Vulvar lesions: Diagnostic evaluation

INTRODUCTION — A wide spectrum of benign, premalignant, and malignant lesions may occur on the vulva. The challenge to the clinician is to differentiate between normal variants, benign findings, and potentially serious diseases.

This topic will discuss the diagnostic evaluation of women with vulvar lesions. The differential diagnosis of vulvar lesions is reviewed separately. (See "Vulvar lesions: Differential diagnosis of vesicles, bullae, erosions, and ulcers".)

HISTORY — Ideally, the history is obtained before the patient undresses for her initial physical examination. In addition to a standard medical history, answers to the following questions can help identify possible causes of the vulvar lesion and exclude others. The answers to these questions may suggest a systemic disease rather than a primary localized vulvar disorder. The answers may also increase the clinician's suspicion of dermatitis or infection as the etiology of the lesion.

●How long has the lesion been present? Was the onset sudden or gradual? Could it be related to trauma or another trigger?

●How did the lesion look when it first appeared? Is it different now? Does it come and go?

●What symptoms are associated with the lesion(s): itching, burning, pain, stinging, bleeding, and discharge? Does anything improve or exacerbate the symptoms? Do you have other non-vulvar symptoms, such as fever, urinary tract or bowel symptoms, abnormal uterine bleeding, weight loss, or joint pain?

The evaluation of women whose chief complaint is vulvar pain is reviewed separately. (See "Vulvar pain of unknown cause (vulvodynia): Clinical manifestations and diagnosis".)

●Do you have other skin lesions, such as oral, vaginal, or anal lesions?

●Are you incontinent of urine or stool? Incontinence can cause vulvar irritation.

●Do any family members have a history of vulvar disease? Genetic factors play a role in some disorders that affect the vulva, such as psoriasis, lichen sclerosus, and hidradenitis suppurativa.

●What are your normal skin care and hygiene routines? Do you use a face cloth to cleanse? What type of cleanser do you use and how often? Do you douche or use cleansing wipes? Do you use feminine hygiene sprays, sanitary napkins, tampons, or lubricants for sexual activities? Women often erroneously regard their personal practices as safe since they have engaged in them for a long time.

●Have you had any recent changes in medications, personal care products (eg, deodorants, fragrances, detergents, fabric softeners, soaps, lubricants, moisturizers), or occupational (such as wearing tight clothing) or recreational (such as bicycle riding) exposures?

●Did you travel before developing the lesion? A history of travel abroad widens the differential diagnosis of infectious diseases.

●Has there been a change in sexual partner(s), which may suggest a sexually transmitted infection?

●What treatments have you used (home remedies, prescription and over-the-counter products, drugs). What was the response to these treatments?

The clinician should also assess how the lesion impacts activities of daily living and sexual activity. They should try to obtain documentation of laboratory studies, biopsy results, and treatments from previous clinicians.

BASIC EXAMINATION — Several steps can be taken to improve patient comfort during physical examination of the genitalia, including having a female assistant in the examination room (to help with visualization of the vulva) and talking to the patient during the examination. It is useful to have a mirror available so the patient can aid in identifying the concerning lesion. This also allows you the opportunity to help the patient become more familiar and comfortable with her vulva. After the examination, patients should be allowed to dress before discussing the findings and management plan.

Vulva — The entire vulva and external genitalia (figure 1) should be examined under a good light. The labia should be spread and carefully examined to avoid missing lesions hidden in redundant skin or hair.

The following characteristics of the vulvar lesion should be evaluated, and help to guide differential diagnosis (see "Vulvar lesions: Differential diagnosis of vesicles, bullae, erosions, and ulcers"). Magnification with a magnifying lens, colposcope, or other forms of magnification can be helpful.

●Lesion morphology (eg, macule, papule, patch, nodule, ulcer, tumor, plaque, vesicle, bulla, pustule, cyst) (table 1)

●Size and shape of individual lesions

●Edge clearly demarcated or poorly defined

●Number, location, and distribution of multiple lesions (eg, scattered, grouped, linear, etc)

●Color

●Consistency and feel (tenderness, thickness, hard/soft/firm/fluctuant)

●Presence of secondary changes (excoriation, lichenification, edema, scale, crust, fissure, erosion, bleeding, hypo-/hyperpigmentation, atrophy, scar)

●Acute inflammation (edema, pain, erythema)

Related anatomic examinations — The anus should be examined at the completion of the examination. The vagina, cervix, intertriginous regions, eye, mouth, and nares should be examined when the diagnosis is uncertain because vulvar lesions can be an atypical or typical manifestation of a more widespread disease, and recognition of other sites of involvement may help in diagnosis. For example, lichen planus can affect the vulva, vagina, and mouth. Aphthae can be seen on the mouth and genitalia (see "Oral lichen planus: Pathogenesis, clinical features, and diagnosis", section on 'Clinical manifestations'). In women with candida vulvovaginitis, fissures, erosions, and erythema may involve the interlabial sulcus and thigh (picture 1).

