Case Study - A sinister cause of fatigue

Endometrial carcinoma may not always present with postmenopausal bleeding.

X-ray of endometrial cancer (Photograph: SPL)
X-ray of endometrial cancer (Photograph: SPL)

Mrs TK, a 65-year-old retired lawyer, came to see one of the registrars at the practice with a four-month history of increasing fatigue. She was otherwise fit and well and had no other symptoms.

She had a history of irritable bowel syndrome (IBS) for many years which seemed to be exacerbated during periods of stress. However, her GI symptoms had not altered recently.

Her weight had been stable; she had no urinary symptoms and had gone through her menopause uneventfully at the age of 51. She was not taking any regular medication and ate a healthy, balanced diet.

Abdominal examination
The registrar did an abdominal examination which was entirely normal. He arranged for some routine blood tests and these turned out to be normal, other than her FBC which showed a microcytic, hypochromic anaemia, with a haemoglobin level of 9.9g/dL.

In view of this result and her history of IBS, the decision was made for her to have an abdominal CT scan to exclude any GI tract pathology as a potential cause of the anaemia.

The CT scan was normal. However, a CT scan of her pelvis was also performed which showed a large mass arising from the superior aspect of the uterine fundus measuring 11.9cm in height by 7.2cm in width by 10.7cm in depth.

The mass demonstrated central necrosis. Mrs TK was therefore urgently referred to one of the local gynaecologists for further assessment and management. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by radiotherapy.

Diagnosis
About 4,500 women in the UK develop endometrial cancer each year. Worldwide it is the seventh most common cancer in women.

Most cases develop in women in their 50s and 60s and it rarely develops in women under the age of 50. The vast majority of cases are endometrial adenocarcinomas.

The most common presentation of endometrial carcinoma is with postmenopausal bleeding; 90 per cent of endometrial cancers present in this way.

The presentation of Mrs TK's endometrial carcinoma was therefore very usual.

However, it should be noted that only 10 to 20 per cent of patients who present with postmenopausal bleeding actually have endometrial cancer.

Most patients with endometrial carcinoma are diagnosed following a transvaginal ultrasound after being referred for investigations for postmenopausal bleeding. This usually demonstrates a thickened endometrium.

In general, the thicker the endometrium the higher the chance of endometrial cancer. The threshold in the UK is 5mm; a thickness of >5mm gives 7.3 per cent likelihood of endometrial cancer.1 A thickness of <5mm has a negative predictive value of 98 per cent.2

Endometrial biopsy is then usually performed to obtain a histological diagnosis. After diagnosis, patients usually undergo further investigations to assess the cancer preoperatively. Endometrial cancer is then staged based on surgical pathological findings.

Treatment
The treatment of endometrial cancer depends on the stage. Patients with stage Ia and Ib will require total abdominal hysterectomy with bilateral salpingo-oophorectomy. Those with stage Ic and stage II will need pelvic radiotherapy in addition to surgery.

Patients with stage III are also best treated with surgery and also external beam radiotherapy and intracavity radiotherapy. However, not all patients with stage III are operable.

Patients with stage IV who have distant metastases are usually treated with combination radiotherapy and also progestogen-containing agents (usually medroxyprogesterone acetate or megestrol).

However, a recent review found insufficient evidence that hormonal treatment in any form, dose or as part of combination therapy, improves survival of patients with advanced or recurrent endometrial cancer.3 Chemotherapy is also sometimes used.4

The overall 20-year survival rate for all forms of endometrial carcinoma is about 80 per cent. However, the five-year survival of patients with stage Ia is 91 per cent, compared with only 5 per cent for those with stage IVb. The majority of endometrial cancers are curable.

Risk factors

The following are recognised risk factors for endometrial carcinoma:

  • Increased exposure to estrogen (obesity, late menopause, nulliparous)
  • Endometrial hyperplasia
  • Tamoxifen
  • Diabetes
  • Polycystic ovary syndrome.
  • Dr Newson is a GP in the West Midlands.

References
1. Smith-Bindman R, Weiss E, Feldstein V. How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet Gynecol 2004; 24: 558-65.

2. Sahdev A. Imaging the endometrium in postmenopausal bleeding. BMJ 2007; 334: 635-6.

3. Kokka F, Brockbank E, Oram D et al. Hormonal therapy in advanced or recurrent endometrial cancer. Cochrane Database Syst Rev 2010; (12): CD007926.

4. Hogberg T. Adjuvant chemotherapy in endometrial cancer. Int J Gynecol Cancer 2010; 20(11 Suppl 2): S57-9.

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