Cervix, Vagina, and Vulva

Here is a normal cervix with a smooth, glistening mucosal surface. There is a small rim of vaginal cuff from this hysterectomy specimen. The cervical os is small and round, typical for a nulliparous woman. The os will have a fish-mouth shape after one or more pregnancies.

This is normal cervical non-keratinizing squamous epithelium. The squamous cells show maturation from basal layer to surface.

The normal adult vaginal mucosa with a wrinkled appearance that is seen in women of reproductive years appears at the left. The cervix has been opened to reveal an endocervical canal leading to the lower uterine segment at the right that has an erythematous appearance extending to the cervical os consistent with chronic inflammation.

Genital Infections
Sexually Transmitted Genital Infections

Infectious diseases of the female genital tract are common and are caused by many pathogenic organisms Most of the important infectious diseases affecting the female genital tract are sexually transmitted

VIRAL INFECTIONS
Human Papillomavirus

Human papillomavirus (HPV) is a DNA virus that infects a number of skin and mucosal surfaces to produce wart-like lesions, referred to as verrucae and condylomata (Fig. 18-2).

FIGURE 18-2. Human papillomavirus-induced condylomatous infections. A. Condyloma acuminatum on the cervix, visible with the naked eye as cauliflowerlike excrescences. B. A cervical smear contains characteristic koilocytes with a perinuclear halo and a wrinkled nucleus that contains viral particles. C. Biopsy of the condyloma shows koilocytes with perinuclear halos but lacking nuclear atypia.

More than 100 HPV serotypes are known, one-third of which cause genital tract lesions. In the United States, as many as two thirds of graduating college women have genital HPV infections, which result from sexual contact with an infected person. Approximately 20 million people are currently infected with HPV in this country. HPV types 6 and 11 are detected in more than 80% of macroscopically visible condylomata. Several strains of HPV are the major etiologic factors for squamous cell cancer in the female lower genital tract. Types 16 and 18 are associated with about 60% of cases; types 31, 33, 45, 52, and 58 account for most other occurrences of intraepithelial neoplasia and invasive cancer (see the section on the cervix below).

Most cases of HPV are diagnosed by cervical Pap smear. Tests that directly assay for HPV DNA are seeing increasing clinical use. Treatment for HPV infection has been inadequate, and most infections spontaneously disappear. A recently approved prophylactic vaccine directed against four common serotypes of HPV potentially provides protection against the HPV strains responsible for 70% of cervical cancer and 90% of cervical warts and is recommended for all females between the ages of 9 and 26.

This is chronic cervicitis at the squamo-columnar junction of the cervix. Small round dark lymphocytes are seen in the submucosa, and there is also hemorrhage. Chronic cervicitis is quite common.

The normal cervical squamous epithelium at the left transforms to dysplastic changes on the right. There is also underlying chronic inflammation because abnormal epithelial surfaces do not provide the same protective barrier as normal epithelial surfaces do.

Cervical squamous dysplasia is seen at medium magnification, extending from the center to the right. The epithelium is normal at the left. Note how the dysplastic cell nuclei at the right are larger and darker, and the dysplastic cells have a disorderly arrangement. This dysplastic process involves the full thickness of the epithelium, but the basal lamina is intact, so this is a high grade squamous intraepithelial lesion (HSIL) that can also be termed cervical

Dysplasias may also involve the vulvar epithelium, seen here at the right with overlying hyperkeratosis (producing an area of leukoplakia), with more normal (but atrophic) keratinizing squamous epithelium at the left. Most cases of vulvar intraepithelial neoplasia (VIN) do not progress to invasive cancer. Many are multicentric, and some occur in association with cervical or vaginal

This is a Pap smear. The cytologic features of normal squamous epithelial cells can be seen at the center top and bottom, with orange to pale blue plate-like squamous cells that have small pyknotic nuclei. The dysplastic cells in the center extending to upper right are smaller overall with darker, more irregular

This is why you do Pap smears--to prevent invasive squamous cell carcinomas from occurring. With Pap smears, pre-neoplastic and neoplastic cervical lesions can be detected when small and treated. Nests of squamous cell carcinoma have invaded underlying stroma at the center and left.

At high magnification, nests of neoplastic squamous cells are invaded through a chronically inflamed stroma. This cancer is welldifferentiated, as evidenced by keratin pearls. However, most cervical squamous carcinomas are non-keratinizing.

This is the gross appearance of a cervical squamous cell carcinoma that is still limited to the cervix (stage I). The tumor is a fungating red to tan to yellow mass.

Here is another cervical squamous cell carcinoma. Note the IUD string protruding from the cervix. This implies that someone could have done a Pap smear when it was inserted. There is a natural history of progression of dysplasia to carcinoma, so don't leave dysplasias alone.

This is a larger cervical squamous cell carcinoma which spread to the vagina. A total abdominal hysterectomy with bilateral salpingooopherectomy (TAH-BSO) was performed.

This is a pelvic exenteration done for stage IV cervical carcinoma. At the left, dark vulvar skin leads to vagina and to cervix in the center, where an irregular tan tumor mass is seen infiltrating upward to the bladder. A slit-like endometrial cavity is surrounded by myometrium at the mid-right. The rectum and sigmoid colon are at the bottom extending to the right.

This is another pelvic exenteration for cervical squamous cell carcinoma. The irregular grey-brown tumor extends toward bladder

VULVA
CYSTS Bartholin Gland Cysts: The paired Bartholin glands located immediately posterolateral to the introitus produce a clear mucoid secretion that continuously lubricates the vestibular surface. The ducts are prone to obstruction and consequent cysts. In turn, cyst infection leads to abscess formation. Staphylococci, chlamydia, and anaerobes are frequently the cause. Treatment consists of incision, drainage, marsupialization, and appropriate antibiotics.

