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New Treatments for for Vulvar Intraepithelial Neoplasia

Vulvar intraepithelial neoplasia is a relatively uncommon condition first alluded to when Bowen described a vulvar skin condition called precancerous dermatosis in 1912. Thirty-one years later, Knight reported on VIN and described several cases in which the lesions were adjacent to invasive vulvar carcinoma, suggesting VIN as a precursor lesion. Currently, VIN is defined histologically as a disorientation of epithelial Paget's disease vulvar intraepithelial neoplasia.

Vulvar intraepithelial neoplasia is most commonly seen in immunocompromised and postmenopausal women, but the incidence is increasing among healthy patients in younger age groups. Risk factors are similar to those observed for CIN. Race, parity, and comorbid medical conditions (except an immunocompromise status) seem to have no role in the development of VIN, whereas cigarette smoking is believed to be associated. An etiologic relationship exists between the development of VIN and human papillomavirus (HPV) infection, and HPV-16 is the

Patients may present with a variety of symptoms, including itching or burning and associated vulvar irritation, dyspareunia, labial erythema or swelling, or they may simply note the development of a lesion. Most patients are completely asymptomatic, and their lesions are identified during routine gynecologic examination.

Vulvar intraepithelial neoplasia may be unifocal or multifocal. Lesions are frequently white and raised, although they may also be gray or reddened macules. These lesions are most commonly found on the non-hair-bearing areas, such as the posterior vulva and periclitoral area, but may extend to involve the anus, vagina, clitoris, or urethra.

The clinical diagnosis is suspected after direct visualization. There is no pathognomonic finding on physical examination. Application of acetic acid with colposcopic magnification may be helpful, but several minutes are required for the keratinized squamous epithelium to take up the solution. Abnormal vessel patterns are not commonly seen owing to the keratinization of vulvar skin. Toluidine blue staining may be

Management

Management efforts are directed at relieving symptoms and preventing malignant conversion. These goals, combined with the increasing incidence in the younger population, have led to the adoption of treatment techniques that give optimal results but preserve normal tissue and function. Unfortunately, recurrence rates after treatment have been reported to range from 10% to 50% and are thought to be related to the grade

As is true for CIN, VIN has the potential to progress to invasive carcinoma or to regress completely. VIN is found associated with invasive disease in 2% to 18% of patients. The precise biology is unknown because only rare cases of severe dysplasia are managed with observation

Once malignancy has been ruled out, the authors believe a brief period of observation is reasonable in young, compliant, asymptomatic women with only mild dysplasia. Observation is especially indicated for patients who have recently completed a course of corticosteroids or a pregnancy and who are temporarily immunocompromised. If the condition worsens or does not resolve in 6 to 12 months, treatment should be initiated.

Popular treatment modalities include topical chemotherapy, carbon dioxide (CO2 ) laser ablation, and surgical excision. Cryotherapy, a loop electrosurgical excision procedure (LEEP), cavitron ultrasonic aspiration (CUSA), and interferon injections are additional treatment techniques that have been reported.

The usefulness of cryotherapy is limited owing to the inability to control the area of treatment precisely. It is not routinely recommended for the treatment of VIN. LEEP seems applicable for small lesions and is certainly more economical than the laser or CUSA, but limited literature support its efficacy. Likewise, CUSA and interferon require further study before they can be recommended as a standard treatment for VIN.

Topical Chemotherapy

Topical treatments include 5-fluorouracil (5-FU), dinitrochlorobenzene, and bleomycin. 5-FU is the most widely used and studied agent. This approach results in considerable local irritation and is not consistently successful, most likely related to poor patient compliance. Six to 10 weeks of treatment is necessary, and patients begin to experience a severe inflammatory response after approximately 2 weeks. This response

The avoidance of surgery and minimal scarring are obvious advantages to this approach; however, neoplastic epithelium of hair-bearing areas may not be adequately treated because the superficial sloughing of 5-FU may spare the sebaceous ducts and hair follicles. This potential ineffectiveness combined with the frequent premature discontinuation of therapy leads the authors to conclude that topical treatment for VIN is of limited value. This modality is reserved for women who refuse or are unable to undergo other ablative or excisional therapies.

Laser Ablation

Ablation with the CO2 laser is an effective option for diseased epithelium in non-hair-bearing areas, and there is cosmetic healing. Laser ablation is typically accomplished in the outpatient setting, and the extent of tissue destruction can be controlled precisely in experienced hands with colposcopic guidance. Disadvantages of laser therapy are its painful nature and prolonged healing time. No tissue is available for pathologic

Wide Local Excision

Because of the added expense and prolonged healing associated with the laser, the authors' preferred treatment modality is surgical excision in most instances. This treatment can frequently be accomplished in the office setting and provides a tissue specimen for pathologic review. Surgical excision can be diagnostic and therapeutic on select lesions. Several options are available for surgical excision. Specific details of surgical technique are beyond the scope of this article, and the interested reader is referred to a previous publication by the authors.

Although no definitive studies have evaluated margin size, most authorities believe that a 5-mm margin of normal epithelium is adequate for VIN. The authors follow these recommendations where possible without sacrificing important uninvolved structures, such as the clitoris,