11.1 Gynaecological tumours Flashcards
What are the 2 most common gynaecological cancers (in order)?
Which has a higher death rate?
1) Uterine tumours
2) Ovarian cancer
Ovarian cancer deaths > uterine cancer
Describe the normal histology of the Cervix and what is a common site for neoplastic change may occur
Comprised of both stratified squamous epithelium (non-keratinised) and columnar epithelium
Epithelium change occurs at the “squamocolumnar junction” and is a common site for neoplastic change
Describe cervical and HPV screening guidelines If results are abnormal what would the next steps be?
Every girl is invited at the age of 25 every 3 years untill the age of 50 for a primary HPV screen (every 5 years from the age of 50-65)
- If sample shows no HPV the women return to screening programme
- If HPV positive cytology is analysed and if no abnormal cells women are retested in 12 months time
- If abnormal cells women are referred for colposcopy
What is the purpose of cervical screening?
It picks up CIN (pre-cancerous lesions) and treatment can be given before invasionoccurs. This is therefore curative
What does CIN stand for and what is it? What would CIN I, II and III indicate?
Cervical intraepithelial neoplasia: refers to the potentially precancerous transformation of cells of the cervix
CIN I: mild epithelial dysplasia confined to the basal 1/3 of the epithelium
CIN II: moderate dysplasia confined to the basal 2/3 of the epithelium
CIN III: severe dysplasia with undifferentiated neoplastic cells that span entire thickness
What are the 2 HPV strains linked with cervical cancer?
HPV 16,18
Is HPV a direct or Indirect carcinogen and why?
A direct carcinogen because it expresses the E6 and E7 proteins that inhibit p53 and pRB protein function
What 2 proteins does HPV produce and how can these lead to cervical cancer?
1) E6 protein: binds to and mediates degradation of P53 and activates telomerase 2) E7 protein: promotes progression through the G1-S cell cycle checkpoint by binding to pRB protein. It also inactivates CDK inhibitors and activates some cyclins.
What is p53 and pRB?
Both are a tumour suppressor gene
Give 4 risk factors for development of cervical carcinoma
1) sexual intercourse, multiple partners (exposure to STD) 2) immunosuppression 3) cigarette smoking 4) Familial tendency
Describe the early presentation of cervical cancer and include symptoms that may appear as disease progresses
Early stages: asymptomatic As it progresses presentation may include: • abnormal vaginal bleeding • postcoital bleeding • blood stained discharge • pain radiating to sacral region Advanced disease: death as a consequence of local tumour invasion-ureteral obstruction/pyelpnephritis/uremia Death is NOT distant metastasis.
What is generally the cause of death in advanced cervical carcinoma?
Death as a consequence of local tumour invasion (eg. ureteral obstruction/pyelpnephritis/uremia) Death is NOT often causes by distant metastasis!!
What are the 2 most common primary cervical tumours? Give 2 rare variants of primary malignancies
1) Squamous cell carcinoma (most common) 2) Adenocarcinoma (CGIN) Rare: adenosquamous/neuroendocrine/ lymphoma/sarcoma Can metastasis (secondary tumours)
What is CGIN?
Cervical glandular intra-epithelial neoplasia: pre-cancerous abnormality of the glandular cells. It’s much less common that CIN, but is similar
List the 4 most common local invasions of a cervical carcinoma
1) around cervix: ureters
2) around uterus
3) To rectum: causing fistulas
4) to urinary bladder: causing fistulas
Why may patients present with uraemia in advanced stage cervical cancer?
Because cervix is in close proximity to the ureter, it can directly invade here and may lead to ureteric obstruction. In advanced stages patient may experience uraemia because of this (high levels of urea in the blood)
Which lymph nodes are commonly involved in cervical carcinoma spread? (5)
1) parametrial nodes 2) obturator nodes 3) external Iliac nodes 4) common Iliac nodes 5) para-aortic nodes
What is the name of the cervical cancer vaccination and what types of HPV does it cover? How effective is it?
Gardasil: covers 8, 11, 16, 18 100% effective if never been exposed to HPV prior
Who is eligible for the HPV vaccination and does it protect against other HPV linked tumours? If you gave had the vaccination, do you still get screened?
Girls and boys aged 12-13 The vaccine protects from other HPV inked tumours (vulval, penile and head and neck tumours) BUT we do need to continue screening
What is the most common endometrial cacinoma?
Adenocarcinoma
What hormone can cause hyperplasia of the uterine lining? (endometrium)
Oestrogen can stimulate hyperplasia of the epithelium
What are the 2 types of hyperplasia that can occur and what does it depend on?
