Gynaecological Cancers Flashcards
What does cervical screening look for
It is now a primary HPV screen
All samples are first tested for hrHPV
If no HPV is found no cytology is needed and women are recalled for screening in 3-5 years
If HPV is found ‘reflex’ cytology is done ( on the same sample)
What are the symptoms of cervical cancer
Unusual vaginal discharge or bleeding
Inc. bleeding after sex/between periods
Dyspareunia
In early stages it is asymptomatic and therefore picked up by screening
What ages are offered cervical screening
Women aged 25 – 64 years old
Every 3 years, 25 - 49 years
Every 5 years, 50 – 64 years
Where do you take the smear sample from
The transformation zone of the cervix - most likely to be abnormal
What is the most common cause of cervical cancer
HPV
Types 16 and 18 are the highest risks - cause around 70% of cases
Types 6, 11 and others can lead to low grade abnormalities
Which gynae cancers does obesity increase the risk of
Womb and Ovarian
How does endometrial hyperplasia present
Abnormal bleeding - either dysfunctional or post-menopausal
Can be simple, complex or pre-cancerous
Often benign but must always be investigated
What type of hyperplasia are most endometrial cancers
Usually complex with disordered nuclei - precursor lesion
The glands become fused
Describe simple endometrial hyperplasia
General distribution
Made up of glands and stroma
Glands are dilated and have irregular shape but not crowded
Normal cytology
Describe complex endometrial hyperplasia
Focal distribution
Made up of glands
Glands are crowded (not much stroma between them)
Normal cytology
Describe atypical endometrial hyperplasia
Focal distribution Made up of glands Glands are crowded Atypical cytology This is the stage just before cancer - very high risk
Which age group typically gets endometrial carcinoma
Peak incidence 50-60
Uncommon in women under 40
Which gynae conditions can predispose to endometrial cancer
Polycystic ovary syndrome and Lynch syndrome
This increases the risk in younger women
What are the two main types of endometrial carcinoma
Endometrioid carcinoma
Related to unopposed oestrogen
Serous carcinoma
How does endometrial carcinoma spread
Directly into myometrium and cervix
Lymphatic
Haematogenous
How do you investigate endometrial carcinoma
Do a pipelle or a hysteroscopy
If high grade you can then do a scan to assess for spread
Which type of carcinoma is Lynch syndrome associated with
Endometrioid carcinoma - type 1
Due to germline mutation of mismatch repair genes
Why does obesity increase risk of endometrial cancer
Adipose tissue can convert ovarian androgens into oestrogens
Oestrogen drives the endometrial proliferation
The more fat cells you have the more oestrogen you have
How does being post-menopausal affect oestrogen driven proliferation
In post menopausal women there is no progesterone release to stop the proliferation – just constant oestrogen stimulation
What is Lynch Syndrome
It is a genetic disorder caused by a defective DNA mismatch repair gene
Autosomal dominant
It is a cancer predisposition syndrome - high risk of colorectal, endometrial and increases chance of ovarian
What annual tests are offered to those with Lynch syndrome
Endometrial pipelles every year to check for cancer
Annual colonoscopies to look for colorectal cancer
How can you tell if a tumour is caused by Lynch syndrome
Immunohistochemistry staining of the tumour for mismatch repair proteins
They also show microsatellite instability
This can help diagnose the syndrome and lead to genetic counselling
Which type of endometrial cancer is more aggressive
Type II
Serous and clear cell type
Spreads to the peritoneum quickly which makes it harder to treat
How does serous endometrial cancer spread
Spreads along fallopian tube mucosa and peritoneal surfaces
Can present with extrauterine disease
What are the characteristics of serous endometrial carcinoma
Characterised by a complex papillary and/or glandular architecture with diffuse, marked nuclear pleomorphism
