BENIGN VULVAR DISEASE
In the past, the classification of benign, noninfectious vulvar disease used descriptive terminology based on gross clinical morphologic appearance such as leukoplakia, kraurosis vulvae, and hyperplastic vulvitis. Currently, these diseases are classified into three categories: squamous cell hyperplasia, lichen sclerosus, and other dermatoses.
In 2006, the International Society for the Study of Vulvar Disease (ISSVD) constructed a new classification using histologic morphology based on consensus among gynecologists, dermatologists, and pathologists involved in the care of women with vulvar disease. Common ISSVD classifications are outlined in Table 42.1.
Lichen sclerosus has confused clinicians and pathologistsbecause of inconsistent terminology and its frequent asso-ciation with other types of vulvar pathology, including those of the acanthotic variety. As with the other disorders, chronic vulvar pruritus occurs in most patients. Typically,the vulva is diffusely involved, with very thin, whitish epithe-lial areas, termed “onion skin” epithelium (Fig. 42.1B). Theepithelium has been termed “cigarette paper” skin and described as “parchment-like.” Most patients have involve-ment on both sides of the vulva, with the most common sites being the labia majora, labia minora, the clitoral and periclitoral epithelium, and the perineal body. The lesion may extend to include a perianal “halo” of atrophic, whitish epithelium, forming a figure-8 configuration with the vul-var changes. In severe cases, many normal anatomic landmarksare lost, including obliteration of the labial and periclitoral archi-tecture as well as severe stenosis of the vaginal introitus. Somepatients have areas of cracked skin, which are prone to bleeding with minimal trauma. Patients with these severe anatomic changes complain of difficulty in having normal coital function.
The etiology of lichen sclerosus is unknown, but a familial association has been noted, as well as disorders of the immune system, including thyroid disorders and Class II human leukocyte antigens.
However, the response to topical steroids furtherindicates the underlying inflammatory process and the role of prostaglandins and leukotrienes in the hallmark symptom of pruritus. Histologic evaluation and confirmation of lichen scle-rosis is often necessary and useful, because they allow specific ther-apy. The histologic features of the lichenoid pattern includea band of chronic inflammatory cells, consisting mostly of lymphocytes, in the upper dermis with a zone of homoge-neous, pink-staining, collagenous-like material beneath the epidermis due to cell death. The obliteration of boundaries between collagen bundles gives the dermis a “hyalinized” or “glassy” appearance. This dermal homogenization/ sclerosis pattern is virtually pathognomonic.
In 27% to 35% of patients, there are associated areas of acanthosis characterized by hyperkeratosis—an increase in the number of epithelial cells (keratinocytes) with flat-tening of the rete pegs.
These areas may be mixed through-out or adjacent to the typically lichenoid areas. In patients with this mixed pattern, both components need to be treated to effect resolution of symptoms. Patients in whom a large acanthotic component has been histologically confirmed should be treated initially with well-penetrating cortico-steroid creams. With improvement of these areas (usually 2 to 3 weeks), therapy can then be directed to the lichenoid component.
Treatment for lichen sclerosis includes the use of topical steroid (clobetasol) preparations in an effort to ameliorate symp-toms. The lesion is unlikely to resolve totally. Intermittenttreatment may be needed indefinitely, which is in marked contrast to acanthotic lesions, which usually totally resolve within 6 months.
Lichen sclerosus does not significantly increase the patient’s risk of developing cancer.
It has been estimated that this risk is in the 4% range. However, due to the frequent coexistence with acanthosis, the condition needs to be followed carefully and a rebiopsy performed, because therapeutically resistant acanthosis can be a harbinger of squamous cell carcinoma (SCC).
In contrast to many dermatologic conditions that may be described as “rashes that itch,” lichen simplex chronicus can be described as “an itch that rashes.” Most patients develop this disorder secondary to an irritant dermatitis, which progresses to lichen simplex chronicus as a result of the effects of chronic mechanical irritation from scratch-ing and rubbing an already irritated area. The mechanicalirritation contributes to epidermal thickening or hyperplasia and inflammatory cell infiltrate, which, in turn, leads to heightened sensitivity that triggers more mechanical irritation.
Accordingly, the history of these patients is one of progres-sive vulvar pruritus and/or burning, which is temporarilyrelieved by scratching or rubbing with a washcloth or some similar material. Etiologic factors for the original pruritic symptoms often are unknown, but may include sources of skin irritation such as laundry detergents, fab-ric softeners, scented hygienic preparations, and the use of colored or scented toilet tissue. These potential sources of symptoms must be investigated. Any domestic or hygienic irritants must be removed, in combination with treatment, to break the cycle described.
