Vulval & Endometrial Cancers

Question 1

Vulval cancers are which (cell type) of cancer? [1]

Which part of the vulva do they commonly affect? [1]

Answer 1

80% are squamous cell carcinomas

Anatomically, vulval carcinoma often presents on the labia majora or minora but can involve other structures like the clitoris or perineum as it advances

Question 2

Name some risk factors for vulval cancer [5]

Answer 2

• Older age
• Human papilloma virus (HPV) infection
• Vulval intraepithelial neoplasia (VIN)
• Immunosuppression
• Lichen sclerosus - big one (5% get vulval cancer)

Question 3

Describe the pathophysiology of vulval cancer [1]

Answer 3

Transformation of vulvar epithelial cells, typically squamous cells, into malignant cells.

The pathophysiological process begins with genetic mutations within these epithelial cells. These mutations often occur in tumour suppressor genes such as TP53 and oncogenes like HRAS, leading to dysregulated cell growth and division.

Question 4

How do vulval carcinomas present? [3]

Answer 4

Lump or ulcer on the labia majora
- May be associated with itching, irritation

Question 6

What causes high grade [1] and differentiated [1] VIN?

Answer 6

High grade:
HPV infection - younger women

Differentiated:
- Lichen sclerosis - older women

Question 7

What is the referral criteria for vulval cancer? [1]

Answer 7

Consider a suspected cancer pathway referral (for an appointment within 2 weeks) for vulval cancer in women with an unexplained vulval lump, ulceration or bleeding.

Question 8

Describe the management for vulval carcinoma? [4]

Answer 8

Surgical Treatment
* Wide local excision: This is usually recommended for early-stage tumours (stage 1A). The goal is to remove the tumour along with a rim of normal tissue around it.
* Vulvectomy: Depending on the extent of disease either partial or total vulvectomy may be performed. Sentinel lymph node biopsy or inguinal lymphadenectomy may be required in cases where there is clinical or radiological evidence of nodal involvement.

Radiation Therapy

Chemotherapy
- Chemotherapy is generally reserved for recurrent or metastatic disease that cannot be managed surgically. Platinum-based chemotherapy regimens are commonly used.

Question 9

TOM TIP: For your exams, any woman presenting with postmenopausal bleeding has [] cancer until proven otherwise.

Answer 9

TOM TIP: For your exams, any woman presenting with postmenopausal bleeding has endometrial cancer until proven otherwise..

Question 10

Explain the key risk factors for endometrial cancaer

Answer 10

Unopposed oestrogen (oestrogen without progesterone)
- this stimulates the endometrial cells and increases hyperplasia and cancer
- risk factors are associated w/ factors that cause increased lifetime exposure to oestrogen, such as

Age
Early onset of menstruation
Late menopause
Oestrogen only HRT
Fewer / no pregnancies
Obesity
PCOS
Tamoxifen
DMT2

Question 11

Explain why obesity increases the risk of endometrial cancer [3]

Answer 11

adipose tissue (fat) is a source of oestrogen:
- primary source in post-menopausal woemn
- contains aromatase, which converts testosterone into oestrogen
- This extra oestrogen is unopposed as there is no corpus luteum making progesterone

Question 12

Explain why PCOS increases the risk of endometrial cancer [3]

Answer 12

Polycystic ovarian syndrome leads to lack of ovulation - which causes an increased exposure to oestrogen
- Usually, when ovulation occurs, a corpus luteum is formed in the ovaries from the ruptured follicle that released the egg.
- It is this corpus luteum that produces progesterone, providing endometrial protection during the luteal phase of the menstrual cycle
- Women with polycystic ovarian syndrome are less likely to ovulate and form a corpus luteum causing more unopposed oestrogen exposure

Question 13

For endometrial protection, women with PCOS should have one of: [3]

Answer 13

The combined contraceptive pill
An intrauterine system (e.g. Mirena coil)
Cyclical progestogens to induce a withdrawal bleed.

Question 14

Why does tamoxifen have an increased risk of endometrial cancer? [1]

Answer 14

Tamoxifen has an anti-oestrogenic effect on breast tissue, but an oestrogenic effect on the endometrium. This increase the risk of endometrial cancer.

Question 15

Why is DMT2 linked with increased risk of endometrial cancer? [1]

Answer 15

Type 2 diabetes may increase the risk of endometrial cancer due to the increased production of insulin. Insulin may stimulate the endometrial cells and increase the risk of endometrial hyperplasia and cancer

Also related to PCOS

Question 16

When would you refer women with ?endometrial cancer

Answer 16

• if they are aged 55 and over with post-menopausal bleeding (unexplained vaginal bleeding more than 12 months after menstruation has stopped because of the menopause).
• Consider a suspected cancer pathway referral (for an appointment within 2 weeks) for endometrial cancer in women aged under 55 with post-menopausal bleeding.

