Primary adenocarcinoma of the vagina is rare, constituting 9% of primary tumors of the vagina. The most common adenocarcinoma of the vagina is metastatic, originating from the colon, endometrium, ovary, or, rarely, pancreas and stomach. In general, adenocarcinomas affect a younger population of women, regardless of whether they were exposed to diethylstilbestrol (DES) in utero (222). Adenocarcinomas may arise in wolffian rest elements, periurethral glands, and foci of endometriosis (223). In women exposed to DES in utero, adenocarcinoma may develop in vaginal adenosis.
DES was used in the United States from 1940 until 1971 to maintain high-risk pregnancies in women with a history of spontaneous abortions. In 1970, seven young women were reported with clear cell adenocarcinoma of the vagina (Fig. 36.10); later, an association between this cancer and maternal ingestion of DES during pregnancy was identified (224). Subsequently, more than 500 cases of clear cell cancer of the vagina and cervix were reported to the Registry for Research on Hormonal Transplacental Carcinogenesis.
The estimated risk for developing clear cell adenocarcinoma for an exposed offspring is 1 in 1,000 or less. The mean age of diagnosis is 19 years (225). Clear cell adenocarcinoma in women with a history of in utero exposure to DES typically presents in the exocervix or anterior, upper one-third of the vagina. These tumors vary greatly in size and are most frequently exophytic and superficially invasive. Stage is the most important prognostic factor. Other statistically significant
Figure 36.10 Vaginal clear cell carcinoma. Note the formation of tubules with hobnail cells lining the lumen. These cells are characterized by nuclear protrusion into the apical cytoplasm.
factors include a tubulocystic growth pattern, size less than 3 cm2, and less than 3 mm of stromal invasion. Because the use of DES in pregnant women was discontinued in 1971, most of these tumors probably have been discovered. It is uncertain, however, what will happen to this cohort of women as they move into their fifth, sixth, and seventh decades of life. Continued surveillance of these women is indicated.
Ninety-seven percent of cases of vaginal clear cell adenocarcinoma are associated with adenosis. Adenosis is characterized by the presence of persistent m¨ullerian-type glandular epithelium. Although adenosis is the most common histologic abnormality in women exposed to DES in utero, adenosis can be found in women without a history of exposure. Adenosis typically appears as red, grapelike clusters in the vagina.
Malignant melanoma of the vagina is rare and lethal, occurring most often in white women. The average age of these patients is 58 years (226). Most lesions are deeply invasive, corresponding to a Clark level IV when compared with the staging for vulvar melanomas. The most common location of these tumors is in the lower one-third of the vagina (227). Melanomas have a wide variety of size, color, and growth patterns (225,228). Radical excision (vaginectomy, hysterectomy, and pelvic lymphadenectomy) is the mainstay of treatment. The goal of treatment is to avoid local (vaginal) recurrence, which is the most common site of recurrence (226,227). The need to dissect regional lymph nodes is uncertain. Because the disease is deeply invasive, hematogenous spread is the most common lethal recurrence. There is no difference in overall survival of patients with local as opposed to radical excision (226). The survival rate is approximately 10% at 5 years.