Ovarian cancer is the most lethal malignancy of gynecologic origin in the United States and other countries that have organized and effective cervical cancer screening programs. In 2010, 21,880 cases of ovarian cancer with 13,850 deaths are expected in the United States. The ovary is a complex and dynamic organ and, between the ages of approximately 11 and 50 years, is responsible for follicle maturation associated with egg maturation, ovulation, and cyclical sex steroid hormone production. These complex and linked biologic functions are coordinated through a variety of cells within the ovary, each of which possesses neoplastic potential. By far the most common and most lethal of the ovarian neoplasms arise from the ovarian epithelium found both on the surface of the ovary and in subsurface locations, known as cortical inclusion cysts, believed to be entrapped epithelium from the healing associated with prior follicle rupture during ovulation. The ovarian epithelium in good health appears as a simple epithelium, but with neoplastic transformation, it undergoes metaplastic changes into what is termed müllerian epithelium. The müllerian epithelium has a variety of subtypes each of which provide a specific phenotype of the tumor and in some cases different clinical presentations. Epithelial tumors are the most common ovarian neoplasm; they may be benign (50%), malignant (33%), or of borderline malignancy (16%). Age influences risk of malignancy; tumors in younger women are more likely benign. The most common of the ovarian epithelial malignancies are serous tumors (50%); tumors of mucinous (25%), endometrioid (15%), clear cell (5%), and transitional cell histology or Brenner tumor (1%) represent smaller proportions of epithelial ovarian tumors. In contrast, stromal tumors arise from the steroid hormone-producing cells and likewise have different phenotypes and clinical presentations largely dependent on the type and quantity of hormone production. Tumors arising in the germ cell are most similar in biology and behavior to testicular tumors in males (Chap. 96).
Tumors may also metastasize to the ovary from breast, colon, gastric, and pancreatic primaries. Bilateral ovarian masses from metastatic mucin-secreting gastrointestinal cancers are termed Krukenberg tumors.
Ovarian Cancer of Epithelial Origin
A female has approximately a 1 in 72 lifetime risk (1.6%) of developing ovarian cancer, with the majority of affected women developing epithelial tumors. Epithelial tumors of the ovary have a peak incidence in women in their sixties, although age at presentation can range across the extremes of adult life, with cases being reported in women in their twenties to nineties. Known risk factors that increase the chance of subsequent ovarian cancer include epidemiologic, environmental, and genetic factors such as nulliparity, use of talc agents applied to the perineum, obesity, and probably hormone replacement therapy. Protective factors include the use of oral contraceptives, multiparity, and breast-feeding. These protective factors are thought to work through suppression of ovulation and perhaps reduction of ovarian inflammation and damage associated with the repair of the ovarian cortex associated with ovulation, and perhaps suppression of gonadotropins. Other protective factors, such as fallopian tube ligation are thought to protect the ovarian epithelium (or perhaps the distal fallopian tube fimbriae) from carcinogens that migrate from the vagina to the tubes and ovarian surface epithelium (see below).
A variety of genetic syndromes substantially increases a woman's risk of developing ovarian cancer. Approximately 10% of women with ovarian cancer have a somatic mutation in one of two DNA repair genes: BRCA1 (chromosome 17q12-21) or BRCA2 (chromosome 13q12-13). Individuals inheriting a single copy of a mutant allele have a very high incidence of breast and ovarian cancer. Most of these women have a family history that is notable for multiple cases of breast and/or ovarian cancer, although inheritance through male members of the family can camouflage this genotype through several generations. The most common malignancy in these women is breast carcinoma, although women harboring germ-line BRCA1 mutations have a marked increased risk of developing ovarian malignancies in their forties and fifties with a 30–50% lifetime risk of developing ovarian cancer. Women harboring a mutation in BRCA2 have a lower penetrance of ovarian cancer with perhaps a 20–40% chance of developing this malignancy, with onset typically in their fifties or sixties. Women with a BRCA2 mutation also are at slightly increased risk of pancreatic cancer. Screening studies in this select population suggest that current screening techniques, including serial evaluation of the CA-125 tumor marker and ultrasound, are insufficient at detecting early-stage and curable disease, so women with these germ-line mutations are advised to undergo prophylactic removal of ovaries and fallopian tubes typically after completing childbearing and ideally before ages 35–40. Early prophylactic oophorectomy also protects these women from subsequent breast cancer with a reduction of breast cancer risk of approximately 50%.
Ovarian cancer is also one form of cancer (along with colorectal and endometrial cancer) that may develop in women with Lynch syndrome, type II, caused by mutations in DNA mismatch repair genes (MSH2, MLH1, MLH6, PMS1, PMS2). Ovarian cancer may appear in women younger than 50 years of age in this syndrome.
Neoplasms of the ovary tend to be painless unless they undergo torsion. Symptoms are therefore typically related to compression of local organs or due to symptoms from metastatic disease. Women with tumors localized to the ovary do have an increased incidence of symptoms including pelvic discomfort, bloating, and perhaps changes in a woman's typical urinary or bowel pattern. Unfortunately, these symptoms are frequently dismissed by either the woman or her health care team. It is believed that high-grade tumors metastasize early in the neoplastic process. Unlike other epithelial malignancies, these tumors tend to exfoliate throughout the peritoneal cavity and thus present with symptoms associated with disseminated intraperitoneal tumors. The most common symptoms at presentation include a multimonth period of progressive complaints ...