Vulvar Atypias - Cancer of the Vulva

There has been a lack of uniformity in defining vulvar atypias. There are minimal data to support vulvar dystrophies being a cause of cancer. The International Society for the Study of Vulvar Disease has provided a standard nomenclature for these lesions, and this has been adopted by the International Society for Gynecologic Pathology (

Table 100-1). In 1985, the nomenclature was replaced by the terms carcinoma in situ or vulvar intraepithelial neoplasia (VIN). In addition, the nonpremalignant squamous changes previously termed hyperplastic dystrophy are now considered under the classification of squamous hyperplasia.

Vulvar atypias can present with a variety of symptoms. The most common is irritation or itching; however, 20% of patients are asymptomatic.

Grossly, the lesions can be flat, raised (maculopapular), or verrucous. In color, they may be brown (hyperpigmented), red (erythroplastic), white, or discolored.

White lesions can appear to have a whitish, thickened keratin layer (leukoplakia) or a diffuse, white, brittle, paperlike appearance (lichen sclerosus) (

Figure 100-2). Areas of squamous hyperplasia (hyperplastic dystrophy) and dysplasia can also have a white appearance. Unlike lichen sclerosus, however, the tissue often is thickened, and the process tends to be focal or multifocal rather than diffuse.

Microscopically, atypical changes in the vulvar epithelium consistent with preinvasive lesions usually are marked by loss of maturation of the squamous epithelium. There is increased mitotic activity and an increase in the nuclear cytoplasmic ratio. Mild dysplasia (VIN I) is diagnosed if changes involve the lower third of the epithelium. If there is moderate dysplasia (VIN II), then half to two-thirds of the epithelium is affected. If there is severe dysplasia (VIN III), then two-thirds of the epithelium is affected. For carcinoma in situ (also classified as VIN III) of the vulva, the full thickness of the epithelium usually is abnormal.

It often is difficult to distinguish between benign squamous hyperplasia and intraepithelial neoplasia. Crum and colleagues suggested that nuclear size may be helpful in diagnosis because intraepithelial neoplasia of the vulva almost always contains nuclei that are fourfold or greater in size compared with benign condyloma or non-neoplastic epithelium.

The best method of establishing a diagnosis is a high index of suspicion and early biopsy.

Several methods also can be used to help assess these lesions. Cytology, colposcopy, and toluidine blue O can be used cautiously before biopsy. In general, however, cytologic evaluation of the vulva has not been helpful as a screening examination because the vulvar skin often is thickened and keratinized. Colposcopic examination of the vulva is difficult because unlike cervical lesions, the changes are difficult to recognize. Therefore, colposcopic examination is not used for routine vulvar examination; rather, it is primarily employed for patients who are being evaluated or followed for vulvar atypia or intraepithelial malignancies. The toluidine blue O test is nonspecific and stains nuclei in the superficial part of the epithelium. Colposcopy is performed after applying a 1% aqueous solution of toluidine blue O to the vulva for 1 minute and decolorizing the tissue with 1% acetic acid. Areas that retain the stain are biopsied. A positive test, however, does not always indicate a premalignant condition because 20% of benign areas on the vulva stain positively.

To obtain the entire thickness of the skin for a definitive diagnosis, a biopsy of the vulva usually is done with a Keyes dermal punch. Occasionally, a larger biopsy is needed, in which case, a larger field can be locally anesthetized with lidocaine and a small scalpel or cervical biopsy punch used to obtain a specimen.

Once the correct diagnosis has been established by biopsy, appropriate therapy can be undertaken. For lichen sclerosus, 2% topical testosterone propionate in petrolatum, used twice daily, is an effective preparation to overcome the epithelial atrophy. The medication should be given continuously or the atrophy returns. Side effects such as clitoral hypertrophy and increased hair growth can occur.

Local measures, for example, wearing cotton underclothes and avoiding strong soaps and detergents, often are used to diminish irritation. Topical fluorinated corticosteroids applied twice daily for 1 to 2 weeks are helpful in controlling pruritus, but prolonged use of these steroid preparations can lead to vulvar atrophy or contracture. If long-term therapy is needed, a nonfluorinated compound such as 1% hydrocortisone is used. Some patients with lichen sclerosus have severe contracture in the area of the posterior fourchette. Treating these areas surgically with plastic repair of the fourchette has been suggested.

VIN can be treated by a variety of methods, and many authors have reported successful control of the disease by wide local excision. Buscema and colleagues reported that 68% of 62 patients had no evidence of recurrence when treated by wide excision. Adequate margins must be obtained with wide excision; however, this often may be difficult because of the multifocal nature of the disease. Friedrich and colleagues reported a 50% risk of recurrence if the margins were involved with neoplasia.

Other modalities also have been reported in the treatment of VIN.

Carbon dioxide laser vaporization of the vulva to a depth of 3 mm has been used, and current evidence indicates that laser therapy is as effective as surgical excision for the control of this disease. Before lasering the vulva, however, it is necessary to ascertain by histologic confirmation that invasive disease does not exist. Leuchter and colleagues treated 142 patients with carcinoma in situ of the vulva. Of those treated by laser, 17% had a recurrence, a result that is similar to that in lesions treated by local excision.

5-Fluorouracil (5-FU) cream has been used successfully to treat carcinoma in situ of the vulva, and application of this has been reported to be successful in 75% of cases. With continuous application, however, this treatment causes edema and pain.

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