OBG M ANAGEMENT

Philip J. DiSaia, MD Professor and Director Division of Gynecologic Oncology Dorothy Marsh Chair in Reproductive Biology University of California, Irvine

Dr. DiSaia is also Chairman of the Gynecologic Oncology Group and Past President and Chairman of the Board of the American Board of Obstetrics and Gynecology

Atrophic minora, pale and scarified from scratching, may be caused by . The microscopic view shows a hypertrophic keratin layer with an excoria- tion penetrating the epithelium.

® Dowden Health Media NoninvasiveCopyright vulvar lesions An illustratedFor personal guide use only to diagnosis and treatment IN THIS ARTICLE Dystrophies, , and other noncancerous lesions S Distinguishing CASE of nightly application, the skin should be and dysesthesia Postmenopausal softer and more pliable, and dyspareunia should be resolved. The patient can then Page 73 A 60-year-old widow who recently remarried reduce the clobetasol application to twice S complains of dyspareunia. Examination of weekly—but she must continue the treat- Paget disease: the reveals firm but thin white skin ment indefinitely. Not just a breast over the periclitoral area and complaint and shrinking of the vulvar skin. The vulva over the lifespan Page 76 What is the likely diagnosis? The vulva is sensitive to both physiologic and pathologic changes, as well as to the ichen sclerosus is the probable diag- sex hormones that govern the menstrual nosis, given her age and the appear- cycle. The mucosa on the inner aspects of L ance of the vulva, although it is the labia minora is very similar to the skin impossible to assure the diagnosis without of the and thus very sensitive to I M A

a biopsy. The preferred treatment is clobe- . The skin of the and G tasol, an ultrapotent , applied daily. the outer surface of the labia minora is E: K I M B

True, powerful can cause atro- more consistent with -bearing skin in E R L Y

phy if applied regularly to other areas of the perineal area and more sensitive to M A R T

the skin, but clobetasol does not cause androgens, which help thicken the skin. At E of vulvar skin. After several weeks menopause, the loss of estrogen leads to NS

62 OBG MANAGEMENT • December 2006

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atrophy, and the vulvar epithelium is reduced to a few layers of mostly interme- ACOG opinion on vulvodynia diate and parabasal cell types. The labia The new ACOG Committee Opinion reflects recommendations minora and majora as well as the of the American Society for Colposcopy and Cervical Pathology.17 gradually become less prominent with age. The skin of the vulva consists of both • Vulvodynia may be localized or generalized. Pain localized to the vulvar vestibule, formerly termed vulvar dermis and epidermis, which interact with vestibulitis, is now classified as localized vulvodynia. each other and respond to different nutri- • The cause is unknown, and therefore it cannot be tional and hormonal influences. For determined whether localized and generalized vulvodynia example, estrogen has little effect on vul- are different manifestations of the same disease or var epidermis, but considerable effect on completely different entities. the dermis, thickening the skin and pre- • Treatment can be difficult, and improvement can take venting atrophy. weeks or months, even with appropriate therapy. Postmenopausal atrophic changes can – No single agent is successful in all women become a clinical problem when a woman – Pain may never subside completely resumes after a long peri- – Patients may need us to help them develop od of abstinence, as in the opening case. If realistic expectations for improvement atrophy is the main complaint, estrogen • Some women need psychological support, such as replacement therapy will alleviate symptoms sex therapy and counseling. of tightness, irritation, and dyspareunia, but Vulvodynia. American College of Obstetricians and Gynecologists Committee it may take 6 weeks to 6 months to achieve Opinion No. 345. Obstet Gynecol. October 2006;108:1049–1052. optimal results. In the interim, women need to be reassured that reasonable function can International Society for the Study of be achieved. Vulvovaginal Disease has proposed multi- ple classifications since 1975. I prefer the Hygienic considerations clarity of the 1987 classification system.1 I With any vulvar irritation, the patient also consider these terms out-of-date: should discontinue the use of synthetic lichen sclerosus et atrophicus, carcinoma undergarments in favor of cotton panties, simplex, leukoplakic , , FAST TRACK which permit more adequate circulation hyperplastic vulvitis, neurodermatitis, Vulvar dystrophies and do not trap moisture. , leukokeratosis, erythro- S Sitz baths often help relieve local dis- plasia of Queyrat, and Bowen’s disease. Lichen sclerosus comfort, but should be followed by thor- S Squamous cell ough drying. What makes the lesions white? hyperplasia The white appearance of dystrophic Formerly “hyperplastic lesions is due to excessive keratin, at times dystrophy” T Vulvar dystrophies: deep pigmentation, and relative avascular- S Other dermatosis ity. All 3 of these characteristics are present Think “white” in the spectrum of vulvar dystrophies. S Squamous cell In the past, these diseases have been Biopsy of the affected skin is the key to carcinoma in situ defined as non-neoplastic epithelial disor- accurate diagnosis and successful therapy. May present clinically ders of the vulva. Although there have at any age as papules been many attempts to more accurately or macules, coalescent or define vulvar dystrophies, none have com- discrete, single or multiple T Lichen sclerosus pletely described the wide variety of clini- S Paget’s disease cal presentations. Does not raise risk of carcinoma of the vulva In general, dystrophies are disorders of The most common of the 3 groups of Clinicopathologic entity epithelial growth and nutrition that often white lesions described in the 1987 classi- with a pathognomonic result in a white surface color change. This fication of dystrophies, lichen sclerosus histologic appearance definition includes intraepithelial neoplasia usually occurs in postmenopausal women, and Paget’s disease of the vulva. The but can appear at any age, including child- Source: Modified from Voet RL1

