Endometrial Cancer

• Endometrial carcinoma is the fourth most common cancer in American women, exceeded only by cancer of the breast, bowel, and lung
• Over 43,000 women are diagnosed with endometrial cancer each year in the United States alone, accounting for 6% of all cancers in women
• Despite being the most common GYN cancer, endometrial cancer is only the third most common cause of gynecologic cancer deaths (behind ovarian and cervical cancer)
• It accounts for 7,900 deaths each year in the United States
• Factors that lead to increased risk of endometrial hyperplasia and endometrial cancer

  • Obesity
  • Chronic anovulation
  • Nulliparity
  • Late menopause
  • Unopposed estrogen use (without progesterone)
  • Hypertension
  • Diabetes mellitus
• Type I endometrial cancer

  Most common type (80%), occurs in women with a history of chronic estrogen exposure unopposed by progestin, usually starts as atypical endometrial hyperplasia and progresses to carcinomas, tend to be well differentiated with lower grade nuclei and usually have a more favorable prognosis
• Type II endometrial cancer

  Less common type (20%), believed to be an estrogen-independent neoplasm not related to unopposed estrogen stimulation or endometrial hyperplasia, often occur within a background of atrophic endometrium or polyps, often have high-grade nuclear atypia with serous or clear cell histology, many are associated with a mutation in the p53 tumor suppression gene
• Depth of myometrial invasion is an important component in the staging and prognosis of endometrial cancer, the prognosis is dramatically worsened when the cancer has invaded more than one-half of the thickness of the myometrium
• Primary routes of spread for endometrial carcinoma

  • Direct extension of the tumor downward to the cervix or outward through the myometrium and serosa
  • Spread through the lymphatic system to the pelvic and para-aortic lymph nodes
  • Exfoliated cells shed transtubally through the fallopian tubes to the ovaries, parietal peritoneum, and omentum
  • Hematogenous spread to the liver, lungs, and/or bone
• Types of endometrial cancer

  • Endometrioid adenocarcinoma (75-80%)
  • Mucinous carcinomas (5%)
  • Clear cell carcinomas (5%)
  • Papillary serous carcinomas (4%)
  • Squamous carcinomas (1%)
• Histologic grade


  • The most important prognostic factor for endometrial carcinoma, poorly differentiated tumors have a higher grade and a higher percentage of solid (nonglandular) growth, high-grade tumors have a much poorer prognosis due to the likelihood of spread outside of the uterus
• Major independent prognostic factors for endometrial cancer

  • Age
  • Depth of myometrial invasion
  • Histologic grade
  • Histologic type
  • Surgical stage
  • Peritoneal cytology
  • Tumor size
  • Lymphovascular invasion
  • Pelvic lymph node metastasis
• Endometrial cancer occurs in both premenopausal (25%) and postmenopausal (75%) women, 5-10% of those with premenopausal diagnoses are less than 40 years of age, the average age of diagnosis is 61 and the largest affected group is between age 50 and 59
• Most tumors are caught early when they are of low grade and low stage, therefore the overall prognosis for the disease is good and overall mortality rates are declining
• Risk factors for type I endometrial cancer


  • History of unopposed estrogen exposure
  • Obesity
  • Nulliparity
  • Late menopause
  • Chronic anovulation
  • Tamoxifen use
  • Diabetes mellitus
  • Hypertension
  • Cancer of the breast, ovary, or colon
  • Family history of endometrial cancer
• Excess exogenous estrogen exposure can result from unopposed use of estrogen replacement therapy (ERT) in the absence of progesterone, and tamoxifen can also act as a source of exogenous estrogen
• Endometrial cancer can also be caused by prolonged exposure to excess endogenous estrogen without concomitant progesterone exposure, as seen in obese women and those with chronic anovulation/PCOS
• Diabetes (type II > type I) and hypertension are also independent risk factors for endometrial cancer, potentially due to hyperinsulinemia, insulin resistance, and insulin-like growth factors
• Women with a known family history of Lynch II syndrome (hereditary nonpolyposis colorectal cancer) have an increased risk of endometrial cancer
• Endometrial hyperplasia is another risk factor for endometrial cancer, with the degree of risk depending on the type of hyperplasia
• There are no effective screening mechanisms for endometrial carcinoma, neither annual Pap smears nor endometrial biopsies have been shown to offer cost-effective screening in asymptomatic patients
• Protective factors that decrease lifetime estrogen exposure

  • Combination oral contraceptive pills
  • Progestin-containing contraceptives
  • Combination estrogen and progesterone hormone replacement therapy
• Other protective factors include high parity, pregnancy, physical activity, and smoking
• There are no identifiable risk factors for women who may be at risk for type II endometrial cancer
• Clinical manifestations of endometrial cancer

  90% of women have either postmenopausal bleeding or some form of abnormal vaginal bleeding, 10% may present with a nonbloody vaginal discharge, pelvic pain, pelvic mass, and weight loss are seen in women with more advanced disease
• Physical examination may reveal obesity, acanthosis nigricans, hypertension, or stigmata of diabetes, and signs of metastatic disease
• Differential diagnosis for postmenopausal bleeding

  • Endometrial atrophy
  • Exogenous estrogens/HRT
  • Endometrial cancer
  • Endometrial or cervical polyps
  • Endometrial hyperplasia
  • Miscellaneous
• Endometrial cancer is responsible for up to 20% of postmenopausal hyperplasia and/or bleeding, and the older the patient and the higher the number of years since menopause, the higher the proportion of endometrial cancer as the cause
• Uterine metastasis and/or coexistent ovarian carcinoma
• Differential diagnosis


  Most common presenting symptom of endometrial cancer is abnormal uterine bleeding
• Differential diagnosis for premenopausal bleeding

  • Uterine fibroids
  • Endometrial polyps
  • Adenomyosis
  • Endometrial hyperplasia
  • Ovarian cysts
  • Thyroid dysfunction
• Differential diagnosis for postmenopausal bleeding

  • Endometrial atrophy
  • Exogenous estrogens/HRT
  • Endometrial cancer
  • Endometrial or cervical polyps
  • Endometrial hyperplasia
  • Miscellaneous
• Endometrial cancer is responsible for up to 20% of postmenopausal hyperplasia and/or bleeding
• The older the patient and the higher the number of years since menopause, the higher the probability of malignancy
• The amount of bleeding does not correlate with risk of malignancy
• Endometrial biopsy (EMB)


  Accuracy of 90% to 98% without the need for anesthesia and operative time
• Transvaginal ultrasound


  Can be helpful in triaging suspicious lesions from the most common source of postmenopausal bleeding-atrophy
• Endometrial thickness of 4 mm or less


  Indicative of low risk for malignancy
• Premenopausal women are subject to a high degree of variability in the thickness of the endometrial lining
• Persistent abnormal bleeding, even in the setting of normal imaging, warrants a tissue diagnosis for women ≥ 45 and those at risk for malignancy regardless of age