Diethylstilbestrol and Adenocarcinoma of the Vagina
The rare primary adenocarcinoma of the vagina usually occurs in postmenopausal women. These lesions may arise from residual glands of müllerian origin. Metastatic lesions (from breast, bowel, cervix, endometrium, and ovary) should be ruled out.
Exposure in utero to DES has been epidemiologically associated with vaginal clear-cell adenocarcinoma since 1971. The registry for this disease now includes more than 600 cases, although millions of women were treated with DES during pregnancy, starting in the 1950s. Thus, the risk that a woman exposed to DES will develop a clear-cell lower genital tract cancer is about 1 per 1,000 women.
Registry-updated reports indicate that the age at diagnosis ranges from 7 to 42 years old. Since 1990, 35 new cases have been reported, raising concern about a second peak of occurrence. Depending on what years the registry is analyzed, 65-80% of women with clear-cell adenocar-cinoma will have a documented history of DES exposure. No history of DES exposure is noted in 20-25% of women with clear-cell adenocarcinoma. When clear-cell adeno-carcinoma is diagnosed, DES-negative patients have a worse prognosis and higher rate of distant metastases than patients who were exposed to DES. Diethylstilbestrol-associated clear-cell adenocarcinomas have a predilection for the exocervix and upper one third of the vagina.
As of 1993, 20 women under observation had developed clear-cell adenocarcinoma. Because most of the clear-cell adenocarcinomas were detected by noting submucosal nodules, careful palpation of the cervix and vagina is recommended when examining these patients. Tall, overweight adolescents may be at a relatively higher risk of developing this neoplasm.
Radical hysterectomy, upper vaginectomy, and bilateral pelvic lymphadenectomy with ovarian preservation are recommended for patients with cervical and upper-vaginal clear-cell adenocarcinoma. For tumors smaller than 2 cm in diameter and with less than 3-mm invasion, wide local excision with node dissection, supplemented by local radiation, has been used with preservation of reproductive potential. For advanced stages, irradiation is recommended.
Although 5-year survival for stage I clear-cell adenocarcinomas is higher than 93%, the 10-year survival rate is 87%. Most recurrences happen within the first 3 years, but late recurrences, 8-20 years later, have been reported. In addition to pelvic examinations during follow-up, careful attention should be directed to the supraclavicular nodes and lungs.