LARGE-CELL TRANSFORMATION FOLLOWING DETECTION OF MINIMAL RESIDUAL DISEASE IN CUTANEOUS T-CELL LYMPHOMA - MOLECULAR AND IN-SITU ANALYSIS OF A SINGLE NEOPLASTIC T-CELL CLONE EXPRESSING THE IDENTICAL T-CELL RECEPTOR

Purpose: One of the unique characteristics of cutaneous T-cell lymphom a (CTCL) is its ability to undergo cytologic transformation in which t he malignant T-cells develop the morphologic appearance of a large-cel l lymphoma. Reported to occur in vp to 20% of advanced cases, large-ce ll transformation (LCT) is associated with an aggressive clinical cour se, Little is known about the risk factors or the molecular mechanisms of LCT. Before current immunohistochemical and molecular techniques, it was not possible to determine if LCT represented changes of the ini tial neoplastic T-cell clone or, in fact, was a distinct second malign ancy. The goal of this study was to define the clonal evolution of LCT in CTCL. Patients and Method: Polymerase chain reaction (PCR) amplifi cation of T-cell receptor-beta (TCR-beta) gene rearrangements and immu nohistochemistry with monoclonol antibodies to TCR-V beta regions were used as markers of T-cell clonality to analyze the skin and periphera l blood of a patient with CTCL and LCT. Results: We first detected the presence of minimal residual disease (MRD) in a CTCL patient with a c omplete clinical response to biologic response modifiers (BRMs). When clinical relapse occurred and demonstrated LCT, TCR-beta-PCR and in si tu immunohistochemistry with a specific TCR-V beta monoclonal antibody identified a single neoplastic T-cell clone that expressed the identi cal TCR as the original clone. Conclusion: Our results confirm a commo n clonal origin for CTCL and LCT. We also provide evidence of MRD in C TCL by molecular analysis, implying that residual malignant cells main tain a potential for clinical relapse and possibly LCT, The role of MR D detection remains to be defined in the clinical assessment of CTCL. LCT in CTCL provides a unique model to investigate the molecular event s that underlie terminal-stage tumor progression.