Vulvar lesions: Differential diagnosis of white lesions

INTRODUCTION — A wide variety of lesions occurs on the vulva. Some of the disorders causing these lesions are limited to the vulva, while others also involve skin or mucocutaneous membranes elsewhere on the body. This topic provides a morphology-based classification system that can help clinicians with the differential diagnosis of these lesions after performing a history and physical examination. This classification system is also useful for guiding the choice of diagnostic tests and procedures.

This topic will focus on the differential diagnosis of white vulvar lesions. Discussions of red, other pigmented, erosive and ulcerative, and skin-colored or yellow lesions are presented in related content.

●(See "Vulvar lesions: Differential diagnosis of red lesions".)

●(See "Vulvar lesions: Differential diagnosis of pigmented (black, brown, blue) lesions".)

●(See "Vulvar lesions: Differential diagnosis of vesicles, bullae, erosions, and ulcers".)

●(See "Vulvar lesions: Differential diagnosis of yellow, skin-colored, and edematous lesions".)

The pertinent history, physical examination, and diagnostic tests and procedures used to evaluate patients with vulvar lesions are described separately (see "Vulvar lesions: Diagnostic evaluation"). Treatment is also discussed separately in topic reviews on these disorders.

In this topic, when discussing study results, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. We encourage the reader to consider the specific counseling and treatment needs of transgender and gender-expansive individuals.

MORPHOLOGIC DEFINITIONS FOR MUCOCUTANEOUS VULVAR LESIONS — Mucocutaneous vulvar lesions can be classified using the morphologic definitions described in the table (table 1).

DIAGNOSTIC EVALUATION

Practical tips — Based on the authors' experience, clinicians should be aware of the following points when evaluating dermatologic lesions of the vulva:

●Alternate appearance of vulvar lesions – Many skin conditions may appear differently on the vulva than on other parts of the skin as the vulva is so moist and the area is commonly subject to friction.

●Concomitant conditions – Concomitant conditions to consider with vulvar lesions include infections, other dermatoses, and neoplasia/cancer. For example, irritant contact dermatitis from the use of caustic soaps or overwashing is commonly seen in individuals with vulvar lichen sclerosis.

●Impact of topical therapies – Vulvar conditions may be significantly altered by the use of topical treatments. It is important to ask patients about use of prescription, over-the-counter, compounded, and alternative topical preparations.

●Role of biopsy – Be prepared to perform a biopsy, especially if a vulvar lesion is atypical, bleeding, the patient is immunocompromised, the lesion is not responding to appropriate treatment, or there is concern for a malignancy [1]. For any lesions with variable or irregular areas, more than one biopsy may be needed. At times, the biopsy results can be inconclusive. If there are ever concerns or questions about the biopsy report, it is important to speak with the pathologist. Sending a clinical photograph to the pathologist can also aid the diagnosis.

●Consider possibility of systemic disease – Vulvar lesions can represent diseases that commonly present on the vulva (eg, herpes simplex virus) or systemic diseases that manifest in multiple sites including the vulva (eg, psoriasis). Providers are encouraged to ask patients with vulvar lesions about generalized symptoms and presence of lesions or skin changes on other body parts.

●Specialist referral – Patients whose symptoms do not respond, or worsen, despite usual treatment should be referred to a gynecologist, dermatologist, family medicine physician, or other health care providers who specialize in vulvar skin disorders.

How to use this topic — After a history, physical examination, and morphologic classification (table 1) have been performed, the information in this topic can be used to begin a differential diagnosis of the lesion. Diagnostic entities are listed for each morphologic classification and often listed under more than one morphologic classification since many lesions have more than one presentation (morphologic type, color). The complete description of the diagnostic entity is provided only once; for morphologic variants, the entity is noted and linked to its descriptive section.

This topic is an overview of white dermatologic lesions of the vulva. Detailed text specific to each type of vulvar lesion is available separately, and links are provided throughout the text where available. Brief summaries of pertinent history, physical examination, and diagnostic tests and procedures are provided in this topic. Discussions of the presentation, evaluation, and diagnosis of vulvar lesions are described in detail separately.

●(See "Vulvar lesions: Diagnostic evaluation".)