How do you grade endometrioid carcinoma by architecture
Grade 1 = 5% or less solid growth
Grade 2= 6-50% solid growth
Grade 3= >50% solid growth
How do you grade serous carcinoma
not formally graded
How do you grade endometrial cancer by spread
Stage I = Tumour confined to the uterus
II = Tumour invades cervical stroma
III = local and/or regional tumour spread
IV = Tumour invades bladder and or bowel mucosa (IVA) and/or distant metastases (IVB)
Describe endometrial stromal sarcoma
It is rare
Cells resemble endometrial stroma
Infiltrate myometrium and often lymphovascular spaces
Typically presents with abnormal uterine bleeding but initial presentation may be as metastasis (most commonly ovary or lung)
Which tumours can affect the myometrium
Leiomyoma (fibroid) - very common
May not cause issue if small but may cause menorrhagia, infertility if large
Leiomyosarcoma (rare) - the malignant version
How do fibroids cause bleeding
If it lies right below the endometrium it can stretch it and lead to bleeding
Also harder for embryo to implant properly so can affect fertility
How does a uterine leiomyosarcoma usually present
Most occur in women >50 years
Commonest symptoms abnormal vaginal bleeding, palpable pelvic mass and pelvic pain
What are the typical symptoms of ovarian pathology
Pain
Swelling
Endocrine effects
Are you more concerned about solid or cystic ovarian tumours
Solid is more worrying
What are the different classifications of ovarian tumours
Epithelial
- Serous- most common
- Mucinous
- Endometroid
- Clear cell
- Germ cell
- Urothelial-like tumour - Brenner
Sex‐cord/stromal
- Granulosa cell
- Thecoma/Fibroma
- Sertoli/Leydig
Germ
- Teratoma
- Dysgerminoma
- Endodermal sinus or yolk sac tumour
Metastatic
How are epithelial ovarian tumours catergorised
Benign = No cytological abnormalities, proliferative activity absent or scant and no stromal invasion
Borderline = cytological abnormalities, proliferative but no stromal invasion
Malignant -stromal invasion
Describe a high grade serous carcinoma of the ovary
Most cases originate from the fallopian tube as a serous tubal intraepithelial carcinoma
It is more common than the low grade version
Can spread to peritoneum if cells from the tubes reach it
Describe a low grade serous carcinoma of the ovary
Serous borderline tumour is the precursor lesion
Less common than high grade
It is much less aggressive and managed with surgery
Which type of ovarian tumour is commonly seen with the BRCA mutation
High grade serous carcinoma
What conditions are associated with endometroid and clear cell ovarian carcinomas
Endometriosis of the ovary
Lynch syndrome
has a good prognosis
How is ovarian cancer usually diagnosed
Often presents with ascites so can diagnosed by taking a sample of the cells from the fluid
Combined with a high CA125 (blood test) - raised in 80% of cases
Urgent pelvic ultrasound
Gold standard is a CT guided biopsy
CXR/CT chest can be used to identify any pleural effusion or chest disease
How does an ovarian serous neoplasia appear
Benign: multicystic mass (thin serous watery fluid if pop them, no solid elements)
Borderline tumours will develop papillary structures
Are most ovarian germ cell tumours benign or malignant
Vast majority are benign - very rare for them to become malignant
Also called a dermoid cyst
What cell types can be found in an mature ovarian tertatoma
They are cystic, containing sebum and hair
Can also contain skin, respiratory epithelium, gut, fat common
Contains elements from ectoderm, mesoderm and endoderm
What are the different types of ovarian germ cell tumours
Mature teratoma - dermoid cyst Immature teratoma - rare Dysgerminoma - most common malignant one Yolk sac tumour Choriocarcinoma Mixed germ cell tumour
What is the most common malignant germ cell tumour of the ovaries
Dysgerminoma,
Describe an ovarian fibroma
Type of sex cord/stromal tumour
Made up of fibroid tissue and theca cells
