Differentiating normal and abnormal findings of the vulva
Barbara S. Apgar
Nonspecific findings of the vulva are common and often confusing. The recent extension of colposcopy to evaluation of the vulva has opened for many physicians an unfamiliar area fraught with the risk of overdiagnosis and overtreatment, since nonspecific or equivocal Vulvar findings may be present in up to 50 percent of normal women. Significant expense and morbidity have resulted from the overaggressive treatment of these findings. In evaluating the vulva, it must first be determined whether definitive disease is present. Biopsy is often the only way to answer this question.
Descriptions of Vulvar Lesions
It is best to fully describe vulvar lesions with dermatologic characteristics that include (1) the manifestation of the primary lesion, (2) the pattern of the lesion and (3) the lesion distribution.2 The primary lesion is the skin manifestation of the underlying disease process and is described in terms such as macule, papule, vesicle or plaque. Changes in the appearance of the primary lesion or the surrounding skin that occur as a result of external factors are called secondary changes. They include such descriptions as crust, fissure, erosion, ulcer, excoriation, atrophy and scarring.
Recognition of Normal Vulvar Findings
The overdiagnosis made most commonly in the past few years is that of micropapillae of the inner labia minora, secondary to infection with human papillomavirus HPV). Papillae are usually small (1 to 3 mm), symmetric and visible to the naked eye. The papillae may be single or cover most of the mucosal surface of the labia minora (Figure 1). Vestibular micropapillomatosis is the term that describes the presence of multiple papillae over the entire inner labia. These papillae are probably congenital in origin but may be accentuated by any inflammatory condition. Visualization is enhanced with the use of 3 to 5 percent acetic acid. Although koilocytes are often reported in biopsies of these papillae, attempts to ditect HPV-DNA have not been successful. The papillae uniformly lack true koilocytosis (marked by nuclear atypia), which is necessary to make a firm diagnosis of HPV-related disease. Papillary HPV disease is more likely to be patchy, with more starkly acetowhite papillae on a background of normal mucosa (Figure 2).
The labia majora are covered with stratified squamous epithelium (hair-bearing skin) in the lateral and mid portions of the labial surface and are hairless on the medial surface. The hair-bearing areas are endowed with sebaceous glands. At the inferior portion of the labia majora, the sebaceous glands disappear medial to Hart’s line, a demarcation line that marks the lateral posterior boundary of the vestibule. These glands may be visible only with magnification or may be enlarged enough to create a “cobblestone” appearance (Figure 3). Age or inflammation may result in hypertrophy of these glands, but such hypertrophy should never be interpreted as a primary disease process.
Nonspecific Findings, on the Vulva
Areas of acetowhitening may be found at the junction of the inferior part of the vestibule with the perineum (Figure 5), as well as on the inner labia. These acetowhite changes are also frequently misdiagnosed as being secondary to HPV infection. These changes may occur as a result of the trauma of intercourse, or yeast infections or other inflammatory conditions of the vulva and, therefore, should always be considered nonspecific. Acetowhitening resulting from trauma or inflammation is more likely to be diffuse and flat, whereas acetowhite changes caused by HPV infection are more likely to be slightly raised and to have satellite lesions.
OTHER NONSPECIFIC CHANGES
Atrophy of the estrogen-dependent introital epithelium allows the underlying vascular pattern to be more prominent. Such atrophy may be secondary to estrogen deficiency or to the long-term use of topical steroids and may be associated with fissuring, erosion or microhemorrhages. Hyperkeratosis results from the production of excessive surface keratin and is identified as an area that is white without the application of acetic acid. The term “leukoplakia” refers to an extreme form of hyperkeratosis (Figure 6). The term “inflammation” refers to a nonspecific change characterized by the absence of a definite etiology on the basis of visual inspection alone.
