Fine Jo-David, Johnson Lorraine B, Weiner Madeline, Li Kuo-Ping, Suchindran Chirayath
National Epidermolysis Bullosa Registry, Nashville, Tennessee, USA.
J Am Acad Dermatol. 2009 Feb;60(2):203-11. doi: 10.1016/j.jaad.2008.09.035. Epub 2008 Nov 20.
Case series have demonstrated that potentially lethal cutaneous squamous cell carcinomas arise in patients with recessive dystrophic epidermolysis bullosa (RDEB), although the magnitude of this risk is undefined.
Systematic case finding and data collection were performed throughout the continental United States (1986-2002) by the National EB Registry on 3280 EB patients to determine cumulative and conditional risks for squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM) within each major EB subtype, as well as the cumulative risk of death from each tumor. Study design was cross-sectional, with a nested randomly sampled longitudinal subcohort (N = 450).
SCCs arose primarily in RDEB, especially the Hallopeau-Siemens subtype (RDEB-HS), first beginning in adolescence. Less frequently, SCCs occurred in junctional EB (JEB). Cumulative risks rose steeply in RDEB-HS, from 7.5% by age 20 to 67.8%, 80.2%, and 90.1% by ages 35, 45, and 55, respectively. In Herlitz JEB, the risk was 18.2% by age 25. SCC deaths occurred only in RDEB, with cumulative risks in RDEB-HS of 38.7%, 70.0%, and 78.7% by ages 35, 45, and 55, respectively. MM arose in RDEB-HS, with a cumulative risk of 2.5% by age 12. BCCs arose almost exclusively in the most severe EB simplex subtype (Dowling-Meara) (cumulative risk = 43.6% by age 55).
Mutational analyses were performed on only a minority of enrollees in the National EB Registry, preventing evaluation of the possible influence of specific genotypes on the risk of developing or dying from cutaneous SCCs.
SCC is the most serious complication of EB within adults, especially those with RDEB-HS. By mid-adulthood, nearly all will have had at least one SCC, and nearly 80% will have died of metastatic SCC despite aggressive surgical resection. When compared with SCCs arising within the normal population, the remarkably high risk of occurrence of and then death from SCCs among RDEB patients suggests likely differences in pathogenesis. Additional studies of EB-derived tumors and SCC cell lines may not only provide new insights into the mechanisms of carcinogenesis but also means whereby these particular tumors may be prevented or more effectively treated.
病例系列研究表明，隐性营养不良性大疱性表皮松解症（RDEB）患者会发生具有潜在致命性的皮肤鳞状细胞癌，尽管这种风险的程度尚不清楚。
美国国家大疱性表皮松解症登记处（1986 - 2002年）在美国大陆对3280例大疱性表皮松解症患者进行了系统的病例查找和数据收集，以确定每种主要大疱性表皮松解症亚型中鳞状细胞癌（SCC）、基底细胞癌（BCC）和恶性黑色素瘤（MM）的累积风险和条件风险，以及每种肿瘤导致的累积死亡风险。研究设计为横断面研究，并嵌套了一个随机抽样的纵向亚队列（N = 450）。
SCC主要发生在RDEB患者中，尤其是Hallopeau - Siemens亚型（RDEB - HS），最早始于青春期。较少见的是，SCC发生在交界型大疱性表皮松解症（JEB）患者中。RDEB - HS患者的累积风险急剧上升，20岁时为7.5%，35岁、45岁和55岁时分别为67.8%、80.2%和90.1%。在Herlitz JEB患者中，25岁时的风险为18.2%。SCC导致的死亡仅发生在RDEB患者中，RDEB - HS患者35岁、45岁和55岁时的累积风险分别为38.7%、70.0%和78.7%。MM发生在RDEB - HS患者中，12岁时的累积风险为2.5%。BCC几乎仅发生在最严重的单纯型大疱性表皮松解症亚型（Dowling - Meara）中（55岁时的累积风险 = 43.6%）。
仅对美国国家大疱性表皮松解症登记处的少数参与者进行了突变分析，无法评估特定基因型对皮肤SCC发生或死亡风险的可能影响。
SCC是大疱性表皮松解症患者尤其是RDEB - HS患者成年人中最严重的并发症。到中年时，几乎所有人都会至少患过一次SCC，尽管进行了积极的手术切除，近80%的患者会死于转移性SCC。与正常人群中发生的SCC相比，RDEB患者中SCC发生及随后死亡的风险极高，这表明其发病机制可能存在差异。对大疱性表皮松解症衍生肿瘤和SCC细胞系的进一步研究不仅可能为致癌机制提供新见解，还可能为预防或更有效治疗这些特定肿瘤提供方法。