It is usually benign
May produce oestrogen causing uterine bleeding
Describe ovarian granulosa cell tumours
Type of sex cord/stromal tumour
All are potentially malignant
Can produce lots of oestrogen (have thickened endometrium and abdnormal/post menopausal bleeding)
Which cancers are the most common causes of mets in the ovaries
Stomach Colon Breast Endometrium Pancreas
If ovarian tumours are bilateral and small then you should consider mets
How can you stage ovarian cancer by spread
I- confined to 1 or both ovaries
II-spread to other pelvic organs eg uterus, fallopian tubes
III- spread beyond the pelvis within the abdomen
IV- spread into other organs eg liver, lungs
How does ovarian cancer present
May be mass, swelling, pressure symptoms Malignant ascites - peritoneal spread Heartburn/indigestion Early satiety Weight loss/anorexia. Bloating Change of bowel habit SOB/ Pleural effusion Leg oedema or DVT Very variable and non-specific
What can lead to a raised CA125
Ovarian cancer - 80% of cases Endometriosis Peritonitis/infection pregnancy Pancreatitis Ascites Other cancers
If CA125 is normal does it exclude cancer
NO
How can you treat germ cell ovarian tumours
Fertility sparing if needed - common in younger women
Then salpingoopherectomy +/- chemo
How do you treat ovarian cancers (non-germ cell)
Chemo and Surgery
Surgery is usually in the form of debulking which is the process where tumour
deposits are removed as much as possible
Chemo used adjuvantly or first line in those unfit for surgery
What are the risk factors for cervical cancer
HPV Smoking Age of onset of intercourse “High Risk” male OCP - long term use Multiple partners Immunosuppression
How does cervical cancer present
Often asymptomatic and picked up on screening
Some women present with abnormal bleeding - post coital/menopausal
Pelvic pain
Haematuria / urinary infections
Some present with acute renal failure – will go to doctor feeling very acutely unwell
How do you stage cervical cancer
Stage 1a – microscopic Stage 1b - visible lesion Stage 2 a – vaginal involvement 2b - parametrial involvement Stage 3 - lower vagina or pelvic sidewall involved Stage 4 - bladder/rectum or metastases
How do you treat cervical cancer
Surgery - removal of the transition zone (early stage)
For further stage disease you would need a hysterectomy
Use combination of chemo and radiotherapy
How is radiotherapy delivered in cervical cancer
Targeted to include tumour +/- nodes
Give fractions of the dose over several days – gives normal cells time to start repairing
Brachytherapy – give a very high dose to the cervix and use packing to push the bladder and rectum away from the source (internal treatment)
How can you mark the tumour location for delivering treatment
Can place gold marker seeds into the tumour to mark the edges
Planning CT is done in the same position as they will receive the treatment in
They are given pinpoint tattoos to mark out the targets so that it can be accurately found each day
What is neoadjuvant chemotherapy
Given before the definitive treatment to try and shrink the tumour
What is concomitant chemotherapy
Given alongside radiotherapy and sensitises the tumour
Which drugs are used in the treatment of ovarian cancer
Cisplatin
Carboplatin/paclitaxol
What is the mainstay of endometrial cancer treatment
Surgery - total hysterectomy and potentially salpingoopherectomy
Only use chemo/radio if the patient is inoperable
Also used adjuvantly
What can cause endometrial cancer
Obesity
Oestrogens – HRT, Tamoxifen
Genetic - HNPCC
WHat is the most common site of recurrence of endometrial cancer post-hysterectomy
The top of the vaginal vault
Therefore this area is often directly treated with radiotherapy
Who is most at risk of ovarian cancer
Women over 50 Nullparity or low parity Delayed pregnancy Family history of breast or ovarian cancer BRCA
is it useful to screen everyone for ovarian cancer
No evidence that screening the general population is useful
