title: Clear cell adenocarcinoma of the vagina and cervix. An update of the central Netherlands registry showing twin age incidence peaks.
abstract: 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.
authors.affiliation: Institute of Pathology, University Hospital Nijmegen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Hanselaar
authors.forename: M
authors.initials: M
authors.lastname: van Loosbroek
authors.forename: O
authors.initials: O
authors.lastname: Schuurbiers
authors.forename: T
authors.initials: T
authors.lastname: Helmerhorst
authors.forename: J
authors.initials: J
authors.lastname: Bulten
authors.forename: J
authors.initials: J
authors.lastname: Bernhelm
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology; D000328:Adult; D017677:Age Distribution; D000368:Aged; D004054:Diethylstilbestrol / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011247:Pregnancy; D012042:Registries; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology; D014625:Vaginal Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology
chemical_list: D004054:Diethylstilbestrol