Several types of speculums are available for vaginal examination. The two main types are the Pederson-type (narrow blade) and the Graves-type (wide blade) (picture 2). A pediatric Pederson speculum may be required in patients with pain or scarred, foreshortened vaginas. Each type of speculum has options for view size: standard 30 mm width opening, 40 mm wide view opening, or 70 mm full view opening. Although larger sizes provide better visualization, they can also be more uncomfortable for patients. Alternatives for better visualization include use of an open-sided speculum; a Guttman style speculum, which functions without an upper blade; or a transparent plastic speculum for 360-degree visibility. Warming the speculum to body temperature and lubricating it with water or small amounts of lubricant enhance patient comfort.

Regional lymph nodes should be palpated for lymphadenopathy, which could be indicative of infection or malignancy.

If bruising or lacerations are noted, intimate partner violence and/or sexual assault should be considered. (See "Evaluation and management of adult and adolescent sexual assault victims in the emergency department".)

ADDITIONAL PROCEDURES

Evaluation for infection — A vaginal pH and wet mount may be helpful in patients with vaginal discharge to evaluate for conditions such as Candida, bacterial vaginosis, trichomonas, and desquamative inflammatory vaginitis, which may cause vulvar erythema. Saline wet mount preparation for viewing under the microscope, vaginal pH, and amine odor (whiff) test are rapid and inexpensive methods to evaluate vaginal discharge, which may be the source of vulvar irritation. Point of care tests for vaginal discharge are also available. A potassium hydroxide (KOH) preparation is used to detect fungal elements in vulvar skin scrapings (picture 3). All of the tests discussed have limitations.

●(See "Vaginitis in adults: Initial evaluation", section on 'Diagnostic evaluation'.)

●(See "Office-based dermatologic diagnostic procedures", section on 'Potassium hydroxide preparation'.)

Vulvar ulcers may be present with certain sexually transmitted diseases (STDs). While genital herpes has traditionally been considered an ulcerative STD, it more often presents as an erosion. However, herpes infections are frequently associated with ulcers in immunocompromised women. Other ulcerative STDs include syphilis and chancroid (very rare in the United States). The clinical characteristics and diagnosis of these and other ulcerative infections of the vulva are reviewed separately. (See "Approach to the patient with genital ulcers", section on 'General approach'.)

Bacterial cultures of the vulva are reserved for patients in whom there is suspicion the clinical findings are suggestive of bacterial infection.

Evaluation for dermatitis — The diagnosis of atopic or contact vulvar dermatitis or psoriasis can usually be made clinically. It is based upon characteristic symptoms; a personal or family history of atopy; psoriasis; or a personal history of vulvar exposure to medications, perfumes, or other chemicals. It is important to review vulvar hygiene/cleansing routines with patients, as they can often cause irritation. In uncertain cases and in those not responding to treatment, patch testing and/or biopsy may be necessary to identify the allergen/irritant or an underlying dermatosis. (See "Vulvar dermatitis".)

Evaluation for intraepithelial lesions and cancer — Most high-grade squamous intraepithelial lesions of the vulva (HSIL), previously known as vulvar intraepithelial neoplasia (VIN), are related to infection with human papillomavirus (HPV) [1,2]. They tend to be multifocal and located in the non-hairy part of the vulva [3-5]. The lesions are often raised or verrucous and white (picture 4), but the color may be red (picture 5), pink, gray, or brown (picture 6). Macular lesions mostly occur on adjacent mucosal surfaces. There is no pathognomonic clinical appearance, and more than one of these patterns may be seen in the same patient. In addition, lichen sclerosus, lichen planus, condylomata acuminata, and condylomata lata can mimic HSIL of the vulva. Therefore, biopsy is generally required for diagnosis. Vulvar cytology should not be performed because of poor correlation with tissue diagnosis [6]. (See "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)" and "Vulvar cancer: Epidemiology, diagnosis, histopathology, and treatment" and "Virology of human papillomavirus infections and the link to cancer".)

●Colposcopy – Use of a magnifying lens or colposcope (picture 7) may identify subclinical HSIL of the vulva not appreciated on physical examination and helps to define the extent of disease and guide biopsy. Because of the high prevalence of multicentric synchronous or metachronous intraepithelial lesions, comprehensive colposcopic evaluation of the perianal area is indicated in any patient with HSIL of the vulva. (See "Colposcopy", section on 'Vulvar colposcopy' and "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)", section on 'Colposcopy'.)

