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Endometrial Cancer for USMLE Step 2

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Endometrial Cancer for the USMLE Step 2 Exam
Definition and Epidemiology
  • Definition
    • Endometrial cancer is a malignancy of the endometrial lining of the uterus, the most common gynecologic cancer in the United States.
    • Two main types:
    • Type I (Endometrioid): Estrogen-dependent, often linked with endometrial hyperplasia, and accounts for 80-90% of cases.
    • Type II (Non-endometrioid): Estrogen-independent, including serous and clear cell carcinomas, and is more aggressive.
  • Epidemiology
    • Primarily affects postmenopausal women, with peak incidence in ages 55-65.
    • Incidence is increasing due to rising obesity rates, as obesity elevates estrogen levels.
Risk Factors
  • Hormonal Factors:
    • Unopposed Estrogen: Increased estrogen without progesterone counteraction promotes endometrial proliferation, raising cancer risk.
    • Obesity: Enhances peripheral conversion of androgens to estrogens.
    • Polycystic Ovarian Syndrome (PCOS): Anovulation causes continuous estrogen exposure without progesterone.
  • Genetic Predisposition:
    • Lynch Syndrome (HNPCC): Increases endometrial cancer risk and affects younger women.
    • Cowden Syndrome: PTEN mutation associated with a heightened risk for endometrial and other cancers.
  • Other Factors:
    • Early Menarche and Late Menopause: Prolonged estrogen exposure.
    • Nulliparity: Absence of pregnancy reduces progesterone exposure.
    • Tamoxifen Use: Acts as a partial estrogen agonist on endometrial tissue.
Pathophysiology
  • Type I Pathway:
    • Estrogen exposure leads to endometrial hyperplasia, which can progress to atypical hyperplasia and, eventually, carcinoma.
    • Commonly involves mutations in PTEN and KRAS genes.
Endometrioid Cancer Pathophysiology
  • Type II Pathway:
    • Estrogen-independent pathway often arising from atrophic endometrium, commonly involves p53 mutations, and is more aggressive.
Clinical Manifestations
  • Abnormal Uterine Bleeding (AUB):
    • Most common symptom, especially postmenopausal bleeding.
    • In premenopausal women, can present as irregular, heavy, or intermenstrual bleeding.
  • Pelvic Pain and Mass:
    • Typically seen in advanced disease stages due to tumor expansion.
  • Asymptomatic:
    • Some early cases may be detected incidentally on imaging or endometrial biopsy.
Diagnosis
  • Transvaginal Ultrasound (TVUS):
    • First-line imaging for evaluating endometrial thickness in postmenopausal bleeding; >4 mm thickness warrants further evaluation.
  • Endometrial Biopsy:
    • Gold standard for diagnosis, providing histologic confirmation.
    • Recommended for postmenopausal bleeding or premenopausal women with high-risk factors and abnormal bleeding.
  • Hysteroscopy:
    • Allows visualization and biopsy of endometrial cavity, especially useful in cases where biopsy is nondiagnostic.
Staging
  • FIGO Staging System:
    • Stage I: Confined to uterus.
    • IA: Less than 50% myometrial invasion.
    • IB: Greater than 50% myometrial invasion.
    • Stage II: Cervical stromal involvement.
    • Stage III: Local or regional spread.
    • Stage IV: Distant metastasis to bladder, bowel, or other organs.
Treatment
  • Surgical Management:
    • Total Hysterectomy with Bilateral Salpingo-Oophorectomy (THBSO) is the mainstay, often with lymph node evaluation.
  • Adjuvant Therapy:
    • Radiation Therapy: Used postoperatively in high-risk or advanced disease to reduce recurrence risk.
    • Chemotherapy: For advanced or high-grade tumors, typically involving carboplatin and paclitaxel.
  • Hormonal Therapy:
    • High-dose progestins or levonorgestrel IUD may be used in patients with estrogen receptor-positive tumors or for fertility preservation.
Key Points
  • Endometrial Cancer is the most common gynecologic malignancy, frequently presenting with postmenopausal bleeding.
  • Types:
    • Type I is estrogen-dependent and linked to endometrial hyperplasia.
    • Type II is independent of estrogen and more aggressive.
  • Risk Factors include unopposed estrogen exposure, obesity, nulliparity, PCOS, Lynch syndrome, and tamoxifen.
  • Diagnosis relies on transvaginal ultrasound and endometrial biopsy as primary diagnostic tools.
  • Staging: FIGO staging assesses myometrial invasion, cervical involvement, and spread beyond the uterus.
  • Treatment:
    • Surgery (THBSO) is standard; adjuvant radiation and chemotherapy are used for advanced or high-risk disease.
    • Hormonal therapy may be used for specific cases, including fertility preservation.

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