Vulval & Endometrial Cancers Flashcards
Vulval cancers are which (cell type) of cancer? [1]
Which part of the vulva do they commonly affect? [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
Name some risk factors for vulval cancer [5]
- Older age
- Human papilloma virus (HPV) infection
- Vulval intraepithelial neoplasia (VIN)
- Immunosuppression
- Lichen sclerosus - big one (5% get vulval cancer)
Describe the pathophysiology of vulval cancer [1]
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.
How do vulval carcinomas present? [3]
Lump or ulcer on the labia majora
- May be associated with itching, irritation
What causes high grade [1] and differentiated [1] VIN?
High grade:
HPV infection - younger women
Differentiated:
- Lichen sclerosis - older women
What is the referral criteria for vulval cancer? [1]
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.
Describe the management for vulval carcinoma? [4]
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.
TOM TIP: For your exams, any woman presenting with postmenopausal bleeding has [] cancer until proven otherwise.
TOM TIP: For your exams, any woman presenting with postmenopausal bleeding has endometrial cancer until proven otherwise..
Explain the key risk factors for endometrial cancer [+]
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
Explain why obesity increases the risk of endometrial cancer [3]
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
Explain why PCOS increases the risk of endometrial cancer [3]
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
For endometrial protection, women with PCOS should have one of: [3]
The combined contraceptive pill
An intrauterine system (e.g. Mirena coil)
Cyclical progestogens to induce a withdrawal bleed.
Why does tamoxifen have an increased risk of endometrial cancer? [1]
Tamoxifen has an anti-oestrogenic effect on breast tissue, but an oestrogenic effect on the endometrium. This increase the risk of endometrial cancer.
Why is DMT2 linked with increased risk of endometrial cancer? [1]
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
When would you refer women with ?endometrial cancer
- 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.
Describe the clincial presentation of endometrial cancers [5]
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
Name three pelvic examination findings that may indicate endometrial cancer [3]
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.
How do you investigate for endometrial cancer? [4]
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.
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
What are the 4 stage of endometrial cancer? [4]
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
How do you treat stage 1 and 2 endometrial cancers?
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
How do you treat stage 3-4 endometrial cancers? [4]
Stage 3-4 disease:
- Individualised treatment depending on symptoms
- Consideration of hysterectomy – can be minimal access
- Lymphadenectomy – removal of bulky lymph nodes versus full lymphadenectomy (less benefit)
- Removal of all visible disease – likely to improve survival but evidence not as strong as in ovarian cancer
A patient wants fertility sparing treatment for their endometrial cancer
What is the treatment that can be given [1]
What stage of cancer would they need to have for this? [1]
Hormonal treatment: Grade 1A
- Mirena Coil +/- oral progesterones
NB: also if unfit for surgical management
Endometrial cancer may easily be confused with other causes of abnormal vaginal bleeding. Name three causes [3]
Atrophic vaginitis
Endometrial hyperplasia
Endometrial polyp
Describe how you differentiate endometrial cancer from atrophic vaginitis [1]
Often improves upon the administration of oestrogen cream.
Describe how you differentiate endometrial cancer from endoemetrial hyperplasia [1]
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.
Describe how you differentiate endometrial cancer from endoemetrial polyps [1]
Polyps can usually be differentiated from malignancy using a transvaginal ultrasound scan, where localised endometrial thickening will be present instead of generalised, uniform thickening.
Describe the two types of endometrial tumours [2]
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.
A 60-year-old obese, nulliparous woman presents with vaginal bleeding
polycystic ovarian syndrome
Early menarche
Tamoxifen
Strong family history of colorectal and endometrial cancer - hereditary non-polyposis colorectal carcinoma
Describe the difference in referral for endometrial thickness and PV bleeding/not for ?endometrial cancer [2]
If PV bleeding and endometrial thickness >4mm - refer
If no PV bleeding and endometrial thickness >11mm - refer
What does this image show? [1]
TVS of uterus – thickened endometrium
Which are the most common type of endometrial cancer? [1]
Adenocarcinomas:
- more than 75% are endometrioid
- also clear cell, uterine serous carcinomas
An endometrial cancer is dx as being a sarcoma.
What is the most common type? [1]
Leiomyosarcoma
Endometrial stromal sarcoma, low grade or high grade
Undifferentiated sarcoma
What is important to note about carcinosarcoma endometrial cancers? [1]
carcinosarcoma are aggressive tumours with a poor prognosis
- they are adenocarcinoma but behave like both types of cancer (adeno and sarcoma)
Endometrial cancers are classified according to TCGA (The Cancer Genome Atlas) classification.
Which mutations determine this? [2]
TP53 and POLE (polymerase epsilon) mutation
The following are all types of endometrial carcinoma based off molecular stratification.
Which of the following is aggressive and will require adjuvant treatment?
MMR abnormal
POLE mutant
P53 wild type
P53 mutant
The following are all types of endometrial carcinoma based off molecular stratification.
Which of the following is aggressive and will require adjuvant treatment?
MMR abnormal
POLE mutant
P53 wild type
P53 mutant
The following are all types of endometrial carcinoma based off molecular stratification.
Which of the following is associated with Lynch syndrome?
MMR abnormal
POLE mutant
P53 wild type
P53 mutant
The following are all types of endometrial carcinoma based off molecular stratification.
Which of the following is associated with Lynch syndrome?
MMR abnormal
POLE mutant
P53 wild type
P53 mutant
Radiotherapy is an adjuvant treatment for endometrial cancer.
Which stages are indicated for it? [2]
What are the modalities? [3]
Radiotherapy:
- improves local control but not survival
Indications
* ?stage 1b grade 3
* Stage II-III
Modalities:
* Brachytherapy
* External beam pelvic RT
* Extended field
Where is the most common place for endometrial cancer to occur? [1]
How do you treat? [+]
Vault
Lecture:
Describe the bimodal development of vulval cancers and how this is clinically significant [+]
Important to note - he said in lecture
Bimodal developmental pathway: HPV dependent and HPV independent
HPV dependent:
- younger age group and radiosensitive, better prognosis
- HPV dependent associated with anal, vaginal and cervical tumours
- Associated with VIN
HPV Independent
- Older women; from lichen sclerosus
- Worse prognosis
