Characterization of the cellular infiltrate during successful topical treatment of lentigo maligna with imiquimod

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Abstract
Lentigo maligna (LM) is an in situ melanoma which usually occurs in sun-damaged skin on the head and neck of elderly patients. Depending on the anatomical site and its size treatment of LM can be problematic and usually includes surgical excision or radiotherapy. Recent reports indicate that topical imiquimod may be an effective treatment. However, no data on the underlying immune response in the skin during treatment of LM with topical imiquimod are available so far. We report a 62-year-old caucasian woman with a histologically verified LM which was successfully treated with topical imiquimod 5% cream. Skin biopsy specimens were obtained before, during (at week 10) and 4 weeks after cessation of topical treatment with imiquimod 5% cream. Histological and immunohistochemical examination was performed in order to detect residual atypical melanocytes and to characterize the inflammatory infiltrate. A complete clinical and histological clearance of the skin lesion was achieved, with no recurrence up to 9 months after the end of treatment. During topical application of imiquimod 5% cream a depletion of epidermal and dermal CD1a+ dendritic cells was observed. The inflammatory infiltrate consisted of CD68+ macrophages and mainly of CD3+ T cells with a slight predominance of CD8+ T cells. An enhanced expression of granzyme B and TIA-1 was also noted particularly in the epidermis and near the dermoepidermal junction. In conclusion, our data indicate that imiquimod 5% cream induces a cytotoxic T-cell-mediated immune response in situ which may account for the complete destruction of the malignant melanocytes in LM. Further clinical trials and longer follow-up periods on the use of imiquimod for LM are warranted.

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