Chapter 46 Vulvar and Vaginal Disease and Neoplasia

This chapter deals primarily with APGO Educational Topic Area:

TOPIC 51 VULVAR NEOPLASMS

Students should be able to identify the risk factors for vulvar neoplasms and list indications for vulvar biopsy.

Clinical Case

A 51-year-old patient comes to see you secondary to vulvar itching. She reports that it has been going on for about 5 months and she has tried over-the-counter vaginal preparations for yeast, but these have not helped. She even went to an urgent care clinic and obtained a prescription for metronidazole for bacterial vaginosis, but that too did not help. On examination, you notice some erythema with a keyhole lesion around the vulva and anus.

Evaluation of vulvar symptoms and examination of patients for vulvar disease and neoplasia constitute a significant part of health care for women. The major symptoms of vulvar disease are pruritus, burning, nonspecific irritation, and/or appreciation of a mass. The vulvar region is particularly sensitive to irritants, more so than other regions of the body. It has been suggested that the layer overlying the vulva—the stratum corneum—may be less of a barrier to irritants, thereby making the vulva more susceptible to irritations and contributing to the “itch–scratch” cycle. Noninflammatory vulvar pathology is found in women of all ages but is especially significant in perimenopausal and postmenopausal women because of concern regarding the possibility of vulvar neoplasia.

Diagnostic aids for the assessment of noninflammatory conditions are relatively limited in number and include careful history, inspection, and biopsy. Because vulvar lesions are often difficult to diagnose, use of vulvar biopsy is central to good care. Punch biopsies of vulvar abnormalities are most helpful to determine if cancer is present or to histologically determine the specific cause of a perceived abnormality of the vulva.

This chapter provides discussions of a range of vulvar pathologic conditions, including nonneoplastic dermatoses, localized vulvodynia (formerly known as vestibulitis), benign vulvar mass lesions, vulvar intraepithelial neoplasia (VIN), and vulvar cancer. Benign vaginal masses and vaginal neoplasia are also discussed. Inflammatory conditions of the vulva are discussed in Chapter 28.

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 46.1.

Lichen Sclerosus

Lichen sclerosus has confused clinicians and pathologists because of inconsistent terminology and its frequent association 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 epithelial areas, termed “onion skin” epithelium (Fig. 46.1B). The epithelium has been termed “cigarette paper” skin and described as “parchment-like.” Most patients have involvement 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 etiology of lichen sclerosus is unknown, but a familial association has been noted, as well as associations with disorders of the immune system, including thyroid disorders and class II human leukocyte antigens. However, the response to topical steroids further indicates the underlying inflammatory process and the role of prostaglandins and leukotrienes in the hallmark symptom of pruritus. Histologic evaluation and confirmation of lichen sclerosis are often necessary and useful because they allow specific therapy. The histologic features of the lichenoid pattern include a band of chronic inflammatory cells, consisting mostly of lymphocytes, in the upper dermis with a zone of homogeneous, pink-staining, collagenous-like material beneath the epidermis due to cell death. The rete pegs, normally projectile in appearance, are flattened. The obliteration of boundaries between collagen bundles gives the dermis a “hyalinized” or “glassy” appearance. This dermal homogenization/sclerosis pattern is virtually pathognomonic.

FIGURE 46.1. The three “lichens.” (A) Lichen simplex chronicus. (B) Lichen sclerosus. (C) Lichen planus. (Used with permission from Foster DC. Vulvar disease. Obstet Gynecol. 2002;100(1):149.)

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 flattening of the rete pegs.

Treatment for lichen sclerosis includes the use of topical steroid (clobetasol) preparations in an effort to ameliorate symptoms. The lesion is unlikely to resolve totally. Intermittent treatment may be needed indefinitely, which is in marked contrast to acanthotic lesions, which usually totally resolve within 6 months.

Lichen sclerosus is associated with an increased risk of developing squamous cell cancer (SCC) of the vulva. It has been estimated that this risk is in the 4% range. Due to the frequent coexistence with acanthosis, the condition needs to be followed carefully and a repeat biopsy performed, because therapeutically resistant acanthosis can be a harbinger of SCC.

Lichen Simplex Chronicus

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 scratching and rubbing an already irritated area. The mechanical irritation 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 progressive vulvar pruritus and/or burning, which is temporarily relieved by scratching or rubbing with a washcloth or some similar material. Etiologic factors for the original pruritic symptoms are often unknown, but may include sources of skin irritation such as laundry detergents, fabric softeners, scented hygienic preparations, and the use of colored or scented toilet tissue.

