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咪喹莫特成功局部治疗恶性雀斑样痣过程中细胞浸润的特征分析

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

作者信息

Michalopoulos P, Yawalkar N, Brönnimann M, Kappeler A, Braathen L R

机构信息

Department of Dermatology, University of Bern, Inselspital, 3010 Bern, Switzerland.

出版信息

Br J Dermatol. 2004 Oct;151(4):903-6. doi: 10.1111/j.1365-2133.2004.06176.x.

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.

摘要

恶性雀斑样痣(LM)是一种原位黑色素瘤,通常发生于老年患者头颈部受阳光损伤的皮肤。根据其解剖部位和大小,LM的治疗可能存在问题,通常包括手术切除或放疗。最近的报告表明,局部应用咪喹莫特可能是一种有效的治疗方法。然而,迄今为止,尚无关于局部应用咪喹莫特治疗LM期间皮肤潜在免疫反应的数据。我们报告了一名62岁的白种女性,其组织学证实为LM,经5%咪喹莫特乳膏局部治疗成功。在使用5%咪喹莫特乳膏局部治疗前、治疗期间(第10周)和停止治疗后4周获取皮肤活检标本。进行组织学和免疫组化检查以检测残留的非典型黑素细胞并对炎性浸润进行特征描述。皮肤病变实现了完全的临床和组织学清除,治疗结束后长达9个月无复发。在局部应用5%咪喹莫特乳膏期间,观察到表皮和真皮CD1a+树突状细胞减少。炎性浸润由CD68+巨噬细胞组成,主要为CD3+T细胞,其中CD8+T细胞略有优势。还特别注意到颗粒酶B和TIA-1在表皮和真皮表皮交界处附近表达增强。总之,我们的数据表明,5%咪喹莫特乳膏原位诱导细胞毒性T细胞介导的免疫反应,这可能是LM中恶性黑素细胞完全破坏的原因。有必要对咪喹莫特用于LM进行进一步的临床试验和更长时间的随访。

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