On clinical inspection, the skin of the labia majora, labia minora, and perineal body often shows diffusely reddened areas with occasional hyperplastic or hyperpigmented plaques of red to reddish brown (see Fig. 42.1A). One may also find occasionalareas of linear hyperplasia, which show the effect of grossly hyperkeratotic ridges of epidermis. Biopsy of patients who have these characteristic findings is usually not warranted.
Empiric treatment to include antipruritic medications such as diphenhydramine hydrochloride (Benadryl) or hydroxyzine hydrochloride (Atarax) that inhibit nighttime, unconscious scratching, combined with a mild to moder-ate topical steroid cream applied to the vulva, usually pro-vides relief. A steroid cream, such as hydrocortisone (1% or 2%) or, for patients with significant areas of obvious hyperkeratosis, triamcinolone acetonide or betamethasone valerate may be used. If significant relief is not obtained within3 months, diagnostic vulvar biopsy is warranted.
The prognosis for this disorder is excellent when the offend-ing irritating agents are removed and a topical steroid prepara-tion is used appropriately. In most patients, these measurescure the problem and eliminate future recurrences.
Although lichen planus is usually a desquamative lesion of the vagina, occasional patients develop lesions on the vulva near the inner aspects of the labia minora and vulvar vestibule. Patients may have areas of whitish, lacy bands (Wickham striae) of keratosis near the reddish ulcerated-like lesions characteristic of the disease (see Figure 42.1C). Typically, complaints include chronic vulvar burning and/or pruritus and insertional (i.e., entrance) dyspareunia and a pro-fuse vaginal discharge. Because of the patchiness of thislesion and the concern raised by atypical appearance of the lesions, biopsy may be warranted to confirm the diagnosis in some patients. In lichen planus, biopsy shows no atypia. Examination of the vaginal discharge in these patients fre-quently reveals large numbers of acute inflammatory cells without significant numbers of bacteria. Accordingly, the diagnosis most often can be made by the typical history of vaginal/vulvar burning and/or insertional dyspareunia, coupled with a physical examination that shows the bright red patchy distribution; and a wet prep that shows large numbers of white cells. Histologically the epithelium is thinned, and there is a loss of the rete ridges with a lym-phocytic infiltrate just beneath, associated with basal cell liquefaction necrosis.
Treatment for lichen planus is topical steroid prepa-rations similar to those used for lichen simplex chronicus. This may include the use of intravaginal 1% hydrocorti-sone douches. Length of treatment for these patients is often shorter than that required to treat lichen simplex chronicus, although lichen planus is more likely to recur.
Psoriasis is an autosomal dominant inherited disorder that caninvolve the vulvar skin as part of a generalized dermatologic process. With approximately 2% of the general populationsuffering from psoriasis, the physician should be alert to its prevalence and the likelihood of vulvar manifestation, because it may appear during menarche, pregnancy, and menopause.
The lesions are typically slightly raised round or ovoid patches with a silver scale appearance atop an erythema-tous base. These lesions most often measure approximately 1 × 1 to 1 × 2 cm. Though pruritus is usually minimal, these silvery lesions will reveal punctate bleeding areas if removed (Auspitz sign). The diagnosis is generally known because ofpsoriasis found elsewhere on the body, obviating the need for vul-var biopsy to confirm the diagnosis. Histologically, a prominentacanthotic pattern is seen, with distinct dermal papillaethat are clubbed and chronic inflammatory cells between them.
Treatment often occurs in conjunction with consulta-tion by a dermatologist. Like lesions elsewhere, vulvar lesions usually respond to topical coal tar preparations, followed by exposure to ultraviolet light as well as cortico-steroid medications, either topically or by intralesional injection. Coal tar preparations are extremely irritating to the vagina and labial mucous membranes and should not be used in these areas. Because vulvar application of some of thephotoactivated preparations can be somewhat awkward, topical steroids are most effective, using compounds such as betametha-sone valerate 0.1%.
Vulvar dermatitis falls into two main categories: eczema and seborrheic dermatitis. Eczema can be further sub-divided into exogenous and endogenous forms. Irritant and allergic contact dermatitis are forms of exogenous eczema. They are usually reactions to potential irritants or allergens found in soaps, laundry detergents, textiles, and feminine hygiene products. Careful history can be helpful in identifying the offending agent and in preventing recur-rences. Atopic dermatitis is a form of endogenous eczema that often affects multiple sites, including the flexural sur-faces of the elbows and knees, retroauricular area, and scalp. The lesions associated with these three forms of dermatitis can appear similar: symmetric eczematous lesions, with underlying erythema. Histology alone will not distinguish these three types of dermatitis. They all exhibit a spongi-otic pattern characterized by intercellular edema withinthe epidermis, causing widening of the space between the cells. Therefore, these entities must often be distinguished clinically.
