Haenssle Holger A, Kraus Sophie L, Brehmer Franziska, Kretschmer Lutz, Völker Bernward, Asper Hiba, Kapp Alexander, Gutzmer Ralf
Arch Dermatol. 2012 Oct;148(10):1183-5. doi: 10.1001/archdermatol.2012.2649.
BACKGROUND Therapy with vemurafenib, an inhibitor of mutated BRAF, yields a response rate of approximately 50% in patients with metastatic melanoma harboring a BRAF V600E mutation. As an adverse effect of vemurafenib, proliferative disorders of keratinocytes, including squamous cell carcinoma, have been described. Low concentration of vemurafenib as present in the epidermis were found to activate wild-type RAF, which, in combination with a preexisting RAS mutation, can promote keratinocyte proliferation. While activating BRAF mutations occur in approximately 50% of melanomas, they are even more frequently observed in melanocytic nevi. OBSERVATION We present the case of a patient with dynamic changes of melanocytic nevi well documented by sequential digital dermoscopy during vemurafenib therapy. A variety of dermoscopic changes were observed. First, nevi involuted, and all of these originally showed a centrally elevated papillomatous and predominant globular pattern. Second, preexisting nevi increased in size, and pigmentation that rendered them atypical. Such lesions were flat and showed a predominant reticular pattern at baseline. Third, multiple new nevi occurred. One example of each of the latter 2 categories was excised and showed wild-type BRAF. CONCLUSION Our findings of changing nevi in a patient treated with vemurafenib highlight the need for sequential skin examinations, including dermoscopy.
维莫非尼是一种突变型BRAF抑制剂，对携带BRAF V600E突变的转移性黑色素瘤患者的有效率约为50%。维莫非尼的不良反应包括角质形成细胞增殖性疾病，如鳞状细胞癌。研究发现，表皮中低浓度的维莫非尼可激活野生型RAF，若与预先存在的RAS突变共同作用，可促进角质形成细胞增殖。虽然约50%的黑色素瘤存在激活BRAF突变，但在黑素细胞痣中更常见。
我们报告1例患者在维莫非尼治疗期间，通过连续数字皮肤镜检查详细记录了黑素细胞痣的动态变化。观察到多种皮肤镜改变。首先，痣消退，所有这些痣最初均表现为中央隆起的乳头状和主要为球状的形态。其次，原有痣增大，色素沉着使其变得不典型。这些病变在基线时是扁平的，主要表现为网状形态。第三，出现多个新痣。后两类各取1例切除，结果显示为野生型BRAF。
我们在维莫非尼治疗患者中发现痣的变化，强调了包括皮肤镜检查在内的连续皮肤检查的必要性。
