Gynaecological Cancers Flashcards
What type of cancer is 80% of endometrial cancers?
Adenocarcinoma
Adenocarcinoma = oestrogen-dependent cancer
(Oestrogen = stimulates the growth of endometrial cancer cells)
If a postmenopausal presents with bleeding. What is the diagnosis until proven otherwise?
Endometrial cancer
(Key risk factors = obesity + diabetes)
Define endometrial hyperplasia
Precancerous condition - thickening of the endometrium
2 Types of endometrial hyperplasia
- Hyperplasia without atypia
- Atypical hyperplasia
What condition is endometrial hyperplasia is like, in terms of risk factors, presentation and investigations?
Endometrial cancer
Management for endometrial hyperplasia
Progesterons:
* Intrauterine system (e.g. Mirena coil)
* Continuous oral progestogens (e.g. medroxyprogesterone or levonorgestrel)
Most cases will return to normal over time
Less than 5% become endometrial cancer
What is the underlying thing that causes the risk factors for enometrial cancer and hyperplasia?
Unopposed oestrogen
Unopposed oestrogen = oestrogen without progesterone
Unopposed oestrogen = stimulates the endometrial cells → increasing risk
The risk endometrial cancer is associated with the amount of unopposed oestrogen the endometrium is exposed to during the patient’s life
Why is PCOS a risk for endometrial cancer?
PCOS → increased unopposed oestrogen due to lack of ovulation
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 (the second half of the menstrual cycle). Women with polycystic ovarian syndrome are less likely to ovulate and form a corpus luteum. Without developing a corpus luteum during the menstrual cycle, progesterone is not produced, and the endometrial lining has more exposure to unopposed oestrogen.
Name some situations in which there is increased exposure to unopposed oestrogen
- Increased age
- Earlier onset of menstruation
- Late menopause
- Oestrogen only hormone replacement therapy
- No or fewer pregnancies
- Obesity
- Polycystic ovarian syndrome (PCOS)
- Tamoxifen
What should women with PCOS be given to lower their risk of endometrial cancer?
- The combined contraceptive pill
- An intrauterine system (e.g. Mirena coil)
- Cyclical progestogens to induce a withdrawal bleed
Why is obesity a risk factor for endometrial cancer?
Because adipose tisse (fat) = a source of oestrogen
- Adipose tissue = contain aromatase → enzyme that converts androgens (testosterone) into oestrogen
- Androgens = mainly produced by the adrenal glands
- Bigger women → more adipose tissue → more aromatase enzyme → more androgens into oestrogen → extra oestrogen = unopposed in women not ovulating (PCOS or postmenopausal) - because no corpus luteum → more progesterone
Why is Tamoxifen a risk factor for endometrial cancer?
Tamoxifen = has an anti-oestrogenic effect on breast tissue → but oestrogenic effect on the endometrium → increasing endometrial cancer risk
How is Type 2 Diabetes a risk factor for endometrial cancer?
Increased insulin production
* Insulin = stimulates endometrial cells → increase risk of endrometrial hyperplasia + cancer
PCOS = also associated with insulin resistance + increased insulin production (adding to risk)
Name protective factors against endometrial cancer
- Combined contraceptive pill
- Mirena coil
- Increased pregnancies
- Cigarette smoking
Smoking appears to be protective against endometrial cancer in postmenopausal women by being anti-oestrogenic. Interestingly, it is not protective against other oestrogen dependent cancers, such as breast cancer (where it increases the risk). Smoking may have anti-oestrogenic effects in several ways:
- Oestrogen may be metabolised differently in smokers
- Smokers tend to be leaner, meaning they have less adipose tissue and aromatase enzyme
- Smoking destroys oocytes (eggs), resulting in an earlier menopause
Clinical presentation of endometrial cancer
Signs:
* Abnormal vaginal discharge
* Anaemia
* Haematuria
* Raised platelet count
Symptoms:
* POSTMENOPAUSAL BLEEDING
* Postcoital bleeding
* Intermenstrual bleeding
* Unusually heaving menstrual bleeding
What is the main indicator for endometrial cancer?
