Primary vaginal adenocarcinoma arising in vaginal adenosis after CO2 laser vaporization and 5-fluorouracil therapy

Abstract

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 CO(2) 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.

FIG. 1

(A) A low-power magnification of the vaginal biopsy hematoxylin and eosin section revealed a well-differentiated adenocarcinoma, and the overlying squamous mucosa showed high-grade vaginal intraepithelial neoplasia (10×). (B) The adenocarcinoma component consisted of back-to-back glands with slight nuclear atypia and few mitotic figures (40×). (C) The squamous mucosa overlying the adenocarcinoma shows a high-grade vaginal dysplasia in which the cells lacked normal maturation and reached the entire thickness of the squamous epithelium. Koilocytosis resulting from human papilloma virus effect are also present.

FIG. 2

Human papilloma virus in situ hybridization for 16 and 18 subtypes show nuclear staining in the squamous and glandular epithelium (20×).

FIG. 3

(A) The radical upper vaginectomy specimen shows residual well-differentiated adenocarcinoma positive for CEA antibody (B).

FIG. 4

(A) In the background, areas of vaginal adenosis consistent with benign-looking endocervical-like glands are also present. These glands are negative for CEA antibody (B).