Although seborrheic dermatitis is a common problem, iso-lated vulvar seborrheic dermatitis is rare. It involves a chronicinflammation of the sebaceous glands, but the exact cause is unknown. The diagnosis is usually made in patients com-plaining of vulvar pruritus who are known to have sebor-rheic dermatitis in the scalp or other hair-bearing areas of the body. The lesion may mimic other entities such as pso-riasis or lichen simplex chronicus. The lesions are pale red toa yellowish pink and may be covered by an oily appearing, scaly crust. Because this area of the body remains continuallymoist, occasional exudative lesions include raw “weeping” patches, caused by skin maceration, which are exacerbated by the patient’s scratching. As with psoriasis, vulvar biopsy isusually not needed when the diagnosis is made in conjunction with known seborrheic dermatitis in other hair-bearing areas. Thehistologic features of seborrheic dermatitis are a combina-tion of those seen in the acanthotic and spongiotic patterns.
Treatment for vulvar dermatitis involves removing the offending agent, if applicable, initial perineal hygiene and the use of a 5% solution of aluminum acetate several times a day, followed by drying. Topical corticosteroid lotions or creams containing a mixture of an agent that penetrates well, such as betamethasone valerate, in conjunction with crotamiton, can be used for symptom control. As with LSC, the use of antipruritic agents as a bedtime dose in the first 10 days to 2 weeks of treatment frequently helps break the sleep/scratch cycle and allows the lesions to heal. Table 42.2 summarizes the clinical characteristics of the common vul-var dermatoses.
Vulvar vestibulitis is a condition of unknown etiology. Itinvolves the acute and chronic inflammation of the vestibu-lar glands, which lie just inside the vaginal introitus near the hymeneal ring. The involved glands may be circumferential to include areas near the urethra, but this condition most commonly involves posterolateral vestibular glands between the 4 and 8 o’clock positions (Fig. 42.2). The diagnosis shouldbe suspected in all patients who present with new onset insertional dyspareunia. Patients with this condition frequently com-plain of progressive insertional dyspareunia to the point where they are unable to have intercourse. The history may go on for a few weeks, but most typically involves progres sive worsening over the course of 3 or 4 months. Patients also complain of pain on tampon insertion and at times dur-ing washing or bathing the perineal area.
Physical examination is the key to diagnosis. Because the vestibular glands lie between the folds of the hymenal ring and the medial aspect of the vulvar vestibule, diagno-sis is frequently missed when inspection of the perineum does not include these areas: Once the speculum has been placedin the vagina, the vestibular gland area becomes impossible to identify. After carefully inspecting the proper anatomic area,a light touch with a moistened cotton applicator recreates the pain exactly and allows for quantification of the pain. In addition, the regions affected are most often evident as small, reddened, patchy areas.
Because the cause of vestibulitis is unknown, treatments vary and range from changing or eliminating environmen-tal factors, temporary sexual abstinence, and application of cortisone ointments and topical lidocaine (jelly); to more radical treatments such as surgical excision of the vestibular glands. A combination of treatment modalities may be nec-essary. Treatment must be individualized, based on the severity of patient symptoms and the sexual disability.
Some patients may benefit from low-dose tricyclic medication (amitriptyline and desipramine) or fluoxetine to help break the cycle of pain. Other limited reports suggest the use of calcium citrate to change the urine composition by removing oxalic acid crystals. Those advocating chang-ing the urine chemistry cite evidence to suggest that oxalic acid crystals are particularly irritating when precipitated in the urine of patients with high urinary oxalic acid composi-tion. Other modalities include biofeedback, physical ther-apy with electrical stimulation, or intralesional injections with triamcinolone and bupivacaine.
Sebaceous or inclusion cysts are caused by inflammatoryblockage of the sebaceous gland ducts and are small, smooth, nodular masses, usually arising from the inner sur-faces of the labia minora and majora, that contain cheesy, sebaceous material. They may be easily excised if their size or position is troublesome.
The round ligament inserts into the labium majus, car-rying an investment of peritoneum. On occasion, peritoneal fluid may accumulate therein, causing a cyst of the canalof Nuck or hydrocele. If such cysts reach symptomaticsize, excision is usually required.
Fibromas (fibromyomas) arise from the connectivetissue and smooth muscle elements of vulva and vagina and are usually small and asymptomatic. Sarcomatous change is extremely uncommon, although edema and degenerative changes may make such lesions suspicious for malignancy. Treatment is surgical excision when the lesions are symp-tomatic or with concerns about malignancy. Lipomas appear much like fibromas, are rare, and are also treated by excision if symptomatic.
Hidradenoma is a rare lesion arising from the sweatglands of the vulva. It is almost always benign, is usually found on the inner surface of the labia majora, and is treated with excision.
Nevi are benign, usually asymptomatic, pigmentedlesions whose importance is that they must be distinguished from malignant melanoma, 3% to 4% of which occur on the external genitalia in females. Biopsy of pigmented vulvar lesions may be warranted, depending on clinical suspicion.