Endometrial cancer Flashcards
SBA: What cell type is endometrial carcinoma (also called womb/ uterine cancer)?
a) . Adenocarcinoma
b) . Squamous cell carcinoma
c) . Small cell carcinoma
d) . Non-small cell carcinoma
The answer is a - endometrial adenocarcinoma
Caused by abnormal proliferation of endometrial cells as a result of chronic exposure to unopposed oestrogen
Epidemiology of endometrial cancer (EC):
a) . How common is endometrial cancer?
b) . Which age group is most commonly affected by endometrial cancer? What is the mean age of diagnosis?
c) . Endometrial cancer is more common in obese women - true or false
d) . Which genetic syndrome is associated with endometrial cancer? (please specify its pattern of inheritance)
a) . Endometrial cancer is the most common gynaecological malignancy in developed countries. It’s the 4th most common female cancer in the UK (and 6th worldwide)
b) . Most commonly seen in postmenopausal women (mean age of diagnosis is 60 yrs old) due to prolonged exposure to oestrogen
c) . TRUEEEEE! Obesity is strongly linked to EC
d) . Hereditary non-polyposis colorectal cancer (HNPCC)/ Lynch syndrome is an autosomal dominant condition associated with a high risk of colorectal cancer, endometrial cancer, and ovarian cancer
Caused by a mutation in a DNA mismatch repair gene (e.g. MLH1, MSH2, MSH6, PMS2). Abnormal DNA repair –> DNA replication errors –> microsatellite instability
Which genetic syndrome can cause endometrial cancer?
HNPCC (also called Lynch syndrome) - autosomal dominant
It can cause early onset of colorectal, endometrial and ovarian cancers!
What is the prognosis of endometrial cancer?
Usually good prognosis due to early presentation with abnormal uterine bleeding in postmenopausal women
What diagnosis must you rule out if a postmenopausal woman presents with abnormal vaginal bleeding?
All vaginal bleeding in postmenopausal women is endometrial cancer until proven otherwise!
There are 2 different types of endometrial cancer and they are categorised according to histology. What are they?
Types of endometrial cancer:
-
Type 1 endometrioid cancer (most common - 80% of all ECs) - ‘endometrioid’ means the tumour looks like normal endometrial glands
- Early presentation hence better prognosis
- Caused by chronic/ increased exposure to unopposed oestrogen
- Typically followes a period of endometrial hyperplasia
-
Type 2 non-endometrioid cancer (less common)
- Multiple subtypes of tumour e.g. serous, clear cell, mucinous
- Late presentation, more aggressive, and worse prognosis
- NOT associated with obesity and oestrogen exposure
What is the main cause of endometrial cancer?
Prolonged/ increased exposure to oestrogen - this can be endogenous due to obesity or exogenous due to administration of oestrogen unopposed by progesterone (e.g. oestrogen-only replacement therapy)
Oestrogen causes the endometrium to proliferate –> increased cell division –> higher risk of mutations –> endometrial cancer
Give 3 protective factors for endometrial cancer
COCP
*Smoking
Pregnancy
Give 5 risk factors for endometrial cancer
Risk factors for endometrial cancer:
(Think about things that can cause prolonged/ increased exposure to oestrogen)
Causes of excess unopposed oestrogen:
-
Obesity
- Adipose tissue increases the level of oestrogen because the enzyme aromatase is able to convert androgens to oestrogens
- Oestrogen-secreting ovarian tumour e.g. granulosa cell tumours
-
Polycystic ovarian syndrome (PCOS)
- The cystic follicles on the ovary can all secrete oestrogen –> high oestrogen level
- The follicles don’t ovulate –> no corpus luteum formed –> no progesterone secreted –> low progesterone level
- Unopposed oestrogen –> increases the risk of endometrial hyperplasia –> endometrial cancer
-
Drugs (exogenous oestrogens)
-
Oestrogen-only hormone replacement therapy
- Mainly used to relieve menopausal symptoms e.g. hot flushes, vaginal dryness
- The addition of a progesterone to oestrogen greatly reduces this risk!
-
Tamoxifen (selective estrogen receptor modulator, SERM)
- Used to treat breast cancer that are ‘oestrogen receptor +’
- It blocks the oestrogen receptors on the breast BUT at the same time, it stimulates those on the endometrium –> endometrial cancer
-
Oestrogen-only hormone replacement therapy
A person could have normal oestrogen production throughout their life, but the number of years the endometrium is exposed to oestrogen is also a factor for developing endometrial hyperplasia. Oestrogen exposure is increased in people who have:
- Early menarche and late menopause
- Nullparity
- Increasing age
(These patients have experienced a greater number of menstrual cycles, where more follicles have grown, and more oestrogen was secreted by these follicles)
Causes independent of hormone levels:
- Genetics - HNPCC/ Lynch syndrome
- Mutations of a tumour suppressor gene, called PTEN, which normally acts like a brake on the cell cycle. When this gene becomes defective, cells in the endometrium will grow and proliferate out of control, leading to hyperplasia
What are the clinical features of endometrial cancer?