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. 46.1A). Occasionally, areas of linear hyperplasia are also seen, 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 moderate topical steroid cream applied to the vulva, usually provides 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 within 3 months, diagnostic vulvar biopsy is warranted.

The prognosis for this disorder is excellent when the offending irritating agents are removed and a topical steroid preparation is used appropriately. In most patients, these measures cure the problem and eliminate future recurrences.

Lichen Planus

Lichen planus is a rare inflammatory skin condition that can be generalized or isolated to the vulva and vagina. In the latter situation, it usually presents as a desquamative lesion of the vagina; occasionally, 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 Fig. 46.1C). Typically, complaints include chronic vulvar burning and/or pruritus, insertional dyspareunia, and a profuse vaginal discharge.

Treatment for lichen planus is topical steroid preparations similar to those used for lichen simplex chronicus. This may include the use of intravaginal 1% hydrocortisone 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

Psoriasis is an autosomal-dominant inherited disorder that can involve the vulvar skin as part of a generalized dermatologic process. With approximately 2% of the general population suffering 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 erythematous 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 of psoriasis found elsewhere on the body, obviating the need for vulvar biopsy to confirm the diagnosis. Histologically, a prominent acanthotic pattern is seen, with distinct dermal papillae that are clubbed and chronic inflammatory cells between them.

Treatment often occurs in conjunction with consultation by a dermatologist. Like lesions elsewhere, vulvar lesions usually respond to topical coal tar preparations, followed by exposure to ultraviolet light as well as corticosteroid medications, either topically or by intralesional injection. However, coal tar preparations are extremely irritating to the vagina and labial mucous membranes and should not be used in these areas. With very severe disease, systemic therapy may need to be implemented. Emollients to keep the skin moist help reduce itching. Other therapies include topical vitamin D analogues, retinoids, and calcineurin inhibitors. Because vulvar application of some of the photoactivated preparations can be somewhat awkward, topical steroids are most effective, using compounds such as betamethasone valerate 0.1%.

Dermatitis

Vulvar dermatitis falls into two main categories: eczema and seborrheic dermatitis. Eczema can be further subdivided 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 recurrences. Atopic dermatitis is a form of endogenous eczema that often affects multiple sites, including the flexural surfaces of the elbows and knees, retroauricular area, and scalp. The lesions associated with these three forms of dermatitis can appear similarly as symmetric eczematous lesions, with underlying erythema. Histology alone will not distinguish these three types of dermatitis. They all exhibit a spongiotic pattern characterized by intercellular edema within the epidermis, causing widening of the space between the cells. Therefore, these entities must often be distinguished clinically.

Although seborrheic dermatitis is a common problem, isolated vulvar seborrheic dermatitis is rare. It involves a chronic inflammation of the sebaceous glands, but the exact cause is unknown. The diagnosis is usually made in patients complaining of vulvar pruritus who are known to have seborrheic dermatitis in the scalp or other hair-bearing areas of the body. The lesion may mimic other entities, such as psoriasis or lichen simplex chronicus. The lesions are pale red to a yellowish pink and may be covered by an oily appearing, scaly crust. Because this area of the body remains continually moist, occasional exudative lesions include raw “weeping” patches, caused by skin maceration, which are exacerbated by the patient’s scratching. As with psoriasis, vulvar biopsy is usually not needed when the diagnosis is made in conjunction with known seborrheic dermatitis in other hair-bearing areas. The histologic features of seborrheic dermatitis are a combination 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 lichen simplex chronicus, 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 46.2 summarizes the clinical characteristics of the common vulvar dermatoses.

Localized Vulvodynia

Localized vulvodynia is a condition of unknown etiology. It involves the acute and chronic inflammation of the vestibular glands, which lie just inside the vaginal introitus near the hymenal 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. 46.2). The diagnosis should be suspected in all patients who present with new onset insertional dyspareunia. Patients with this condition frequently complain 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 progressive worsening over the course of 3 or 4 months. Patients also complain of pain on tampon insertion; on sitting; and, at times, during 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, diagnosis is frequently missed when inspection of the perineum does not include these areas. After carefully inspecting the proper anatomic area by applying gentle traction to the vestibule, 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. Using a speculum is not recommended during this examination because it causes too much patient discomfort.