Vulvar biopsy is a rapid and simple office procedure that is indicated in the following clinical situations: (1) Lesions surrounded by either thickened skin or color changes (Figure 7). (2) Slightly raised, red or pigmented lesions (Figures 8 and 9). (3) Lesions presumed to be genital warts, especially flat ones, that do not respond to two or three office treatments (Figure 2). (4) Chronic dermatoses that do not respond to medical therapy (Figure 10). (5) Any lesion suspicious for neoplasia (Figure 11). (6) A lesion with equivocal changes that cannot be reliably diagnosed by visual inspection alone (Figure 6).
Three biopsy methods are commonly used on the vulva: a shave biopsy performed with a cervical biopsy instrument, a scalpel or scissors; a Keyes punch biopsy, and an excisional biopsy performed with a scalpel. The cervical punch biopsy or the shave method using scissors or scalpel are the quickest methods and result in an adequate sample for evaluation of most vulvar conditions. Either the Keyes punch or an excisional biopsy are best employed when invasive cancer is suspected.
Anesthesia may be accomplished by local infiltration, which is usually quite sufficient to make the patient comfortable during the procedure. The anesthesia may be administered at a single site or in a field block, depending on the size of the lesion, its location and the type of biopsy. Because of the rich vascular and lymphatic supply of the vulva, small amounts of anesthetic may dissipate quickly, reducing the anesthetic, effect. This dissipation can be avoided by using an adequate amount of anesthetic at the outset (1 to 3 mL per site). The wheal created by the infiltration actually facilitates the biopsy by raising the lesion and producing some local vasoconstriction, thus minimizing blood loss. For larger lesions, it is reasonable to add epinephrine to 1 percent lidocaine (Xylocaine) to prolong the anesthetic effect and create better hemostasis.
Non-neoplastic Epithelial Diseases
The non-neoplastic epithelial diseases of the vulva are readily classified on the basis of color. They include “white” lesions, “red” lesions and “dark” lesions.
Lichen Sclerosis. The characteristic appearance of lichen sclerosis (formerly called lichen sclerosis et atrophicus) is secondary to the thin atrophic epithelium and the underlying pale, sclerotic dermis. The surface of the labial tissue looks like parchment paper–shiny, delicate, pale and wrinkled. Lichen sclerosis may begin as tiny white macules that coalesce into large areas of leukoplakia. In patients with long-standing disease, the typical symmetric “keyhole” pattern may surround the vulva or the perianal area (Figure 7). Localized periclitoral or perianal lesions may also be present. Longstanding lichen sclerosis usually results in progressive resorption and obliteration of the labia minora, resulting in introital stenosis. Agglutination of the prepuce can gradually result in phimosis of the glans of the clitoris. Ecchymosis and superficial ulcers can occur secondary to scratching. Synechiae may develop in agglutinated areas, resulting in pain with physical activity Pruntus is almost always present.
Lichen sclerosis may occur at any age. Although there appear to be familial linkages and autoimmune associations, the etiology of lichen sclerosis is still a question. Although lichen sclerosis may not be an oncogenic process in itself, any chronic irritative process of the vulva may increase the risk of invasive cancer. Such risk is estimated to range between 1 and 5 percent. Therefore, any ulceration, chronic fissure, induration or hyperkeratotic plaque should be biopsied at the initial evaluation, and any epithelial change that subsequently arises or does not respond to treatment should be sampled on subsequent visits.
Squamous Cell Hyperplasia. The term “squamous cell hyperplasia” replaces the former term “hyperplastic dystrophy.” Although squamous cell hyperplasia includes lesions with no known cause, most hyperplastic lesions are secondary to the surface trauma of scratching or rubbing. Any area of the vulva and perianal region may be affected, but the inner labia minora and vestibule are rarely involved.9 Chronic scratching may result in excoriations, fissures and thickened hyperkeratotic white patches (Figure 12). In order to rule out coexistent carcinoma, any ulcerated or indurated area should be biopsied, as well as any area not responding quickly to treatment. Unlike lichen sclerosis, squamous cell hyperplasia does not result in agglutination of the labia or clitoral hood, and there is no hereditary linkage.
Any proliferative disorder, whether secondary to inflammation or to neoplasia, results in an enhanced vascular bed, imparting a red appearance to the lesion.
