Mycosis Fungoides Epidermal Malignant T Cell Mechanisms

Background:Mycosis fungoides is the most common and prototypic cutaneous T cell lymphoma that presents epidermotropism which is manifested as infiltration of atypical CD4+T lymphocytes in the epidermis in the early stage as patch and plaque lesions. Existence of epidermotropism is highly suggestive of the diagnosis of mycosis fungoides. With the clinical progress and histopathologic transformation to large lymphocytes, the epidermotropism is gradually lost. Current studies concerning epidermotropism of mycosis fungoids are mainly focused on two aspects, chemokines with receptors, for example IP-10/CXCR3, and intraepithelial Langerhans cell/regulatory T cells. Yet it requires more investigation as to which mechanism dominates.Objective:To investigate the expression of CXCR3and CD1a in different stages of mycosis fungoides skin lesions so as to dip into the mechanism underlying epidermotropism which is a prominent pathologic feature of mycosis fungoides.Methods:The expression and distribution profiles of CD1a and CXCR3were detected by immunohistochemistry in the skin biopsy tissue of16normal subjects,16MF cases of patch/plaque stage and8MF cases of tumor stage. The correlation of CXCR3and CD1a expression with epidermotropism was then analyzed.Results:1) CXCR3staining:CXCR3positivity of intraepithelial neoplastic cells in the patch/plaque stage of MF was38.9±20.6%,while that in the tumor stage was17.5±27.6%. Significant difference was seen between two groups. CXCR3positivity of intraepithelial neoplastic cells was also shown to be strongly correlated with epidermotropism (r=0.56). CXCR3positivity of lymphocytes in the dermal compartment was higher than in the epidermis in both the patch/plaque and tumor stage of MF.2) CD1a staining:The average number of LCs in the epidermis of normal control was7.3±3.6/HPF while that figure for patch/plaque and tumor was10.6±3.2/HPF and6.7±2.3/HPF, respectively. Significant difference was appreciated between patch/plaque stage and tumor stage. No association has been found between epidermal LC amount and epidermotropism. As to the distribution, LCs were dispersed evenly in the middle-upper and basal layer of epidermis for the normal control. By contrast, LCs tend to form clusters with prominent neoplastic cell infiltrate in the epidermis of patch/plaque stage. Substantial staining of dermal compartment in both patch/plaque stage and tumor stage was found with patch/plaque stage even stronger.Conclusion:1) The initiation of epidermotropism in MF was partially contributed by CXCR3expression on malignant T cells.2)The maintenance and promotion of epidermotropism in MF was related with the quantity of intraepithelial LCs.