Primary Vaginal Adenocarcinoma Arising in Vaginal Adenosis After CO2 Laser Vaporization and 5-Fluorouracil Therapy

Abstract

Summary We present a case of a 45-year-old woman with a long-standing history of persistent cervical dysplasia that resulted in a hysterectomy. Subsequent vaginal smears revealed high-grade vaginal intraepithelial neoplasia (VAIN III) on Pap smear with positive human papilloma virus (HPV) testing. Over the course of 2 years, the patient underwent 2 CO2 laser vaporization procedures of the upper vagina and intermittent 5-fluorouracil therapy. A biopsy performed at the time of the second laser procedure revealed endocervical-type well-differentiated adenocarcinoma, associated with VAIN III. HPV in situ hybridization for HPV types 16 and 18 was positive in both the glandular and squamous mucosa. The patient has no known history of intrauterine diethylstilbestrol exposure or mullerian developmental abnormalities. Subsequently, the patient underwent a radical upper vaginetcomy with bilateral pelvic lymph nodes dissection and bilateral salpingo-oophorectomy. The vaginectomy specimen showed residual adenocarcinoma associated with VAIN-III and extensive vaginal adenosis with free resection margins. This is the second reported case in the literature of adenocarcinoma arising in vaginal adenosis after 5-fluorouracil. Herein, we highlight these important findings and shed some light on the pathogenesis of vaginal adenosis and the subsequent development of vaginal adenocarcinoma.

Clinicopathologic features and outcomes of primary vaginal adenosis as a dermatologic and gynecologic burden

“…Besides, the effect of vaginal adenosis on infertility had been ruled out in this study, which is in contrast to the findings of another study. [1] In accordance with reported studies, [3,4,6–8,10–13] the common clinical presentations of vaginal adenosis are vaginal pain (7/20) and bleeding (8/20) (Table 1 ). However, some patients are asymptomatic and are diagnosed incidentally during a general physical examination or treatment for other ailments.…”

“…Even if the pathogenesis of vaginal adenosis is still not completely understood, in the cases of adenosis after vaginal inflammation, it is suggested that adenosis develops as a metaplastic process similar to other well-known types of metaplasia that occur as a result of noxious stimuli in other parts of the body. [6] The present study's data might contribute to a better understanding of this rare condition.…”

“…DES was found to have a strong association with the development of CCC or adenocarcinoma from adenosis. [1,4] Other sporadic case reports suggested alternative causes of vaginal adenosis, such as sulfonamide-induced Stevens-Johnson syndrome, [5] carbon dioxide laser treatment, 5-fluorouracil therapy, [6] and tamoxifen uterine-exposure. [7] However, the low incidence rate hindered the study of the etiology of vaginal adenosis.…”

Squamous cell carcinoma of the vagina: natural history, treatment modalities and prognostic factors

“…Adenocarcinoma usually develops from vaginal adenosis in women exposed to diethylstilbestrol prescribed to prevent miscarriages during intrauterine life [12], although this malignancy can also arise in patients without antenatal exposure to this synthetic estrogen [4,13,14]. Cases of endometrioid carcinoma [15] or mullerian adenosarcoma [16] developing from vaginal endometriosis have been reported.…”

The development of cervical and vaginal adenosis as a result of diethylstilbestrol exposure in utero

“…In fact, the presence of glands in vaginae were described in women who were born before DES was clinically used, or after the administration of DES to pregnant women was stopped (Plaut, 1940; Sandberg et al, 1965; Sandberg, 1967; Blaikley et al, 1971; Ruffolo et al, 1971; Kurman and Scully, 1974; Robboy et al, 1986; Chattopadhyay et al, 2001; Paczos et al, 2010; Cebesoy et al, 2007; Accetta et al, 2001; Charlton et al, 2001). In utero exposure to other hormones or environmental chemicals may be the cause of non-DES associated adenosis in the cervix and vagina.…”