In addition, women with HSIL of the vulva should have cervical/vaginal cytology with HPV testing before vulvar surgery. They should undergo follow-up set forth by the American Society for Colposcopy and Cervical Pathology [7]. Additionally, it is important to perform anal cytology with HPV testing in women who have had HPV-associated lesions due to the high prevalence of anal lesions in this population [8].

In patients in which the provider is concerned about HSIL of the vulva, application of gauze soaked with 3 to 5 percent acetic acid for three to five minutes will highlight (whiten) areas that represent HSIL, genital warts, hyperkeratosis, or carcinoma. This is useful for colposcopy-directed biopsy, but also for choosing biopsy sites performed under direct visualization.

Use of biopsy — One or more vulvar biopsies should be performed in the following settings:

●Lesions clinically suspicious for malignancy – Asymmetry, border irregularity, color variation, rapid change, bleeding, or non-healing ulcers. Also, a biopsy should be considered for lesions that are firm to the touch.

●If a diagnosis cannot be made confidently by visual inspection and other noninvasive methods.

●If the lesion does not resolve after standard therapy.

●To address patient concerns.

●In patients with vulvar lichen sclerosus who have any suspicious new lesions, areas of previous lesions that have developed concerning changes or are not responsive to appropriate treatment.

For example, we advise a biopsy for a woman who has been treated for candidiasis in an appropriate manner but continues to have itching, erythema, and skin changes. She may have contact dermatitis, lichen sclerosus, HSIL of the vulva, extramammary Paget disease, carcinoma, or one of numerous other conditions; thus, a biopsy is indicated for definitive diagnosis to direct further therapy. Once a vulvar biopsy is performed, it should be sent to a gynecologic pathologist with a special interest in vulvar pathology or a dermatopathologist.

Procedure — Vulvar biopsies can usually be performed in the office. The indications and procedure should be discussed with the patient. Risks include bleeding, infection, scarring, and allergic reaction. It is important to know that biopsies do not always provide a diagnosis due to sampling and interpretation errors. Additionally, lesions may be nonspecific at times as is seen often with lichen planus.

After proper positioning on the examination table, the selected site is prepped with a cleansing solution. One should avoid taking the biopsy from the clitoris, urethra, or anal opening, if another representative site can be biopsied, because of patient discomfort and risk of complications. However, these areas can be sampled if needed.

For patient comfort, at times, a topical anesthetic (eg, 2.5% lidocaine 2.5% prilocaine in a cream base) to desensitize the skin may be used before the anesthesia is injected. Before prepping the vulva, the topical anesthetic should be applied sparingly for 15 to 20 minutes on modified mucous membranes and longer on keratinized skin (up to 60 minutes depending on the agent and depth of the skin) before biopsy to be maximally effective [9]. Effectiveness is enhanced when applied under occlusion [10]. After application of a topical antiseptic, the site is infiltrated with 1 to 2% lidocaine with or without epinephrine. Adequacy of anesthesia should be checked before proceeding with the biopsy; analgesia is achieved several minutes before vasoconstriction. One small trial reported lower median pain scores with the use of lidocaine-prilocaine cream alone compared with lidocaine injection alone [11].

The choice of biopsy technique depends on the amount of tissue to be removed.

●Shave biopsy – A shave biopsy removes the top layer of skin and is used when the lesion is small and confined to the epidermis. It should not be used when melanoma is suspected.

●Punch biopsy – A punch biopsy removes a small (2 to 6 mm) circular piece of skin and is used when all skin layers need to be examined (picture 8). A punch biopsy is indicated when the pathologic process is dermal or in the subcutaneous fat. Use rotary and gentle downward pressure to cut through the skin surface and into the dermis. For lesions not suspicious for cancer, the depth to the halfway mark of the punch biopsy apparatus is generally adequate. At times, a depth up to the hub of the punch biopsy is required to get a full-depth biopsy for lesions suspicious for cancer. Do not crush the specimen with forceps. Lift the lesion outward and cut the base with curved iris scissors.

●Suture lift technique – In areas where tissue is fragile and likely to tear, a "suture, lift, and cut technique" is useful. A fine suture is placed to gently lift the skin and then iris or Metzenbaum scissors are used to cut the base of the tissue under the suture (picture 9). The suture is then removed from the excised skin specimen, and the specimen is sent to pathology.