Psoriasis. Psoriasis is a chronic skin disease that most commonly affects the extensor surfaces of the extremities, the scalp, trunk, sacral areas, palms and soles, but may also be found on the vulva. The presence of psoriasis on other areas of the body usually makes the diagnosis of vulvar psoriasis relatively easy. Most of the psoriatic lesions of the vulva have sharply limited borders and a dull red surface (Figure 10). As the scales are scratched off, pinpoint bleeding may result.
Seborrheic Dermatitis. Another generalized erythematous papulosquamous disorder that can affect the vulva is seborrheic dermatitis. The finding of a dry to greasy scale superimposed on red to yellow-brown plaques on the vulva (Figure 13) should result in a search for similar lesions elsewhere on the head and neck area.10 Like psoriasis, seborrhea is a chronic skin disorder with spontaneous remissions and flares. The increased moisture in the vulvar area may result in increased pruritus.
Lichen Planus. Lichen planus on the vulva is usually part of a systemic manifestation of this skin and mucous membrane-associated disease. On keratinized skin, small, polygonal violaceous papules appear. They are commonly pruritic. Mucous membrane involvement is manifested by erosions or white patches, which may be found both in the gingival and buccal mucosa and the vulvar vestibule and vagina. Erosion results in a denuded, red, tender mucosa, which may be patchy and sharply marginated (Figure 14). Large denuded areas may become quite inflamed, resulting in profuse leukorrhea, with symptoms resembling persistent vulvovaginitis. Denuded areas may also adhere, resulting in eventual obliteration of the vagina. An autoimmune, cell-mediated response may be responsible for the disease.
It is important to biopsy the full thickness of the epithelium in an area where ulceration is not present, because erosion of the vagina and vestibule results in highly nonspecific histologic findings that are not helpful in securing the diagnosis.
Genital skin contains a large number of melanocytes per square millimeter of skin surface, resulting in the usual darker appearance of this skin in comparison with other body surfaces. Since both benign and malignant dark lesions of the vulva can look exactly alike, biopsy is important to distinguish the conditions. Melanoma accounts for less than 2 percent of all dark lesions of the vulva but is so aggressive that the clinician must always have a high index of suspicion in evaluating any pigmented vulvar lesion. As a general rule, any change in color, size or texture, as well as the presence of bleeding or ulceration of dark lesions, should be regarded as a possible malignant change.
Lentigo. Lentigo is the most common of the pigmented vulvar lesions, usually first appearing in early to middle adult life. The lesion has a characteristic flat, circumscribed appearance. Lentigo are frequently multifocal and display varying sizes (Figure 15). A lentigo closely resembles a large freckle. Only biopsy can distinguish lentigo from a level 1 melanoma (lentigo maligna).
Nevi. Vulvar nevi exhibit a wide variation of depth and color, ranging from amelanotic flesh-colored) to brown-black. The risk of subsequent development of a melanoma is low, but 30 percent of melanomas do develop from preexisting nevi. Therefore, any sudden change in growth, or ulceration, bleeding or development of satellite pigmentation requires excisional biopsy. Dysplastic and congenital nevi carry a higher risk of malignant transformation.
Three types of nevi, as they evolve over time, have less malignant potential. The junctional nevus develops in the basal epithelium in young patients and usually becomes pigmented at puberty. In this state, they closely resemble lentigo. The compound nevus develops as the cells from the junctional nevus begin to occupy the dermis. Compound nevi are more raised and often less pigmented. The intradermal nevus observed in later adult life is paler, usually more polyploid and occupies only the dermis (Figure 16). In order to include all the cells in the sample, the biopsy should extend deep into the dermal layer. Nevi should not be treated with destructive techniques that preclude histologic examination.
