Gynae Cancer Flashcards
1
Q
What is the cervix?
A
The cervix is an anatomical region which facilitates the passage of sperm into the uterine cavity and maintains sterility of the upper female reproductive tract.
2
Q
The cervix is composed of 2 regions. What are they?
A
- Endocervical canal - ends t a narrowing called the internal os which marks the beginning of the uterine cavity
- Ectocervix - distal part of cervix that projects into vagina
3
Q
What epithelium lines the endocervical canal?
A
Mucus-secreting simple columnar epithelium
4
Q
What epithelium lines the ectocervix?
A
Stratified squamous non-keratinised epithelium which is resistant to the low pH of the vagina
5
Q
What marks the tranition from the ectocervix to the endocervical canal?
A
External os
6
Q
What is the squamocolumnar junction (SCJ)?
A
The location where the squamous epithelium of the ectocervix and columnar epithelium of the endocervix meet
7
Q
What happens when the columnar epithelium of the endocervix is exposed to the acidic environment in the vagina?
A
it undergoes squamous metaplasia
8
Q
What happens during squamous metaplasia?
A
During this process, the original SCJ everts from its original position onto the ectocervix; the area between the original SCJ and the new SCJ is known as the transformation zone.
9
Q
What is the most common cause of cervical cancer?
A
infection with human papillomavirus (HPV)
10
Q
Primary transmission of HPV?
A
Sexually transmitted infection
11
Q
There are over 100 strains of HPV. What are the 2 most important ones?
A
Type 16 and type 18 - they are responsible for around 70% of cervical cancers and also the strains targeted with the HPV vaccine
12
Q
What strains of HPV are targeted by the HPV vaccine?
A
Type 16 and 18
13
Q
Pathogenesis/carcinogenesis behind cervical cancer?
A
- Microtrauma to the epithelial cells of the transformation zone provides HPV with access to basal keratinocytes.
- HPV infects these cells with its surface proteins and uses its E6 and E7 oncoproteins to inhibit the tumour suppressors p53 and pRb, resulting in uncontrolled cellular proliferation.
- The ensuing accumulation of mutations results in pre-malignant cellular abnormalities, named cervical intraepithelial neoplasia (CIN).
- Eventually, CIN can progress to invasive carcinomas
14
Q
What is the most common type of cervical cancer?
A
Squamous cell carcinoma (80%) of the epithelial lining of the ectocervix.
15
Q
Where are cervical squamous cell carcinomas found?
A
ectocervix
16
Q
What is the 2nd most common type of cervical cancer?
A
Adenocarcinomas (of the glands within the lining of the cervix)
17
Q
Give some other, rarer, routes of transmission of HPV
A
- Contact with contaminated surfaces or objects
- Oro-genital transmission
- Perinatal vertical transmission
- Autoinoculation
18
Q
What are P53 and pRb?
A
Tumour supressor genes
19
Q
How does HPV inhibit tumour suppressor genes?
A
HPV produces two proteins (E6 and E7) that inhibit these tumour suppressor genes
Therefore, HPV promotes the development of cancer by inhibiting tumour suppressor genes.
20
Q
Which protein produced by HPV inhibits p53?
A
E6 protein
21
Q
Which protein produced by HPV inhibits pRb?
A
E7
22
Q
What are some risk factors of cervical cancer?
A
The greatest risk factor for developing cervical cancer is HPV infection. Other factors include:
- Smoking
- Inadequate cervical screening
- High parity
- Oral contraceptive use
- Lower socioeconomic status
- Co-infection with other sexually transmitted infections, such as HIV, herpes simplex and chlamydia
- Previous cancers of the vagina, vulva, kidneys and urinary tract
Risk factors for CATCHING HPV:
- Early sexual activity
- Increased number of sexual partners
- Sexual partners who have had more partners
- Not using condoms
23
Q
What should be asked about in a patient’s history when assessing for cervical cancer?
A
- Symptoms e.g. bleeding
- Attendance to smears
- Sexual history: number of sexual partners, type of sexual intercourse, use of barrier contraception, risk of other sexually transmitted infections
- Family history
- Smoking/OCP use
- Obstetric history: parity and gravidity
- HPV infection & vaccination history
24
Q
Majority of HPV infections are ASYMPTOMATIC.
Give some symptoms seen in cervical cancer/HPV infection:
A
- Abnormal vaginal bleeding (intermenstrual, postcoital, postmenopausal)
- Vaginal discharge (blood-stained, mucoid or purulent)
- Pelvic pain
- Dyspareunia
N.B. These symptoms are non-specific, and in most cases, not caused by cervical cancer. The next step is to examine the cervix with a speculum. During examination, swabs can be taken to exclude infection.
25
What is dyspareunia?
Pain or discomfort with sex
26
What is the next stage in assessment in a patient presenting with potential cervical cancer symptoms?