1) simple hyperplasia (non-neoplastic) 2) complex hyperplasia (sometimes neoplastic) With or without Atypia (neoplastic) The extent of hyperplasia is determined by the amount of stroma present between glands and architectural complexity
If hyperplasia develops with atypia why is this concerning?
How would you treat an endometrial carcinoma, give an example
Much more likely to progress to endometrial carcinoma, if it does treat by giving progesterone and suppressing oestrogen.
Eg. Tamoxifen (anti-oestrogen): should supress tumour growth as it acts as an antagonist of the oestrogen receptor (ER) and decreases cell replication
Describe the sequence of events that occur in cervical epithelium that results in the development of invasive cervical carcinoma
Normal epithelium → viral infection → CIN I →CIN II → CIN III → invasion
As you progress along this sequence you see a progressive loss of differentiation and increasing atypia in more layers of the epithelium. At the end of the sequence the epithelium is totally replaced by immature atypical cells exhibiting no surface differentiation
What are the 2 types of endometrial adenocarcinoma and briefly explain each
Type I (80%) “endometrial carcinoma”
- related to unopposed estrogen
- usually seen in younger patients (50-55)
- associated with pre-hyperplasia
- low grade (good prognosis)
Type II: “uterine papillary serous carcinoma”
- clear cells and serous papillary in uterus
- usually seen in elderly (>65)
- not associated with pre-hyperplasia
- high grade (poor prognosis)
Give 4 risk factors for developing Type I endometrial carcinoma
1) nulliparous (woman who has never given birth)
2) early menarche/late menopause
3) Iatrogenic/ HRT
4) obesity/ diabetes /hypertension
Which age group is most affected by endometrial carcinoma and what is the clinical presentation?
Peak incidence 55-65 years
Common clinical presentation: post menopausal bleeding, with excessive leukorrhoea (white discharge)
Rare: uterine enlargement (only seen in advanced stage)
Describe the staging of endometrial carcinoma
Stage I: depth <1/2, >1/2 myometrial thickness (confined to the uterus)
Stage II: Involvement of cervical stroma/adnexa (spread to the cervix)
Stage III: cancer that has spread to the vagina, ovaries, and/or lymph nodes
Stage IV: cancer that has spread to the urinary bladder, rectum and beyond pelvis
- or organs located far from the uterus (lungs or bones)
What are the 4 common lymph spread sites of an endometrial carcinoma?
1) Obturator nodes
2) External Iliac nodes
3) Common Iliac nodes
4) pariarotic nodes
What is the most common tumour of the uterus and are they usually benign or malignant?
How do these usually present?
Myometrial tumours: smooth muscle leiomyomas (seen as fibroids). These are Oestrogen dependent
Can be single or multiple but are benign mesenchymal tumours. Can become very large so usually present with “uterine enlargement”
How do leiomyomas present?
Also state how they may present in pregnancy and following?
May be asymptomatic but progression will always present with heavy/painful periods, if they become very large there can also be uterine enlargement and mass symptoms (urinary frequency due to bladder compression)
In pregnancy: these fibroids get infarcted leading to sudden acute abdominal pain. Also because of position within uterine cavity it can result in fetal malpresentation
Following pregnancy presentation can be with postpartum haemorrhage
Can result in Infertility and increased frequency of abortions
Give 2 malignant mesenchymal tumours of the uterus
1) Leiomyosarcoma
2) Endometrial stromal sarcomas
These are rare
Ovarian cancers can be classfied by their origin, what are the 4 classifications?
1) Surface epithelial cells
2) Germ cells
3) Sex-chord stroma (produce hormones- estrogen/androgens)
4) Metastisis to ovaries (secondary tumours)
Are the majority of ovarian neoplasms benign or malignant and what age group is most commonly affected?
80% benign and mostly occur in young women 20-45 years (borderline tumours are seen at slightly older age)
Malignant tumours are most commonly seen in older women 45-65 years
Why are malignant ovarian cancers the major cause of gynaecological cancer deaths?
These are usually asymptomatic and are very silent tumours and hence they do not present untill advanced
There are also usually no precursors hence no symptoms from these
Why is there no national screening programme for ovarian cancer in the UK?
What is CA125 and give its use in ovarian cancer
because there isn’t a test that reliably picks up ovarian cancer at an early stage
CA125 protein is a tumour marker but unfortunalty is not very specifc to ovarian cancer so cannot be used as a screening tool or as a 100% diagnostic marker
- anything that causes peritonial irritation can lead to a rise in CA125
BUT if patient is known to have ovarian cancer it can be used to monitor disease progression
Give 3 late clinical presentations of ovarian cancer and state what condtion it may often be confused with and why
These tumours do not have a precursor so are most often asymptomatic in early stages.
