Twenty-one cases of
clear cell adenocarcinoma of the cervix and vagina have been reviewed. Fifteen cases occurred in females under 25 years of age and four in women over 45 years. In seven cases, a positive history of maternal ingestion of
diethylstilbestrol (DES) was obtained. One mother gave a history of medication with
conjugated estrogens and
ethisterone. Of the 13 patients with a negative history, three were born during the time period when DES was commonly used to prevent abortion. Fifteen
carcinomas were cervical in origin; seven of these also involved the vagina. In six cases the
carcinoma was entirely vaginal. Vaginal involvement of the
carcinomas was more common in the
estrogen-related group. Two non-
estrogen-related cases had coexisting congenital malformations with
double uterus and vagina and
unilateral renal agenesis. The histopathologic appearance was similar in both groups. In most cases, a mixture of papillary, microcystic, tubular, and solid features was seen. Vaginal adenosis was found in nine cases, six of which were
estrogen-related. Surgical
therapy was employed in most cases and was generally superior to
radiation therapy. Five patients had lymphatic involvement. All died from
carcinoma. The survival rate among sixteen patients followed for 2 years or more was 62.5%. The probable müllerian origin of
clear cell adenocarcinoma is discussed. It is suggested that DES, by virtue of being an
estrogen, interferes with the normal process of differentiation and degeneration of müllerian epithelium in the fetal vagina. The persistence of müllerian cells altered at the subcellular level could form the basis for development of
carcinoma in later life. However, a similar sequence of events must also be accepted to occur "spontaneously" since
clear cell adenocarcinoma can develop in women without a history of maternal
estrogens.