Consider a direct access ultrasound scan 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
* report haematuria, or
* visible haematuria and:
* low haemoglobin levels or
* thrombocytosis or
* high blood glucose levels.

Question 17

Describe the clincial presentation of endometrial cancers [5]

Answer 17

Abnormal Uterine Bleeding
- most common
- menorrhagia or irregular, intermenstrual spotting in pre-menopausal women
- any form of vaginal bleeding in post-menopausal women

Pelvic pain
Discharge - non bloody
Systemic features
Dysuria
Bowel changes

Question 18

Name three pelvic examination findings that may indicate endometrial cancer [3]

Answer 18

An enlarged uterus:
- While this finding is not specific to endometrial cancer, a significantly enlarged uterus may suggest the presence of a neoplasm.

Cervical stenosis or an irregular cervical canal:
- These findings may suggest malignancy and warrant further investigation

A palpable pelvic mass:
- A mass could indicate advanced disease or a different gynaecological malignancy such as ovarian cancer.

Question 19

How do you investigate for endometrial cancer? [4]

NB: ZtF:

The referral criteria for a 2-week-wait urgent cancer referral for endometrial cancer is:
- Postmenopausal bleeding (more than 12 months after the last menstrual period)

NICE also recommends referral for a transvaginal ultrasound in women over 55 years with:
- Unexplained vaginal discharge
- Visible haematuria plus raised platelets, anaemia or elevated glucose levels

Answer 19

TVUS:
- An endometrial thickness of >5mm is associated with a 96% probability of endometrial cancer.

Endometrial bx:
- confirmatory diagnosis of endometrial cancer and provides a means of histological identification.
- pipelle biopsy - can be taken in the outpatient clinic. It involves a speculum examination and inserting a thin tube (pipelle) through the cervix into the uterus

Hysteroscopy, dilatation and curettage:
- performed under general anaesthesia and is useful for histological confirmation if endometrial biopsy cannot be performed/will not be tolerated by the patient.

CT chest, abdomen and pelvis:
- useful for staging if significant, advanced disease is suspected.

Question 20

What are the 4 stage of endometrial cancer? [4]

Answer 20

Stage 1: Confined to the uterus
Stage 2: Invades the cervix
Stage 3: Invades the ovaries, fallopian tubes, vagina or lymph nodes
Stage 4: Invades bladder, rectum or beyond the pelvis

Question 21

How do you treat stage 1 and 2 endometrial cancers?

Answer 21

Treatment for stage 1 and 2 endometrial canceri:
- a total abdominal hysterectomy with bilateral salpingo-oophorectomy, also known as a TAH and BSO (removal of uterus, cervix and adnexa).
- if a younger patient wishes to retain fertility, can be counselled on alternative therapy like using progestin (not common use)

Radiotherapy may be used for stage 1B+
- Vaginal brachytherapy and pelvic external beam radiotherapy (EBRT)
- Also for palliative care

Chemotherapy

Question 22

Endometrial cancer may easily be confused with other causes of abnormal vaginal bleeding. Name three causes [3]

Answer 22

Atrophic vaginitis
Endometrial hyperplasia
Endometrial polyp

Question 23

Describe how you differentiate endometrial cancer from atrophic vaginitis [1]

Answer 23

Often improves upon the administration of oestrogen cream.

Question 24

Describe how you differentiate endometrial cancer from endoemetrial hyperplasia [1]

Answer 24

Endometrial hyperplasia: occurs when the endometrial lining becomes too thick and mainly affects post-menopausal women.
- Can only be differentiated from endometrial cancer by biopsy.

Question 25

Describe how you differentiate endometrial cancer from endoemetrial polyps [1]

Answer 25

Polyps can usually be differentiated from malignancy using a transvaginal ultrasound scan, where localised endometrial thickening will be present instead of generalised, uniform thickening.

Question 26

Describe the two types of endometrial tumours [2]

Answer 26

Type 1 tumours (adenocarcinomas) account for the majority of endometrial cancers, and are directly linked to long term exposure to increased oestrogen levels.
- Endometrial adenocarcinoma results from the abnormal proliferation of the endometrial glands due to chronic oestrogen stimulation of the endometrium

Type 2 tumours are rarer and have non-endometrioid histology.
* They are made up of serous and clear cell carcinomas.
* 90% of type 2 tumours are associated with p53 mutations.

Question 27

Answer 27

A 60-year-old obese, nulliparous woman presents with vaginal bleeding

Question 28

Answer 28

polycystic ovarian syndrome

Question 29

Answer 29

Early menarche

Question 30

Answer 30

Tamoxifen

Question 31

Answer 31

Strong family history of colorectal and endometrial cancer - hereditary non-polyposis colorectal carcinoma