Chapter 093. Gynecologic Malignancies (Part 1)

Harrisons Internal Medicine Chapter 93. Gynecologic MalignanciesOvarian CancerIncidence and Epidemiology Ovarian cancer can develop from three distinctive cell types (germ cells, stromal cells, and epithelial cells), and each of these presents with distinctive features and outcomes and requires widely different management approaches. Epithelial ovarian cancer is the most common of the three and the leading cause of death from gynecologic cancer in the United States. In 2007, 22,430 new caseswere diagnosed, and 15,280 women died from ovarian cancer. Epithelial ovarian cancer accounts for 5% of all cancer deaths in women in the United States; more women die of...
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Chapter 093. Gynecologic Malignancies (Part 1) Chapter 093. Gynecologic Malignancies (Part 1) Harrisons Internal Medicine > Chapter 93. Gynecologic Malignancies Ovarian Cancer Incidence and Epidemiology Ovarian cancer can develop from three distinctive cell types (germ cells,stromal cells, and epithelial cells), and each of these presents with distinctivefeatures and outcomes and requires widely different management approaches.Epithelial ovarian cancer is the most common of the three and the leading cause ofdeath from gynecologic cancer in the United States. In 2007, 22,430 new caseswere diagnosed, and 15,280 women died from ovarian cancer. Epithelial ovariancancer accounts for 5% of all cancer deaths in women in the United States; morewomen die of this disease than from cervical and endometrial cancer combined. The age-specific incidence of the common epithelial type of ovarian cancerincreases progressively and peaks in the eighth decade. Epithelial tumors, unlikegerm cell and stromal tumors, are uncommon before the age of 40. Epidemiologicstudies suggest higher incidences in women with a family history; in those whohave been exposed to asbestos or talc; in industrialized nations; and in womenwith disordered ovarian function, including infertility, nulliparity, and frequentmiscarriages. The use of ovulation-inducing drugs such as clomiphene has beenimplicated, but the studies have produced mixed results. Reduction in ovariancancer risk is associated with pregnancy (each pregnancy reduces the ovariancancer risk by about 10%), breast-feeding, and tubal ligation. Oral contraceptivesreduce the risk of ovarian cancer in patients with a family history of cancer and inthe general population. Many of these risk-reduction factors support the incessantovulation hypothesis for ovarian cancer etiology, which implies that an aberrantrepair process of the surface epithelium is central to ovarian cancer development.Estrogen replacement after menopause does not appear to increase the risk ofovarian cancer, although its use has declined substantially since the HRT trialsdemonstrated an increased cardiovascular risk. Familial cases account for about 10% of all ovarian cancer. Compared to alifetime risk of 1.6% in the general population, women with one affected first-degree relative have a 5% risk. In families with two or more affected first-degreerelatives, the risk may exceed 50%. Two types of autosomal dominant familialcancers have been identified: (1) breast/ovarian cancer syndrome; and (2) theLynch type II cancer family syndrome with nonpolyposis colorectal cancer,endometrial cancer, and ovarian cancer. Etiology and Genetics In women with hereditary breast/ovarian cancer, two susceptibility locihave been identified: BRCA1, located on chromosome 17q12-21, and BRCA2, on13q12-13. Both are tumor-suppressor genes that produce nuclear proteins thatinteract with RAD 51, which effects genomic integrity. Both genes are large, andnumerous mutations have been described; most are frameshift or nonsensemutations, and 86% produce truncated protein products. The implications of themany other mutations, including many missense mutations, are not known. Thecumulative risk of ovarian cancer with critical mutations of BRCA1 or -2 is 25%.Mutated genes can be inherited from either parent, so a complete family history isrequired. Men in such families have an increased risk of prostate cancer. The Lynch type II syndrome is associated with an increased risk of ovariancancer. Affected women often present at a younger age (predisposition results from germline mutations of mismatch repair genes (MSH2,MLH1, MLH6, PMS1, and PMS2). Because the risk of both endometrial andovarian cancer is high, intensified screening and prophylactic surgery are oftenconsidered. Clinical Presentation and Differential Diagnosis Seventy percent of patients with ovarian cancer are first diagnosed whenthe disease has already spread beyond the true pelvis. The occurrence ofabdominal pain, bloating, and urinary symptoms usually indicates advanceddisease. Localized ovarian cancer is generally asymptomatic. However,progressive enlargement of a localized ovarian tumor can produce urinaryfrequency or constipation. Rarely, torsion of an ovarian mass causes acuteabdominal pain or a surgical abdomen. In contrast to cervical or endometrialcancer, vaginal bleeding or discharge is rarely seen with early ovarian cancer. Thediagnosis of early disease usually occurs with palpation of an asymptomaticadnexal mass during routine pelvic examination or as an incidental finding atsurgery. However, most ovarian enlargements discovered on physicalexamination, especially in pre ...