Presentations:
Symptoms
- Post-menopausal bleeding (PMB) - defined as abnormal vaginal bleeding >/= 12 months after the last menstrual period in patients not on hormone replacement therapy (HRT)
- Premenopausal women may have abnormal uterine bleeding - intermenstrual, frequent, heavy or prolonged
- Constitutional symptoms - weight loss, anorexia, lethargy
- Usually painless
Signs
- Abdominal and bimanual pelvic examinationusually normal but a fixed, hard uterus suggests advanced disease
- Cervical speculum examination - may reveal abnormal tissues
What investigations are needed to diagnose endometrial cancer?
Ix:
- 1st line - Transvaginal USS to assess endometrial thickness
- Endometrial thickness < 4 mm (normal) - no further investigation needed unless recurrent postmenopausal bleeding
-
Endometrial thickness >/= 4 mm - outpatient endometrial sampling (also called pipelle biopsy where a small straw-like tube is passed through the cervix to take the endometrial sample)
- For high-risk patients, those with focal area of irregularity, or patients who can’t tolerate outpatient pipelle biopsy (e.g. due to cervical stenosis, discomfort) or if pipelle biopsy is inconclusive –> offer hysteroscopy with biopsy
- Requires regional or general anaesthesia
- For high-risk patients, those with focal area of irregularity, or patients who can’t tolerate outpatient pipelle biopsy (e.g. due to cervical stenosis, discomfort) or if pipelle biopsy is inconclusive –> offer hysteroscopy with biopsy
(*Remember that a thickness level of 4 mm is the cut-off for further Ix!)
- Blood tests - FBC to rule out anaemia and infection (e.g. STI) as the cause of bleeding
- In patients with high-risk features or suspicion of advanced disease –> CT scan to look for distant metastasis and MRI pelvis to characterise local disease
a) . What classification is used to grade and stage the tumour?
b) . How is the cancer graded and staged?
a) . International Federation of Gynaecology and Obstetrics (FIGO) classication
b) . The grade of a cancer describes how much resemblance the cancer cell has to the original cell type. There are 3 grades:
- Well-differentiated - highly resembling hence better outcome
- Moderately-differentiated
- Poorly-differentiated - doesn’t resemble at all hence most aggressive and worse outcome
The stage of a cancer is important in determining treatment. It uses TNM staging:
- Tumour - size of tumour in cm
- Nodes - number and location of lymph nodes involved
- Metastasis - presence or absence of spread to a distant site
How do you manage endometrial cancer?
Mx:
Primary care
- Refer using a suspected cancer pathway referral (2 week wait): age >/= 55 + PMB (defined as unexplained vaginal bleeding more than 12 months after menstruation has stopped because of menopause)
- Consider to refer using a suspected cancer pathway referral (2 week wait): age < 55 + PMB
- Consider a USS to assess for endometrial cancer in women aged 55 and over with:
- Unexplained symptoms of vaginal discharge who:
- Are presenting with these symptoms for the first time, or
- Have thrombocytosis, or
- Have haematuria, or
- Visible haematuria, and:
- Low Hb, or
- Thrombocytosis, or
- High blood glucose levels
- Unexplained symptoms of vaginal discharge who:
Secondary care
-
Early stage disease (localised i.e. Stage I/ II) –> total hysterectomy with bilateral salpingo-oophorectomy
- Those unfit for surgery (e.g. frail elderly women) –> vaginal hysterectomy, pelvic radiotherapy or hormonal therapy with progesterone or aromatase inhibitors
- Stage IIB –> Wertheim’s radical hysterectomy
- Chemoradiotherapy can be combined with surgery. Can be given before surgery to shrink tumour (neo-adjuvant chemotherapy). Patients with high-risk disease may have post-operative radiotherapy
- For those under 45 yrs old –> requires gynae-oncology input to discuss risks and benefits of the surgery, particularly fertility issues
What are the referral criteria for a woman with suspected endometrial cancer in primary care?
- Refer using a suspected cancer pathway referral (2 week wait): age >/= 55 + PMB (defined as unexplained vaginal bleeding more than 12 months after menstruation has stopped because of menopause)
- Consider to refer using a suspected cancer pathway referral (2 week wait): age < 55 + PMB
- Consider a USS to assess for endometrial cancer in women aged 55 and over with:
- Unexplained symptoms of vaginal discharge who:
- Are presenting with these symptoms for the first time, or
- Have thrombocytosis, or
- Have haematuria, or
- Visible haematuria, and:
- Low Hb, or
- Thrombocytosis, or
- High blood glucose levels
- Unexplained symptoms of vaginal discharge who:
