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Cancer. 1976 Feb;37(2):858-71.

Clear cell adenocarcinoma of the cervix and vagina. A clinicopathologic study of 21 cases with and without a history of maternal ingestion of estrogens.


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.

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