DETECTION OF LOW-LEVEL TUMOR-CELLS IN ALLERGIC CONTACT-DERMATITIS INDUCED BY MECHLORETHAMINE IN PATIENTS WITH MYCOSIS-FUNGOIDES

Two patients with histologically proven mycosis fungoides, a malignanc y of phenotypically mature T cells, received a topical challenge with mechlorethamine to areas of clinically uninvolved skin to exclude poss ible hypersensitivity reactions to this chemotherapeutic agent, In bot h patients, allergic contact dermatitis (ACD) developed at the sites o f the application and resolved completely after withdrawal of mechlore thamine. The lesions were biopsied and analyzed for the presence of cl onal T-cell receptor (TCR)-gamma gene rearrangements using two polymer ase chain reaction (PCR)-based assays involving denaturing gradient ge l electrophoresis (PCR/DGGE) and ribonuclease protection analysis (PCR /RPA), The former method has a clonal detection threshold of 10(-3)-10 (-2), while the latter has a sensitivity of 10(-5), In both cases, the ACD lesions were polyclonal by PCR/DGGE, In contrast, PCR/RPA detecte d tumor-specific TCR-gamma gene rearrangements in these same lesions, This indicates that the ACD lesions contained tumor cells at a density within the 10(-5)-10(-2) range, Analysis of peripheral blood mononucl ear cells from both patients failed to detect the malignant clone and showed the same result as blood from four normal individuals, The norm al skin fi om one patient also lacked detectable TCR-gamma gene rearra ngements, These results indicate that mycosis fungoides tumor cells ar e present within ACD lesions induced in mycosis fungoides patients and that this phenomenon does not appear to be due to the ubiquitous pres ence of detectable levels of these tumor cells in the blood or shin. T hese findings might be explained by nonspecific recruitment of maligna nt T cells to sites of local inflammation mediated by non-neoplastic a ntigen-specific T cells. Alternatively, they might be due to the local proliferation of very rare tumor cells in apparently normal skin in r esponse to cytokines generated during the ACD reaction, In either case , the present study offers evidence that the malignant cells in mycosi s fungoides retain at least some capability of responding in vivo to p hysiologic stimuli.