Endometrial carcinoma

Endometrial carcinoma is generally considered the most common gynaecological malignancy ^1,5. It frequently presents with vaginal bleeding and both ultrasound and pelvic MRI are useful modalities for evaluation.

Epidemiology

Incidence peaks at around the 6^th decade, though 12% of cases present in premenopausal women. The incidence is thought to be increasing. In the United States, there is a greater incidence among patients of European descent compared those of African American descent.

Clinical presentation

Patients commonly present at an early stage, with postmenopausal bleeding as the initial symptom.

Pathology

Endometrial carcinoma is divided to two subtypes:

• type I (80%): arising in setting of unopposed hyperestrogenism and endometrial hyperplasia; mostly seen in women between 55 to 65 years old and are well differentiated tumours with relatively slow progression and more favourable outcome. PTEN gene mutation in 30 -80% of cases

  • risk factors -anything anything that leads to increased oestrogen exposure

    • oestrogen replacement therapy
    • polycystic ovarian syndrome and anovulatory cycles 
    • Tamoxifen
    • obesity
    • early menarche or late menopause
    • nulliparity
    • oestrogen producing tumours like granulosa cell cancer of ovaries
    • diabetes mellitus
• type II (20%): arising in the setting of endometrial atrophy, in a female between 65 to 75 years old, and endometrial intraepithelial carcinoma. P53 mutation in up to 50%. This type tends to be less differentiated and spread early via lymphatics or through fallopian tubes into peritoneum, hence it is associated with poorer prognosis compared to type I lesions

Histology

Histological subtypes include: 

• type I 
  • endometrioid carcinoma of the endometrium: commonest histological type: ~85%
• type II
  • papillary serous carcinoma of the endometrium: 5-10% ¹²
  • clear cell carcinoma of the endometrium: 1-5.5% ¹¹
  • adenosquamous carcinoma of the endometrium: ~2%
  • adenocarcinoma of the endometrium with squamous differentiation: 0.25-0.50% ¹⁰
  • undifferentiated carcinoma of the endometrium
    • small cell undifferentiated carcinoma of the endometrium

Associations

• hereditary non-polyposis colon cancer (HNPCC) ⁴: estimated 30-50x increased the lifetime risk
• precursor lesions of complex hyperplasia with atypia are associated with an endometrial carcinoma in over 40% of cases ⁴

Staging

See: endometrial carcinoma staging  most tumours (~80%) present as stage I disease.

Endometrial cancer is one of the (less common) causes of cannonball metastases to the lung.

Radiographic features

General imaging guidelines

Transvaginal ultrasound is the initial imaging investigation of choice for patients presenting with the usual symptom of a postmenopausal bleed. A thickened endometrium requires endometrial sampling. 

Staging of endometrial carcinoma is a based on the FIGO staging system, which is a surgical and pathological staging following total abdominal hysterectomy, salpingo-oopherectomy, lymphadenectomy and peritoneal washings. Such radical surgery may not be suitable in elderly patients or those with co-morbidities. MRI has a role in these patients in determining tumour extent and suitable therapy.

Transvaginal ultrasound

Endometrial carcinoma usually appears as thickening of the endometrium though may appear as a polypoid mass

• premenopausal: normal endometrial thickness varies through the menstrual cycle
  • diagnosing abnormally thickened endometrium depends on knowing what the patient's point in the menstrual cycle
• postmenopausal: >5 mm is thickened (if not on Tamoxifen)

Sonographic features are non-specific and endometrial thickening can also be due to benign proliferation, endometrial hyperplasia or polyps. 

Disruption of a subendometrial halo on ultrasound may be suggestive of myometrial involvement.

CT

CT has a role in assessing for distant metastases.

Although not generally used for initial diagnosis or local staging, endometrial carcinoma may be encountered on CT:

• noncontrast CT: difficult to differentiate from normal uterus (especially in local disease)
• post contrast CT: may show diffuse thickening or mass within endometrial cavity

Pelvic MRI

A dedicated pelvic MRI protocolis recommended for optimal assessment.

MRI is considered superior to CT for local staging ^1,6. Contrast enhanced MRI imaging improves accuracy in detecting myometrial invasion.

• T1: hypo- to isointense to normal endometrium
• T1 C+(Gd): carcinomatous tissue will enhance less than normal endometrium
• T2: hyperintense or heterogeneous relative to normal endometrium 

MR Imaging findings according to FIGO stage

• stage 1: tumour confined to the uterus 
  • stage 1a: tumour confined to the uterine endometrium
    • normal or widened endometrium
    • normal low T2 signal junctional zone
    • complete subendometrial enhancement on T1 contrast imaging
  • stage 1b: an invasion of less than half of the myometrium
    • disruption or irregularity of the low T2 signal junctional zone
    • disruption of subendometrial early enhancement
  • stage 1c: an invasion of the outer half of myometrium
    • disruption or irregularity of the low T2 signal junctional zone
    • disruption of subendometrial early enhancement
    • preservation of band of outer myometrium
• stage 2: tumour extends to the cervix
  • stage 2a
    • widening of internal os and endocervical canal by high/isointense T2W signal tumour mass.
    • intact low T2W signal of normal cervical stroma
  • stage 2b
    • widening of internal os and endocervical canal by high/isointense T2W signal tumour mass
    • disruption of low T2 signal cervical stroma
• stage 3: tumour extension beyond the uterus
  • stage 3a
    • irregularity to the uterine contour
    • disruption of low T2 signal uterine serosa
  • stage 3b
    • thickening of the vaginal wall
    • high T2 signal tumour infiltrating low signal vaginal wall
  • stage 3c
    • pelvic/para-aortic lymph node involvement
    • short axis >/= 8 mm in pelvic nodes
• stage 4: bladder/rectal or distant metastasis
  • stage 4a 
    • disruption of low T2 signal bladder or rectal wall
    • intraluminal bladder mass

Treatment and prognosis

Prognosis depends on various factors including:

• stage: depth of myometrial invasion, lymphovascular invasion, and nodal status
• histological grade

Differential diagnosis

In early disease, differential is essentially that of endometrial thickening: 

• benign endometrial proliferation
• endometrial hyperplasia
• endometrial polyp
• submucosal uterine leiomyoma

Differential considerations for advanced lesions include:

• uterine sarcoma(s)
  • endometrial stromal sarcoma (ESS)
  • leiomyosarcoma of the uterus
  • malignant mixed Mullerian tumour (MMMT) of the uterus
• uterine lymphoma: rare
  • primary uterine lymphoma
  • secondary uterine involvement with lymphoma
• cervical cancer with uterine invasion
• metastasis to the uterus from a non gynaecological malignancy: rare

Practical points

• endometrial hyperplasia is a histologic diagnosis, it cannot be differentiated from early stage endometrial carcinoma
• postmenopausal vaginal bleeding is an important clinical sign for risk stratification of imaging findings
  • if present: endometrium >5 mm has 96% sensitivity in the detection of endometrial carcinoma
  • if not present: endometrium of >11 mm has been proposed as a threshold for endometrial biopsy ¹⁴ 

See also

• malignant neoplasms involving the uterus