Because the etiology of localized vulvodynia is unknown, treatments vary and range from changing or eliminating environmental 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 necessary. Treatment must be individualized, based on the severity of patient symptoms and the disability.

FIGURE 46.2. Vestibular glands.

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 changing 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 composition. Other modalities include biofeedback, physical therapy with electrical stimulation, and intralesional injections with triamcinolone and bupivacaine.

Vulvar Lesions

Sebaceous or inclusion cysts are caused by inflammatory blockage of the sebaceous gland ducts and are small, smooth, nodular masses, usually arising from the inner surfaces 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, carrying an investment of peritoneum. On occasion, peritoneal fluid may accumulate therein, causing a cyst of the canal of Nuck, or hydrocele. If such cysts reach symptomatic size, excision is usually required.

Fibromas (fibromyomas) arise from the connective tissue 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 symptomatic or with concerns about malignancy. Lipomas appear much like fibromas, are rare, and are also treated by excision if symptomatic.

Hidradenitis suppurativa is a chronic skin condition involving follicles in areas with a high density of sweat glands, including the groin, axillae, and perineal and inner thigh regions. The clinical presentation can range from a few indurated, occluded follicles to a more serious confluence, leading to scarring, draining, and fistula formation. Effective medical treatments include antibiotics, anti-inflammatories, and even anti-androgens, particularly in women. More serious disease requires surgical management in the form of incision and drainage or even excision of the glands of the affected area.

Hidradenoma is a rare lesion arising from the sweat glands of the vulva. It is almost always benign, is usually found on the inner surface of the labia majora, and is treated with excision. It is not related to hidradenitis suppurativa.

Nevi are benign, usually asymptomatic, pigmented lesions 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.

VULVAR INTRAEPITHELIAL NEOPLASIA

Much like the vulvar dermatoses, the classification and terminology of VIN is still evolving and has undergone multiple revisions and reclassifications over the years. There are currently three grading systems: 1) the World Health Organization (WHO) three-grade system of VIN 1, 2, and 3; 2) the clinical, Bethesda-like, two-grade system of low- and high-grade vulvar intraepithelial lesions; and 3) the revised 2004 ISSVD classification, which divides VIN into two types: usual and differentiated. VIN, usual type is further divided into three subtypes: warty, basaloid, and mixed. These grading systems are summarized in Table 46.3.

VIN 1

VIN 1, or mild dysplasia, is a low-grade lesion that demonstrates minimal to mild squamous atypia limited to the lower epidermis. VIN 1 is either a nonneoplastic, reactive atypia or an effect of an HPV infection. VIN 1 occurs most often in condylomata acuminata. Lesions that are condylomatous in origin do not have the features of attenuated maturation, pleomorphism, and atypical mitotic figures that are found in other forms of VIN.

Because the features of VIN 1 are uncommon histologic findings, and there is little evidence that VIN 1 is a cancer precursor, it may be misleading to classify these lesions as true intraepithelial neoplasia. In 2004, the ISSVD abolished the term VIN 1 from their classification system. The diagnosis of VIN 1 must be made by biopsy, and treatment is the same as for condyloma.

Vin, Usual Type

The ISSVD combined VIN 2 and 3 into VIN, usual type. These are high-grade, HPV-related lesions distinguished only by the degree of abnormality. They represent true neoplasia with a high predilection for progression to severe intraepithelial lesions and, eventually, carcinoma, if left untreated. Almost 60% of women with VIN 3 or vaginal intraepithelial neoplasia (VAIN) 3 will also have cervical intraepithelial neoplasia (CIN) lesions. Furthermore, 10% of women with CIN 3 will have either VIN or VAIN.

Smoking or second-hand smoke is a common social history finding in patients with VIN. Presenting complaints include vulvar pruritus, chronic irritation, and a development of raised mass lesions. Normally, the lesions are localized, fairly well-isolated, and raised above the normal epithelial surface to include a slightly rough texture. They are usually found along the posterior, hairless area of vulva and in the perineal body but can occur anywhere on the vulva. The color changes in these lesions range from white, hyperplastic areas to reddened or dusky, patch-like involvement, depending on whether associated hyperkeratosis is present. Figure 46.3 illustrates the variation in appearance of VIN.