The next step is to examine the cervix with a speculum. During examination, swabs can be taken to exclude infection.
27
If there is an abnormal appearance of the cervix suggestive of cancer during speculum, what is the next step?
An urgent cancer referral for colposcopy should be made to assess further.
28
During a speculum examination, what appearances may suggest cervical cancer?
Ulceration
Inflammation
Bleeding
Visible tumour
29
What happens if there is an abnormal appearance of the cervix suggestive of cancer during speculum exam?
an urgent cancer referral for colposcopy should be made to assess further.
30
Give some differentials for suspected cervical cancer
- Cervicitis
- Ectropion
- Endometrial cancer
31
What is cervicitis?
Inflamed, friable cervix prone to bleeding
Commonly caused by chlamydia trachomatis
32
What is cervicitis commonly caused by?
Chlamydia trachomatis
33
What is ectropion?
A benign condition involving the presence of columnar epithelium on the outside of the cervix
Prone to bleeding/infection although if asymptomatic then no treatment required
Could cauterise if wished
34
How are most cases of cervical cancer diagnosed?
Through cervical screening
35
What does cervical screening involve?
It involves a cervical smear test, performed by a qualified person, often a practice nurse
36
What is a smear test?
The test consists of a speculum examination and collection of cells from the cervix using a small brush. The cells are deposited from the brush into a preservation fluid. This fluid is transported to a lab where the cells are examined under a microscope for precancerous changes (dyskaryosis).
37
What is dyskaryosis?
Dyskaryosis relates to pre-cancerous cell changes,
38
What are cervical smear samples initially tested for before the cells are examined?
High risk HPV
39
If the HPV test is negative (the person does not have HPV) when testing the cervical smear sample, what happens?
the smear is considered NEGATIVE and the woman is returned to the routine screening program.
40
Who is invited to the cervical screening program? How often?
women (and transgender men that still have a cervix):
- Every three years aged 25 – 49
- Every five years aged 50 – 64
41
Some notable exceptions to the cervical screening program:
- Women with HIV are screened annually
- Women over 65 may request a smear if they have not had one since aged 50
- Women with previous CIN may require additional tests (e.g. test of cure after treatment)
- Certain groups of immunocompromised women may have additional screening (e.g. women on dialysis, cytotoxic drugs or undergoing an organ transplant)
- Pregnant women due a routine smear should wait until 12 weeks post-partum
42
If the HPV test is positive (the person does have HPV) when testing the cervical smear sample, what happens?
The cells are examined
43
Potential cytology results during cervical screening:
- Inadequate
- Normal
- Borderline changes
- Low-grade dyskaryosis
- High-grade dyskaryosis (moderate)
- High-grade dyskaryosis (severe)
- Possible invasive squamous cell carcinoma
- Possible glandular neoplasia
N.B. Infections such as bacterial vaginosis, candidiasis and trichomoniasis may be identified and reported on the smear result.
44
What happens if the cervical smear sample is inadequate?
repeat the smear after at least three months
45
What happens if the cervical smear sample is HPV negative?
continue routine screening
46
What happens if the cervical smear sample is HPV positive with normal cytology?
repeat the HPV test after 12 months
47
What happens if the cervical smear sample is HPV positive with abnormal cytology?
Refer for colposcopy
48
Who should fast track colposcopy be offered to?
Fast-track colposcopy should be offered to women with visible suspicion of cervical cancer or persistent unexplained cervical symptoms.
A gynaecology 2-week wait referral should be made in the following cases:
- Postmenopausal women with unexplained vaginal bleeding
- Premenopausal women with persistent intermenstrual bleeding and negative pelvic exam
- Women with clinical features suggesting cervical cancer if they have not been screened, or if the bleeding persists beyond 3 months
Consider referring premenopausal women to gynaecology or genitourinary services if they have persistent abnormal bleeding and the presence of polyps, ectropion, cervicitis or warts.
49
What is cervical intraepithelial neoplasia (CIN) ?
A grading system for the level of dysplasia (premalignant change) in the cells of the cervix.
50
When is CIN diagnosed?
CIN is diagnosed at colposcopy (not with cervical screening)
51
What are the CIN grades?
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 (sometimes called cervical carcinoma in situ)
52
What is a colposcopy?
A specialist performs colposcopy. It involves inserting a speculum and using equipment (a colposcope) to magnify the cervix. This allows the epithelial lining of the cervix to be examined in detail.
Can using stains to differentiate abnormal areas.
A punch biopsy or large loop excision of the transformational zone can be performed during the colposcopy procedure to get a tissue sample.
53
What stains can be used during colposcopy to differentiate abnormal areas?
acetic acid and iodine solution
54
What is the effect of acetic acid on abnormal cells during colposcopy?
