BACKGROUND:The objective of this study was to update the registry of women in the Netherlands with clear cell adenocarcinoma (CCAC) of the cervix or vagina with or without intrauterine exposure to diethylstilbestrol (DES). METHODS:From a nationwide search in PALGA, the automated pathology registry in the Netherlands, data were gathered on women with CCAC born after 1947. Information obtained from the clinical files of the patients included reported exposure to DES, patterns of complaints previous to diagnosis, the current status of the patients, and the results of cytopathologic examinations previous to histopathologic diagnosis. After review of the histopathologic slides, the specific pathologic characteristics of CCAC were determined. The age distribution of women born after 1947 was compared with that of women born before 1947. RESULTS:Information about possible exposure to DES during pregnancy was available for 73 of 88 women with CCAC born after 1947. Exposure to DES was reported for 47 (64%) of these women. The DES medication was most often reported as having started before the 18th week of pregnancy. Cytopathologic examination was informative in 81% of the cases of CCAC of the cervix, but only in 41% of the cases of CCAC of the vagina. Most patients had Stage I or II tumors at diagnosis. Tumor Stage III and IV and a high grade of nuclear atypia were related to unfavorable outcome. The age distribution of all patients with CCAC showed two distinct peaks; one at young age, (a mean age of 26 years), and one at older age (a mean age of 71 years). This bimodal age distribution still applied when the cases in which DES exposure was reported had been excluded. CONCLUSIONS:Despite the fact that DES has not been prescribed to pregnant women in the Netherlands in the last 20 years, CCAC is still relevant in our times. It is important to stay alert and periodically to update and evaluate the data of this registry, including data on women born outside the DES exposure period. The bimodal age distribution in this study of women without intrauterine exposure to DES suggests a carcinogenesis-promoting role of menarche and menopause and/ or the existence of a subpopulation with genetic risk factors or exogenous risk factors other than exposure to DES. Postmenopausal observation of women exposed to DES must be encouraged for clinical reasons and may help facilitate differentiation between these two hypotheses. If these risk factors of CCAC were better documented and their interrelationships better defined, CCAC could become an important model of multistep carcinogenesis in tissues sensitive to sex hormones.

译文

摘要背景:这项研究的目的是更新荷兰妇女宫颈或阴道透明细胞腺癌(CCAC)宫腔内或不暴露于己烯雌酚(DES)的女性登记资料。
方法:通过在荷兰的自动病理注册机构PALGA进行的全国性搜索,收集了1947年以后出生的CCAC妇女的数据。从患者的临床档案中获得的信息包括报告的DES暴露,诊断前的投诉模式,患者的当前状况以及组织病理学诊断之前的细胞病理学检查结果。在回顾了组织病理学切片之后,确定了CCAC的具体病理学特征。比较了1947年以后出生的妇女和1947年之前出生的妇女的年龄分布。
结果:1947年后出生的88例CCAC妇女中有73例可获得有关怀孕期间可能暴露于DES的信息。据报道,这些女性中有47例(64%)接触DES。据报道,DES药物是在怀孕第18周之前开始服用的。在81%的子宫颈CCAC病例中,细胞病理学检查是有益的,但在阴道的CCAC病例中仅41%。大多数患者在诊断时患有I期或II期肿瘤。肿瘤的第三和第四阶段以及高度的核非典型性与不良预后有关。所有CCAC患者的年龄分布均出现两个明显的高峰。一位年龄较小(平均年龄26岁),一位年龄较大(平均年龄71岁)。当排除了报道有DES暴露的病例时,这种双峰年龄分布仍然适用。
结论:尽管在过去的20年中荷兰没有为孕妇开具DES,但CCAC在我们这个时代仍然具有现实意义。重要的是要保持警惕,并定期更新和评估该注册表的数据,包括有关DES暴露期以外出生的妇女的数据。在这项研究中,没有宫内暴露于DES的妇女的双峰年龄分布表明,月经初潮和更年期的致癌作用和/或除了暴露于DES之外,还存在具有遗传危险因素或外源危险因素的亚群。出于临床原因,必须鼓励对接受DES的妇女进行绝经后观察,这可能有助于促进这两种假说之间的区分。如果更好地记录CCAC的这些危险因素并更好地定义它们之间的相互关系,CCAC可能会成为对性激素敏感的组织中多步骤癌变的重要模型。

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