●(See "Approach to the clinical dermatologic diagnosis".)

●(See "Skin biopsy techniques".)

WHITE MACULES, PATCHES, AND PLAQUES — Patches are typically an area of color change >1 cm that are not palpable, while plaques represent lesions >1 cm that are palpable and flat topped (table 1). The differential diagnosis of white patches and plaques of the vulva can be divided into common, less common, and rare diseases (table 2).

Common diseases — The lesions below are commonly seen in clinical practice. The order does not reflect the frequency of presentation as frequency may vary based on the patient population and type of clinical practice (dermatology, gynecology, or internal medicine). These diagnoses are typically made using the patient's history and physical examination findings. Rarely, biopsy may be required.

Lichen sclerosus — Lichen sclerosus is a chronic, inflammatory, immune-mediated, skin disease of unknown etiology that primarily affects the vulva and anogenital areas in prepubertal and peri-/post-menopausal females, although it can present in any age group [2,3]. While lesions predominantly occur in the anogenital region, they may also occur on other areas of the skin. (See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis".)

●Physical examination – The earliest lesions of lichen sclerosus are ivory white macules and patches (picture 1 and picture 2), which may be hard to differentiate from both vitiligo and postinflammatory hypopigmentation. However, close inspection of the skin surface shows slight wrinkling ("cigarette paper" or "cellophane" wrinkling) [4]. These early lesions are most notable on the medial labia majora and the periclitoral tissue. They commonly involve the perineum and the perianal skin in a figure-eight, or hourglass, pattern (picture 3). The disease may be unilateral or bilateral and symmetric. There is no constellation of signs or architectural changes that correlate to disease severity [5]. Extragenital involvement of the skin occurs in approximately 15 percent of females (picture 4 and picture 5 and picture 6 and picture 7 and picture 8).

The whitened tissue becomes increasingly thickened (lichenoid) as the disease progresses (picture 9) [6]. The vagina is not involved; however, the labia may become adherent in the midline, partially closing off the vestibule. Gradually, the labia minora shrink and may become completely effaced (picture 10). There can be swelling and scarring of the clitoral hood that often leads to partial or full entrapment of the clitoris. The vulva can appear flat with a loss of the clitoral ridge and/or the labia minora. The introitus can shrink and the edges become firm and inflexible (picture 11). The most common cause of loss of normal vulvar architecture/scarring with whitening is lichen sclerosus. (See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Physical findings'.)

Secondary changes include purpura and fissuring (picture 12). The presence of purpura and fissures in these young girls may have led to an investigation to exclude the possibility of childhood sexual abuse.

Erosions can develop in lichen sclerosus; bullae are very rare. Lichenification may occur if there is a lot of rubbing and scratching.

Public access patient information with images is available online.

●Symptoms – Itching is usually prominent, but it can be replaced by pain if there are fissures and/or erosions. Dyspareunia and tearing with intercourse are common, which may result in sexual dysfunction [7]. Often, however, lichen sclerosus is completely asymptomatic. Prepubertal onset in girls may lead to constipation due to fissuring of the perianal skin, resulting in pain at the time of defecation. It may be associated with urinary tract symptoms [8]. (See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Symptoms'.)

●Diagnosis – Lichen sclerosus is commonly diagnosed clinically with the classic skin lesions. Photo documentation is recommended. A biopsy is performed at times (except in children) to confirm the diagnosis or to rule out a precancer or cancer [9]. A biopsy to confirm the diagnosis, exclude other dermatoses, and exclude cancer is necessary when the clinical presentation is atypical or ulcers or thickened areas fail to respond to therapy (picture 13). Vulvar lichen sclerosus can be associated with squamous cell carcinoma (SCC) of the vulva in up to 5 percent of patients [6,10-12]. (See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Diagnosis'.)

Lichen simplex chronicus — Lichen simplex chronicus is the end-stage of the itch-scratch-itch cycle. It is produced by scratching and rubbing any chronically itchy skin disease resulting in inflammation, thickened skin (referred to as lichenification), and excoriations. The skin of the vulva is moist and occluded. The trapped moisture results in whitening of the thickened/lichenified skin areas.