Only screen those at high risk (FH or BRCA)
Can have an oophorectomy to reduce risk
What test should be offered to women with a high RMI
CT of the abdomen and pelvis
How does ovarian cancer spread
Peritoneal seeding within pelvis → abdominal cavity
Common for it to spread to omentum and even the underside of the diaphragm
para-aortic node metastases are a fairly common finding
Haematogenous spread → liver, lungs, brain
What are the symptom burdens of gynae cancer
Pain Nausea/ vomiting Constipation Bleeding Treatment related side effects Altered body image Fertility issues Worry and fear
Which drugs can be used to treat vomiting triggered by the GI tract
Metoclopramide, Levomepromazine, Ondansetron, Dexamethasone
Which drugs can be used to treat vomiting triggered by the chemoreceptors
Haloperidol, Levomepromazine, Ondansetron
Which drugs can be used to treat vomiting triggered by motion (vestibular system)
Cyclizine, Levomepromazine, Hyoscine
Which drugs can be used to treat vomiting triggered by the cerebral cortex (emotions, smell etc)
Dexamethasone, Aprepitant, Benzodiazepines
How can cancer cause nausea and vomiting
Compression / irritation by tumour = raised ICP Anxiety Chemotherapy/Radiotherapy Induced Impaired gastric emptying Metabolic disturbance
How can you manage cancer induced N&V
Trial anti-emetics Small meals Keep bowels moving Calm environments Acupressure bands
What is a malignant bowel obstruction
Clinical evidence of bowel obstruction in the setting of a diagnosis of intra-abdominal cancer
Occurs with abdominal cancers – either primary or spread from another place (most commonly ovarian)
How does a malignant bowel obstruction present
Nausea Vomiting Pain - Continuous or Colicky Anorexia/thirst Systemic symptoms from underlying cancer Reduced then absent bowel motions/flatus Paradoxical diarrhoea - as will still have secretions from below obstruction Gradual onset
How do you manage malignant bowel obstructions
If they have obstruction in one area you can treat them surgically and cut out the offending area and reconnect
Advances cancer not suitable for this
Manage these cases medically – break the secretion/distention cycle
Use anti-emetics and pro-kinetics (encourage the bowel to move) – metoclopramide does both
Can also use steroids and anti-secretory agents
How long does it take for a HPV infection to progress to cancer
HPV infection to high grade CIN takes 6 months - 3 years
High Grade CIN to invasive cancer takes 5 -20 years
What is Cervical Intraepithelial Neoplasia (CIN)
Pre-invasive stage of cervical cancer - dysplasia of the squamous cells
Occurs at the transformation zone
Asymptomatic
Detected on screening
How is CIN graded
CIN I - Basal 1/3 of epithelium occupied by abnormal cells.
Surface quite normal but nuclei slightly abnormal
CIN II - Abnormal cells extend to middle 1/3
Abnormal mitotic figures
CIN III - Abnormal cells occupy full thickness of epithelium.
Mitoses, often abnormal, in upper 1/3.
This is the most severe change
What is the most common malignant cervical tumour
Invasive Squamous Carcinoma
It develops from pre-existing CIN so can be prevented by screening
How does cervical squamous carcinoma spread
Local- uterine body, vagina, bladder, ureters, rectum
Lymphatic - early spread to pelvic, para-aortic nodes
Haematogenous - late spread to liver, lungs, bone
What is Cervical Glandular Intraepithelial Neoplasia (CGIN)
Origin from endocervical epithelium
CGIN is preinvasive phase of endocervical adenocarcinoma
More difficult to diagnose on cervical smear than squamous
Which type of cervical cancer has the worse prognosis
Endocervical Adenocarcinoma has a worse prognosis than squamous carcinoma
What can lead to cervical adenocarcinoma
Higher S.E. Class
Later onset of sexual activity
Smoking
HPV again incriminated, particularly HPV18.
Which types of cancer can affect the vagina
Vaginal intraepithelial neoplasia
Squamous carcinoma - seen in elderly
Melanoma: Rare. May appear as a polyp.
