9. The Female Genital System

Question 1

Nonneoplastic Epithelial Disorders

Answer 1

• Lichen sclerosus is characterized by atrophic epithelium, subepithelial dermal fibrosis, and bandlike chronic inflammation.
• Lichen sclerosus carries a slightly increased risk for development of squamous cell carcinoma.
• Lichen simplex chronicus is characterized by thickened epithelium (hyperplasia), usually with a dermal inflammatory infiltrate.
• The lesions of lichen sclerosus and lichen simplex chronicus must be biopsied to distinguish them definitively from other causes of leukoplakia, such as squamous cell carcinoma of the vulva.

Question 2

Tumors of the Vulva

Answer 2

• HPV-related vulvar squamous cell carcinomas usually are poorly differentiated lesions and sometimes are multifocal. They often evolve from vulvar intraepithelial neoplasia.
• Non-HPV-related vulvar squamous cell carcinomas occur in older women and usually are well differentiated and unifocal. They are often preceded by “differentiated” vulvar intraepithelial neoplasia associated with lichen sclerosus.
• Vulvar Paget disease is characterized by a red, scaly plaque caused by proliferation of epithelial cells within he epidermis; usually, there is no underlying carcinoma, unlike Paget disease of the nipple.

Question 3

Cervical Neoplasia

Answer 3

• Risk factors for cervical carcinoma are related to HPV exposure, such as early age at first intercourse, multiple sexual partners, and other factors including cigarette smoking and immunodeficiency.
• Nearly all cervical carcinomas are caused by HPV infections, particularly high-risk HPV types 16, 18, 31, and 33; the HPV vaccine is effective in preventing infection resulting from the HPV types most commonly associated with carcinoma.
• HPV expresses E6 and E7 proteins that inactivate the p53 and RB tumor suppressors, respectively, resulting in increased cell proliferation and suppression of DNA damage-induced apoptosis.
• In cervical cancer, high-risk HPV is integrated in the host genome, an event that increases the expression of E6 and E7 and contributes to progression to cancer.
• The Pap smear is a highly effective screening tool for the detection of SIL and carcinoma. HPV testing is currently being used in conjunction with the Pap smear.

Question 4

Nonneoplastic Disorders of the Endometrium

Answer 4

• Adenomyosis refers to growth of endometrium into the myometrium often with uterine enlargement.
• Endometriosis refers to endomterial glands and stroma located outside the uterus and most often involves the pelvic or abdominal peritoneum. Rarely, distant sites such as the lymph nodes and the lungs are also involved.
• The ectopic endometrium in endometriosis undergoes cyclic bleeding, and the condition is a common cause of dysmenorrhea and pelvic pain.

Question 5

Endometrial Hyperplasia and Endometrial Carcinoma

Answer 5

• ndometrial hyperplasia results from unopposed endogenous or exogenous estrogen.
• Risk factors for developing endometrial hyperplasia include anovulatory cycles, polycystic ovary syndrome, estrogen-producing ovarian tumor, obesity, and estrogen therapy without counterbalancing progestin.
• Hyperplasia is classified based on cytologic atypia, which termines the risk of developing endometrioid carcinoma.
• On the basis of clinical and molecular data, two major types of endometrial carcinoma are recognized:
  
  • Endometrioid carcinoma is associated with estrogen excess and endometrial hyperplasia. Early molecular changes include inactivation of DNA mismatch repair genes and the PTEN gene.
  • Serous carcinoma of the endometrium arises in older women and usually is associated with endometrial atrophy and a distinct precursor lesion, serous intraepithelial carcinoma. Mutations in the TP53 gene are an early event, usually being present in serous endometrial intraepithelial carcinoma as well as invasive serous carcinoma.
• Stage is the major determinant of survival in both types. Serous tumors tend to manifest more frequently with extrauterine extension and therefore have a worse prognosis than endometrioid carcinomas.

Question 6

Ovarian Tumors

Answer 6

• Tumors may arise from epithelium, sex cord-stromal cells, or germ cells.
• Epithelial tumors are the most common malignant ovarian tumor and are more common in women older than 40 years of age.
• The major types of epithelial tumors are serous, mucinous, and endometrioid. Each has a benign, malignant, and borderline counterpart.
• Serous carcinoma is the most common and many arise in the distal fallopian tube.
• Sex cord-stromal tumors may display differentiation toward granulosa, Sertoli, Leydig, or ovarian stromal cell type. Depending on differentiation, they may produce estrogens or androgens.
• Germ cell tumors (mostly cystic teratomas) are the most common ovarian tumor in young women; the vast majority are benign.
• Germ cell tumors may differentiate toward oogonia (dysgerminoma), primitive embryonal tissue (embryonal), yolk sac (endodermal sinus tumor), placental tissue (choriocarcinoma), or multiple tissue types (teratoma).