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.

Incidence peaks at around the 6th 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.

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

Endometrial carcinoma is divided to two subtypes - type I and type II. 

Type I endometrial carcinoma

Type I (80%) arises in the setting of unopposed hyperestrogenism and endometrial hyperplasia. It is 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 occurs in 30-80% of cases.

Risk factors are 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 ovarian tumours, e.g. granulosa cell cancer
  • diabetes mellitus 
Type II endometrial carcinoma

Type II (20%) arises in the setting of endometrial atrophy, in females between 65 to 75 years old, and endometrial intraepithelial carcinoma. P53 mutation occurs 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: 

Associations
Staging

Most tumours (~80%) present as stage I disease. Endometrial cancer is one of the (less common) causes of cannonball metastases to the lung. See: endometrial carcinoma staging for further information. 

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
MRI

A dedicated pelvic MRI protocol is 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 
MRI 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
Nuclear medicine

PET-CT is inferior to MRI and ultrasound in the assessment of primary tumours, especially when small or in premenstrual women where there is normally increased physiological endometrial uptake 16.

Prognosis depends on various factors including:

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

In early diseasedifferential is essentially that of endometrial thickening: 

Differential considerations for advanced lesions include:

  • 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 
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Article information

rID: 13098
Section: Pathology
Synonyms or Alternate Spellings:
  • Endometrial cancer
  • Carcinoma of the endometrium
  • Endometrial cancer : General
  • Endometrial carcinomas

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