BETHESDA, MD. — An older age, a history of cervical intraepithelial neoplasia, and the presence of multifocal lesions in the upper third of the vagina are among the features associated with vaginal intraepithelial neoplasia, Thomas C. Wright Jr. said at a conference on vulvovaginal diseases.
Vaginal intraepithelial neoplasia (VAIN) is not common, accounting for only 0.4% of intraepithelial lesions of the lower genital tract, according to Dr. Wright, director of obstetrics, gynecology, and pathology at Columbia University College of Physicians and Surgeons, New York.
Women at higher risk include those with vulvar intraepithelial neoplasia (VIN), cigarette smokers, and those who have had radiation therapy. A woman who has had radiation therapy for endometrial cancer and presents with an abnormal Pap smear exemplifies one clinical scenario in which the index of suspicion for VAIN should be high, he noted.
Another typical VAIN case is a postmenopausal patient who has been treated for cervical intraepithelial neoplasia (CIN), even 10 years earlier, often with a hysterectomy, and has been considered cured. She then unexpectedly has a high-grade squamous lesion on cytology, with no lesion on the vagina that is visible to the naked eye.
Some of these risk factors were associated with VAIN in a 2001 study of 121 women with biopsy-confirmed VAIN, which found that 41% smoked, 39% had a history of human papilloma virus (HPV), 22% had undergone surgery for CIN, and 23% had undergone a total abdominal hysterectomy. The mean age of the patients was 35 years, and the majority had VAIN-1, a diagnosis Dr. Wright said he is “very leery” about classifying “as true VAIN lesions.”
Most of the patients he sees with VAIN are in their 40s to late 60s. VAIN is rare among women in their 20s and 30s, but when it does occur among younger women, there usually is a history of immunosuppression or CIN, Dr. Wright said.
The sensitivity of cytology in diagnosing VAIN remains uncertain. Most VAIN patients are postmenopausal, raising the question of whether a patient has high-grade VAIN or “severe atrophy, which is causing the cytology to mimic high-grade VAIN,” he said at the conference, sponsored by the American Society for Colposcopy and Cervical Pathology.
On cytology, squamous intraepithelial neoplasia and VAIN “look exactly the same,” he added. And on histopathology, VAIN looks “exactly the same” as CIN, VIN, or anal intraepithelial neoplasia.
He advised caution about the diagnosis of VAIN-1. “A lot of us are trying not to make low-grade diagnoses of VIN or VAIN,” and instead, “classify the majority of these lesions as flat condylomas, because the natural history of these low-grade lesions is not really well characterized,” he explained.
It is unclear whether a flat, low-grade appearing lesion in a 60-year-old has any premalignant potential, he added. Low-grade VAIN has many features of a flat condyloma, compared with VAIN-3, which is more clearly a high-grade lesion, he said.
As for the location of VAIN lesions, most are found in the upper third of the vagina, usually contiguous with CIN, if a cervix is present. Most cases are multifocal, often with lesions found in the “dog-ears of the vault after hysterectomy,” which makes colposcopy very difficult. Colposcopy is required to diagnose VAIN, but is quite difficult, especially in postmenopausal women who have had a hysterectomy, because it is necessary to look inside the folds and “dog-ears,” he said.
VIN may be present as well, so the vulva needs to be carefully examined, said Dr. Wright, adding that “a fair number of patients” will have VIN, CIN, and VAIN at the same time.
On colposcopy, VAIN “frequently appears as slightly raised, acetowhite lesions,” which can be subtle, especially in postmenopausal patients who have low estrogen levels, he said.
In the vagina, with high-grade lesions, vascular patterns such as mosaicism in the vagina usually are not present as they are with cervical lesions. These lesions usually are not acetowhite and are identified only after the application of Lugol's solution, he said.
On colposcopy, conditions that can mimic VAIN are congenital transformation zones that extend into the vagina and leukoplakia, which can appear on the vagina, not just the cervix, Dr. Wright said.
Vaginal ulcers or trauma and granulation tissue also can look like VAIN lesions on colposcopy. Inflammation caused by trichomonas, candida, atrophic vaginitis, or radiation atrophy can obscure VAIN lesions, Dr. Wright added.
Treatments for VAIN include excisional biopsy in the office, intravaginal 5-fluoracil, laser ablation or electrofulguration, and partial vaginectomy. Cryosurgery is not used very much now, he added. VAIN-1 usually is not treated aggressively, but followed, except in women suspected of having a higher-grade lesion, such as those who have had a hysterectomy for CIN 2 or 3 or cancer, or a conization for CIN 2 or 3, he said.