In patients without obvious raised or isolated lesions, careful inspection of the vulva is warranted, using a colposcope. Applying a 3% to 5% solution of acetic acid to the vulva for 2 to 5 minutes often accentuates the white lesions and may also help in revealing abnormal vascular patterns. These areas must be selectively biopsied in multiple sites to thoroughly investigate the type of VIN and reliably exclude invasive carcinoma.

VIN, usual type is subdivided into three histologic subtypes—warty, basaloid, and mixed—depending on the features present. They all have atypical mitotic figures and nuclear pleomorphism, with loss of normal differentiation in the lower one third to one half of the epithelial layer. Full thickness loss of maturation indicates lesions that are at least severely dysplastic, including areas that may represent true carcinoma in situ (CIS).

The goal in treating VIN, usual type is to quickly and completely remove all involved areas of skin. These lesions can be removed after appropriate biopsies confirm the absence of invasive cancer. Removal options include wide local excision or laser ablation. A variety of nonsurgical treatments for patients with VIN, usual type have been reported, including phototherapy, corticosteroids, 5-fluorouracil (5-FU), and imidazoquinolones (particularly imiquimod). Results to date are mixed. 5-FU is poorly tolerated, although it has acceptable response rates; imidazoquinolones have been shown to be effective. Careful evaluation to exclude invasive disease is of paramount importance, insofar as VIN, usual type is seen adjacent to 30% of SCCs of the vulva.

VIN, Differentiated Type

The less common simplex type of VIN (CIS) in the WHO system is now called VIN, differentiated type by the ISSVD (see Table 46.3). The lesion is either a hyperkeratotic plaque, warty papule or an ulcer, seen primarily in older women. It is often associated with keratinizing SCCs or lichen sclerosus and is not HPV-related. It is thought that VIN, differentiated type is underdiagnosed due to a relatively short intraepithelial phase before progression to invasive carcinoma. Clinical awareness of this entity and its features as different from VIN, usual type would help improve diagnosis before cancer has supervened. Biopsy is mandatory, and the mainstay of treatment is excision.

FIGURE 46.3. Variation in appearance of vulvar intraepithelial neoplasia. (A) Large, hypertrophic, pigmented lesion; (B) associated with erosive lichen planus; and (C) isolated to the clitoris. (Used with permission from Foster DC. Vulvar disease. Obstet Gynecol. 2002;100(1):157.)

PAGET DISEASE

Paget disease is characterized by extensive intraepithelial disease whose gross appearance is described as a fiery, red background mottled with whitish hyperkeratotic areas. The histology of these lesions is similar to that of the breast lesions, with large, pale cells of apocrine origin below the surface epithelium (Fig. 46.4). Although not common, Paget disease of the vulva may be associated with carcinoma of the skin. Similarly, patients with Paget disease of the vulva have a higher incidence of underlying internal carcinoma, particularly of the colon and breast.

The treatment for vulvar Paget disease is wide local excision or simple vulvectomy, depending on the amount of involvement. Recurrences are more common with this disorder than with VIN, necessitating wider margins when local excision or vulvectomy is performed.

VULVAR CANCER

Vulvar carcinoma accounts for approximately 5% of all gynecologic malignancies. Approximately 90% of these carcinomas are SCCs. The second most common variety is melanoma, which accounts for 2% of all vulvar carcinomas, followed by sarcoma. Less common types include basal cell carcinoma and adenocarcinoma.

The typical clinical profile of vulvar carcinoma includes women in their postmenopausal years, most commonly between ages 70 and 80 years. However, about 20% of these cancers are discovered in women younger than age 50 years. Vulvar pruritus is the most common presenting complaint. In addition, patients may notice a red or white ulcerative or exophytic lesion arising most commonly on the posterior two thirds of either labium majus. An exophytic ulcerative lesion need not be present, further underscoring the need for thorough biopsy in patients of the age group who complain of vulvar symptoms. Patients in this older age group may be reluctant to consult their physicians about these signs and symptoms, which can result in a delay in treatment.

FIGURE 46.4. Paget disease. Large, pale cells of apocrine origin involving the surface epithelium. (Used with permission from Berek JS. Berek and Novak’s Gynecology. 14th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007:figure 17.20.)

Although a specific cause for vulvar cancer is not known, progression has been shown from prior intraepithelial lesions, including those that are associated with certain types of HPV. Smokers have a high preponderance in this population of patients.