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L Noninvasive vulvar lesions: An illustrated guide

FIGURE 1 Lichen sclerosus affects all ages

3-year-old child. Note the inflam- 20-year-old woman. The glans 70-year-old woman. The introitus mation secondary to excoriations. clitoris has begun the hooding has shrunk, making intercourse process. impossible.

hood (FIGURE 1). Despite claims to the con- ent use of this steroid on vulvar skin does trary, there is no good evidence that not cause the atrophy commonly seen with women with lichen sclerosus face a higher prolonged use of high-potency steroids on risk for vulvar carcinoma. other areas of the skin. Start with twice-daily application and taper Signs and symptoms to less frequent use as the symptoms come In lichen sclerosus, the skin of the vulva under control. Most patients in remission appears very thin, atrophic, and dry, can be maintained with twice-weekly resembling parchment. It is also white, application. Pruritus should disappear with loss of pigmentation. completely, and the skin itself will become FAST TRACK Pruritus is the most common symptom and less “leathery.” There is no good is usually the presenting symptom. Scratching during sleep may create ulcera- Surgical treatment is not advised evidence that tions and areas of ecchymosis, and there is does not appear to have a role women with lichen generalized shrinking of the vulvar skin, because lichen sclerosus often recurs out- sclerosus face with eventual loss of the labia minora. side excised areas. Several reports have The edema and shrinking that occur even described the return of disease in skin a higher risk for around the clitoris cause a “hooding” of grafts used to replace large diseased areas. vulvar carcinoma the glans clitoris. If the process continues I do not recommend surgery except in unchecked, it can involve the labia majora dire circumstances, when symptom relief is as well as the skin of the inner thigh and essential to the patient’s quality of life and anal region. all other therapies have failed.

Prescribe clobetasol ointment The patient should be instructed to use clo- betasol 0.05% ointment on a continuing T Squamous cell hyperplasia basis. This drug is so successful it has This disease is probably the same entity as eclipsed the use of testosterone propionate lichen simplex chronicus. Changes in vul- for this indication. Lorenz and colleagues2 var skin appear to result from chronic found very high success rates in 81 symp- scratching secondary to intense pruritus. tomatic patients with biopsy-proven dis- This complaint often involves a vicious ease who had failed previous therapy. cycle of scratching, increased pruritus, and For reasons that are unknown, persist- more scratching, until excoriations occur.

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Noninvasive vulvar lesions: An illustrated guide L

The aim of therapy is to eliminate the pru- FIGURE 2 ritus (FIGURE 2). Squamous cell hyperplasia

Signs and symptoms Vulvar skin is typically white or pink. Biopsy will confirm the diagnosis, reveal- ing a markedly thickened keratin layer (hyperkeratosis) and irregular thickening of the Malpighian ridges (acanthosis). Inflammatory changes are also pres- ent, especially when there are areas of excoriation.

