Endometrial Carcinoma

Cancer that arises from the endometrium (innermost lining of the uterus)

Aetiology

  • Peak incidence: 50-60 years, uncommon under 40
  • In young women, consider underlying predisposition e.g. PCOS or Lynch syndrome

Risk factors

  • Prolonged period of anovulation e.g. early menarche/late menopause, low parity, PCOS
  • Obesity
    • Excess risk is associated with the endocrine and inflammatory effects of adipose tissue

Pathophysiology

Endometrioid and mucinous carcinoma (type 1 tumours) - 80%

  • Atypical hyperplasia is the precursor, related to unopposed oestrogen
  • PTEN, KRAS, PIK3CA mutations
  • Can occur in association with Lynch syndrome (defective
    DNA mismatch repair gene)

Serous and clear cell carcinoma (type 2 tumours) - 20%

  • Serous intraepithelial carcinoma is the precursor, not associated with unopposed oestrogen
  • Affects elderly post-menopausal women
  • TP53 mutation and overexpression
  • Spreads along Fallopian tube mucosa and peritoneal surfaces so can present with extrauterine disease
  • More aggressive than endometrioid/mucinous carcinoma

Spread

  • Spread can be directly into the myometrium and cervix, through lymphatics, or haematogenous

Clinical presentation

Symptoms

  • Generally presents with abnormal bleeding, most commonly postmenopausal bleeding

Signs

  • Abdominal examination - abdominal or pelvic masses
  • Speculum examination - vulval/vaginal atrophy, or cervical lesions
  • Bimanual examination - assess size and axis of the uterus prior to endometrial sampling

Investigations

  • Transvaginal US scan first line
    • Best method of establishing abnormally thickened endometrium in a post-menopausal patient with PMB
  • If an endometrial thickness of >4mm in a postmenopausal woman is identified, an endometrial biopsy should be obtained
  • If malignancy is confirmed, an MRI or CT scan may be used for staging
    • MR scanning can be used to assess the degree of myometrial invasion, CT scanning is used to look for distant nodal metastases and pulmonary metastases
  • If suspect underlying Lynch syndrome:
    • Immunohistochemistry staining of the tumour for mismatch repair proteins can help identify tumours due to Lynch syndrome
    • Lynch syndrome tumours also show microsatellite instability (MSI), a characteristic of defective mismatch repair; testing cancer tissue for MSI can be useful

FIGO staging

  • Stage I - carcinoma confined to within uterine body
  • Stage II - carcinoma may extend to cervix but is not beyond the uterus
  • Stage III - carcinoma extends beyond uterus but is confined to the pelvis
  • Stage IV - carcinoma involves bladder or bowel, or has metastasised to distant sites

Management

Depends on stage, histological grade, and depth of myometrial invasion:
  • Stage I - total hysterectomy and bilateral salpingo-oophorectomy
  • Stage II - radical hysterectomy, may be offered adjuvant radiotherapy
  • Stage III - maximal de-bulking surgery, additional chemotherapy is usually given prior to radiotherapy
  • Stage IV - maximal de-bulking surgery, palliative approach is preferred (e.g. low dose radiotherapy)
  • Type 2 tumours usually involve more extensive surgery and adjuvant chemo/radiotherapy is used more frequently