis and either CD30+ large-cell lymphoma or early patch/plaque mycosis fungoides that developed in three patients. In each case, the dual specimens exhibited an identical band pattern by PCR/DGGE analysis, suggesting a common clonal origin. To confirm this clonal relationship, the dominant TCR-γ gene rearrangements were eluted, amplified, cloned, and sequenced. In each case, they showed identical junctional sequences. These findings are significant for several reasons: 1) they demonstrate the common clonal origin of lymphomatoid papulosis and CD30+ large-cell lymphoma or mycosis fungoides occurring in individual patients; 2) they confirm that co-migrating PCR/DGGE bands exhibit identical nucleotide sequences; and 3) they provide a method for determining the sequence of a tumor derived TCR-γ gene rearrangement in early lesions containing a low tumor clone density. This latter feature should allow the prospective molecular staging of early cutaneous lymphoproliferative disorders.