Follicular Cysts: The follicular cyst recapitulates the most distal portion of the hair follicle. Also termed epithelial inclusion cysts or keratinous cysts, follicular cysts frequently appear on the vulva, especially the labia majora. They contain a white cheesy material and

Mucinous Cysts: Mucinous glands of the vulva occasionally become obstructed and subsequently cystic. Mucinous columnar cells line the cyst and may become infected.

Malignant Tumors and Premalignant Conditions

Vulvar Intraepithelial Neoplasia (VIN) is a Precursor of Invasive Cancer

VIN reflects a spectrum of neoplastic changes that range from minimal cellular atypia to the most marked cellular changes short of invasive cancer. Between 1983 and 2000, there has been about a twofold increase in the frequency of VIN, much of which occurs in women under the age of 40 years. As with comparable lesions in the cervix (cervical intraepithelial neoplasia [CIN]), VIN is a precursor of vulvar squamous cell carcinoma, of which at least 30% to 40% of cases are caused by HPV.

Pathology:

The lesions of VIN may be single or multiple, and macular, papular, or plaque-like. Microscopically, the grades are labeled VIN I, II, and III, corresponding to mild, moderate, and severe dysplasia, respectively. Grade III also includes squamous cell carcinoma in situ (CIS). VIN, even if locally excised, often recurs (25%), in which case it may progress to invasive squamous cell carcinoma (6%). Women with VIN may have squamous neoplasms similar to VIN elsewhere in the lower genital tract.

Squamous Cell Carcinoma Follows VIN

Squamous cell carcinoma of the vulva (Fig. 18-3) is the end result of a multistep process that begins with VIN. This tumor accounts for 3% of all genital cancers in women and is the most common cancer of the vulva. In the past, it mainly affected older women, but like VIN, it now occurs with increasing frequency in younger women. Two thirds of larger tumors are exophytic; the others are ulcerative and endophytic. Pruritus of long duration is commonly the first symptom. Ulceration, bleeding, and secondary infection may develop. The tumors grow slowly and then extend to the contiguous skin, vagina, and rectum. They metastasize to superficial inguinal and then deep inguinal, femoral, and pelvic lymph nodes. The outlook correlates with the stage of disease and lymph node status. The prognosis of patients with vulvar cancer is generally good, with an overall 5-year survival rate of 70%.

FIGURE 18-3. Squamous cell carcinoma of the vulva. A. The tumor is situated in an extensive area of lichen sclerosus (white). B. Small nests of neoplastic squamous cells, some with keratin pearls, are evident in this well-differentiated tumor.

Figure 18-4. Interrelations of naming systems in premalignant cervical disease. This complex chart integrates multiple aspects of the disease complex. It lists the qualitative and quantitative features that become increasingly abnormal as the premalignant disease advances in severity. It also illustrates the changes in progressively more abnormal disease states and provides translation nomenclature for the dysplasia/carcinoma in situ (CIS) system, cervical intraepithelial neoplasia (CIN) system, and the Bethesda system. Finally, the scheme illustrates the corresponding cytologic smear resulting from exfoliation of the most superficial cells, indicating that even in the mildest disease state, abnormal cells reach the surface and are

Endometrium

This is the microscopic appearance of normal proliferative endometrium in the menstrual cycle. The proliferative phase is the variable part of the cycle. In this phase, tubular glands with columnar cells and surrounding dense stroma are proliferating to build up the endometrium following shedding with previous

Here is early secretory endometrium. The appearance with prominent subnuclear vacuoles in cells forming the glands is consistent with post-ovulatory day 2. The histologic changes following ovulation are quite constant over the 14 days to menstruation and can be utilized to

This is normal secretory phase endometrium. Note the larger tortuous glands with secretions. The secretory phase follows a set 14 day course leading to either implantation of a fertilized ovum or menstruation.

The endometrial cavity is opened to reveal lush fronds of hyperplastic endometrium. Endometrial hyperplasia usually results with conditions of prolonged estrogen excess and can lead to metrorrhagia (uterine bleeding at irregular intervals), menorrhagia (excessive bleeding with menstrual periods), or menometrorrhagia.

This uterus has been opened anteriorly through cervix and into the endometrial cavity. High in the fundus and projecting into the endometrial cavity is a small endometrial polyp. Such benign polyps may cause uterine bleeding.

This is endometrial cystic hyperplasia in which the amount of endometrium is abnormally increased and not cycling as it should. The glands are enlarged and irregular with columnar cells that have some atypia. Simple endometrial hyperplasias can cause bleeding, but are not thought to be premalignant. However, adenomatous hyperplasia is premalignant.

This uterus is not enlarged, but there is an irregular mass in the upper fundus that proved to be endometrial adenocarcinoma on biopsy. Such carcinomas are more likely to occur in postmenopausal women. Thus, any postmenopausal bleeding should make you suspect that

This adenocarcinoma of the endometrium is more obvious. Irregular masses of white tumor are seen over the surface of this uterus that has been opened anteriorly. The cervix is at the bottom of the picture. This enlarged uterus was no doubt palpable on physical examination. Such a neoplasm often present with abnormal bleeding.

The endometrial adenocarcinoma is present on the lumenal surface of this cross section of uterus. Note that the neoplasm is superficially invasive. The cervix is at the right.

The endometrial adenocarcinoma in the polyp at the left is moderately differentiated, as a glandular structure can still be discerned. Note the hyperchromatism and pleomorphism of the cells, compared to the underlying endometrium with cystic atrophy at the right.

This is endometrial adenocarcinoma which can be seen invading into the smooth muscle bundles of the myometrial wall of the uterus. This neoplasm has a higher stage than a neoplasm that is just confined to the endometrium or is superficially invasive.