I. NORMAL STRUCTURE. The vagina is derived from the müllerian ducts and is composed of three layers: mucosa, muscularis propria, and adventitia. The mucosa is composed of squamous epithelium overlying a lamina propria that contains a rich vascular and lymphatic network with scattered stromal cells that may show multinucleation.
II. BENIGN CONDITIONS
A. Infectious diseases
1. Vulvovaginal candidiasis is a common condition that predominantly affects adult women in their second and third decades. Up to 70% of women will experience at least one episode in their lifetime. Common predisposing factors include antibiotic use, steroid use, oral contraceptive use, immunosuppression, and uncontrolled diabetes. Pruritus, erythema, and thick white vaginal discharge are the most common symptoms. Histologically, squamous epithelial hyperplasia with hyperkeratosis and/or parakeratosis is seen. Foci of neutrophilic infiltration of the squamous epithelium are commonly present. Candida can be present in the form of budding yeasts as well as pseudohyphae, highlighted on GMS or other special stains.
2. Bacterial vaginosis is most commonly found among adult women. It is caused by Gardnerella vaginalis, a bacillus which usually grows when the vaginal flora shifts toward a more acidic environment. A watery, malodorous discharge without significant inflammation is a common symptom. Microscopically, the bacteria overgrow and cover the squamous cells, producing so-called clue cells.
3. Trichomoniasis, a sexually transmitted disease, is caused by Trichomonas vaginalis, an oval protozoon with flagella. Microscopically, the organisms are identified by their bluish-pink body, elongated nuclei, and flagella.
4. Herpes simplex infection is a sexually transmitted disease caused by herpes simplex virus (HSV). Grossly, the virus causes a mucosal ulceration within a few days to 2 weeks following the exposure. These lesions are highly infectious until crusting, with final scarring occurring within 2 to 3 weeks of initial symptoms. The majority of cases are caused by HSV-2, and recurrence is higher with infection by HSV-2 than by HSV-1.
Microscopically, the ulcerated lesions are characterized by epithelial necrosis with associated degenerated cells containing viral inclusions, best identified at the periphery of the ulcer. The cells with viral inclusions have characteristic features including multinucleation and ground glass nuclei with a rim of chromatin condensation at the nuclear border surrounded by a cytoplasmic halo.
5. Actinomyces-like organisms are most commonly seen in women with noncopper intrauterine contraceptive devices.
B. Inflammatory diseases
1. Atrophic vaginitis occurs most commonly in postmenopausal women, but can also occur during the postpartum period. Grossly, the primary finding is punctate hemorrhage of the vaginal mucosa. Microscopically, the squamous cells show decreased glycogen due to lower estrogen levels. Atrophy can be distinguished from vaginal intraepithelial neoplasia (VAIN) by the monotony
of the cell population, uniform chromatin, the lack of cytologic atypia, and the low mitotic rate.
2. Crohn disease can result in rectovaginal fistula formation and is associated with fibrosis, chronic inflammation, and granulomas. The differential diagnosis includes vaginal fistulas of other etiologies including radiation therapy, perforated colonic diverticulum, or as a complication of hysterectomy.
3. Stenosis, ulceration, and necrosis are well-described sequelae of radiation therapy. Stenosis can also follow severe bullous erythema multiforme (Stevens-Johnson syndrome).
1. Müllerian cysts are the most common type of vaginal cyst and can be lined by endocervical-, endometrial-, or endosalpingeal-type epithelium (e-Fig. 35.1).*
2. Epithelial inclusion cysts are lined by keratinizing squamous epithelium and filled with white sebaceous and keratinous debris. They most commonly arise in areas of previous trauma such as episiotomy sites.
3. Mesonephric cyst. Also known as Gartner duct cysts, they are usually located along the anterolateral wall of the vagina (along the path of the mesonephric duct). This type of cyst is lined by low cuboidal, nonmucinous epithelium.
4. Bartholin gland cysts are thought to develop from obstruction of the ducts of Bartholin glands, which normally open on to the vestibule. The cyst lining varies from squamous to transitional to mucin secreting (e-Fig. 35.2).
D. Adenosis occurs in about 30% of women who were exposed to diethylstilbestrol (DES) in utero and is associated with an increased risk of clear cell adenocarcinoma (see section on clear cell adenocarcinoma below). Adenosis usually involves the upper third of the vagina, but the middle third or lower third are affected in about 10% of cases. Grossly, adenosis presents as a red erythematous granular lesion. Microscopically, adenosis is defined by the presence of columnar epithelium of endometrial or endocervical type in the vaginal mucosa or underlying submucosa (e-Fig. 35.3).
E. Endometriosis of the vagina comprises <10% of cases of pelvic endometriosis. The diagnosis requires the presence of müllerian-type epithelium (most commonly endometrioid) and endometrial-type stroma. Hemosiderin-laden macrophages are often present as well. The presence of endometrial type stroma can be used to distinguish endometriosis from adenosis (e-Fig. 35.4).
III. BENIGN NEOPLASMS. The WHO classification of vaginal tumors is given in Table 35.1.
1. Squamous papilloma is usually asymptomatic and can occur at any age. Grossly, it usually presents as a cluster of papillary lesions. Microscopically, squamous papillomas have a fibrovascular core and are lined by benign squamous epithelium.
2. Fibroepithelial polyps most commonly occur in adult women during their reproductive years. They occur in the lower third of the vagina and grossly have a soft and papillary surface. Microscopically, they are composed of squamous epithelium with underlying hypocellular fibrovascular stroma. Atypical myofibroblasts are common in the stroma, and scattered multinucleated cells with bizarre atypical nuclei may also be seen (e-Fig. 35.5). However, rhabdomyoblasts and a cambium layer are not present and mitotic figures are rare; these features, together with patient age, distinguish fibroepithelial polyp from sarcoma botryoides.
TABLE 35.1 WHO Histologic Classification of Tumors of the Vagina
Squamous tumors and precursors
Squamous cell carcinoma, not otherwise specified
Squamous intraepithelial neoplasia
Benign squamous lesions
Squamous papilloma (vaginal micropapillomatosis)
Clear cell adenocarcinoma
Other epithelial tumors
Adenoid cystic carcinoma
Adenoid basal carcinoma
Small cell carcinoma
Mesenchymal tumors and tumorlike conditions
Endometrioid stromal sarcoma, low grade
Undifferentiated vaginal sarcoma
Postoperative spindle cell nodule
Mixed epithelial and mesenchymal tumors
Carcinosarcoma (malignant müllerian mixed tumor)
Malignant mixed tumor resembling synovial sarcoma
Benign mixed tumor
Tumors of germ cell type
Yolk sac tumor
Peripheral primitive neuroectodermal tumor/Ewing tumor
Lymphoid and hematopoietic tumors
From: Tavassoli FA, Devilee P, eds. World Health Organization Classification of Tumours. Pathology and Genetics. Tumours of the Breast and Female Genital Organs. Lyon: IARC Press; 2003. Used with permission.
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