●Physical examination – The skin is thickened and firm to touch, so it can feel like leather. There can be variable excoriations and scaling. The vulva can have red papules and plaques. Lichen simplex chronicus is in the differential diagnosis of red patches and plaques (table 3). The plaques can become indurated, thickened, and gray to whitish with almost a warty surface. Constant scratching can result in hair loss and also skin injury, with loss of pigmentation in some areas and postinflammatory hyperpigmentation in other areas. The postinflammatory changes are seen most notably in patients with darker skin. Areas of involvement can be localized, generalized, and asymmetric.

●Symptoms – There is a history of relentless, often severe, itching. Scratching feels good to the patient. At times, nothing seems to stop the itching. Commonly, patients wake at night scratching and rubbing the vulva. Patients will scratch until the areas become painful. Many patients deny scratching but will admit to rubbing, especially after using the bathroom. Excessive vulvar cleansing and the use of irritating topical products is common.

●Diagnosis – The diagnosis is clinical with a history of intense, pleasurable, and chronic scratching and awakening at night to scratch and rub. On physical examination, the skin feels thick, and there is usually no scarring of the vulva. Generally, a biopsy is not necessary. Lichen simplex chronicus complicates other skin problems on the vulva, such as lichen sclerosus and psoriasis, which can make interpretation of skin biopsies challenging. Chronic scratching, with possible secondary infection complicated by contact dermatitis due to the many products these patients use, can add more ambiguity to a pathology diagnosis.

•(See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Lichen simplex chronicus'.)

•(See "Vulvar dermatitis", section on 'Clinical manifestations'.)

Squamous intraepithelial lesions — Vulvar squamous intraepithelial lesions (SIL) are the most common vulvar precancerous lesions and include three types of lesions. Low-grade SIL (LSIL) are raised condylomata acuminata (ie, human papillomavirus [HPV]) or flat warty changes related to low-risk HPV, while high-grade SIL (HSIL) are HPV-related precancers [13]. Differentiated vulvar intraepithelial neoplasia (dVIN) is a non-HPV-associated neoplasia most commonly associated with lichen sclerosus. A complete discussion of terminology, presentation, and treatment is reviewed elsewhere. (See "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)".)

●Changing nomenclature of SIL – The terminology relating to SIL has changed over time (table 4 and table 5). In the 1986 and 2004 International Society for the Study of Vulvovaginal Disease (ISSVD) terminologies, vulvar intraepithelial neoplasia (VIN) differentiated was included. However, it was removed in the 2012 Lower Anogenital Squamous Terminology (LAST) system since it is generally not HPV related, and the 2012 terminology focused on HPV-related conditions. In 2015, the ISSVD Terminology of Vulvar Squamous Intraepithelial Lesions (table 5) was developed to address the fact that differentiated VIN (dVIN) was not included as a vulvar precancer in the LAST system because it generally was not related to HPV infection. Differentiated VIN (dVIN) was included in the ISSVD 2015 terminology. (See "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)", section on 'Terminology'.)

●Physical examination

•LSIL lesions can be flat or raised and can be located anywhere on the vulva, perineum, and/or perianal areas (picture 14). LSIL often presents as a firm, irregularly rough papilloma on a broad base. It may be white (due to overgrowth of epithelial cells and a varying degree of increased keratin in a moist location). It may also be skin colored, red, pink, tan, brown, black, or gray. Coalescence can lead to formation of large, cauliflower-like masses. However, the morphology can also be small plaques, nodules, or flat-topped papules. Brown lesions can appear similar to seborrheic keratoses.

•HSIL – HSIL can present as red, brown, white, or gray/black lesions (picture 15 and picture 16 and picture 17 and picture 18). HSIL lesions are multifocal, HPV related, and found more commonly in younger than in older females.

•dVIN – The less common SIL, dVIN, is a serious condition because it has a high association with vulvar SCC. In one retrospective database study, the 10-year cumulative risk of vulvar SCC was 50 percent for patients with a diagnosis of dVIN [14].

