Endometrial cancer

Classification

Stages

• FIGO I: Stage FIGO I means tumour confinement to the corpus uteri.
• FIGO II: Stage FIGO II means invasion of the cervical stroma.
• FIGO III: Stage FIGO III means local/regional spread.
• FIGO IIIC: Stage FIGO IIIC1 denotes pelvic, IIIC2 para-aortic LN metastases.
• FIGO IV: Stage FIGO IV means invasion of bladder/bowel mucosa; distant metastases.
• New feature: A new feature in the current FIGO classification is integration of molecular groups/LVSI.

Why it was introduced

• The old classification into Type I and Type II was prognostic, but not predictive.
• The molecular classification is now part of the staging classification.
• For the classification, the following are determined: IHC for MMR/p53, molecular for POLE.

Four groups

• POLE-mutated means POLE exonuclease domain mutation.
• MMRd means loss of mismatch repair proteins.
• p53abn means aberrant p53 staining, high copy number.
• NSMP stands for “no specific molecular profile”.
• L1CAM is prognostic marker for NSMP group (poorer).

Aetiopathogenesis

Basic Principle

• Pathogenesis: The majority of endometrial carcinomas develop with oestrogen dominance without progestogen.
• Oestrogen-independent carcinomas: In contrast, a portion of carcinomas, especially the serous types, develop oestrogen-independent with atrophy.

Risk Factors

• Metabolic factors: Metabolic risk factors include obesity, type 2 diabetes mellitus, hypertension.
• Reproductive factors: Reproductive risk factors are nulliparity, early menarche, late menopause.
• Hereditary factors: A hereditary risk factor is Lynch syndrome (mismatch repair defect).

Clinical features

Basic Principle

• Principle: Any bleeding after menopause is considered requiring workup until cancer is excluded.
• Most common finding: The most common finding is endometrial atrophy.
• Carcinoma incidence: A carcinoma is found in approx. 10% of cases, rising with age.
• Definition: Menopause is defined as final period (after 12 months of amenorrhea).

More facts from the study questions

• Lynch syndrome is a hereditary risk factor.
• It is characterised by a defect in the mismatch repair genes.
• An investigation, e.g. by hysteroscopy, is only performed if bleeding occurs.
• The grading of endometrioid carcinoma is based on the proportion of solid, non-glandular tumour areas.
• G1 and G2 are grouped as low-grade, G3 as high-grade.
• Aggressive, non-endometrioid types (serous, clear cell, etc.) are classified as high-grade (G3) by definition.
• Endometrioid adenocarcinoma is by far the most common histological subtype of endometrial carcinoma.
• Infiltration of the cervical stroma, with the tumour confined to the uterus, defines FIGO stage II.
• FIGO stage I is confined to the uterine corpus.
• Molecular classification is no longer just an additional prognostic factor.

Histology

Histological Types

• Most common type: The most common histological type of endometrial carcinoma is endometrioid adenocarcinoma.
• Aggressive types: The aggressive, non-endometrioid types include serous, clear cell, undifferentiated ca, carcinosarcoma.
• Serous carcinoma: Serous carcinoma is p53-aberrant with atrophy.
• Carcinosarcoma: Carcinosarcoma is now considered carcinoma with sarcomatoid differentiation.

Grading

• Grading criterion: The grading of endometrioid carcinoma is based on the proportion of solid, non-glandular tumour areas.
• Grade classification: G1 and G2 are classified together as low grade, G3 as high grade.
• Non-endometrioid types: The non-endometrioid types are considered high grade, regardless of the growth pattern.

Diagnosis

Staging Investigations

• Pelvic MRI: The pelvic MRI is primarily used for assessing myometrial invasion/cervical involvement.

Examination

• Clinical examination: The examination procedure includes inspection, speculum, palpation, vaginal ultrasound.
• Cervical work-up: Cytological and colposcopic investigation is performed if bleeding is from cervical canal or smear is abnormal.

Endometrial Thickness

• Cut-off value with bleeding: The cut-off value for postmenopausal bleeding is an endometrium of 3–4 mm.
• Fluid in the cavity: Postmenopausal fluid in the uterine cavity is a finding requiring workup (suspected carcinoma).

Typical imaging findings

• Ultrasound: The cavity is filled by a chaotically structured mass, partly hypoechoic and partly echogenic. Over a long stretch the border between endometrium and myometrium can no longer be identified; the uterine wall looks irregular there.
• Ultrasound: The cavity is filled by a 17 mm inhomogeneous mass with irregular margins. The interface with the myometrium can no longer be traced in places; internal echoes are mixed hypo- and hyperechoic.

Keep learning in the app

Further reading (selection)

1. StatPearls: Endometrial Cancer (NCBI Bookshelf)
2. DocCheck Flexikon, Endometriumkarzinom

Cross-references