Description

Malignancy that arises from the epithelium (90–95%), sex cord stromal, or germ cells of the ovary as well as tumors metastatic to the ovary. Histologic types include the following:

• Epithelial
  • High grade serous (most common, 70–80%)
  • Low grade serous
  • Mucinous
  • Endometrioid
  • Clear cell
  • Malignant Brenner tumor (transitional cell epithelium)
  • Carcinosarcoma (malignant mixed müllerian tumor)
• Sex cord stromal
  • Granulosa cell tumor
  • Sertoli-Leydig cell tumors
  • Lipid (steroid) cell tumor
  • Fibrosarcoma
• Germ cell
  • Teratoma (immature)
  • Dysgerminoma
  • Embryonal carcinoma
  • Endodermal sinus tumor (yolk sac tumor)
  • Choriocarcinoma
• Metastatic disease from the following:
  • GI tract (Krukenberg tumor)
  • Breast
  • Endometrium
  • Lymphoma
• System(s) affected: GI, genitourinary, endocrine

Epidemiology

• 22,440 new cases per year in the United States; 14,070 deaths per year
• Leading cause of gynecologic cancer death in women
• Majority of ovarian cancer is diagnosed at an advanced stage.
• Average age of diagnosis
  • Epithelial: 63 years
  • Sex cord stromal: 50 years
  • Germ cell: 10 to 30 years

Prevalence
Lifetime risk for general population: 1 in 78 American women develop ovarian cancer.

Etiology and Pathophysiology

• Malignant transformation of the ovarian epithelium may result from repeated trauma and inflammation during ovulation.
• Ovarian, fallopian tube, and primary peritoneal carcinomas have identical histologic and morphologic features. A higher percentage of ovarian cancers are now known to originate in the fallopian tube and other components of the secondary müllerian system, including primary peritoneal cancers.

• Hereditary breast/ovarian cancer syndrome: early-onset breast or ovarian cancer, autosomal dominant transmission with variable penetrance, usually associated with BRCA-1 or BRCA-2 (tumor suppressor gene) mutation
• Lynch syndrome: autosomal dominant inheritance; increased risk for colorectal, endometrial, stomach, small bowel, breast, pancreas, and ovarian cancers; defect in DNA mismatch repair genes

Risk Factors

• 90% of ovarian cancer is sporadic and not inherited, but family history is the most significant risk factor. Multiple relatives with breast or ovarian cancer increase risk: Refer these patients for genetic counseling. Individuals in families with familial cancer syndromes have 20–60% risk of developing ovarian cancer.
• Risk factors: older age, white race, infertility, nulligravidity, early menarche or late menopause, endometriosis, postmenopausal estrogen replacement therapy, residence in an industrialized Western country (i.e., North America, Northern Europe)
• Association between fertility medications and risk of ovarian cancer is controversial, but women with infertility who have a successful live birth do not have an increased risk of ovarian cancer.
• Obesity as a risk factor for ovarian cancer remains inconclusive; some studies do suggest an increased risk with BMI >30 and increased mortality related to BMI >35.

General Prevention

• Use of oral contraceptives: 5 years of use decreases risk by 20%; 15 years of use decreases risk by 50% (1)[A]
• Multiparity
• Breastfeeding
• Tubal ligation or hysterectomy
• Risk-reducing salpingo-oophorectomy
• Protective effect of aspirin and NSAIDs in ovarian cancer is controversial.
• Recommendations for high-risk (family history of a hereditary ovarian cancer syndrome) population
  • Women should undergo pelvic examinations, CA-125 level measurement, and transvaginal ultrasound (US) every 6 to 12 months beginning at age 30 or 10 years prior to the earliest age of diagnosis of ovarian cancer in the family.
  • Women with family histories of ovarian cancer or premenopausal breast cancer should be referred for genetic counseling.
  • Prophylactic oophorectomy is advised for mutation carriers after childbearing is completed or by age 35 years.
    • Risk of primary peritoneal carcinoma remains 1–2% after prophylactic oophorectomy.
• Screening: No effective screening exists for ovarian cancer in the general population.
  • Routine use of CA-125 and transvaginal US for screening in women of average risk is not recommended. Annual pelvic examinations may be performed, particularly in postmenopausal women. An adnexal mass in a premenarchal female or a palpable adnexa in a postmenopausal female warrants further evaluation.

Commonly Associated Conditions

• Ascites
• Pleural effusion
• Carcinomatosis
• Bowel obstruction
• Breast cancer
• Endometrial cancer