The "differentiated type" (non-HPV related) dVIN often presents with a solitary (ie, unifocal), white to pink, red, skin-colored, or brownish papule or nodule on occasion [13,15-18]. The lesions are generally 2 to 5 cm in diameter. However, these lesions also can present with one or several red, sharply marginated plaques with varying amounts of overlying scale. Although these lesions are generally not HPV related, they can be similar in appearance to HSIL if they arise de novo from normal-appearing skin. However, more commonly, dVIN develops against a background of other diseases, most often in the setting of lichen sclerosus or, at times, in association with lichen planus. It tends to occur in older females [13].

●Symptoms – Vulvar SIL may be asymptomatic. For those with symptoms, pruritus and/or pain may be noted. (See "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)", section on 'Clinical presentation'.)

●Diagnosis – Biopsy/excision should be performed on a representative sample of the lesions to confirm the diagnosis, exclude other concomitant SIL, and exclude invasive SCC and/or lichen sclerosus [19].

The biopsy should be taken from a notably thickened area or the margin of any chronic erosion or ulcer that fails to respond to medical therapy, especially in the setting of vulvar lichen sclerosus or erosive lichen planus. If dVIN is suspected, the biopsy request form should indicate this because, without that information, the pathologist may interpret the specimen as a benign acanthotic process, such as occurs in psoriasis, psoriatic dermatitis, and lichen simplex chronicus. (See "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)", section on 'Diagnosis and histopathology'.)

Postinflammatory hypopigmentation — Postinflammatory hypopigmentation is an acquired partial or total loss of skin pigmentation that may occur following a wide range of inflammatory or infectious dermatoses (algorithm 1). The disorder is a consequence of inflammation-induced damage to pigment-producing melanocytes. (See "Acquired hypopigmentation disorders other than vitiligo", section on 'Postinflammatory hypopigmentation'.)

●Clinical presentation – Postinflammatory hypopigmentation presents as flat, white patches of skin similar to those seen in vitiligo. However, the patches are not as white, and the margins of the patches are less clearly defined than in vitiligo. Moreover, there is a history of preceding inflammation at the site. Postinflammatory hypopigmentation occurs more often, or at least is recognized more often, in individuals with naturally darker skin color (picture 19).

●Diagnosis – The diagnosis is made clinically when the lightening of the skin occurs at the site of previous or concomitant inflammatory disease. In rare cases, a biopsy is necessary to demonstrate that melanocytes remain present.

Vitiligo — Vitiligo represents depigmentation of the skin due to autoimmune lymphocytic attack against melanocytes.

Specific to vulvar vitiligo:

●Physical examination – Vitiligo presents as flat, white, sharply marginated patches that can expand centrifugally (picture 20). There is no scale. There is no texture change. The borders of white skin may be hyperpigmented. The milk-white patches may have skin-colored macules around the hair follicles giving the patch a polka dot appearance. In the anogenital region, it may involve the labia majora, perineum, and perianal skin (picture 21). Although in some patients vitiligo is restricted to the anogenital area [20], more commonly, other sites, such as the axillae, dorsal hands, elbows, knees, and periorificial facial skin, are involved. (See "Vitiligo: Pathogenesis, clinical features, and diagnosis", section on 'Clinical features'.)

●Symptoms – While the lesions of vitiligo are typically asymptomatic, the disease can also present with other autoimmune or immune-related disorders that may be symptomatic, such as lichen sclerosus. (See "Vitiligo: Pathogenesis, clinical features, and diagnosis", section on 'Associated disorders'.)

●Diagnosis – A clinical diagnosis of vulvar vitiligo is possible when the classic sites are also involved (table 6). Vitiligo must be differentiated from lichen sclerosus and from postinflammatory hypopigmentation, in which only partial loss of pigmentation occurs. If necessary, a biopsy can be performed to demonstrate the absence of melanocytes.

•(See "Vitiligo: Pathogenesis, clinical features, and diagnosis", section on 'Diagnosis'.)

•(See 'Postinflammatory hypopigmentation' above.)

•(See 'Lichen sclerosus' above.)

Discussions specific to generalized vitiligo are presented elsewhere:

●(See "Vitiligo: Pathogenesis, clinical features, and diagnosis".)

●(See "Vitiligo: Management and prognosis".)

