Department of Dermatology, Oregon Health and Science University, Portland, OR, USA.
Dermatology Research Centre, The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia.
Pigment Cell Melanoma Res. 2021 Nov;34(6):1123-1130. doi: 10.1111/pcmr.12979. Epub 2021 May 7.
Here, we present a rare case of a patient who developed multiple primary melanomas within the boundaries of two nevi depigmentosa. The melanomas were excised, and as a preventive measure, the remainder of the nevi depigmentosa were removed. We performed whole-exome sequencing on excised tissue from the nevus depigmentosus, adjacent normal skin, and saliva to explain this intriguing phenomenon. We also performed a GeneTrails Comprehensive Solid Tumor Panel analysis on one of the melanoma tissues. Genetic analysis revealed germline MC1R V92M and TYR R402Q polymorphisms and a MET E168D germline mutation that may have increased the risk of melanoma development. This genetic predisposition, combined with a patient-reported history of substantial sun exposure and sunburns, which were more severe within the boundaries of the nevi depigmentosa due to the lack of photoprotective melanin, produced numerous somatic mutations in the melanocytes of the nevi depigmentosa. Fitting with this paradigm for melanoma development in chronically sun-damaged skin, the patient's melanomas harbored somatic mutations in CDKN2A (splice site), NF1, and ATRX and had a tumor mutation burden in the 90-95th percentile for melanoma.
在这里，我们报告了一例罕见病例，患者在两个色素减退性痣的边界内发生了多个原发性黑色素瘤。黑色素瘤被切除，作为预防措施，其余的色素减退性痣也被切除。我们对切除的色素减退性痣组织、相邻正常皮肤和唾液进行了全外显子组测序，以解释这一有趣的现象。我们还对其中一个黑色素瘤组织进行了 GeneTrails 全面实体瘤面板分析。遗传分析显示种系 MC1R V92M 和 TYR R402Q 多态性以及 MET E168D 种系突变，可能增加了黑色素瘤发展的风险。这种遗传倾向，加上患者报告的大量阳光暴露和晒伤史，由于色素减退性痣缺乏光保护黑色素，这些晒伤在色素减退性痣的边界内更为严重，导致色素减退性痣中的黑素细胞产生了大量体细胞突变。符合这种慢性阳光损伤皮肤中黑色素瘤发展的模式，患者的黑色素瘤在 CDKN2A（剪接位点）、NF1 和 ATRX 中存在体细胞突变，并且肿瘤突变负担在黑色素瘤的 90-95%百分位。
