Description

• Endometrial cancer: malignancy of the endometrial lining of the uterus
  • Two types
    • Type I: estrogen-dependent, grade 1 or grade 2, better prognosis, endometrioid histology
    • Type II: estrogen-independent, higher grade, more aggressive, includes grade 3 endometrioid and nonendometrioid: serous, clear cell, mucinous, poor prognosis (1)[A]
• Cell types: adenocarcinoma, adenosquamous (malignant squamous elements), clear cell, and papillary serous
• Sarcomas: malignancy of the uterine mesenchyme and mixed tumors
  • Mixed müllerian sarcoma (carcinosarcoma): Heterologous sarcoma elements are not native to the müllerian system (e.g., cartilage or bone); homologous sarcoma elements are native to the müllerian system (40–50% prevalence of all sarcomas).
  • Leiomyosarcoma develops in the myometrium, characterized by cellular atypic mitoses and coagulative necrosis (30% prevalence of all sarcomas).
  • Endometrial stromal sarcoma develops from the stromal component of the endometrium (15% prevalence of all sarcomas).
  • Poorer prognosis (2)[C]
• Predominant age
  • Endometrial cancer: Most patients are postmenopausal:
    • Average age of diagnosis: 63 years old
  • Sarcomas: occur in both pre- and postmenopausal:
    • Average age of diagnosis: 40 to 69 years old (2)[C]
• 70% of endometrial cancer is stage I at the time of diagnosis.
• System(s) affected: reproductive
• Synonym(s): uterine cancer; endometrial cancer; corpus cancer

Pregnancy Considerations
This malignancy is not associated with pregnancy.

Epidemiology

Incidence

• Endometrial cancer is the most common gynecologic malignancy, fourth most common cancer in women, and eighth leading cause of cancer-related death in women worldwide.
• In the United States, it is estimated that endometrial cancer will account for 61,380 new cases and 10,920 deaths in 2017 according to SEER database.
• Incidence higher in Caucasian than African American, but African Americans have stage matched higher mortality (3).

Prevalence
Approximately 500,000 women in the United States

Etiology and Pathophysiology

Continuous estrogen stimulation unopposed by progesterone

• Endometrial: unopposed estrogen
  • Estrogen replacement therapy without concomitant progesterone increases the risk. Addition of progesterone decreases risk to that of general population.
• Sarcomas: etiology unknown

Genetics

• Endometrial: Lynch syndrome (hereditary nonpolyposis colorectal cancer); lifetime risk up to 30% (3); Cowden syndrome
• Sarcoma: African American, higher incidence of leiomyosarcoma, childhood retinoblastoma survivors

Risk Factors

• Early menarche/late menopause
• Nulliparity
• Personal or family history of colon or reproductive system cancer
• Obesity
• Diabetes mellitus
• Hypertension
• Polycystic ovarian syndrome
• Increasing age
• Estrogen-secreting tumor
• Endometrial hyperplasia
• Unopposed estrogens
• Tamoxifen use

General Prevention

• In young women who are obese or anovulatory, the risk of endometrial cancer can be reduced by taking oral contraceptive pills, permanently losing weight, or taking cyclic progesterone to prevent unopposed estrogen’s effects on the uterus.
• Estrogen replacement therapy should always include progesterone unless the woman has had a hysterectomy.
• Cigarette smoking has been associated with a lower risk of type I endometrial cancer; however, it is not recommended secondary to its many health risks and increase risk of type II endometrial cancer.

Commonly Associated Conditions

• Endometrial hyperplasia: 1–25% will progress to endometrial adenocarcinoma:
  • Simple without atypia
  • Complex without atypia
  • Simple with atypia
  • Complex with atypia
    • 43% with complex hyperplasia with atypia have concurrent endometrial cancer.
• Endometrial cancer patients should be screened regularly for breast and colon cancer per routine screening guidelines.
• Patients who have breast or colon cancer are at increased risk for endometrial cancer.
• Granulosa cell tumors of the ovary produce estrogen; these patients will have an increased risk of endometrial cancer.