Describe the types, risk factors, clinical features, FIGO staging and management of carcinoma Endometrium.

Postmenopausal bleeding is endometrial cancer until excluded.

Definition

Carcinoma of the endometrium is a malignant tumour of the endometrial lining of the uterus, the majority being adenocarcinomas. It is predominantly a cancer of post-menopausal women and is the commonest pelvic genital malignancy in many developed countries.

Types of Endometrial Carcinoma

Types

• Type I (≈ 80%, endometrioid) — oestrogen-dependent, arises from endometrial hyperplasia, occurs in younger/peri-menopausal obese women, is well-differentiated and carries a good prognosis.
• Type II (serous, clear-cell) — non-oestrogen-dependent, occurs in older women on an atrophic endometrium, is poorly-differentiated and aggressive.

Risk Factors

Conditions of unopposed oestrogen — obesity, nulliparity, late menopause, anovulation/PCOS, oestrogen-only HRT, oestrogen-secreting tumours (granulosa cell) and tamoxifen — together with diabetes, hypertension and Lynch syndrome (HNPCC). The precursor is atypical endometrial hyperplasia.

Clinical Features

Post-menopausal bleeding is the cardinal symptom (and any post-menopausal bleeding is endometrial cancer until proven otherwise); peri-menopausal women present with irregular/intermenstrual bleeding, and there may be a blood-stained or watery discharge. Pain and a mass occur late.

Investigations

• Transvaginal ultrasound — an endometrial thickness > 4 mm in a post-menopausal woman with bleeding warrants sampling.
• Endometrial biopsy/aspiration (e.g. Pipelle) or hysteroscopy with dilatation and curettage — the definitive diagnosis.
• MRI/CT for myometrial invasion and spread, and chest imaging.

Figo Staging (surgical)

• Stage I — confined to the corpus uteri (IA < ½ myometrial invasion, IB ≥ ½).
• Stage II — invades the cervical stroma but not beyond the uterus.
• Stage III — local/regional spread to serosa/adnexa, vagina/parametrium, or pelvic/para-aortic nodes.
• Stage IV — invasion of bladder/bowel mucosa (IVA) or distant metastasis (IVB).

Management

• Surgery (mainstay) — total hysterectomy with bilateral salpingo-oophorectomy, peritoneal washings and pelvic ± para-aortic lymphadenectomy (surgical staging).
• Adjuvant radiotherapy (vault brachytherapy/pelvic) for intermediate/high-risk disease, and chemotherapy for advanced or high-grade (serous) tumours.
• Progestins — for fertility preservation in selected young women with early well-differentiated tumours, and for advanced/recurrent hormone-responsive disease.

WHY Unopposed Oestrogen Is the Common Thread

The single concept that explains nearly every risk factor for endometrial carcinoma is unopposed oestrogen. Oestrogen stimulates the endometrium to proliferate; progesterone opposes this, converting it to a stable secretory endometrium and limiting its growth. Whenever the endometrium is exposed to oestrogen without adequate progesterone — that is, in the absence of ovulation, since it is the corpus luteum that produces progesterone — it proliferates unchecked, passing through hyperplasia (which, once atypical, is frankly premalignant) to carcinoma. Every classical risk factor is an instance of this: obesity (adipose tissue converts androgens to oestrogen by aromatase, and this oestrogen is unopposed after the menopause); nulliparity and late menopause (more ovulatory-free or oestrogen-exposed years); PCOS (chronic anovulation → chronic unopposed oestrogen — which is why young women with PCOS need progestogen protection); oestrogen-only HRT; tamoxifen (an anti-oestrogen in the breast but an oestrogen agonist in the uterus); and oestrogen-secreting granulosa cell tumours. Diabetes and hypertension travel with obesity. Understanding this single mechanism explains why the pill (which supplies progestogen) is protective, and why the treatment of hyperplasia is progestogen.

WHY It Presents Early — and WHY That Is Fortunate

A striking contrast with ovarian cancer is why endometrial carcinoma generally has a good prognosis. It is not because the tumour is less aggressive but because it announces itself early: any growth of the endometrium bleeds, and since the disease occurs chiefly after the menopause, that bleeding is immediately abnormal and alarming. Hence about 90% of women present with postmenopausal bleeding, and most are diagnosed in stage I, when the disease is confined to the uterus and is curable by surgery alone. This gives the cardinal rule of gynaecology: postmenopausal bleeding is endometrial carcinoma until proved otherwise, and must always be investigated — by transvaginal ultrasound (an endometrial thickness above 4–5 mm demands sampling) and by endometrial biopsy or hysteroscopy with curettage, which gives the histological diagnosis. The contrast with the ovary is instructive: the same woman's ovarian cancer would have grown silently to stage III, while her endometrial cancer bled at stage I. Understanding that the symptom appears at the earliest stage of the disease explains both the favourable prognosis and why no woman with postmenopausal bleeding may ever be reassured without investigation.

• Endometrial carcinoma arises from unopposed oestrogen → hyperplasia (atypical = premalignant) → carcinoma; usually postmenopausal.
• Risk factors (all reflect unopposed oestrogen): obesity, nulliparity, late menopause, PCOS/anovulation, oestrogen-only HRT, tamoxifen, diabetes, hypertension.
• ~90% present with postmenopausal bleeding — which is endometrial cancer until proved otherwise; most are therefore diagnosed in stage I.
• Investigate with transvaginal ultrasound (endometrial thickness >4–5 mm) and endometrial biopsy/hysteroscopy + curettage.
• Treatment: total hysterectomy with bilateral salpingo-oophorectomy ± lymphadenectomy; adjuvant radiotherapy in higher-risk disease. Prognosis is good.