Treatment is similar to therapy for lichen sclerosus 75-year-old woman. The skin is Intense pruritus and aggressive thickened and may be leathery. scratching lead to excoriations. Potent topical corticosteroids are the back- bone of treatment; clobetasol is the pre- ferred drug. The frequency of application is • History of yeast infection, 64% identical to that described for lichen sclero- • Vulvar burning, 57% sus, and response to therapy usually takes 2 • Vulvar itching, 46% months. In the interim, it is advisable to pre- • Problems with sexual response, 33% scribe other for the pruritus. Women with vulvar dysesthesia who Lichen sclerosus and squamous cell hyper- appear to have urinary tract symptoms plasia sometimes coincide. Fortunately, the should undergo a urine culture, though it therapies are quite similar and both condi- will often be negative and antibiotic thera- tions tend to respond. py will have little effect.

A diagnosis of exclusion The pain of dysesthesia appears to be neu- FAST TRACK T Vulvodynia ropathic in origin in that it mimics pain of Vulvodynia pain This disorder consists of chronic vulvar the sensory nervous system. It may be dif- discomfort due to itching, burning, and/or fuse or focal, unilateral or bilateral, con- may never subside pain that causes physical, sexual, and psy- stant or sporadic. Thus, it is a diagnosis of completely chological distress.3,4 Once referred to as exclusion. essential vulvodynia, it now is defined as generalized vulvar dysesthesia. Recommended therapies Vulvar dysesthesia should be regarded as a Signs and symptoms syndrome and treated accord- Women with this condition tend to have ingly, with emphasis on generalized difficulty localizing their pain. They often improvements in health and attitude rather present with a complaint of recurrent yeast than single-therapy approaches. infection or constant irritation at the Potent topical corticosteroids are usu- introitus. Dyspareunia may or may not be ally of no benefit. Nor does topical estro- a presenting symptom, although inter- gen produce long-term relief. course often triggers this condition. Tight Once all possible causes of symptoms pants or rough undergarments also may are excluded, refer the patient for educa- trigger symptoms. tion, support, and treatment of depression, Common symptoms. In a study by if present. Occasionally, topical anesthetics Sadownik,5 women with vulvar dysesthe- will provide short-term relief. sia reported the following symptoms: At least 2 vulvar pain societies—the • Dyspareunia, 71% National Vulvodynia Association and the

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Noninvasive vulvar lesions: An illustrated guide L

Vulvar Pain Foundation—have newsletters, TABLE 1 outreach programs, and Web sites. Distinguishing vulvar vestibulitis and dysesthesia

VULVAR VESTIBULITIS ESSENTIAL VULVAR DYSESTHESIA Pain is usually not constant Pain is a constant burning sensation T Vulvar vestibulitis Erythema in sensitive areas No erythema or abnormal appearance A more readily definable condition in the quells sensitivity Lidocaine has no effect same category as vulvodynia is so-called Cause is dermal Cause is allodynia (heightened vulvar vestibulitis, also known as localized nerve sensitivity) vulvodynia (as classified by the new ACOG Committee Opinion on vulvodynia). TABLE 2 Impressive track record Signs and symptoms for surgical treatment of vestibulitis The defining presentation is severe pain on vestibular touch (eg, entry at intercourse), % RESPONSE with tenderness to pressure localized with- STUDY COMPLETE PARTIAL NONE in the vulvar vestibule in a horseshoe dis- Bornstein et al7 76 24 0 tribution pattern encompassing 3, 6, and 9 Bergeron et al12 63 37 0 o’clock on the vestibule. Erythema is often Kehoe and Luesley13 60 29 11 present, especially at the 5 and 7 o’clock Mann et al14 66 2113 positions (FIGURE 3). Schover et al15 47 37 16 Patients have no symptoms during nor- 16 mal daily activities, but complain of dys- Marinoff and Turner 82 15 3 pareunia and an inability to use . Adapted from Bornstein et al7