Neoplastic Lesions of the Vulva
VULVAR INTRAEPITHELIAL NEOPLASIA
Vulvar intraepithelial neoplasia (VIN) is the only vulvar lesion that may be either white, red or dark. Excessive keratin results in a white lesion (Figure 8), whereas angiogenesis in the absence of obscuring keratin presents as a red lesion. From 10 to 33 percent of high-grade VIN lesions are dark because of increased melanin production (Figure 9). The loss of pigmentation in a dark VIN lesion is most commonly the result of invasion below the basement membrane and destruction of melanocytes in the basal layer of the epidermis. Thus, any dark lesion with a hypopigmented area should be biopsied.
VIN is a precancerous lesion of squamous origin that excludes Paget’s disease and melanoma in situ. In 1986, the International Society for the Study of Vulvar Disease (ISSVD) recommended a terminology for VIN that deleted such confusing terms as atypia, Bowen’s disease, carcinoma in situ and dysplasia. Instead, the following categories were formulated: VIN I equals mild dysplasia, VIN III equals moderate dysplasia and VIN III equals severe dysplasia (carcinoma in situ).
The VIN terminology defines an intraepithelial process that is characterized by nuclear atypia. The epithelial layers form a disordered arrangement, with increasing degrees of hyperplasia, hyperkeratosis, nuclear atypia and bizarre mitotic figures as lesion severity increases. The distinction between VIN I, VIN II and VIN III depends on the extent of the epithelium that is displaying the abnormal features.
The multifocal nature of VIN requires careful assessment of each individually involved area, and multiple biopsies should be taken to detect possible invasion. There is no predilection for any one site on the vulva. Colposcopic examination with acetic acid may make the VIN pattern easier to distinguish from other vulvar conditions, but the acetowhite change is, nevertheless, nonspecific. In addition to acetowhitening, erythema and lichenification, punctation and mosaic patterns may be seen colposcopically when VIN occurs on the mucosal surface of the vulva.
Papule formation is a classic sign of high-grade VIN, which is most commonly positive for HPV type 16. High-grade VIN tends to be sharply demarcated from the surrounding skin, whereas in low-grade VIN, the border with the surrounding skin is often not as well defined.
The incidence of VIN is unknown, but the number of cases has increased over the past 30 years, reflecting either a real increase in incidence or better recognition of the disease process. HPV appears to be strongly associated with VIN in young women, and HPV types 16 and 31 account for 80 to 90 percent of lesions.[21,22] At least 20 percent of young women with VIN III have associated cervical intraepithelial neoplasia. In young women, VIN III may regress and rarely progresses to invasion, but when invasion does occur, it may develop over a period of 20 to 30 years. HPV-positive invasive vulvar cancer is also more common in young women.
Since in the older woman VIN is much less likely to be secondary to an acute HPV-induced viral change, it has a higher risk of progression. In older women, VIN is most likely to occur in areas of chronic inflammation, especially areas of hyperplasia or atrophy. However, the risk of subsequent development of invasive vulvar cancer is only 3 percent in women with squamous cell hyperplasia and up to 4 percent in women with lichen sclerosis7 (Figure 11).
Figures 4, 7, 10 and 14 courtesy of I. Keith Stone, M.D., associate professor in the Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville. Figures 8, 9, 11, 12, 13, 15 and 16 courtesy of Williams & Wilkins, 428 E. Preston St., Baltimore, MD 21202. Used with permission.
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The Authors BARBARA S. APGAR, M.D., M.S. is a clinical associate professor in the Department of Family Practice at the University of Michigan Medical School, Ann Arbor. Dr. Apgar graduated from Texas Tech University Health Sciences Center School of Medicine, Lubbock, where she also completed a residency in family practice. She completed a faculty development fellowship at Michigan State University College of Human Medicine, East Lansing.
J. THOMAS COX, M.D. is director of the gynecology clinic and consultant in gynecology and colposcopy at the Student Health Center at the University of California, Santa Barbara, Calif. Dr. Cox graduated from Baylor College of Medicine, Houston, and completed a residency in obstetrics and gynecology at the Kaiser Foundation Hospital, San Francisco.
Address correspondence to Barbara S. Apgar, M.D., M.S., University of Michigan, 14700 E. Old U.S. 12, Chelsea, MI 48118.
COPYRIGHT 1996 American Academy of Family Physicians
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