Department of Dermatology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Curr Treat Options Oncol. 2018 Jun 27;19(8):42. doi: 10.1007/s11864-018-0560-y.
Melanoma is one of the most aggressive malignant skin tumors and its incidence has been increasing worldwide in recent decades. Among the four subtypes, acral lentiginous melanoma (ALM) shows the highest incidence in Asian countries, whereas ALM comprises only 1% of all melanomas in white populations. Early clinical diagnosis of ALM is essential, but early ALM lesions are often difficult to diagnose because the pigmentation of the lesions sometimes follows the skin marking of the palms and soles, resulting in an asymmetrical appearance and an irregular border in both ALM and benign melanocytic nevus. To overcome this difficulty, dermoscopy was introduced, and determination of the patterns by this method is essential for accurate clinical diagnosis of ALM. Although recent clinical trials have demonstrated that immune checkpoint inhibitors and BRAF/MEK inhibitors showed significantly improved overall survival of patients with advanced melanoma, ALM may be less susceptible to immune checkpoint inhibitors because of the poor immune response to the tumor. Therefore, strategies for enhancing the immune response to the tumor cells may be required when we apply immune checkpoint inhibitors in advanced ALM. In this context, imiquimod, dacarbazine, or interferon are possible therapies that may enhance the effectiveness of the immune checkpoint inhibitors. In addition to being known to have poor immunogenicity, ALM is also known to have infrequent BRAF mutation. Therefore, the majority of ALM patients may not benefit from therapy with BRAF/MEK inhibitors. However, some ALMs have mutations such as KIT and NRAS mutations, and therefore, targeted therapies may improve the survival of ALM patients in the future.
黑素瘤是最具侵袭性的恶性皮肤肿瘤之一，近几十年来，其发病率在全球范围内呈上升趋势。在这四种亚型中，肢端雀斑样黑素瘤（ALM）在亚洲国家的发病率最高，而 ALM 在白种人群中仅占所有黑素瘤的 1%。早期临床诊断 ALM 至关重要，但早期 ALM 病变通常难以诊断，因为病变的色素沉着有时会遵循手掌和脚底的皮肤标记，导致 ALM 和良性黑素细胞痣的外观不对称和边界不规则。为了克服这一困难，引入了皮肤镜检查，通过这种方法确定模式对于准确的 ALM 临床诊断至关重要。尽管最近的临床试验表明，免疫检查点抑制剂和 BRAF/MEK 抑制剂显著改善了晚期黑色素瘤患者的总生存率，但由于对肿瘤的免疫反应不佳，ALM 可能对免疫检查点抑制剂的敏感性较低。因此，当我们在晚期 ALM 中应用免疫检查点抑制剂时，可能需要增强对肿瘤细胞的免疫反应的策略。在这种情况下，咪喹莫特、达卡巴嗪或干扰素可能是增强免疫检查点抑制剂效果的可行治疗方法。除了已知具有低免疫原性外，ALM 还具有罕见的 BRAF 突变。因此，大多数 ALM 患者可能不会从 BRAF/MEK 抑制剂治疗中获益。然而，一些 ALM 存在 KIT 和 NRAS 突变等突变，因此，未来针对这些突变的靶向治疗可能会改善 ALM 患者的生存。