Clinical presentations that may occur in late stage include:
1) mass effect
2) bleeding: due to hormonal menstrual disturbances caused by inappropriate secretion of oetrogen
3) ascites, obstruction, perforation and death (often confused with IBS)
If peritoneal implants are detected in ovarian cancer what does this mean?
it is associated with peritoneal disease
Give 4 risk factors for development of ovarian cancer
1) IVF: risk of super-ovulation due to repeated rupture of surface epithelium
2) HRT: oestrogen effect
3) smoking = x2
4) obesity
5) endometriosis: because endometrial tissue growth in the ovaries can lead to benign cyst formation which can prgress into ovarian tumours
6) Talcum powder
7) prior cyst
Give a common gene associated with familial ovarian cancer
BRCA 1 and BRCA 2
What is the effect of OCP use and pregancy on development of ovarian cancer?
Thought to have a protective effect by decreasing ovulation/repeated trauma to surface epithelium
Which type of ovarian tumour origin is the most common and is it usually benign or malignant?
What are the 5 sub-types of these?
Tumours arsising from surface epithelial cells and are most commonly malignant (but can be benign or boarderline).
Type depends on which specific tissue tumour is arising from, can be:
1) serious
2) mucinous
3) endometrioid
4) clear cell
5) brenner (transitional)
Describe a benign, boarderline and malignant neoplasm of an epithelial tumour
Benign: nuclei aligned basally
Borderline (low malignant potential): nuclear arrangement begins to stratify (abnormal)
Malignant: abnormal nuclei invades into stroma
What a mucinous tumour and describe its appearance
How may these present?
Ovarian mucinous adenomas are a benign tumour that arises from the surface epithelium of the ovary.
It is a multilocular cyst with smooth outer and inner surfaces. It tends to be huge in size and contains mucoid material
Cysts may undergo tortion resulting in infarction which can present as acute abdominal pain
What is a serous tumour and describe its appearance
Serous tumours develop from the surface epithelium of ovary and they secrete serous fluid.
They are generally benign but can be borderline or malignant
Serous adenomas usually have papillary projections on surface
Describe the classic characteristic of Sex chord stromal tumours
Are these usually benign or malignant
What are the 3 common types?
These are neoplasms which frequently produce steroid hormones. May be benign or malignant
1) granulosa cell tumour
2) Thecoma
3) Leydig cell tumours (very rare)
What are the most common sex chord tumour ?
Is it more likly to be benign or malignant and when does it most commonly occur?
What is it associated with?
Thecoma
Most commonly occurs in reproductive years and is benign
Associated with oestrogenic stimulation *meigs syndrome
What is Meigs syndrome?
Triad of:
- benign ovarian tumor (Thecoma)
- ascites
- pleural effusion
If tumour is removed the ascites and pleural effusion resolves
What age group do Granulosa tumours most commonly affect and are they more likly to be benign or malignant?
Give 2 facts special to these tumours
What is it associated with?
Occurs at any age and is potentially malignant
They can present many years after tumour has developed and have a large propensity for late recurrence
Associated with oestrogenic stimulation (hyperplasia within endometrial lining may occur)
How common are Leydig cell tumours and what do they commonly secrete?
Describe their differentiation
RARE: can secrete androgens which can lead to virilisation (development of masculine characteristics)
Can be well-moderate or poorly differentiated
Are germ cell tumours more likly to be benign or malignant?
Give 3 substances these tumours produce and state why these may this be useful?
Can be benign or malignant
Produce HCG, AFP (α-fetoprotein) and LDH which can be used to monitor disease
Must consider that these substance may also indicate other tumours hence should not be relied upon for diagnosis alone
What is the most important germ cell tumour we must be aware of?
Give 4 features of this tumour and state whether it is usually benign or malignant
Mature cystic teratoma (dermoid cyst) usually benign but can become malignant
features: skin, hair, teeth, bone, thyroid tissue, glia
When may a dermoid cyst be malignant?
Immature teratoma: when it contains neuroepithelium and/or other primitive embryonic tissues (foetal tissue)
Give 2 other malignant germ cell tumours that arise from embryonic tissue in the ovary
1) Dysgerminoma: germ cell tumour (like a seminoma in the testis), radiosensitive and associated with LDH secretion
2) Monodermal: comprised on one particular epithelium
- Thyroid epithelium, condtion known as Struma ovarii, but this is usually benign
- Carcinoid is malignant
Give 3 extra-embryonic germ cell tumours of the ovary
1) yolk sac tumours: associated with AFP
2) choriocarcinoma: associated with HCG secretion
3) endodermal sinus tumour
Give 2 sites that a secondary tumour in the ovary may have metastasised from
1) Genital tract from an endometrial tumour
2) extragenital: colonic, gastric (krukenberg tumours) breast
What is VIN and what does it stand for?
