Chapter 093. Gynecologic Malignancies (Part 1) ppt

Gynecologic Malignancies Ovarian Cancer Incidence and Epidemiology Ovarian cancer can develop from three distinctive cell types germ cells, stromal cells, and epithelial cells, and ea

Chapter 093 Gynecologic

Malignancies

(Part 1)

Harrison's 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 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 cases

were 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 this disease than from cervical and endometrial cancer combined

The age-specific incidence of the common epithelial type of ovarian cancer increases progressively and peaks in the eighth decade Epithelial tumors, unlike germ cell and stromal tumors, are uncommon before the age of 40 Epidemiologic studies suggest higher incidences in women with a family history; in those who have been exposed to asbestos or talc; in industrialized nations; and in women with disordered ovarian function, including infertility, nulliparity, and frequent miscarriages The use of ovulation-inducing drugs such as clomiphene has been implicated, but the studies have produced mixed results Reduction in ovarian cancer risk is associated with pregnancy (each pregnancy reduces the ovarian cancer risk by about 10%), breast-feeding, and tubal ligation Oral contraceptives reduce the risk of ovarian cancer in patients with a family history of cancer and in the general population Many of these risk-reduction factors support the "incessant ovulation" hypothesis for ovarian cancer etiology, which implies that an aberrant repair process of the surface epithelium is central to ovarian cancer development Estrogen replacement after menopause does not appear to increase the risk of ovarian cancer, although its use has declined substantially since the HRT trials demonstrated an increased cardiovascular risk

Familial cases account for about 10% of all ovarian cancer Compared to a lifetime 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-first-degree relatives, the risk may exceed 50% Two types of autosomal dominant familial cancers have been identified: (1) breast/ovarian cancer syndrome; and (2) the Lynch 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 loci

have been identified: BRCA1, located on chromosome 17q12-21, and BRCA2, on

13q12-13 Both are tumor-suppressor genes that produce nuclear proteins that interact with RAD 51, which effects genomic integrity Both genes are large, and numerous mutations have been described; most are frameshift or nonsense mutations, and 86% produce truncated protein products The implications of the many other mutations, including many missense mutations, are not known The

cumulative 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 is required Men in such families have an increased risk of prostate cancer

The Lynch type II syndrome is associated with an increased risk of ovarian cancer Affected women often present at a younger age (<50 years) The

predisposition results from germline mutations of mismatch repair genes (MSH2,

MLH1, MLH6, PMS1, and PMS2) Because the risk of both endometrial and

ovarian cancer is high, intensified screening and prophylactic surgery are often considered

Clinical Presentation and Differential Diagnosis

Seventy percent of patients with ovarian cancer are first diagnosed when the disease has already spread beyond the true pelvis The occurrence of abdominal pain, bloating, and urinary symptoms usually indicates advanced disease Localized ovarian cancer is generally asymptomatic However, progressive enlargement of a localized ovarian tumor can produce urinary frequency or constipation Rarely, torsion of an ovarian mass causes acute abdominal pain or a surgical abdomen In contrast to cervical or endometrial cancer, vaginal bleeding or discharge is rarely seen with early ovarian cancer The diagnosis of early disease usually occurs with palpation of an asymptomatic adnexal mass during routine pelvic examination or as an incidental finding at surgery However, most ovarian enlargements discovered on physical examination, especially in premenopausal women, are benign functional cysts that characteristically resolve over one to three menstrual cycles Adnexal masses in premenarchal or postmenopausal women are more likely to be pathologic A solid, irregular, fixed pelvic mass is usually ovarian cancer Ultrasound studies usually show complex cysts with solid elements Other causes of adnexal masses include

pedunculated uterine fibroids, endometriosis, benign ovarian neoplasms, and inflammatory lesions of the bowel

Evaluation of patients with suspected ovarian cancer should include measurement of CA-125 Between 80 and 85% of patients with epithelial ovarian cancer have levels of CA-125 ≥35 U/mL Other malignant tumors can also elevate CA-125 levels, including cancers of the endometrium, cervix, fallopian tubes, pancreas, breast, lung, and colon Certain nonmalignant conditions that can produce moderate elevations of CA-125 levels include pregnancy, endometriosis, pelvic inflammatory disease, and uterine fibroids About 1% of normal females have serum CA-125 levels >35 U/mL However, in postmenopausal women with

an asymptomatic pelvic mass and CA-125 levels ≥65 U/mL, the test has a sensitivity of 97% and a specificity of 78%