Natural History

SCC of the vulva generally remains localized for long periods of time and then spreads in a predictable fashion to the regional lymph nodes, including those of the inguinal and femoral chain. Lesions 2 cm wide and 0.5 cm deep have an increased chance of nodal metastases. The overall incidence of lymph node metastasis is approximately 30%. Lesions arising in the anterior one third of the vulva may spread to the deep pelvic nodes, bypassing regional inguinal and femoral lymphatics.

Evaluation

The staging classification for vulvar cancer was revised by the Federation of Gynecology and Obstetrics in 2009 (Table 46.4). Prior to 1988, vulvar cancers were staged clinically. However, noted discrepancies in regard to predicting nodal metastasis led to a change from clinical to surgical staging. This staging convention uses the analysis of the removed vulvar tumor and microscopic assessment of the regional lymph nodes as its basis.

Treatment

Although the mainstay for the treatment of invasive vulvar cancer is surgical, many advances have been made to help individualize care in an effort to reduce the amount of radical surgery, without compromising survival. Accordingly, not all patients should undergo radical vulvectomy with bilateral nodal dissections. Other approaches include the following:

• Conservative vulvar operations for unifocal lesions

• Elimination of routine pelvic lymphadenectomy

• Avoidance of groin dissection in unilateral lesions 1 mm deep

• Elimination of contralateral groin dissection in unilateral lesions 1 cm from the midline with negative ipsilateral nodes

• Separate groin incisions for patients with indicated bilateral groin dissection

• Postoperative radiation therapy to decrease groin recurrence in patients with two or more positive groin nodes

Concomitant use of radiation and chemotherapy (5-FU plus cisplatin or mitomycin or cisplatin alone) is gaining favor for the treatment of vulvar cancers that require radiation therapy. Treatment with chemotherapy in cases of recurrent vulvar cancer has only limited value.

Prognosis

The corrected 5-year survival rate for all vulvar carcinoma is approximately 70%. Five-year survival rates for SCC are 60% to 80% for stage I and II disease. Survival rates for patients with stage III disease are 45%, and those with stage IV have rates of 15%.

Other Types of Vulvar Cancer

Melanoma

Melanoma is the most common non-SCC of the vulva. Vulvar melanoma usually presents with a raised, irritated, pruritic, pigmented lesion. Most commonly, melanotic lesions are located on the labia minora or the clitoris. Melanoma accounts for approximately 6% of all vulvar malignancies, and, when suspected, wide local excision is necessary for diagnosis and staging. Survival approaches 100% when the lesions are confined to the intrapapillary ridges, decreasing rapidly as involvement includes the papillary dermis; reticular dermis; and, finally, subcutaneous tissues. In the latter instance, survival is generally 20% because of substantial incidence of nodal involvement. Because early diagnosis and treatment by wide excision are so crucial, it is important to recognize that irritated, pigmented, vulvar lesions mandate the excisional biopsy for definitive treatment.

Carcinoma of the Bartholin Gland

Carcinoma of the Bartholin gland is uncommon (1%–2% of all vulvar carcinomas). Malignancies that arise from the Bartholin gland include adenocarcinomas, SCCs, adenosquamous carcinomas, and adenoid cystic and transitional cell carcinomas. These arise mainly as a result of changes occurring within the different histologic areas of the gland and ducts leading from it. Bartholin carcinoma on average occurs in women over age 60 years; however, any new solid Bartholin mass in a woman over age 40 years should be excised. Treatment of diagnosed Bartholin cancers is radical vulvectomy and bilateral lymphadenectomy. Recurrence is disappointingly common, and a 5-year overall survival rate of 85% is noted.

VAGINAL DISEASE

Vaginal disease can be classified into three broad categories: benign, precancerous, and cancerous. There are important differences in the management and prognosis of these conditions. Vaginal neoplasias are rare and usually occur secondary to cervical or vulvar cancers that have spread to the vagina from the primary site.

Benign Vaginal Masses

Gartner duct cysts arise from vestigial remnants of the Wolffian or mesonephric system that course along the outer anterior aspect of the vaginal canal. These cystic structures are usually small and asymptomatic, but, on occasion, they may be larger and symptomatic so that excision is required.

Inclusion cysts are usually seen on the posterior lower vaginal surface, resulting from imperfect approximation of childbirth lacerations or episiotomy. They are lined with stratified squamous epithelium, their content is usually cheesy, and they may be excised if symptomatic.

