Danielle H. Carpenter
John D. Pfeifer
Phyllis C. Huettner
I. NORMAL ANATOMY. The vulva or external female genital region encompasses the mons pubis, labia majora, labia minora, clitoris, and vestibule. The entire vulva except for the vestibule is covered by keratinized, stratified squamous epithelium. The epithelium of the vestibule is glycogenated squamous epithelium. The lateral aspects of the labia majora and the mons pubis contain hair follicles. Sebaceous glands are present in the labia majora and the perineum. The clitoris is lined by keratinizing stratified squamous epithelium overlying paired corpora cavernosa that contain vascular spaces surrounded by nerves.
The urethral meatus, major vestibular glands (Bartholin glands; e-Fig. 36.1),* minor vestibular glands, paraurethral glands (Skene glands), and vagina all open onto the vulva. The Bartholin glands are paired glands that open posterolaterally on the hymenal ring; they are composed of acini lined by cuboidal mucus-secreting epithelium that drain into a duct that may be lined by mucus-secreting, transitional, or squamous epithelium, depending on the location from deep to surface. Skene glands open on either side of the urethral meatus and are composed of acini lined by mucus-secreting epithelium that open into ducts lined by transitional epithelium.
II. GROSS EXAMINATION, TISSUE SAMPLING, AND HISTOLOGIC SLIDE PREPARATION
A. Vulvar biopsies. Vulvar biopsies should be oriented as for skin biopsies (see Chap. 38) and three H&E stained levels examined.
B. Vulvar resections It is helpful to ask the surgeon to orient the specimen with a diagram or labeled sutures so that orientation can be maintained during processing. The margins of resection should be inked and, depending on the location of the resection, the periurethral, vaginal, and perianal margins need to be noted. In cases with an obvious malignant neoplasm, one section per centimeter of tumor, including the areas closest to the deep margin; lateral margin, and/or other margins are recommended. In cases where no tumor is observed grossly, the entire specimen should be submitted. Because many gynecologic oncologists consider resection for squamous cancer in this area to be adequate only if tumor is >8 mm from the margin (Cancer. 2002;95:2331), radial rather than shave margins should be taken of all but the most obviously negative margins so that the distance from tumor to margin can be measured.
III. DIAGNOSTIC FEATURES OF COMMON DISEASES OF THE VULVA. Many inflammatory and neoplastic conditions that affect the skin will also affect the vulva. These are discussed in the skin chapters (see Chaps. 38 and 39). This section only covers those conditions for which the vulva is a common site of disease.
1. Bartholin abscess presents as a painful swelling in the area of the Bartholin gland. Microscopically, there is acute inflammation of the Bartholin duct, glands, and connective tissue, with purulent luminal contents. The etiology includes Neisseria gonorrhea, Staphylococcus, or other aerobic or anaerobic organisms. Treatment includes excision, drainage, and appropriate antibiotics.
2. Hidradenitis suppurativa presents as painful subcutaneous nodules in areas containing apocrine glands, particularly the vulva and axilla. Initial changes
include acute and chronic inflammation around hair follicles, which progress to abscess formation, sinus tract formation, and dermal scarring (e-Fig. 36.2). Treatment may include laser ablation or total excision of the involved area.
3. Crohn’s disease may present as vulvar or perianal erythema, ulceration, abscesses, or fistulas between bowel and vulva or between two different areas of vulva. Microscopically, there is acute and chronic inflammation of the deep dermis, often with associated noncaseating granulomas, fistulas, or sinus tracts (e-Figs. 36.3 and 36.4).
1. Candida infection is often a chronic inflammatory condition of the vulva that may be associated with diabetes. It often presents as pruritis and clinically shows areas of redness with thickened, edematous skin. Microscopically, there is acanthosis with acute and chronic inflammatory cells in the epithelium, and parakeratosis with neutrophils. Often fungal organisms are visible on H&E stain in the keratin layer; they are easily identified by silver stains.
2. Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum. The primary lesion of syphilis, the chancre, develops in about half of the women within 3 weeks of infection and is characterized by one to sometimes multiple painless, clean-based ulcers. The ulcer heals in 2 to 6 weeks without a scar. Secondary syphilis develops within 6 weeks to 6 months and is characterized by the development of a rash on the palms, soles, and mucosal surfaces, as well as elevated plaques and papules (termed condyloma lata) on the vulva and mucosal surfaces. On microscopic sections, the chancre shows epidermal ulceration, dermal acute and chronic inflammation with numerous plasma cells, and severe arteritis. Condyloma lata are characterized by marked epidermal acanthosis and hyperkeratosis, dermal inflammation with numerous plasma cells, and arteritis. The organisms may be detected on Warthin-Starry, Steiner, or Dieterle stains; no organisms are seen in some cases of active infection.
3. Human papilloma virus (HPV) infection. Condyloma acuminatum, also referred to as genital warts, is the result of sexually transmitted infection caused by HPV types 11 (75% of cases) or 6 (25% of cases). They present as asymptomatic, usually multiple or confluent, papillary or papular lesions, and may occur anywhere on the vulva or perianal region.