Less common diseases — While the following diseases are commonly seen on the vulva with red coloration (table 3), they can occasionally present as white lesions. Thus, they are included in the differential diagnosis of white lesions (table 2).

Lichen planus — Lichen planus is an autoimmune, inflammatory, lymphocyte-mediated skin disease. It is most commonly seen in older females and affects the skin and mucous membranes. There are variable clinical patterns (classic, hypertrophic, and erosive), but erosions and erythema are commonly present [21,22]. On the vulva, lichen planus is usually erosive with a surrounding white to gray edge. White changes can be present as white, lacy, or net-like macules or patches and are diagnostic of lichen planus. There can be diffuse white change on the vulva with scarring, indistinguishable from vulvar lichen sclerosus. Also, lichen planus and lichen sclerosus can be seen together in the same patient. Lichen planus is in the differential diagnosis of red patches and plaques (table 3). However, the intact tissue surrounding the erosions in lichen planus (table 7) may appear white or gray. On occasion, squamous malignancy may develop within lesions of lichen planus [23].

●(See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Lichen planus (papulosquamous form)'.)

●(See "Vulvar lichen planus".)

Candidiasis — Candidiasis is in the differential diagnosis of red patches and plaques (table 3) and yellow papules and pustules (table 8). When severe, the surface of the skin can have an adherent white exudate made up of moist, macerated dead skin. There can be sheets of white, fragile papulopustules. Gently wiping these white involved areas with a cotton-tipped applicator or gauze will remove them, revealing an eroded surface. (See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Candidiasis'.)

Squamous cell carcinoma — SCC is often red (table 9), but it may be white (table 10) or skin colored (table 11). Vulvar SCC can be related to HPV infection (HPV-associated SCC) or can be HPV independent [24]. A biopsy is required to confirm the diagnosis. (See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Squamous cell carcinoma'.)

Rare diseases — The following diseases are rare but can present as white vulvar patches and/or plaques. Biopsy confirms these diagnoses.

●White sponge nevus occurs as a rare, asymptomatic, fairly well-marginated, white plaque within the vulvar vestibule [25] and may occur in the oral cavity (picture 22). A positive family history for similar lesions is usually present. The white color occurs because of the moist hyperkeratosis. A biopsy is required to make this diagnosis. (See "Oral lesions", section on 'White sponge nevus'.)

●Hailey-Hailey disease [26] and the related papular acantholytic dyskeratosis [27] usually present as red patches and plaques, often with varying degrees of erosion (picture 23). These lesions mimic the appearance of extramammary Paget disease. However, if there is significant hyperkeratosis, the surface of the lesion may appear white when moist. This disease first appears in younger females, and there are almost always similar plaques on the chest, back, and axillae and a positive family history for similar lesions. Biopsy is required for this diagnosis. (See "Hailey-Hailey disease (benign familial pemphigus)".)

●Extramammary Paget disease is a rare condition that can be both premalignant or malignant [28,29]. It arises primarily from apocrine cells (cell origin is controversial) or secondarily from an underlying anal, rectal, or bladder adenocarcinoma. The most common location is on the vulva. Paget disease can resemble eczema. Usually, there is a red plaque with some scaling and a somewhat erosive surface with islands of white thickened skin. It affects older females with variable itching, discomfort, and, at times, bleeding. A biopsy is needed to make the diagnosis. (See "Vulvar cancer: Epidemiology, diagnosis, histopathology, and treatment", section on 'Paget disease of the vulva'.)

●Verrucous carcinoma usually appears as a large, firm, skin-colored nodule with a papillomatous (cauliflower-like) surface [30]. It is a rare condition (variant of SCC), comprising less than 1 percent of vulvar cancer cases [31]. The surface may be white due to the presence of moist hyperkeratosis, or the surface may be eroded. Excisional biopsy is generally necessary to differentiate this malignant tumor from that of a large, benign wart. (See "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis", section on 'Verrucous carcinoma'.)

WHITE PAPULES AND NODULES — Papules include small (<1 cm) palpable lesions while nodules are large (>1 cm) and dome-shaped lesions (table 1). The differential diagnosis of white papules and nodules of the vulva can be divided into common, less common, and rare etiologies (table 10).