Vaginal Intraepithelial Neoplasia

VAIN can be classified into three types:

• VAIN 1 involves the basal epithelial layers

• VAIN 2 involves up to two thirds of the vaginal epithelium

• VAIN 3 involves more than two thirds of the vaginal epithelium (including CIS)

VAIN is most commonly located in the upper third of the vagina, a finding that may be partially related to its association with the more common cervical neoplasias. It is estimated that one half to two thirds of all patients with VAIN have had cervical or vulvar neoplasia.

Patients with VAIN 1 can be monitored and typically will not require therapy. Many of these patients have HPV infection and atrophic change of the vagina. Topical estrogen therapy may be useful in some women. VAIN 2 and 3 should be treated.

VAIN 3 appears to occur more commonly in the third decade of life onward, although its exact incidence is unknown. Approximately 1% to 2% of patients who undergo hysterectomy for CIN 3 and many patients who undergo radiation therapy for other gynecologic malignancy ultimately develop VAIN 3. Vaginal Pap smears should be performed for a period of time in patients who have a hysterectomy for the treatment of CIN, particularly CIN 2 and 3. The importance of VAIN 3 is its potential for progression to invasive vaginal carcinoma, as the lesions themselves are usually asymptomatic and have no intrinsic morbidity.

VAIN 3 must be differentiated from other causes of red, ulcerated, or white hyperplastic lesions of the vagina such as herpes, traumatic lesions, hyperkeratosis associated with chronic irritation (e.g., from a poorly fitting diaphragm), and adenosis. Inspection and palpation of the vagina are the mainstays of diagnosis, but, unfortunately, this is often done in a cursory fashion during the routine pelvic examination. Pap smears of the vaginal epithelium can disclose findings that are useful in the diagnosis, although colposcopy with directed biopsy is the definitive method of diagnosis, just as it is with CIN.

The goals of treatment of VAIN 3 are ablation of the intraepithelial lesion while preserving vaginal depth, caliber, and sexual function. Laser ablation, local excision, intracavitary radiation, and chemical treatment with 5-FU cream are all used for limited lesions; total or partial vaginectomy with application of a split thickness skin graft is usually reserved for failure of the previously described treatments. The treatment chosen is dependent on the severity of disease, side-effect profile of treatments, certainty of exclusion of carcinoma, patient’s health and associated surgical risks, and patient’s sexual functioning. Cure rates of 80% to 95% may be expected.

Vaginal Cancer

Invasive vaginal cancer accounts for approximately 1% to 3% of gynecologic malignancies. SCC makes up approximately 80% to 90% of these malignancies, which occur primarily in women age 55 years or older. The majority of the remainder of vaginal carcinomas consists of adenocarcinoma of the vagina, vaginal melanoma, and sarcoma. Small cell cancer, lymphoma, and carcinoid cancers together make up 1% of primary vaginal cancers.

The staging of vaginal carcinoma is nonsurgical (Table 46.5). Surgery, radiation, and neoadjuvant chemotherapy are potential treatments. The patient’s sexual functioning and exact anatomic location need to be considered. Radiation would not be appropriate for cancers in close proximity to radiation-sensitive tissues. Some anatomic locations would preclude achieving an appropriate margin of resection; thus, surgery would not be appropriate. The overall 5-year survival rate for SCC of the vagina is approximately 42%, and for clear cell adenocarcinoma of the vagina, 78%, with stage I and II patients having the best prognosis. Melanoma is treated with radical surgery; radiation therapy is used as an alternative or adjunct therapy for specific clinical situations.

Sarcoma botryoides (or, embryonal rhabdomyosarcoma) is a rare tumor that presents as a mass of grape-like polyps protruding from the introitus of pediatric age patients. It arises from the undifferentiated mesenchyme of the lamina propria of the anterior vaginal wall. Bloody discharge is an associated symptom in these tumors. The tumor spreads locally, although it may have distant hematogenous metastases. Combination chemotherapy administered prior to surgery appears to be effective, resulting in a marked reduction in tumor size. This permits more conservative surgery than was performed in the past, preserving as much bowel and bladder function as possible.

Clinical Follow-Up

You perform a vulvar biopsy, which shows lichen sclerosus. You treat her with high-potency steroids for 3 months. At that time, her symptoms have improved and her vulvar examination appears more normal.

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