Endometrial cancer (and hysteroscopy)

Question 1

Define endometrial cancer.

Answer 1

An epithelial malignancy of the uterine corpus mucosa, usually an adenocarcinoma.

Question 2

How common is endometrial cancer?

Answer 2

• The most common gynaecological tumour in the developed world
• 6th most common cancer overall in women
• Incidence increasing which may be linked to obesity
• Median age at diagnosis is 63 years

Question 3

What is the aetiology of endometrial cancer?

Answer 3

Chronic (unopposed by progesterone) oestrogen stimulation –> endometrial hyperplasia –> adenocarcinoma (endometrial cancer)

Question 4

What is the stage between endometrial hyperplasia and endometrial cancer called?

Answer 4

Intra-epithelial endometrial neoplasia

Question 5

What are some causes of unopposed oestrogen stimulation of the endometrium?

Answer 5

• Chronic anovulation e.g. in PCOS
• Post-menopause, obesity - androgens are aromatised into oestrogen in adipocytes
• Tumours of the ovary e.g. granulosa cell tumours producing oestrogen

Question 6

Which familial cancer syndromes predispose to endometrial cancer?

Answer 6

• Lynch syndrome - HNPCC
• FH of endometrial, ovarian, breast or colon cancer
• Cowden syndrome - mutation in PTEN tumour suppressor gene

Question 7

A 65-year-old woman with class III obesity (BMI 41) with hypertension and diabetes presents with post-menopausal vaginal bleeding, 12 years after the menopause. She has never been pregnant. She has a first-degree relative and a second-degree relative who have had endometrial cancer. Bleeding is scant but has persisted for more than 1 month. She has not recently used hormone replacement therapy and she had a normal Pap smear 6 months previously. Vaginal examination reveals evidence of recent bleeding.

What is the diagnosis?

Answer 7

Endometrial cancer -

• Most patients who present are post-menopause, or nulliparous and obese pre-menopausal women*
• Uncommonly, women with undiagnosed endometrial cancer are found to have atypical glandular cells of uncertain significance (AGUS) on routine Pap smear cytology*

Question 8

What are the clinical features of endometrial cancer?

Answer 8

Post-menopausal vaginal bleeding - 5-10% will have endometrial cancer

Signs and symptoms of metastatic disease -

Question 9

What are the risk factors for endometrial cancer?

Answer 9

• Overweight and obese
• Age >50yrs
• Endometrial hyperplasia
• Unopposed oestrogen
• Tamoxifen use
• Insulin resistance
• FH of EC or other syndromes
• PCOS
• Radiotherapy (rare)

Question 10

Which 2 factors are protective against endometrial cancer?

Answer 10

combined oral contraceptive pill and smoking are protective

Question 11

What investigations would you do for endometrial cancer?

Answer 11

Bloods:

• FBC - for anaemia

Imaging:

• TVUSS
• Endometrial biopsy and histopathology + hysteroscopy
• Hysteroscopy, dilation and curettage (D&C - shown below) - if outpatient biopsy is no feasilble or cannot be tolerated

Question 12

What TVUSS finding is suggestive of endometrial cancer?

Answer 12

endometrial thickening (stripe) >5 mm

Question 13

How can diagnostic accuracy of endometrial biopsy be improved?

Answer 13

By outpatient hysteroscopy

Question 14

Why may Pap smears be sometimes useful in diagnosis of endometrial cancer?

Answer 14

Not a screening test for endometrial cancer but sometimes show atypical glandular cells on cervical cytology which should prompt immediate evaluation with endometrial sampling

Question 15

What are some differentials for endometrial cancer?

Answer 15

• Endometrial hyperplasia
• Endometrial polyp - TVUSS may show thickened endometrial lining that is not uniform
• Endometriosis - although more common pre-menopause
• Cervical cancer - patinets typically younger, although PVB usually provoked e.g. post-coital

Question 16

What classification is used for staging endometrial cancer?

Answer 16

FIGO classification for uterine cancer

FIGO = International Federation of Gynecology and Obstetrics

Question 17

Summarise the FIGO classification for uterine cancers.

Answer 17

Stage I:limited to the corpus uteri

• IA: no or <50% myometrial invasion
• IB: ≥50% myometrial invasion.

Stage II: invades cervical stroma, but does not extend beyond the uterus. Endocervical glandular involvement only is stage I.

Stage III: local and regional spread

• IIIA: invades the serosa of the corpus uteri and/or adnexa
• IIIB: vaginal and/or parametrial involvement
• IIIC: metastases to pelvic and/or para-aortic lymph nodes
  
  • IIIC1: positive pelvic nodes
  • IIIC2: positive para-aortic lymph nodes +/- positive pelvic lymph nodes.

Stage IV: invades the bladder and/or bowel mucosa and/or distant metastases

• IVA: invasion of the bladder and/or bowel mucosa
• IVB: distant metastases

Question 18

What is the main management of endometrial cancer?

Answer 18

Surgery is the most important component of management for potentially curable disease.

Standard surgery requires:

• total hysterectomy (laparoscopy/laparotomy) AND
• bilateral salpingo-oophorectomy AND
• lymphadenectomy (not beneficial in stage I)

Patients with high-risk disease may have post-operative radiotherapy

Question 19

What is a treatment option for patients who wish to maintain fertility?

Answer 19

Surgery - first line

Progestin therapy i.e. megestrol - only used in low risk disease alongside careful counselling

Aggressive monitoring, including hysteroscopy with endometrial sampling every 3-6 months is warranted, and these patients are best advised to consider hysterectomy once childbearing is completed

Question 20

When else are progestogens used in endometrial cancer?

Answer 20

In frail patients who are not suitable for surgery

Question 21

What type of prevention is available for endometrial cancer?

Answer 21

Prophylactic hysterectomy and BSO after childbearing e.g. in Lynch syndrome where lifetime risk is 27-71%

Question 22

What are the complications of endometrial cancer and its treatment?

Answer 22

• Menopausual symptoms after surgery
• Bladder instability
• Vaginal stenosis, atrophy or fibrosis after radiotherapy
• Sexual dysfunction
• Metastasis
• Lymphoedema
• Chemo toxicity
• Bowel or bladder fistulae

Question 23

Which ovarian tumour is associated with the development of endometrial hyperplasia?

Answer 23

Sex cord stromal tumours (Thecomas, Fibromas, Sertoli cell and granulosa cell tumours) are associated with an increased production of hormones. Of these only Granulosa cell tumours are associated with the development of endometrial hyperplasia

Atypical hyperplasia of the endometrium is classified as a premalignant condition which develops due to overstimulation of the endometrium by oestrogen.

Question 24

How is hysteroscopy done?

Answer 24

The uterine cavity is inspected with a rigid or flexible
hysteroscope passed through the cervical canal.

The cavity is distended using carbon dioxide or saline. This can be performed without anaesthetic, or with a cervical local anaesthetic block or under general anaesthetic.

It is used as an adjunct to endometrial biopsy or if menstrual problems do not respond to medical treatment.

Question 25

What are some indications for hysteroscopy?

Answer 25

• PMB
• Irregular menstruation, intermenstrual bleeding and PCB
• Persistent HMB

Question 26

What surgery can be done hysteroscopically?

Answer 26

endometrial - transcervical resection of endometrium (TCRE), endometrial roller-ball diathermy, laser ablation or heating with an intrauterine hot balloon or microwave probe

intracavity fibroids - transcervical resection of fibroid (TCRF)

polyp removal

resection of a uterine septum