POSTMENOPAUSAL BLEEDING
(More than 12 months after the last menstrual period)
What is the two-week-wait criteria for endometrial cancer
- 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
Ix for endometrial cancer
- Transvaginal ultrasound for endometrial thickness (normal is less than 4mm post-menopause)
- Pipelle biopsy (highly sensitive for endometrial cancer making it useful for excluding cancer)
- Hysteroscopy with endometrial biopsy
Staging system for endometrial cancer
The International Federation of Gynaecology and Obstetrics (FIGO) staging system is used to stage endometrial cancer:
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
Management for endometrial cancer
The usual treatment for stage 1 and 2 endometrial cancer = Total abdominal hysterectomy with bilateral salpingo-oophorectomy (AKA TAH and BSO) (removal of uterus, cervix and adnexa)
- A radical hysterectomy involves also removing the pelvic lymph nodes, surrounding tissues and top of the vagina
- Radiotherapy
- Chemotherapy
- Progesterone = may be used as a hormonal treatment to slow the progression of the cancer
What are the two types of vuval cancer?
- Squamous cell carcinoma (90%)
- Malignant carcinomas
Risk factors for vuval cancer
- Advanced age (particularly over 75 years)
- Immunosuppression
- Human papillomavirus (HPV) infection
- Lichen sclerosus
Around 5% of women with lichen sclerosus get vulval cancer.
What is vulval intraepithelial neoplasia (VIN)?
Vulval intraepithelial neoplasia (VIN) = precancerous condition - affecting the squamous epithelium of the skin (precedes vulval cancer
(VIN is similar to the premalignant condition that comes before cervical cancer (cervical intraepithelial neoplasia)
What is the type of VIN associated with HPV infection
(Typically occurs in younger women aged 35-50)
High grade squamous intraepithelial lesion
What is the type of VIN associated with lichen sclerosus
(Typically occurs in older women aged 50-60)
Differentiated VIN
Ix for vulval cancer
- Biopsy of lesion
- Sentinel node biopsy (demonstrate lymph node spread)
- CT abdomen and pelvis (staging
Info: Vulval cancer biposy
- Watch and wait with close followup
- Wide local excision (surgery) to remove the lesion
- Imiquimod cream
- Laser ablation
Clinical manifestations of vulval cancer
Signs:
* Vulval lump
* Ulceration
* Lymphadenopathy in groin
Symptoms:
* Bleeding
* Pain
* Itching
Vulval cancer most frequently affects the labia majora, giving an appearance of:
- Irregular mass
- Fungating lesion
- Ulceration
- Bleeding
Management for vulval cancer
- Wide local excision to remove the cancer
- Groin lymph node dissection
- Chemotherapy
- Radiotherapy
Why does ovarian cancer present so late?
Due to its non-specific symptoms → resulting in worse prognosis
More than 70% of patients with ovarian cancer present after it has spread beyond the pelvis.
Types of ovarian cancer
- Epithelial cell tumours (most common 90%)
- Sex Cord-Stromal Tumours (benign or malignant)
- Metastasis (Krunkenberg tumour - ‘signet ring’)
Subtypes of epithelial cell ovarian cancer
- Serous tumours (the most common)
- Endometrioid carcinomas
- Clear cell tumours
- Mucinous tumours
- Undifferentiated tumours
What are sex-cord stromal tumours (ovarian cancer)?
Benign or malignant
* Arise from the stroma (connective tissue) or sex cords (embryonic structures associated with the follicles)
Types:
* Sertoli-Leydig cell tumours
* Granulosa cell tumours
What are ovarian tumour that are due to metastasis called?
Also where are they usually from?
Krunkenberg tumour
Usually from the GI tract - usually stomach
What is the characteristic do Krunkenberg tumours have in histology?