Common etiologies — The lesions discussed in this section are commonly seen in clinical practice. Frequency may vary based on the patient population and type of clinical practice (dermatology, gynecology, or internal medicine). These diagnoses are typically made using the patient's history and physical examination findings. Rarely, biopsy may be required.

Fordyce spots — Fordyce spots, or granules, are normal variants representing harmless enlarged sebaceous glands. The 1 to 2 mm papules are white to yellow, single or multilobular, and can form sheets. They occur in a symmetric pattern on the medial aspects of the labia minora and, less commonly, on the labia majora or the prepuce and clitoris. They are commonly found on oral surfaces (picture 24 and picture 25). When on the vulva, Fordyce spots must be differentiated from condylomata acuminata (low-grade squamous intraepithelial lesions [LSIL]), milia, and molluscum contagiosum. The diagnosis is based on location and morphology. A biopsy is rarely needed to confirm the diagnosis.

Epidermoid cysts — Epidermoid cysts are common cutaneous cysts that can appear anywhere on the body. While often white as a result of the keratin contained within the cyst, they can also be skin colored (picture 26), yellow, or red (if inflamed) (picture 27). (See "Overview of benign lesions of the skin", section on 'Epidermoid cyst'.)

Molluscum contagiosum — Molluscum contagiosum presents with dome-shaped papules, which are often dimpled, and may be white, pink, or skin colored (picture 28).

●(See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Molluscum contagiosum'.)

●(See "Molluscum contagiosum".)

Low-grade squamous intraepithelial lesions — Per the 2015 terminology by the International Society for the Study of Vulvovaginal Disease (ISSVD), squamous intraepithelial lesions (SIL) include LSIL, high-grade SIL (HSIL), and differentiated vulvar intraepithelial neoplasia (dVIN) [13]. LSIL, which includes flat condyloma or human papillomavirus effect, is not precancerous. Though often seen as patches or plaques, this condition may be white papules or nodules.

While condylomata acuminata are more commonly part of the differential diagnosis of brown, blue, or black lesions (table 12) and skin-colored lesions (picture 29 and table 11), they may appear white when they occur in moist areas due to the retention of moisture in thickened surface epithelium (picture 30 and table 2).

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

●(See "Condylomata acuminata (anogenital warts): Treatment of vulvar and vaginal warts".)

Less common etiologies — While the following diseases are less commonly seen on the vulva, when present, they may appear as white lesions (table 2), in addition to other colors.

Squamous intraepithelial lesions — SILs include, HSIL, and dVIN [13].

High-grade squamous intraepithelial lesions — While HSIL can present as red (picture 15) or brown, black, or blue (picture 16) lesions, they may appear white when they occur in moist areas due to the retention of moisture in thickened surface epithelium (picture 17 and table 2). Biopsy is needed to make the correct diagnosis.

Differentiated vulvar intraepithelial neoplasia — dVIN is most frequently seen in association with lichen sclerosus or, at times, in association with lichen planus. It tends to occur in older females. It may appear as a white papule or nodule.

Squamous cell carcinoma — Squamous cell carcinoma (SCC) is in the differential diagnosis of red papules and nodules (table 9) but may appear white when it occurs in moist areas due to the retention of moisture in thickened surface epithelium (picture 31 and picture 32).

●(See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Squamous cell carcinoma'.)

●(See "Vulvar cancer: Epidemiology, diagnosis, histopathology, and treatment".)

Scar — A vulvar scar can be white or skin colored. A previous punch biopsy may leave a round, flat scar. An episiotomy may cause a linear, white scar along the posterior fossa, extending onto the perineum. A history of trauma to the area helps to make the diagnosis. A biopsy is not usually needed but can confirm the diagnosis in settings where the clinical presentation does not correlate with the patient's history.

Milium (plural: milia) — Milia are firm, white, very small (1 to 2 mm) epidermal cysts (picture 33) that are uncommon on the vulva. After nicking the surface with a small needle, the tiny, firm, white material within the cyst can be extracted. While the milia walls often remain intact, the process of extracting the material within the cyst wall destroys the lesions. (See "Overview of benign lesions of the skin", section on 'Milium'.)