How is HPV acquired
Direct physical contact - skin to skin, oral, genital
However, it is so common that you don’t need to go to a sexual health clinic and it isn’t considered an STD
8 out of 10 people carry HPV at some time in their life
Of those 9 out of 10 clear it within 2 years
Smoking is a protective factor against which gynae cancer
endometrial
Which types of cancer can affect the cervix
Squamous cell cancer of the Squamous epithelium - more common
Adenocarcinoma of the glandular epithelium - harder to detect
What happens to the position of the transformation zone of the cervix as a woman ages
It moves upwards
Most abnormal smears detect advanced cancer - true or false
False
Mostly pre-invasive disease which is easily treated
What is colposcopy
Examination of the cervix under magnification using a colposcope
Solutions are used to help the colpscopist decide whether there is an abnormality i.e. CIN
What test is required for a definitive diagnosis of cervical cancer
Histology
How do you diagnose CIN
Colposcopically directed biopsy
Use a punch biopsy and AgNO3 for haemostasis
How do you manage CIN I
Managed expectantly as 80% will resolve
Repeat smear in 1 year
How do you manage CIN II
Usually treat
However selected cases can be managed expectantly if follow up guaranteed
How do you manage CIN III
This requires treatment
Either by ablation or excision
What are the advantages of cervical ablation
Simple, safe ,effective
What are the disadvantages of cervical ablation
Need pre-treatment biopsy
i.e. first visit for biopsy
Second visit for treatment
Can’t use if
Lesion inside cervical canal
Any suspicion of cancer
What are the advantages of cervical excision treatment
Whole lesion sent for pathology
One stop’ see & treat’
Can confidently exclude cancer from sample
What are the disadvantages of cervical excision treatment
If it shortens the cervix there is an increased risk of pre-term labour in subsequent pregnancy
Probably more morbidity ( bleeding etc)
Local anaesthetic essential
What is a LLETZ
Large loop excision of transformation zone
Treatment for CIN/ pre-cancerous cervical lesions
What follow up is required after CIN treatment
‘ Test of cure’ = HPV test and cytology 6 months post treatment
Double negative -> very high NPV, back to routine recall
If HPV or cytology positive recall to colposcopy
If abnormal colposcopy – retreat
If normal colposcopy annual smears for 5 years
How does HPV cause cancer
Person is infected with high-risk HPV types
HPV is integrated into the human genome
This leads to expression of viral genes which trigger the synthesis or upregulation of viral oncogenes - e6 and e7
Can damage the action of p53
Host cell immortilisation and malignant transformation
The HPV screening test only tests for specific types = true or false
False
It is a test for all or any of the 14 high risk types. The test is not type specific.
