CLEAR-CELL ADENOCARCINOMA OF THE VAGINA AND CERVIX - AN UPDATE OF THECENTRAL NETHERLANDS REGISTRY SHOWING TWIN AGE INCIDENCE PEAKS

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 diethylstilb estrol (DES). METHODS. From a nationwide search in PALGA, the automate d pathology registry in the Netherlands, data were gathered on women w ith CCAC born after 1947. Information obtained from the clinical files of the patients included reported exposure to DES, patterns of compla ints previous to diagnosis, the current status of the patients, and th e results of cytopathologic examinations previous to histopath ologic diagnosis. After review of the histopathologic slides, the specific pa thologic 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 pregn ancy was available for 73 of 88 women with CCAC born after 1947. Expos ure to DES was reported for 47 (64%) of these women. The DES medicatio n was most often reported as having started before the 18th week of pr egnancy. Cytopathologic examination was informative in 81% of the case s of CCAC of the cervix, but only in 41% of the cases of CCAC of the v agina. Most patients had Stage I or II tumors at diagnosis. Tumor Stag e III and IV and a high grade of nuclear atypia were related to unfavo rable outcome. The age distribution of all patients with CCAC showed t wo 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 be en excluded. CONCLUSIONS. Despite the fact that DES has not been presc ribed 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 peri odically to update and evaluate the data of this registry, including d ata on women born outside the DES exposure period. The bimodal age dis tribution 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 exog enous risk factors other than exposure to DES. Postmenopausal observat ion of women exposed to DES must be encouraged for clinical reasons an d may help facilitate differentiation between these two hypotheses. If these risk factors of CCAC were better documented and their interrela tionships better defined, CCAC could become an important model of mult istep carcinogenesis in tissues sensitive to sex hormones. (C) 1997 Am erican Cancer Society.