DISEASES OF THE VULVA VULVA NONNEOPLASTIC EPITHELIAL DISORDERS

DISEASES OF THE VULVA

VULVA: NON-NEOPLASTIC EPITHELIAL DISORDERS n There are two forms of NNED: lichen sclerosus n lichen simplex chronicus. n n Both may coexist in different areas in the same patient, and both may appear macroscopically as depigmented white lesions, referred to as leukoplakia.

Condylomas and Low-Grade Vulvar Intraepithelial Neoplasia (VIN I) n n n The more common may be papillary and sometime flat. They occur anywhere on the anogenital surface, sometimes singly but more often in multiple sites. The histologic appearance: perinuclear cytoplasmic vacuolization with nuclear angular pleomorphism-koilocytosis. Cause: HPV infection. there is a strong association with at least two types of HPV (HPV 6 and HPV 11), closely related to the virus that causes common warts. Not precancerous but may coexist with foci of intraepithelial neoplasia in the vulva and cervix.

Carcinoma of the Vulva Carcinoma of the vulva represents about 3% of all genital tract cancers in women n occurring mostly in women older than age 60 years. n Approximately 90% of carcinomas are squamous cell carcinomas; the remainder are adenocarcinomas, melanomas, or basal cell carcinomas n

Carcinoma of the Vulva 2) The other subgroup of vulvar carcinoma occurs in older women. n It is not associated with HPV but is often preceded by years of non-neoplastic epithelial changes, principally lichen sclerosus and, rarely, lichen simplex chronicus.

TUMORS OF THE CERVIX n Cervical carcinoma, despite dramatic improvements in early diagnosis and treatment, continues to be one of the major causes of cancer-related deaths in women, particularly in the developing world.

Cervical Intraepithelial Neoplasia and Squamous Cell Carcinoma n n n Cervical carcinoma was once the most frequent form of cancer in women around the world. but the widespread use of Papanicolaou (cytologic) screening of women has dramatically lowered the incidence of invasive tumors and by contrast, the incidence of precursor cervical intraepithelial neoplasia (CIN) has increased Most invasive cervical squamous cell carcinomas arise from precursor epithelial changes referred to as CIN. However, not all cases of CIN progress to invasive cancer, and indeed many persist without change or even regress.

CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN), SQUAMOUS INTRAEPITHELIAL LESION (SIL) n However, in cytologic smears the precancerous lesions are separated into only two groups: n n n CIN I the likelihood of: n n n The low-grade lesions correspond to CIN I or flat condylomas (described later The high-grade lesions to CIN II or III. regression is 50% to 60%; persistence, 30%; progression to CIN III, 20%. Only 1% to 5% become invasive. CIN III, the likelihood of regression is only 33% and of progression 6% to 74% (in various studies).

CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN), SQUAMOUS INTRAEPITHELIAL LESION (SIL) Epidemiology and Pathogenesis. n n The peak age incidence of CIN is about 30 years, whereas that of invasive carcinoma is about 45 years. precancerous changes take many years, to evolve into overt carcinomas. Prominent risk factors for the development of CIN and invasive carcinoma are as follows: Major risk factors n HPV infection n Early age at first intercourse n Multiple sexual partners n A male partner with multiple previous sexual partners Minor risk factors n lower socioeconomic groups n cigarette smoking n exogenous or endogenous immunodeficiency including HIV infection n Rarity among virgins, and association with multiple pregnancies.

CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN), SQUAMOUS INTRAEPITHELIAL LESION (SIL) Epidemiology and Pathogenesis. n n n HPV can be detected in 85% to 90% of precancerous lesions and invasive neoplasms, and more specifically, certain high-risk types, including 16, 18, 31, 33, 35, 39, 45, 52, 56, 58, and 59. By contrast, condylomas, which are benign lesions, are associated with infection by low-risk types (i. e. , 6, 11, 42, and 44) In low-risk types , the viral DNA does not integrate into the host genome, remaining in the free episomal form.

CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN), SQUAMOUS INTRAEPITHELIAL LESION (SIL) n CIN II (moderate dysplasia) n n CIN III, (severe dysplasia & carcinoma in situ) n n The dysplasia is more severe, affecting most layers (2/3) of the epithelium. It is associated with some variation in cell and nuclear size and with normal-looking mitoses above the basal layer. The superficial layer of cells is still well differentiated, but in some cases it shows the koilocytotic changes described. affect virtually all layers of the epithelium. Cervical cytology and cervical examinations (colposcopy) remain the mainstays of cervical cancer prevention.

INVASIVE CARCINOMA OF THE CERVIX 75% to 90% are squamous cell carcinoma, n peak incidence at about 45 years, some 10 to 15 years after detection of their precursors. n

INVASIVE CARCINOMA OF THE CERVIX MORPHOLOGY GROSS: n n n n Develop in the region of the transformation zone Range from microscopic foci to grossly conspicuous tumors May be invisible or exophytic. Tumors encircling the cervix and penetrating into the underlying stroma produce a "barrel cervix, " which can be identified by direct palpation. Extension into the parametrial soft tissues, pelvic lymph nodes, bladder or rectum. Distant metastases, including para-aortic nodal involvement staged from 1 to 4 depending on clinical spread

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 fishmouth shape after one or more pregnancies.

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 salpingo-oopherectomy (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.

INVASIVE CARCINOMA OF THE CERVIX MICROSCOPIC: n The most common cervical carcinomas are: n n squamous cell carcinomas (75%), followed by adenocarcinomas and adenosquamous carcinomas (20%) small cell neuroendocrine carcinomas (less than 5%). With the exception of neuroendocrine tumors, which are uniformly aggressive in their behavior, cervical carcinomas are graded from 1 to 3 based on cellular differentiation.

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.

Diseases of Uterine Corpus Endometrial hyperplasia n Endometrial Polyp n Endometrial carcinoma n Endometritis n Endometriosis and adenomyosis n Dysfunctional uterine bleeding n Leiomyoma and leiomyosarcoma. n

Endometrial Carcinoma Pathogenesis n Two general groups of endometrial cancer can be identified. n The first and the most common develops on a background of prolonged estrogen stimulation and endometrial hyperplasia. (Type 1 endometrial carcinoma). n Both hyperplasia and cancer, are closely related. n Type 1 endometrial carcinoma is associated with a more favorable prognosis.

Endometrial Carcinoma Pathogenesis n Endometrial carcinomas that are associated with hyperplasia and the mentioned risk factors tend to be well differentiated and mimic normal endometrial glands (endometrioid) in histologic appearance. n Type 2 endometrial carcinoma is seen in a subset of patients with no risk factors that lead to hyperestrinism, no preexisting hyperplasia, and acquires the disease at an older average age. n In type 2 group, tumors are generally more poorly differentiated, and have worse outcome.

Chronic Endometritis n n It is chronic inflammation of endometrium. Causes: n Seen in the following setting: n n n In patients with chronic PID In postpartal or postabortal endometrial cavities, usually due to retained gestational tissue In patients with intrauterine contraceptive devices In patients with tuberculosis. Clinically some women with chronic endometritis complain of abnormal bleeding, pain, discharge, and infertility

Chronic Endometritis n Histologically, it is characterized by presence of chronic inflammatory cells primarily plasma cells.

Theories of Endometriosis Origin

Endometriosis Gross n Endometriosis of the ovary n The ovaries may become markedly distorted by large cystic spaces (3 to 5 cm in diameter) filled with brown blood debris to form so-called chocolate cysts

Follicular and Luteal Cyst (Functional cyst) n n n Very common. Originate on the ovarian cortex in unruptured graafian follicles (follicular cyst) or follicles that ruptured and resealed immediately (Luteal cyst). Usually small, 1 - 1. 8 cm. filled with clear fluid. Occasionally rupture causing pain & intraperitoneal bleeding. Lined by granulosa or luteal cells.

Serous Tumor n n n n These are the most common ovarian tumors. They are usually cystic filled with clear serous fluid. Together the benign, borderline, and malignant types account for about 30% of all ovarian tumors. About 75% are benign or of borderline malignancy, and 25% are malignant. Serous cystadenocarcinomas account for approximately 40% of all cancers of the ovary and are the most common malignant ovarian tumors. Benign and borderline tumors are most common between the ages of 20 and 50 years. Cystadenocarcinomas occur later in life on average.

Serous Tumor Gross

Serous Tumor Gross