The biopsy technique also depends on the lesion:

●Pigmented lesions – Ideally, atypical-appearing pigmented lesions are completely excised to ensure accurate depth assessment. More than one punch biopsy may be necessary to adequately sample a large, heterogeneous lesion and repeat biopsies may be necessary if the clinical and pathologic impressions do not correlate. The biopsies are obtained from the thickest region of the lesion and from any ulcerated areas, at the edge of the ulceration [12].

●Blistering lesions – The suture, lift, and cut technique described above is ideal for obtaining biopsy samples from blistering lesions. It is important to obtain a bit of the normal skin at the margin of the blister rather than just the base of the blister. A separate biopsy of perilesional skin is needed for direct immunofluorescence for the diagnosis of the immunobullous diseases.

●Ulcerated lesions – An incisional biopsy is performed when the ulceration is large and only a portion of the lesion is sampled; the sample should include the edge of the ulcer. An excisional biopsy to remove the entire lesion is appropriate when the lesion is less than 1 cm in size.

Hemostasis is usually achieved with pressure or chemical hemostatic agents (silver nitrate, Monsel's solution [ferric subsulfate]) or aluminum chloride. Alternatively, electrocautery can be used. If bleeding is not controlled or the defect is large, the biopsy site is closed with a 4-0 absorbable suture, but small dry defects can be allowed to heal without closure.

After the procedure, the patient is instructed to keep the site clean and dry, and other wound care instructions (eg, sitz bath), if needed, should be reviewed. Plain petrolatum can be applied daily until the site is healed; dressings are typically avoided.

A detailed description of patient preparation, anesthesia, biopsy technique, wound closure and care, and specimen processing is reviewed elsewhere. (See "Skin biopsy techniques".)

Vulvar biopsy reports may return with nonspecific findings. If the biopsy is nondiagnostic, and a precancer or cancer is in the differential diagnosis, a repeat biopsy should be considered.

Use of imaging — Ultrasound imaging or magnetic resonance imaging (MRI) are used at times for evaluation of cystic and/or subcutaneous lesions [13].

DOCUMENTATION AND PHOTOGRAPHY — In addition to written notes, photography is useful to objectively document the location, size, and morphologic features of vulvar lesions. The photographs should also document adjacent anatomic landmarks and/or include a ruler to facilitate accurate lesion localization and clinical comparison. Photographs may be incorporated into the patient's chart or may be sent home with the patient as a baseline to facilitate periodic self-examination. Alternatively, a diagram of the lesion may be constructed to record the appearance of the vulva.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vulvar dermatitis".)

SUMMARY AND RECOMMENDATIONS

●History – In addition to a standard medical history and review of systems, patients with vulvar lesions should be asked about the presence of non-vulvar lesions and their normal skin care and hygienic routines. This information may suggest a systemic disease rather than a primary vulvar disease or an exogenous rather than endogenous source. (See 'History' above.)

●Physical examination – The vagina, anus, cervix, eye, mouth, nares, and intertriginous regions should be examined when the diagnosis is uncertain because vulvar lesions can be an atypical or typical manifestation of a more widespread disease, and recognition of other sites of involvement may help in diagnosis. Language used to describe vulvar lesions is presented in the table (table 1). (See 'Related anatomic examinations' above.)

●Exclude high-grade squamous intraepithelial lesions – Most high-grade squamous intraepithelial lesions (HSIL) of the vulva are multifocal and located in the non-hairy part of the vulva. The lesions are often raised or verrucous and white (picture 4), but the color may be red (picture 5), pink, gray, or brown (picture 6). Macular lesions mostly occur on adjacent mucosal surfaces. Colposcopy helps to define the extent of vulvar disease and guide biopsy. Because of the high prevalence of multicentric synchronous or metachronous lesions, comprehensive colposcopic evaluation of the perianal area is indicated in any patient with HSIL of the vulva.

•(See 'Evaluation for intraepithelial lesions and cancer' above.)

•(See "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)".)

●Indications for vulvar biopsy – Indications for vulvar biopsy include (see 'Use of biopsy' above):

•Lesions clinically suspicious for malignancy: Asymmetry, border irregularity, color variation, rapid change, bleeding, or non-healing ulcers

•Inability to confidently make a diagnosis by visual inspection and other noninvasive methods

•Lack of resolution of the lesion after standard therapy

•Patient concern

•In patients with vulvar lichen sclerosus who have any suspicious new lesions, areas of previous lesions that have developed concerning changes or are not responsive to appropriate treatment.

●Documentation and photography – In addition to written notes, photography is useful to objectively document the location, size, and morphologic features of vulvar lesions. (See 'Documentation and photography' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Dr. T Minsue Chen, Dr. Aileen Langston, and Dr. Peter Lynch, who contributed to earlier versions of this topic review.