Rare etiologies

●Verrucous carcinoma usually appears as a large, firm, skin-colored nodule with a papillomatous (cauliflower-like) surface that is more commonly seen as an oral lesion (picture 34 and picture 35) [30]. It is a rare condition, comprising less than 1 percent of vulvar cancer cases [31]. The surface may be white due to the presence of moist hyperkeratosis, or the surface may be eroded as in other forms of SCC. Excisional biopsy is generally necessary to differentiate this malignant tumor from that of a large, benign wart. (See "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis", section on 'Verrucous carcinoma'.)

●Condylomata lata is the anogenital form of secondary syphilis. It appears as sharply marginated, smooth, flat-topped, 1 to 2 cm, moist papules and small plaques (picture 36 and picture 37). These lesions may be skin colored, white, pink, or yellow. Differential diagnosis includes LSIL or HSIL of the vulva and SCC. A clinical diagnosis can be suspected but will require confirmation by positive serologic tests for syphilis [32,33].

•(See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV".)

•(See "Syphilis: Screening and diagnostic testing".)

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

●Initial evaluation – For individuals with vulvar lesions, evaluation begins with a history, physical examination, and morphologic classification of the lesion (table 1), which allows formation of the differential diagnosis. (See 'Morphologic definitions for mucocutaneous vulvar lesions' above.)

●Clinical points – Based on the authors' experience, clinicians should be aware of alternate appearances of vulvar lesions, concomitant conditions, topic therapies, role of biopsy, and possibility of systemic disease when evaluating dermatologic lesions of the vulva (see 'Practical tips' above):

•Patients whose symptoms do not respond, or worsen, despite usual treatment should be referred to a gynecologist, dermatologist, family medicine physician, or other health care providers who specialize in vulvar skin disorders.

●White patches and plaques – White patches are typically an area of color change >1 cm that are not palpable while white plaques represent lesions >1 cm that are palpable and flat topped (table 1). The differential diagnosis of white patches and plaques of the vulva can be divided into common, less common, and rare diseases (table 2).

•Common – Diseases that commonly cause white patches or plaques of the vulva include lichen sclerosus, lichen simplex chronicus, squamous intraepithelial lesions (SIL; low-grade SIL [LSIL], high-grade SIL [HSIL], and differentiated vulvar intraepithelial neoplasia [dVIN]), postinflammatory hypopigmentation, and vitiligo. The relative frequency of presentation varies with the patient population and type of clinical practice (eg, dermatology, gynecology, or internal medicine). (See 'Common diseases' above.)

•Less common – Diseases that less commonly appear as vulvar white patches and plaques include lichen planus, candidiasis, and squamous cell carcinoma (SCC). These lesions more commonly present as red or other-colored lesions. (See 'Less common diseases' above.)

•Rare – Rare causes of white vulvar plaques and patches include white sponge nevus, Hailey-Hailey disease, extramammary Paget disease, and verrucous carcinoma. These diagnoses typically require biopsy to confirm. (See 'Rare diseases' above.)

●White papules and nodules – White papules include small (<1 cm) palpable lesions while nodules are large (>1 cm), flat-topped lesions (table 1). As with other vulvar lesions, the differential diagnosis of white papules and nodules of the vulva can be divided into common, less common, and rare etiologies (table 10).

•Common – Common etiologies that result in white papules and nodules of the vulva include Fordyce spots, epidermoid cysts, molluscum contagiosum, and LSIL. As with white patches and plaques, the relative frequency of each varies by patient population and practice type. (See 'Common etiologies' above.)

•Less common – Lesions that less commonly present as vulvar white papules or nodules include HSIL, dVIN, SCC, scar, or milium (plural: milia). SCC typically requires biopsy for confirmation. (See 'Less common etiologies' above.)

•Rare – Rare causes of white vulvar papules and nodules include verrucous carcinoma and condylomata lata. Carcinoma generally requires biopsy for confirmation while condylomata lata, the anogenital form of secondary syphilis, requires syphilis-specific serologic testing. (See 'Rare etiologies' above.)

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