Microscopically, condylomata of the vulva typically have a fibrovascular stalk. The epithelium exhibits acanthosis, papillomatosis, hyperkeratosis, dyskeratosis, and an accentuated granular cell layer (e-Fig. 36.5). Viral cytopathic effect, termed koilocytosis, takes the form of cytoplasmic clearing around enlarged nuclei with irregular nuclear outlines and clumped chromatin (e-Fig. 36.6). Vulvar condylomata usually follow a protracted course. They may grow rapidly during pregnancy and then regress after delivery. Small condylomas may be treated with topical agents while large ones are excised, or treated with laser ablation or cryotherapy.
4. Herpes simplex virus (HSV). Infection with HSV type 2, or less commonly type 1, is typically heralded by fever, dysuria, and severe pain. Painless vesicles then appear which progress to an intensely painful ulcer. The ulcer typically heals in about 2 weeks. Microscopically, epithelial ulceration is surrounded by virally infected keratinocytes that exhibit multinucleation, “ground glass” nuclear chromatin, or eosinophilic nuclear inclusions (e-Fig. 36.7).
5. Molluscum contagiosum is a sexually transmitted disease in adults caused by infection with the Molluscum contagiosum poxvirus. The lesions are small, 3 to 6 mm diameter papules with a characteristic central depression or umbilication, and are usually asymptomatic although perianal lesions may be pruritic. Microscopic features (e-Fig. 36.8) include formation of a cup-shaped papule with marked epidermal acanthosis, and intracytoplasmic inclusions
that are initially eosinophilic but become more basophilic as the lesion ages. Most lesions regress spontaneously.
C. Noninfectious squamous lesions
1. Lichen sclerosus presents as symmetric plaque-like areas of white, thinned epithelium that may be superficially ulcerated. In advanced cases, there may be scarring of involved areas and stenosis of the introitus.
Microscopically, there is typically a band-like lymphocytic infiltrate in the upper dermis with spongiotic changes to the basal layer of the epidermis and loss of melanocytes from the overlying epidermis. Thinning of the epidermis with flattening of the rete and a zone of collagenous connective tissue immediately beneath the epidermis is frequently present (e-Fig. 36.9) and was the basis for the previous nomenclature “lichen sclerosis et atrophicus.” However, it is now recognized that a spectrum of histologic changes can be seen in the disease, ranging from a predominantly lichenoid infiltrate without dermal collagenization to prominent dermal scarring with minimal chronic inflammation. Treatment involves high-dose corticosteroids. Postmenopausal women with lichen sclerosus have a small risk of developing differentiated VIN (see below) and squamous cell carcinoma.
2. Lichen simplex chronicus (formerly “squamous cell hyperplasia”) typically occurs in adults and presents as a localized area of pruritus (J Reprod Med. 2007;52:3). It is thought to be a nonspecific response triggered by a variety of irritants. Clinically, the area is white or red, with accentuated skin markings and sometimes areas of excoriation. The characteristic feature on microscopy is marked acanthosis without atypia, increased mitotic activity, inflammation, often with features that overlap other specific dermatoses (e-Fig. 36.10). Hyperkeratosis may be present. The dermis is normal. Treatment includes limiting exposure to irritants, topical corticosteroids, and antipruritic agents.
D. Cystic lesions
1. Bartholin cyst. Obstruction of the Bartholin duct leads to the accumulation of secretions and the formation of a cystic dilatation of the duct. The epithelium lining these cysts may be squamous, transitional, or mucinous. Cysts can be treated by drainage, marsupialization, or excision of the gland.
2. Keratinous cysts occur at any age and typically affect the labia majora. They are small, measuring just a few millimeters in maximal dimension, and are filled with white cheesy material without hair. Microscopically, they are lined by stratified squamous or flattened epithelium. They can be excised if symptomatic.
3. Mucus cysts occur in the vestibule and are lined by mucinous epithelium with or without squamous metaplasia. They are probably the result of occlusion of minor vestibular glands.
IV. TUMORS. The WHO classification of tumors of the vulva is presented in Table 36.1.
A. Benign tumors and tumor-like lesions
1. Fibroepithelial polyps are also known as acrochordons or skin tags. They may be hyperpigmented, hypopigmented, or flesh-colored, and typically occur on hair-bearing skin. They usually have a papillomatous or pedunculated growth pattern and a soft cut surface. Microscopically, the epithelium may be thickened with hyperkeratosis, or may be flattened. The stroma contains loose bundles of collagen and may be edematous. Fibroepithelial polyps are clinically insignificant but can be excised if they are cosmetically unacceptable.
2. Papillary hidradenoma is a benign tumor that originates from apocrine sweat glands. It presents as a dome-shaped mass, usually <2 cm in diameter, arising between the labium majus and labium minus. The mass may ulcerate and bleed but is usually asymptomatic. Microscopically, papillary hidradenoma forms tubules and acini lined by a luminal layer of epithelial cells and an outer layer of myoepithelial cells (e-Figs. 36.11 and 36.12). Cytologic atypia and mitotic activity are rare. These lesions exhibit a pseudocapsule, and caution should be exercised before interpreting compression of glandular epithelium at the periphery as invasion. Local excision is curative.
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