‘Signet-ring’ cells in histology
Risk factors for ovarian cancer
Modifiable:
* Obesity
* Smoking
* Recurrent use of clomifene
Non-modifiable:
* Age (peaks 60)
* BRCA1 and BRCA2 genes (consider the family history)
* Increased number of ovulations
Factors that increase the number of ovulations, increase the risk of ovarian cancer. These include:
* Early-onset of periods
* Late menopause
* No pregnancies
Protective factors for ovarian cancer
Having a higher number of lifetime ovulations increases the risk of ovarian cancer. Factors that stop ovulation or reduce the number of lifetime ovulations, reduce the risk:
- Combined contraceptive pill
- Breastfeeding
- Pregnancy
Signs and symptoms of ovarian cancer
Symptoms:
* Abdominal bloating
* Early satiety (feeling full after eating)
* Loss of appetite
* Pelvic pain
* Urinary symptoms (frequency / urgency)
Signs:
* Weight loss
* Abdominal mass
* Ascites
An ovarian mass may press on the obturator nerve → causing referred hip or groin pain
Ix for ovarian cancer
- ** CA125 blood test** (>35 IU/mL is significant)
- Pelvic ultrasound (or transvaginal)
- Risk of Malignancy Index (RMI) (menopausal status, ultrasound findings, CA125 level)
Further investigations in secondary care include:
* CT scan (establish the diagnosis and stage the cancer)
* Histology (tissue sample) using a CT guided biopsy, laparoscopy or laparotomy
* Paracentesis (ascitic tap) can be used to test the ascitic fluid for cancer cells
What is the RMI and what 3 things does it take into account
Risk of Malignancy Index (RMI) = estmates the risk of an ovarian mass being malignant
Takes into account:
* CA125 level
* Ultrasound findings
* Menopause status
Women under 40 years with a complex ovarian mass require tumour markers for a possible germ cell tumour. What are these tumour markers?
- Alpha-fetoprotein (a-FP)
- Human chorionic gonadotrophin (HCG)
Main marker for ovarian cancer?
CA125
What are the non-malignant causes of raised CA125?
- Endometriosis
- Fibroids
- Adenomyosis
- Pelvic infection
- Liver disease
- Pregnancy
What is the staging system for ovarian cancer and what are the stages?
The International Federation of Gynaecology and Obstetrics (FIGO) staging system is used to stage ovarian cancer. A very simplified version of this staging system is:
- Stage 1: Confined to the ovary
- Stage 2: Spread past the ovary but inside the pelvis
- Stage 3: Spread past the pelvis but inside the abdomen
- Stage 4: Spread outside the abdomen (distant metastasis)
Management for ovarian cancer (super basic)
Surgery + Chemotherapy
What population does cervial cancer usually effect?
younger women - peaks in reproductive years
What cell type is the most common cervical cancer?
- Squamous cell carcinoma (80%)
- Adenocarcinoma (next common)
- Small cell cancer (rare)
What virus is cervical cancer strongly associated with?
Human papillomavirus (HPV)
Children aged 12 – 13 years are vaccinated against certain strains of HPV to reduce the risk of cervical cancer.
Why is cervical screening performed?
Screen for precancerous + cancerous changes to cervical cell
Early detection of precancerous changes enables prompt treatment to prevent the development of cervical cancer.
Apart from cerival cancer, whoch other cancers is HPV associated with?
Anal, vulval, vaginal, penis, mouth, throat
HPV = primarily a sexually transmitted infection.
Which strains of HPV are responsible for 70% of cervical cancer?
Type 16 and 18
(They are targeted in the vaccine)
What is the treatment for HPV?
No treatment
* Most resolve spontaneously within 2 years
* Some persist
Pathology of HPV and cervical cancer
- P53 + pRb = tumour suppressor genes
- HPV = produces proteins (E6 + E7)
- E6 = inhibits P53
- E7 = inhibits pRb
Therefore HPV = promotes the development of cancer by inhibiting tumour suppressor genes.
Risk factors for cervical cancer
You can think of the risk factors for cervical cancer in terms of:
* Increased risk of catching HPV
* Later detection of precancerous and cancerous changes (non-engagement with screening)
* Other risk factors
Increased risk of catching HPV occurs with:
* Early sexual activity
* Increased number of sexual partners
* Sexual partners who have had more partners
* Not using condoms
Other risk factors:
* Smoking
* HIV (patients with HIV are offered yearly smear tests)
* Combined contraceptive pill use for more than five years
* Increased number of full-term pregnancies
* Family history
* Exposure to diethylstilbestrol during fetal development (this was previously used to prevent miscarriages before 1971)
Tom Tip: Cervical cancer
When you are performing a history in your exams and considering cancer, always ask about risk factors to show your examiners you are assessing that patient’s risk of having cancer. Ask about attendance to smears, number of sexual partners, family history and smoking.