Acetic acid causes abnormal cells to appear white. This appearance is described as acetowhite.
This occurs in cells with an increased nuclear to cytoplasmic ratio (more nuclear material), such as cervical intraepithelial neoplasia and cervical cancer cells.
55
What is Schiller's iodine test?
Used during colposcopy
Schiller’s iodine test involves using an iodine solution to stain the cells of the cervix. Iodine will stain healthy cells a brown colour. Abnormal areas will not stain.
56
What colour will abnormal cells turn when using acetic acid during colposcopy?
White
57
What colour will abnormal cells turn when using iodine during colposcopy?
Abnormal areas will not stain.
58
What colour will normal cells turn when using iodine during colposcopy?
Brown
59
What type of biopsy can be performe during colposcopy to get a tissue sample?
A punch biopsy or large loop excision of the transformational zone
60
What is a Large Loop Excision of the Transformation Zone (LLETZ)?
Is also called a loop biopsy. It can be performed with a local anaesthetic during a colposcopy procedure.
It involves using a loop of wire with electrical current (diathermy) to remove abnormal epithelial tissue on the cervix. The electrical current cauterises the tissue and stops bleeding.
61
Complications of LLETZ?
Bleeding and abnormal discharge can occur for several weeks following a LLETZ procedure. This varies between women.
Intercourse and tampon use should be avoided after the procedure to reduce the risk of infection.
Depending on the depth of the tissue removed from the cervix, the procedure may increase the risk of preterm labour.
62
What is a cone biopsy?
A cone biopsy is a treatment for cervical intraepithelial neoplasia (CIN) and very early-stage cervical cancer.
Involves 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.
63
What are the main risks of cone biopsy?
Pain
Bleeding
Infection
Scar formation with stenosis of the cervix
Increased risk of miscarriage and premature labour
64
What staging system is used to stage cervical cancer?
International Federation of Gynaecology and Obstetrics (FIGO)
65
FIGO staging for 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
66
The treatment for cervical cancer depends on the stage of the cancer, and also whether the woman wants to retain fertility.
What is the management of CIN?
CIN-1 is not routinely offered treatment and should be observed
CIN-2/CIN-3: excision or ablation may be considered (e.g. LLETZ or cone biopsy)
67
What is management of cervical cancer stage 1B-2A (early stage disease)?
Radical hysterectomy and removal of local lymph nodes (lymphadenectomy) with/without chemotherapy and radiotherapy --> NO aim to spare fertility
Radical trachelectomy can be done for slightly more advanced, yet still early-stage cancers --> the aim is to spare fertility
68
What is a radial trachelectomy?
This involves removal of the cervix, the upper vagina and pelvic lymph nodes.
69
What is management of cervical cancer stage 2B-4A (locally advanced disease)?
Chemotherapy and radiation is 1st line
70
What is management of cervical cancer stage 4A (metastatic disease)?
Combination chemotherapy - surgery, radiotherapy, chemotherapy and palliative care
71
What is the 5 year survival rate of stage 1A and stage IV?
1A --> 98%
4 --> 15%
72
Management of women with advanced or incurable cervical cancer?
The goal should be to treat the following issues:
- Pain: analgesia, nerve-blocking therapies or spinal therapy
- Renal failure: conservative management, percutaneous nephrostomy, retrograde stenting
- Bleeding and thrombosis
- Malodour
- Lymphoedema
73
What is pelvic exenteration?
Pelvic exenteration is an operation that may be used in advanced cervical cancer. It involves removing most or all of the pelvic organs, including the vagina, cervix, uterus, fallopian tubes, ovaries, bladder and rectum.
It is a vast operation and has significant implications on quality of life.
74
Who is offered the HPV vaccination?
Recommended for girls and boys aged 12 to 13 (ideally given before they become sexually active)
Now 1 dose.
75
What is the current NHS vaccine against HPV? What 4 strains does it protect against?
Gardasil
6, 11, 16, 18
76
What are strains 6 and 11 of HPV responsible for?
Genital warts
77
What are strains 16 and 18 of HPV responsible for?
Cervical cancer
78
What is Bevacizumab (Avastin)? What is it used in? What does it target?
A monoclonal antibody that may be used in combination with other chemotherapies in the treatment of metastatic or recurrent cervical cancer.
It targets vascular endothelial growth factor A (VEGF-A), which is responsible for the development of new blood vessels
79
What hormone is endometrial cancer dependent on?
Oestogen
80
What is the endometrium?
Lining of the uterus
81
What is the most common type of endometrial cancer?
Adenocarcinoma (80%)
82
What does 'oestrogen-dependent cancer' mean?
oestrogen stimulates the growth of cancer cells.
83
A woman presenting with postmenopausal bleeding has what until proven otherwise?
