We present two patients with stage IV melanoma, the first with BRAF wild-type melanoma with multiple visceral metastases treated with immunotherapy (pembrolizumab) and the second with BRAFV600E melanoma with subcutaneous and lymph nodes metastasis treated with BRAF and MEK-inhibitors (dabrafenib/trametinib). Already after the second cycle of immunotherapy, the first patient developed a diffuse regression of nevi, perceptible only with the use of dermoscopy and 3 months later a clinically evident poliosis of the eyebrows. The second patient, treated with dabrafenib/trametinib, developed small areas of leukoderma on his chest and white halos around nevi with a dermoscopic globular or structureless pattern. Both observations are suggestive for an immune reaction against melanocytic cells, which is further supported by the complete response to systemic therapy in both patients. It has been demonstrated that the development of vitiligo-like depigmentation during immunotherapy is associated with a better prognosis; in our patient, the phenomenon of poliosis appeared much later than the dermoscopic presence of regression among his nevi, suggesting that the latter may be an early sign (along with vitiligo-like phenomena) of good response to immunotherapy. On the other hand, the development of halo nevi and leukoderma during treatment with BRAF/MEK-inhibitors, suggests that not only immunotherapy but also targeted therapy may induce an immunologic response against melanoma and nevi, again indicative of a favorable prognosis. More data are needed to confirm these findings; however, they indicate that dermatologists should be involved in the follow-up of patients with melanoma, both in studies and clinical practice.

中文翻译：

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痣、白癜风样色素脱失和光晕现象的消退可能表明黑色素瘤对免疫治疗和靶向治疗的反应。

我们介绍了两名 IV 期黑色素瘤患者，第一名患有 BRAF 野生型黑色素瘤，伴有多处内脏转移，接受免疫疗法（派姆单抗）治疗，第二名患有 BRAFV600E 黑色素瘤，伴有皮下和淋巴结转移，接受 BRAF 和 MEK 抑制剂（达拉非尼/曲美替尼）治疗）。在第二个周期的免疫治疗后，第一位患者出现了痣的弥漫性消退，只有使用皮肤镜检查才能察觉，3个月后出现临床上明显的眉毛白发。第二位患者接受达拉非尼/曲美替尼治疗，胸部出现小面积白斑，痣周围出现白色晕圈，呈皮肤镜球状或无结构图案。这两项观察结果都提示存在针对黑素细胞的免疫反应，这两位患者对全身治疗的完全反应进一步支持了这一点。已证明，免疫治疗期间白癜风样色素脱失的发生与更好的预后相关；在我们的患者中，白发现象的出现比皮肤镜下痣消退的出现晚得多，这表明后者可能是对免疫治疗产生良好反应的早期迹象（以及白癜风样现象）。另一方面，BRAF/MEK抑制剂治疗期间晕痣和白皮病的发展表明，不仅免疫疗法而且靶向治疗都可以诱导针对黑色素瘤和痣的免疫反应，再次表明良好的预后。需要更多数据来证实这些发现；然而，他们表明皮肤科医生应该参与黑色素瘤患者的随访，无论是在研究还是临床实践中。