Ovarian cancerRisk of Ovarian CancerGroups at High Risk for OCETIOLOGY OF OVARIAN CANCER ETIOLOGY OF OVARIAN CANCERETIOLOGY OF OVARIAN CANCERETIOLOGY OF OVARIAN CANCERMajor Histopathologic Categories of Ovarian CancerEpithelial NeoplasmsSerous NeoplasmsSerous NeoplasmsMucinous NeoplasmsPseudomyxoma PeritoneiPseudomyxoma PeritoneiPseudomyxoma PeritoneiEndometrioid NeoplasmPrimordial Germ Cell MigrationGerm Cell TumorsTeratoma With TeethTeratomaBenign TeratomaGerm Cell NeoplasmsImmature TeratomasDysgerminomaSEX CORD-STROMAL TUMORS OF THE OVARYNEOPLASMS METASTATIC TO THE OVARYOvarian CancerUS – Pelvic MassUS – Multiloculated MassC-T Scan – Omental CakeC-T Scan – Liver MetastasesC-T Scan – Metastatic Ovarian CancerC-T Showing Residual CancerMR – Large Cystic MassMR – Pelvic MassOvarian CancerPlain RadiographImages removed due to copyright reasons.Here is another common incidental finding: a benign paratubal cyst. Sometimes such simple cysts are found adjacent to ovary and are called parovarian cysts. They are filled with clear serous fluid and lined by flattened cuboidal epithelium.Harvard-MIT Division of Health Sciences and TechnologyHST.071: Human Reproductive BiologyCourse Director: Professor Henry KlapholzImages removed due to copyright reasons.This is an adult ovary with two corpora lutea. The larger one at the top is a hemorrhagic corpus luteum of menstruation, and the smaller one at the bottom is involuting from a previous menstrual period. If implantation of a fertilized ovum occurs, then the corpus luteum will persist because of HCG from the placenta. Of 400,000 ovarian follicles present at birth, only about 400 will mature to the point of ovulation during childbearing years.Images removed due to copyright reasons.A normal adult ovary has been sectioned here to reveal a hemorrhagic corpus luteum. Note the dark red-black hemorrhagic region surrounded by a thin rim of yellow corpus luteum.Images removed due to copyright reasons.Here is the microscopic appearance of a hemorrhagic corpus luteum lined by luteinized granulosacells next to the hemorrhagic area at the right.Images removed due to copyright reasons.Here is a benign cyst in an ovary. This is probably a follicular cyst. Occasionally such cysts may reach several centimeters in size and, if they rupture, can cause abdominal pain.Images removed due to copyright reasons.This is a benign theca lutein cyst in an ovary. Note the luteinized cells forming the inner cyst lining at the left, with adjacent surrounding theca cells. These cysts are rarely more than a few centimeters in diameter.Ovarian cancer• Fifth most common cancer in women • Fifth most frequent cause of cancer death• In the year 2000– 23,100 new ovarian cancer cases– 14,000 patients died of it• In the year 1993– About 23,000 cases were diagnosed– 14,000 women died • Approximately 1 in 70 newborn girls will develop ovarian cancer during her lifetime•Disease of– Postmenopausal woman– Prepubescent girl– Documented to occur in females of all ages.Risk of Ovarian Cancer• Advancing age is the most significant risk factor • The risk increases from 15.7 to 54 per 100,000 as one ages from 40 to 79 years• Mean age at diagnosis is 59.4• In the United States approximately one woman in 70 develops ovarian cancer• Other than age, the strongest risk factor for the development ofovarian cancer is a familial history of the disease.• 5% to 10% of all epithelial ovarian cancers result from a hereditary predisposition in which germ line inheritance of a mutant gene confers autosomal dominant susceptibility with high penetrance• Average age of onset for ovarian cancers thought to be familial in origin is up to 10 years lower than that of general populationGroups at High Risk for OC• Women with a strong family history of breast and/or ovarian cancer (two or more first degree relatives and/or a relative with cancer before menopause) – May carry a mutation of the BRCA1 and BRCA2 genes– Have a risk of ovarian malignancy of up to 50%.• Women with a strong family history of colon cancer (at least three affected family members in at least two successive generations, with one case below age 50 years)– At increased risk for endometrial and ovarian malignancy because they carry a mismatch repair gene mutation.– Have a risk of up to 10% for ovarian cancer– 50% for endometrial cancerETIOLOGY OF OVARIAN CANCER• Unknown• Predisposing risk factors– Repeated ovulation is causally related– Ovulation is accompanied by disruption of the germinal epithelium – Activation of cellular repair mechanisms– May provide ample opportunity• Somatic gene deletions•Mutations to occur• Contribute to tumor initiation and progression– Protective• Chronic anovulation• Multiparity• History of breastfeeding• Pregnancy - risk reduction of 13-19% per pregnancy• Oral contraceptives - 50% for users of 5 years and longer–Increased• Infertility treatment• Polycystic ovarian syndrome (PCOS) - 2.5-fold increased risk• Unopposed estrogen therapy–No change in risk• Hormone replacement therapyETIOLOGY OF OVARIAN CANCER• Dietary factors– High in saturated animal fats seem to confer an increased risk - unknown mechanisms– Japanese women who move to the United States - increased ovarian cancer risk– Alcohol and milk product consumption ??• Exposure to talc– Talc granulomas in the ovaries– Never been previously operated on– Continuity of the introitus and peritoneal cavity– Talc and asbestos - carcinogenic substancesETIOLOGY OF OVARIAN CANCER• >90% of ovarian cancer develops sporadically• 10% of epithelial ovarian cancers based on genetic predisposition• Chromosomal abnormalities: Turner's syndrome (45,XO)– Increased risk of dysgerminoma and gonadoblastoma• Two first-degree relatives with ovarian cancer have a 50% likelihood of developing ovarian cancer until age 70.• Hereditary ovarian cancer – Breast and ovarian cancer syndrome (BOC)– Less common Lynch II syndrome (hereditary nonpolyposiscolorectal cancer syndrome (HNPCC syndrome)• Breast and Ovarian Cancer Gene (BRCA) – Germ line mutations in the BRCA1• Located on chromosome 17– Less commonly with BRCA2• Chromosome 13• Frequency of BRCA1 mutation carriers in the United States– Approximately 1 in 800 women– Greater mutation frequencies• Ashkenazi Jews• Icelandic women• Autosomal dominant fashion• Lifetime risk of