Ovarian Cancer

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Basics

There are >22,000 new cases of ovarian cancer annually in the United States, and approximately 14,000 women will die of their disease; as such this the most lethal of gynecologic cancers, which accounts for 2.3% of all cancer deaths nationally.

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

Incidence
  • 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.

Genetics
  • 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

-- To view the remaining sections of this topic, please or --

Basics

There are >22,000 new cases of ovarian cancer annually in the United States, and approximately 14,000 women will die of their disease; as such this the most lethal of gynecologic cancers, which accounts for 2.3% of all cancer deaths nationally.

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

Incidence
  • 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.

Genetics
  • 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

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