Diagnostic strategies taining oxalates precipitate these symptoms. Vulvar vestibulitis can be diagnosed using It may be advisable to have the patient a moistened cotton-tip applicator. Pressure reduce the content of oxalates in her diet in applied in the area of the urethral meatus an effort to address all possible remedies. FAST TRACK will result in minimal discomfort, but pres- Hallmark of sure in the horseshoe area of the vestibule For refractory cases, consider surgery will cause exquisite discomfort. Consider surgical removal of the tender vestibulitis: Severe Careful inspection at 5 and 7 o’clock vestibule if all other therapies fail to pro- pain on touch, in the vestibule usually uncovers intense vide adequate relief. Surgery for this indi- with tenderness 7 erythema over an area of 4 or 5 mm. To cation has a high success rate (TABLE 2). localized within distinguish vestibulitis from dysesthesia, Some surgeons have attempted treat- see the comparison in TABLE 1. ment with laser ablation, but most have the vestibule found excision more satisfactory, with in a horseshoe Recommended therapies faster recovery and excellent cosmesis. pattern Treatment of vulvar vestibulitis is com- Schneider and colleagues8 had 69 plex. It is important to see the patient women complete a questionnaire 6 months often to ensure that this syndrome is truly after surgery, 54 (78%) of whom replied. present rather than vulvar dysesthesia. Moderate to excellent improvement was Xylocaine jelly should be given in an reported by 45 women (83%); 7 had repeat attempt to relieve symptoms; topical surgery, after which 4 improved. steroid ointments are another option. Women with persistent symptoms are WEB RELATED difficult to treat medically. Earlier theories T See the Web version of this article pointing to infection as the cause of Pigmented lesions at www.obgmanagement.com vestibulitis have been discounted. Are they cancer precursors? for a list of selected foods Some experts believe that foods con- Precursors of malignant melanoma of the and their oxalate content

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FIGURE 3 FIGURE 4 guishing one pigmented lesion from Vestibular adenitis Basal cell carcinoma another is difficult even with magnifica- tion, and the clinician often must decide whether or not to biopsy. One set of guidelines recommends excisional biopsy of vulvar nevi when there is a change in: • surface area of the nevus, • elevation of a lesion, ie, it becomes raised, thickened, or nodular, • surface, from smooth to scaly or ulcerated, or • sensation, including itching or tingling.10 Note that a reddish lesion may be basal cell hyperplasia, which has been Intense erythema at the 5 o’clock An uncommon type of , associated with the development of basal position in the vestibule. this tumor rarely metastasizes. cell carcinoma (FIGURE 4).

vulva have yet to be clearly defined. The majority of these melanomas appear to T Premalignant lesions arise de novo; however, some are associat- ed with precursor nevi, especially junction- of squamous epithelium al nevi. The 3 most common types of nevi The variable appearance of vulvar that appear on the vulva are: intraepithelial neoplasia (VIN) necessi- • Junctional—located in the basal layer; tates the liberal use of diagnostic biop- most likely to develop into melanoma. sies, particularly when lesions persist or • Compound—melanocytes at the epi- recur. VIN can present as a white lesion, dermal–dermal interface and within or as pseudopigmented, pink, or raised the dermal layer. and eroded. FAST TRACK • Intradermal—Compound nevus when Cigarette smoking is a risk factor. VIN lesions neval cells in the junctional zone cease to be active. Intradermal nevi have low Clinical appearance are hyper- or malignant potential. Macroscopically, VIN lesions are often pseudopigmented multiple and appear slightly raised and in about 30% Assessing malignant potential papular. Hyper- or pseudopigmented Only a small number of dysplastic nevi lesions are seen in about 30% of cases. of cases progress to malignant melanoma, but the A confluence of VIN can create an frequency increases when the dysplastic appearance of diffuse plaques. In VIN, as nevus is familial and not acquired. for CIN, carcinoma in situ involves a full- In general, the more severe the dys- thickness abnormality. plasia, the greater the likelihood it will progress to malignancy. In dysplastic Terminology nevi, the pattern and appearance of the If the abnormal parabasal layer extends to melanocytic cells are atypical. Bridging of one half to two thirds of the epithelium, melanocytic clusters of atypical cells may moderate dysplasia is present. A lower occur. Often, the atypical melanocytes are degree of involvement is called mild dys- varied in size and shape, increasing in cell plasia, and full-thickness involvement is and nuclear size as severity increases. In severe dysplasia or carcinoma in situ. the most severe cases, nucleoli are very prominent. High rate of persistence, recurrence Many pigmented lesions of the vulva Herod and colleagues9 reported on a 15- are lentigines, similar to freckles. Distin- year follow-up of VIN and found that dis-

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Noninvasive vulvar lesions: An illustrated guide L

