H. Veelken et al., DETECTION OF LOW-LEVEL TUMOR-CELLS IN ALLERGIC CONTACT-DERMATITIS INDUCED BY MECHLORETHAMINE IN PATIENTS WITH MYCOSIS-FUNGOIDES, Journal of investigative dermatology, 106(4), 1996, pp. 685-688
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.