Extramammary Paget disease

This curious and rare lesion of the vulva, and sometimes the perianal region, is similar in its manifestations to Paget disease of the breast (Chapter 23). As a vulvar neoplasm, it presents as a pruritic, red, crusted, sharply demarcated, maplike area, occurring usually on the labia majora. It may be accompanied by a palpable submucosal thickening or nodule.

Morphology. Paget disease is a distinctive intraepithelial proliferation of malignant cells. The diagnostic microscopic feature is the presence of large tumor cells lying singly or in small clusters within the epidermis and its appendages. These cells are distinguished by a clear separation ("halo") from the surrounding epithelial cells (Fig. 22-11) and a finely granular cytoplasm containing mucopolysaccharide that stains with periodic acid-Schiff (PAS), Alcian blue, or mucicarmine stains. Ultrastructurally, Paget cells display apocrine, eccrine, and keratinocyte differentiation and presumably arise from primitive germinal cells of the mammary-like gland ducts of the vulvar skin.17,18

In contrast to Paget disease of the nipple, in which 100% of patients show an underlying ductal breast carcinoma, vulvar lesions are most frequently confined to the epidermis of the skin and adjacent hair follicles and sweat glands. Paget disease is treated with wide local excision and shows a high recurrence rate. Typically, Paget cells spread beyond the confines of the grossly visible lesion, and therefore are frequently present beyond the margins of surgical excision. Intraepidermal Paget disease may persist for many years, even decades, without invasion or metastases. Invasion develops rarely, and in such patients the prognosis is poor.

Malignant Melanoma

Melanomas of the vulva are rare, representing less than 5% of all vulvar cancers and 2% of all melanomas in women. Their peak incidence is in the sixth or seventh decade; they tend to have the same biologic and histologic characteristics as melanomas occurring elsewhere in the skin and are capable of widespread metastatic dissemination. The 5-year survival rate is less than 32%, presumably because of delays in detection and because the majority of these tumors rapidly enter a vertical growth phase following inception (Chapter 25). Prognosis is linked principally to depth of invasion, with greater than 60% mortality for lesions invading deeper than 1 mm.

Because it is initially confined to the epithelium, melanoma may resemble Paget disease, both grossly and histologically. It can usually be differentiated by its uniform reactivity with antibodies to S100 protein, absence of reactivity with antibodies to cytokeratin, and lack of mucopolysaccharides, both of which are present in Paget disease.

VAGINA

The vagina is a portion of the female genital tract that is remarkably free from primary disease. In the adult, inflammations often affect the vulva and perivulvar structures and spread to the cervix without significant involvement of the vagina. Primary lesions of the vagina are rare; the most serious of which is primary vaginal carcinoma. Thus, they are discussed only briefly.

Developmental Anomalies

Septate, or double, vagina is an uncommon anomaly that arises from failure of total fusion of the müllerian ducts and accompanies a double uterus (uterus didelphys). These and other anomalies of the external genitalia may be the manifestations of genetic syndromes, in utero exposure to diethylstilbestrol (DES) used to prevent threatened abortions in the 1940s through 1960s, or other disturbances associated with abnormalities in reciprocal epithelial-stromal signaling during fetal development.19

Vaginal adenosis is a remnant of columnar, endocervical-type epithelium that during embryonal development extends from the endocervix and covers the ectocervix as well as the upper vagina and is subsequently replaced by the squamous epithelium advancing upwardly from the urogenital sinus. Small patches of unreplaced glandular epithelium may persist focally into adult life. Adenosis presents clinically as red, granular areas contrasting with the normal pale-pink vaginal mucosa. On microscopic examination, adenosis consists of columnar mucinous epithelium indistinguishable from endocervical epithelium. Adenosis, while normally present in a small percentage of adult women, has been reported in 35% to 90% of women exposed to DES in utero. Rare cases of clear cell carcinoma (Fig. 22-12) arising in DES-related adenosis were recorded in teens and young women in the 1970s and 1980s, resulting in discontinuation of DES treatment.

Gartner duct cysts are relatively common lesions found along the lateral walls of the vagina and derived from wolffian (mesonephric) duct rests. They are 1- to 2-cm fluid-filled cysts that occur in the submucosal location. Other cysts, including mucus cysts, which occur in the proximal vagina, are derived from müllerian epithelium. Another müllerian-derived lesion, endometriosis (described later), may occur in the vagina and simulate a neoplasm.

Premalignant and Malignant Neoplasms

Most of the benign tumors of the vagina occur in reproductive-age women and include stromal tumors (stromal polyps), leiomyomas, and hemangiomas. The most common malignant tumor of the vagina is carcinoma metastatic from the cervix, followed by a primary squamous cell carcinoma of the vagina. Infants may develop a unique, rare malignancy-embryonal rhabdomyosarcoma (sarcoma botryoides).

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