Clear cell adenocarcinoma of the vagina and cervix secondary to intrauterine exposure to diethylstilbestrol

Abstract

Intrauterine diethylstilbestrol (DES) exposure is associated with an increased risk for the development of clear cell adenocarcinoma (CCA) of the vagina and cervix. The age of the DES-exposed patients has varied from 7 to 34 years with the highest frequency from 14 to 22 years. The risk among the exposed is small and is on the order of 1 per 1,000. Factors that may increase the risk are maternal history of prior miscarriage, exposure to DES in early gestation, a fall season of birth, and prematurity. Pregnancy does not appear to influence adversely the tumor characteristics or prognosis of patients who have developed these malignancies. Criteria for appropriate local therapy of small clear cell adenocarcinomas of the vagina are presented. Recurrent CCA has been observed as long as 20 years after primary therapy emphasizing the importance of prolonged follow-up.

Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure

“…The appearance of these lesions at puberty is reminiscent of the timing of appearance of DESinduced clear cell carcinoma of the vagina in humans, which manifested with a peak incidence at 19 years of age, suggesting that exposure to ovarian hormones contribute to the development of these pathologies [13]. In the mammary gland, the peripubertal period is characterized by intense ductal morphogenesis encompassing tissue remodeling, epithelial invasion of the stroma, increased rates of cell proliferation and cell death; hence, the pubertal mammary gland is particularly prone to neoplastic development [30,44].…”

“…This potent synthetic estrogen was administered to women as an anti-abortive therapy between the years 1948 and 1971 in the US, Europe and Australia. Tragically, this therapy was continued long after it was shown to be ineffective, and was finally stopped in the early 1970's when a rare pathology, clear cell adenocarcinoma of the vagina [10,11], as well as other abnormalities of the uterus, oviduct and cervix were diagnosed in young women that had been exposed to DES in utero [12,13]. These women are now reaching the age at which breast cancer becomes more prevalent.…”

Female sexual maturation and reproduction after prepubertal exposure to estrogens and endocrine disrupting chemicals: A review of rodent and human data

“…This synthetic nonsteroidal estrogenic chemical has been administered in high doses to pregnant women as an antiabortive medication to prevent miscarriage and other pregnancy complications between 1938 and 1971 in the United States (U.S.). By that year, the U.S. Food and Drug Administration issued a warning about its use after having found a relationship between an in utero exposure to this synthetic estrogen and the development of clear cell adenocarcinoma of the vagina and cervix in young women whose mothers had taken this substance while they were pregnant (Herbst and Anderson, 1990). Although DES has not been given for more than about 30 years, its effects continue to be seen.…”

Considerations for Pharmacoepidemiological Studies of Drug–Cancer Associations

“…There are a few examples of relatively rapid cancer development induced by exposure to drug use, for example, the association between use of systemic immunosuppressants and increased risk of non-Hodgkin's lymphoma and skin cancer in organ transplant recipients [51][52][53]. An example of very long cancer development -about 20 years -is the association between use of diethylstilbestrol and adenocarcinoma of the vagina and cervix [54,55].…”