Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
Leiden Cancer Registry, Comprehensive Cancer Center West, Leiden, The Netherlands.
J Am Acad Dermatol. 2011 Aug;65(2):281-288. doi: 10.1016/j.jaad.2010.06.044. Epub 2011 May 12.
About 10% of cutaneous malignant melanomas (CMM) occur in individuals with a family history of melanoma. In 20% to 40% of melanoma families germline mutations in CDKN2A are detected. Knowledge of the clinicohistologic characteristics of melanomas and patients from these families is important for optimization of management strategies, and may shed more light on the complex interplay of genetic and environmental factors in the pathogenesis of melanoma.
We sought to investigate the clinical and histologic characteristics of CMM in CDKN2A-mutated families.
Clinical and histologic characteristics of 182 patients with 429 CMM from families with a founder mutation in CDKN2A (p16-Leiden mutation) were compared with 7512 patients with 7842 CMM from a population-based cancer registry.
Patients with p16-Leiden had their first melanoma 15.3 years younger than control patients. The 5-year cumulative incidence of second primary CMM was 23.4% for patients with p16-Leiden compared with 2.3% for control patients. The risk of a second melanoma was twice as high for patients with p16-Leiden who had their first melanoma before age 40 years, compared with older patients with p16-Leiden. Unlike control patients, there was no body site concordance of the first and second melanoma in patients with p16-Leiden and multiple primary melanomas. Patients with p16-Leiden had significantly more superficial spreading, and less nodular and lentiginous melanomas.
Ascertainment of patients with p16-Leiden was family based. The study was performed in families with a founder mutation, the p16-Leiden mutation.
Our findings are consistent with a pathogenic pathway of melanoma development from nevi, starting early and ongoing throughout life, and not related to chronic sun exposure.
约 10%的皮肤恶性黑色素瘤（CMM）发生在有黑色素瘤家族史的个体中。在 20%至 40%的黑色素瘤家族中，检测到 CDKN2A 的种系突变。了解这些家族中黑色素瘤和患者的临床组织学特征对于优化管理策略很重要，并且可能更深入地了解遗传和环境因素在黑色素瘤发病机制中的复杂相互作用。
我们旨在研究 CDKN2A 突变家族中 CMM 的临床和组织学特征。
将来自具有 CDKN2A 种系突变（p16-Leiden 突变）的家族的 182 名患者的 429 例 CMM 的临床和组织学特征与来自人群癌症登记处的 7512 名患者的 7842 例 CMM 进行比较。
p16-Leiden 的首发黑色素瘤患者比对照组患者年轻 15.3 岁。p16-Leiden 患者的 5 年累积第二原发 CMM 发生率为 23.4%，而对照组患者为 2.3%。对于 40 岁以下发生首发黑色素瘤的 p16-Leiden 患者，其发生第二例黑色素瘤的风险是年龄较大的 p16-Leiden 患者的两倍。与对照组患者不同，p16-Leiden 患者的首发和第二原发黑色素瘤之间没有身体部位的一致性，并且有多发性黑色素瘤。p16-Leiden 患者的浅表扩散型黑色素瘤明显更多，而结节型和色素痣型黑色素瘤明显更少。
p16-Leiden 患者的确定是基于家族。本研究在具有创始人突变 p16-Leiden 突变的家族中进行。
我们的研究结果与黑色素瘤发展的致病途径一致，即从痣开始，早发且贯穿一生，与慢性阳光暴露无关。
