Clear Cell Adenocarcinoma of the Ovary Associated With In Utero Diethylstilbestrol Exposure: Case Report and Clinical Overview

Constantin A. Dasanu, MD, PhD; Thomas J. Herzog, MD


January 07, 2009


It is well known that in utero exposure to diethylstilbestrol (DES) can cause clear cell adenocarcinoma of the vagina and cervix in young women. Until its withdrawal from the market, DES had been used for the treatment of corpus luteum insufficiency to reduce miscarriage in the mid-1940s through the early 1970s. In the registry established by Herbst and colleagues,[1] incidence of this cancer was shown to peak between 14 and 22 years; the youngest known affected patient was 7 years of age and the oldest was 42. In all cases with accurate treatment administration dates, the drug was begun before the 18th week of pregnancy.

Subsequently, it was postulated that DES-exposed offspring may also be at increased risk for high-grade squamous neoplasia of the genital tract because of the large number of transformation zones inherent in this condition. A large prospective study by Hatch and colleagues[2] supports this association, although a role for more intensive screening among DES-exposed women could not be clearly established.

In a murine model, Newbold and coworkers[3]have shown DES to induce various ovarian alterations, such as inflammation, intra- and paraovarian cystic changes, and various oviductal abnormalities. These investigators have also described a condition called "developmental arrest of the oviduct," which was a consistent finding in the offspring of female mice exposed prenatally to DES. More recently, Wise and colleagues[4]linked prenatal DES exposure to an increased risk for paraovarian cysts in humans as well.

We present a report of the first patient with clear cell adenocarcinoma of the ovary probably related to DES exposure in utero. The pathologic specimen also showed high-grade squamous differentiation and inflammatory and paratubal cystic features.


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