Clinical presentation of cervical cancer
Early stages of cervical cancer = may be entirely asymptomatic - hence screening!
Symptoms:
* Abnormal vaginal bleeding (post-coital bleeding; intermenstrual bleeding)
* Vaginal discomfort
* Pelvic pain, urinary or bowel symptoms in advanced disease
* Dyspareunia
Signs:
* Abnormal cervical appearance (white or red patches on the cervix; erosions and ulcerations; mass; bleeding)
* Vaginal discharge
* Dyskaryosis on screening
Dyskaryosis = small changes have been found in the cells of the cervix
What appearance of the cervix warrants an urgent cancer referral for colposcopy?
- Ulceration
- Inflammation
- Bleeding
- Visible tumour
Investigations for cervical cancer
- Colposcopy and biopsy: visualisation of the cervix and allows for biopsy. Assesses for precancerous changes, such as dyskaryosis or CIN, and malignant changes
- Human papillomavirus (HPV) testing: confirmation of HPV
- Staging imaging: chest X-ray, renal ultrasound, PET/CT and MRI may be used to evaluate metastatic spread
- Bloods: test renal function, liver function and bone profile to assess for disease spread
Stages of cervical cancer
- Stage 1: Confined to the cervix
- Stage 2: Invades the uterus or upper 2/3 of the vagina
- Stage 3: Invades the pelvic wall or lower 1/3 of the vagina
- Stage 4: Invades the bladder, rectum or beyond the pelvis
Management of cervical cancer
- Cervical intraepithelial neoplasia and early-stage 1A: LLETZ or cone biopsy
- Stage 1B – 2A: Radical hysterectomy and removal of local lymph nodes with chemotherapy and radiotherapy
- Stage 2B – 4A: Chemotherapy and radiotherapy
- Stage 4B: Management may involve a combination of surgery, radiotherapy, chemotherapy and palliative care
LLETZ = Large Loop Excision of the Transformation Zone
What is a cone biopsy?
A cone biopsy = a treatment for cervical intraepithelial neoplasia (CIN) + very early-stage cervical cancer
It involves a general anaesthetic. The surgeon removes a cone-shaped piece of the cervix using a scalpel. This sample is sent for histology to assess for malignancy.
What is a large loop excision of the transformation zone (LLETZ)?
AKA loop biopsy
A large loop excision of the transformation zone (LLETZ) procedure = also called a loop biopsy.
It can be performed with a local anaesthetic during a colposcopy procedure.
What drug is used in chemotherapy for metastatic or recurrent cervical cancer?
Bevacizumab (Avastin) = a monoclonal antibody
It targets vascular endothelial growth factor A (VEGF-A), which is responsible for the development of new blood vessels
What is cervical intraepithelial neoplasia (CIN)?
Cervical intraepithelial neoplasia (CIN) = a grading system for the level of dysplasia (premalignant change) in the cervix
- CIN I: mild dysplasia, affecting 1/3 the thickness of the epithelial layer → likely to return to normal without treatment
- CIN II: moderate dysplasia, affecting 2/3 the thickness of the epithelial layer → likely to progress to cancer if untreated
- CIN III: severe dysplasia → very likely to progress to cancer if untreated
What is CIN III also called?
Cervical carcinoma in situ
How is cervical intraepithelial neoplasia (CIN) diagnosed?
Colposcopy
(NOT with cervical screening)
TOM TIP: Try not to get mixed up between dysplasia found during colposcopy and dyskaryosis on smear results
What is colposcopy?
Colposcopy = inserting a speculum and using equipment (a colposcope) to magnify the cervix - to exam the epithelial lining of the cervix
Stains used to differentiate abnormal areas:
* Acetic acid
* Iodine solution
Info: Acetic acid
Acetic acid = causes abnormal cells to appear white (acetowhite)
Occurs in cells with an increased nuclear to cytoplasmic ratio (more nuclear material) - such as cervical intraepithelial neoplasia (CIN) and cervical cancer cells.
What is Schiller’s iodine test?
Schiller’s iodine test = involves using iodine solution to stain the cervical cells
* Healthy cells → brown colour
* Abnormal cells → not stain
How can you get a sample from a colposcopy?
Punch biopsy or large loop excision of the transformational zone (LLETZ)