Pre-invasive stages, can be divided into 3
Vulval intraepithelial neoplasia: pre-invasive carcinoma, can be divided into 3 stages: VIN I, II, III
Give 4 types of Vulval tumours and state the most common
1) Squamous carcinoma (most common)
2) adenocarcinoma
3) basal cell carcinoma
4) malignant melanoma
What age group is vulval carcinoma most prominant in and why?
What virus may occasionally be associated and what are the risk factors for this?
Most prominent in older women (70%) who already have pre-existing skin conditions:
- differentiated VIN
- chronic irritation
- lichen sclerosus osquamous hyperplasia
- erosive lichen planus
30% are related to HPV 16 and 18, same risk factors as cervical carcinoma and occur in younger women
What is the main difference between basal and squamous cell carcinomas of the skin?
Describe the appearance of a vulval basal cell carcinoma
Basal cell carcinomas do NOT metastasise (sqaumous cell do), these are locally invasive tumours
Vulval basal cell carcinoma:
- Pearly white or pigmented nodule
- ulcerated
- labium major mainly
- deeply infiltrating if neglected
- does not metastasise
- NOT FOR VULVECTOMY
What is Extramammary Paget disease?
How does it present?
EMPD is a rare cancer related to Paget’s disease of the breast, found most commonly on the vulva of women. It is a chronic condition BUT only 25%of cases have an underlying adenocarcinoma arising within from the adnex
Presents as pruritic red area on labia majora
If an adenocarcinoa does arise it will be mucin containing and originate from cells in the epidermis
What are Adnexal tumors?
Adnexal tumors are growths that form on the organs and connective tissues around the uterus.
What is Gestational trophoblastic disease?
What is the most common tumour type?
GTD is a group of rare tumors which arise within the placental tissue
Hydatidiform mole (partial or complete) is the most common tumor type of GTD
It can become a persistant trophoblastic neoplasia:
- If partial mole begins to invade the myometrium then it becomes an Invasive mole
- if this then becomes malignant it is known as a choriocarcinoma
Neoplastic potential of complete mole is greater than partial mole
How common are Hydatidiform moles?
How does it usually present?
Describe its appearance
Affects 1/100 pregnancies (more risk in <16 and >50 year olds)
Presents as “larger for date” pregnant uterus (meaning uterus is greater in size than gestation) and bleeding in early pregnancy
Placental tissue made up of chorionic villi appears edematous and sometimes grape-like (undermicroscope villi appear enlarged and dilated with cyst formation. Surrounding cells show abnormal trophoblastic proliferation)
How do we get formation of a complete vs partial Hydatidiform mole?
Complete mole: The ovum does not contain ANY chromosmes (empty). Hence, 2 things may occur to form a complete mole
1) sperm enters an empty ovum and duplicate its own chromosomes
2) two spems can invade the empty ovum
Results in a 46 XY/XX state which is a complete mole, usually when patient miscarries there is NO foetus
Partial mole: chromosmal material contained in the ovum fetilised by 2 sperm (dispermy) resulting in a triploid state. When patient miscarries foetal tissue will be present
What can be monitiored in patients with a Hydatidiform mole?
Why are patients advised not to get pregnant?
Monitored by HCG levels (serum and urine)
If levels rise: patient will receive chemotherapy
Patients are followed up and advised not to get pregnant. This is because in pregnancy HCG levels rise and hence we cannot determine if this rise is really due to the pregnancy, or if it is masking the reccurance of the tumour/ failure for mole to completly regress
How common is it for a Hydatidiform mole to become malignant and what is this now known as?
What patients are at highest risk for developing this?
Why do patients present with haemoptysis?
Known as a Choriocarcinoma: rare and associated with high mortality
Malignancies usually arise in patients who have already had a molar pregnancy (80% of the time) but can arise from miscarriages and very rarely normal pregnancy (without history of molar pregnancy)
Patients present with hemoptysis because these tumours have a high propensity for systemic metastasis to lungs (seen on x-ray as cannonball metastasis). Can also metastasise to genital tract and brain
If a Choriocarcinoma develops during a molar pregnancy why is prognosis GOOD?
Because you are continuously monitoring that patient hence, it will be detected much earlier and can be treated before it has metastasised