Which cancers can be caused by HPV
Cervical Oropharygeal Anal Vulval Penile
Who is offered the HPV vaccine
All S2 girls
Boys included since 2019
Adult MSM can be offered it through sexual health
Which strains of HPV are covered by the vaccine
6/11/16/18
If a smear comes back positive for HPV, what is the next step
Reflex cytology is performed on the same sample
If both HPV and cytology come back positive on a smear, what happens next
The patient will be referred to colposcopy
If HPV comes back positive on a smear but cytology is negative, what happens next
The woman will be screened again in a year
HPV infection/carriage is usually aysmptomatic - true or false
True
Usually resolves spontaneously
List factors which increase the levels of oestrogen in the body
PCOS Late menopause Nulliparity Obesity Unapposed oestrogen HRT Tamoxifen Carbohydrate intolerance Oestrogen secreting tumours
Therefore they can increase risk of endometrial cancer
How does endometrial cancer present
Abnormal vaginal bleeding - PMB, any irregular bleeding in women over 40
Vaginal discharge – blood/watery/purulent
Pain is rare in early stage of the disease and may indicate metastases
What is assessed in a TVUS
Measures endometrial thickness
Smooth and regular endometrium with a thickness <4mm makes
endometrial malignancy unlikely
How do you diagnose endometrial hyperplasia
Usually diagnosed by biopsy - increase in the gland-to-stromal ratio
How do you treat endometrial hyperplasia
Progestogens - young women
Mirena IUS
In atypical hyperplasia, hysterectomy is recommended
What is the precursor lesion to endometriod endometrial carcinoma
atypical hyperplasia
List common mutations responsible for endometriod endometrial carcinoma
PTEN, KRAS, PIK3CA mutations
Microsatellite instability – germline mutation of mismatch repair
genes (Lynch syndrome)
What is the precursor lesion to serous endometrial carcinoma
serous endometrial intraepithelial carcinoma
List common mutations responsible for serous endometrial carcinoma
TP53 mutations
What are the prognostic factors for endometrial cancer
- Histological type
- Histological differentiation
- Stage of disease
- Myometrial invasion
- Peritoneal cytology
- Lymph node metastasis
- Adnexal metastasis
Describe endometrial sarcoma
Rare
Arises from endometrial stroma
Locally aggressive and metastasizes early - Initial presentation may be as metastasis (lung or ovary)
What is the most common site of recurrence of endometrial cancer
The vault of the vagina
How do you treat a recurrence of endometrial cancer
Radiotherapy should be considered in isolated vault recurrence if it has not
previously been received.
Otherwise, hormonal therapy (high dose progestogens to
slow the disease) and chemotherapy should be the treatment of choice.
List risk factors for ovarian cancer
Low parity Genetics - 1st degree relatives affected - Lynch Syndrome (HNPCC) - BRCA 1 and 2 Endometriosis
What ovarian screening is offered to women with BRCA mutations
Regular screens
May be
offered bilateral oophorectomy once their family is complete
BRCA1 and 2 mutations increase your risk of which types of cancer
Ovarian
Breast
Lynch Syndrome (HNPCC) increases the risk of which types of cancer
Predisposition to bowel, endometrial, ovarian + other cancers
Ovarian - endometriod and clear cell in particular
What is the peak age for ovarian cancer
75
Affects older women
What is the most common type of primary ovarian tumour
Epithelial
Account for 70% of cases
Describe mucinous ovarian tumours
Often benign but can be malignant
Benign typically unilateral whilst malignant is bi
Usually multiloculated and contain mucinous fluid
o Rarely, pseudomyxoma peritonei may also be present – characterized by a
gelatinous tumour in the peritoneal cavity
Endometriod ovarian tumours are usually benign - true or false
False
They are usually malignant however they often present early
Almost all clear cell ovarian tumours are malignant - true or false
True
Which other conditions are associated with clear cell ovarian tumours
Endometriosis
Lynch syndrome - HNPCC
How do ovarian yolk sac tumour present
Usually present with sudden pelvic mass
hCG levels are normal but alpha-fetoprotein sebum levels are increased
Which types of ovarian tumours can secrete hcg
Choriocarcinoma
Sometimes dysgermioma
Which US features are suggestive of ovarian cancer
Complex mass with solid + cystic areas Multi-loculated Thick septations Associated ascites Bilateral disease.
What is the treatment of choice for ovarian cancer relapse
Chemotherapy
How do you treat benign ovarian tumours
Excision or drainage
- Often can’t distinguish between benign or malignant tumours and diagnosis occurs
after surgery has been performed
How can CIN progress
33% of CIN cases will progress to the next degree classification, 33% will
show no changes, and 33% will regress
CIN is not visible to the naked eye - true or false
True
Only picked up by smear or histology
How might advanced cervical cancer present
Backache Leg pain Haematuria Weight loss Anaemia Changes in bowel habit
How does cervical cancer spread
Cervical cancer spreads to adjacent structures and via the draining lymphatics.
It rarely
metastasizes through the blood