FIGURE 5 VIN III lesions: A trio of presentations

White lesion. Pseudopigmented lesions. Pink lesion. ease persisted or recurred in 48% of branes, whereas the white or pseudopig- women managed surgically, and 7% of mented lesions are usually seen on the patients progressed to frankly invasive car- drier, hair-bearing areas of the vulva. cinoma. These investigators used the fol- Biopsy reveals similar histology. lowing classification system: The cause of the pseudopigmented • VIN I—mild dysplasia (formerly mild lesions is unclear, but is unrelated to a dis- atypia) turbance of the melanin cells. As with • VIN II—moderate dysplasia (formerly other vulvar lesions, biopsy is essential for moderate atypia) a correct diagnosis. • VIN III—severe dysplasia (formerly severe atypia) Recommended therapies • VIN IV—carcinoma in situ VIN is treated by destroying or excising Joura et al10 strongly suggested that the the epithelium involved. When the area is FAST TRACK incidence of this condition is increasing, limited in size, simple excision or laser Biopsy is essential especially in women prior to the 7th vaporization is preferred. A 2- to 3-mm decade of life. Whether this increase is due margin is adequate, because these lesions for correct to better recognition or a true rise in preva- have sharp borders. diagnosis of vulvar lence has been debated. Laser therapy warrants extra care because intraepithelial the epithelium is rarely thicker than 0.5 neoplasia Diagnostic strategies mm. For this reason, vaporization of the Application of 5% acetic acid to the vulvar vulva should be limited to the following skin will, after 3 to 5 minutes, allow areas depths: of involvement to be readily seen with a • Labia minora (hair-free): 0.5 mm handheld magnifying glass. Colposcopy • Labia majora (hair-containing): 1.5 to can be used, but is slower and not as effi- 2 mm cient as a simple magnifying lens. Most cli- These limits will speed healing and nicians have abandoned the use of toluidine prevent the unnecessary destruction of blue to identify multicentric lesions, since dermis. acetic acid appears to be less cumbersome Also be aware that the depth of hair- and just as efficient. follicle involvement rarely exceeds 1 mm. White or pseudopigmented lesions Vaporization of the full thickness of the (FIGURE 5) can be seen anywhere on the dermis will lead to alopecia and vulvar vulva and represent 2 of the 3 presentations dryness. of VIN. Pink lesions (FIGURE 5) are usually When disease is multifocal or confluent, treat- seen on moist surfaces near mucous mem- ment is more challenging. Several decades

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L Noninvasive vulvar lesions: An illustrated guide

FIGURE 6 Paget disease: Not just a breast complaint

Paget disease of the nipple with Vulvar Paget disease: lesion (left) and photomicrograph of the lesion. underlying ductal adenocarcinoma.

ago, simple vulvectomy was performed, but lesion (FIGURE 6), which is very pruritic and the patient was left a sexual cripple. often associated with exfoliation. Margins Since then, laser therapy has been are difficult to identify grossly. attempted in these cases, and has proved On rare occasions, a nodular tumor to be effective when the area treated does can be found in the middle of the skin not exceed 25% of the total area of the involvement, but in most cases no invasive vulva. Extensive laser therapy leads to malignancy is found at extramammary considerable postoperative pain and an sites on the vulva. unhappy result. Extensive involvement may necessitate Diagnostic strategies laser treatment by quadrant to achieve Microscopic appearance of Paget cells FAST TRACK the best results. Another option is “skin- (FIGURE 6) are pathognomonic of the Paget’s disease ning vulvectomy” using a skin graft. This disease. procedure, first described by Felix Older textbooks suggest that 10% to of the vulva often Rutledge,11 requires a 7- or 8-day hospi- 20% of patients have an associated, under- recurs, especially talization, but allows for complete thera- lying, invasive carcinoma of a skin when the initial py in 1 session. appendage, Bartholin’s gland, urinary tract, or bowel or rectal site, but later lesion is large experience has not confirmed this. Rather, the likelihood of concomitant invasive dis- T Paget’s disease of the vulva ease is much lower than 10%. This disease is most frequently seen in the breast nipple (FIGURE 6), where it is usual- Excision is the treatment of choice ly associated with an underlying infiltrat- Any attempt to achieve negative margins ing ductal carcinoma. Extramammary sites must utilize frozen section. Some studies include the vulvar, perianal, and axillary have suggested that negative margins are not regions. The disease has also been seen in associated with a reduced rate of recurrence, the ear canal. but these findings have been inconsistent. Paget’s disease is an intraepithelial ade- nocarcinoma of eccrine or apocrine origin. Recurrence is common Paget’s disease of the vulva often recurs, Clinical appearance especially when the initial lesion is large. Paget’s disease of the vulva appears as a Close monitoring will detect these recur- superficial, red to pink, velvety, eczematoid rences when they’re quite small and easily

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Noninvasive vulvar lesions: L An illustrated guide

removed via local excision. Occasionally, the initial disease is so extensive that skin graft- ing may be necessary to cover the defect. I

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