Endometrial cancer
Need a 2-week-wait urgent cancer referral
84
What age group does endometrial cancer normally affect?
Mainly affects post-menopausal individuals (91% of cases in over 50s)
85
In resource-abundant countries, what is the most common gynaecological malignancy?
Endometrial cancer
86
In resource-limited countries, what is the most common gynaecological malignancy?
Cervical cancer
87
What condition PRECEDES endometrial cancer?
Endometrial hyperplasia
88
What % of cases of endometrial hyperplasia progress to endometrial cancer?
Most cases of endometrial hyperplasia will return to normal over time.
Less than 5% go on to become endometrial cancer if left untreated.
89
What is endometrial hyperplasia?
Endometrial hyperplasia is a precancerous condition involving thickening of the endometrium.
90
What are the 2 types of endometrial hyperplasia?
1) Hyperplasia without atypia
2) Atypical hyperplasia
91
Presentation of endometrial hyperplasia?
Endometrial hyperplasia and cancer commonly present with post-menopausal bleeding (PMB).
In younger individuals, it may present with changes to the menstrual cycle and heavy or irregular periods.
92
What is the main risk factor for endometrial cancer?
Exposure to unopposed oestrogen
93
Give some manifestations of exposure to unopposed oestroen
- Nulliparity
- Obesity
- Early menarche
- Late menopause
- Polycystic ovary syndrome (PCOS)
- Oestrogen-only HRT
- Increased age
- Tamoxifen
94
Why is PCOS a risk factor for endometrial cancer?
Polycystic ovarian syndrome leads to increased exposure to unopposed oestrogen due to a 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 so progesterone is not produced.
95
For endometrial protection, what should women with PCOS have?
One of:
- The combined contraceptive pill
- An intrauterine system (e.g. Mirena coil)
- Cyclical progestogens to induce a withdrawal bleed.
96
Why is obesity a risk factor for endometrial cancer?
Adipose tissue (fat) is a source of oestrogen and adipose tissue is the primary source of oestrogen in postmenopausal women.
This extra oestrogen is unopposed in women that are not ovulating (e.g. PCOS or postmenopause), because there is no corpus luteum to produce progesterone.
97
What enzyme does adipose tissue contain?
Aromatase
98
Function of aromatase?
enzyme that converts androgens such as testosterone into oestrogen.
99
What are androgens primarily produced by?
Adrenal glands
100
What is the primary source of oestrogen in post-menopausal women
adipose tissue
101
Why is oestrogen from adipose tissue or HRT post menopause unopposed?
This extra oestrogen is unopposed in women that are not ovulating (e.g. PCOS or postmenopause), because there is no corpus luteum to produce progesterone.
102
What is the effect of tamoxifen in breast tissue?
BLOCKS oestrogen
103
What is the effect of tamoxifen in endometrial tissue?
Has oestrogenic effect i.e. enhances oestrogen
This increases the risk of endometrial cancer
104
What are 2 risk factors for endometrial cancer NOT related to unopposed oestrogen?
- Type 2 diabetes (due to increased production of insulin)
- Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome
N.B. PCOS is also associated with insulin resistance and increased insulin production. Insulin resistance further adds to the risk of endometrial cancer in women with PCOS.
105
What are the 3 parts of the uterus?
1. Fundus
2. Body
3. Cervix
106
What are the 3 tissue layers of the uterus?
1. Perimetrium (outer)
2. Myometrium (middle)
3. Endometrium (inner)
107
What is the perimetrium?
a double-layered membrane which is continuous with the abdominal peritoneum
108
What is the myometrium?
a thick smooth muscle layer that undergoes hypertrophy and hyperplasia during pregnancy in preparation for the expulsion of the fetus.
109
What is the endometrium?
lines the uterus with a mucous membrane, this layer is subdivided into two parts including the deep stratum basalis and the superficial functionalis
110
What 2 parts is the endometrium divided into
1) deep stratum basalis
2) superficial functionalis
111
Which part of the endometrium proliferates in response to oestrogen?
superficial functionalis
112
what layer of the endometrium is shed during menstruation?
superficial functionalis
113
role of stratum basalis layer of endometrium?
replace the tissue loss during the menstruation.
114
Which hormone causes the endometrium to become receptive to the implantation of a fertilised ovum?
Progesterone
If fertilisation does not take place, a fall in progesterone levels triggers menstruation and shedding of the thickened endometrial layer.
115
What hormone opposes oestrogen?
progesterone
116
what are some protective factors against endometrial cancer?
- Parity (as there is a surge in progesterone during pregnancy)
- Combined oral contraceptive pills (COCP)
- Mirena coil
- Exercise
- Smoking
- Use of aspirin
- Drinking coffee
117
How does smoking in breast cancer and endometrial cancer differ?
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).
118
What is the number one presenting symptom of endometrial cancer?
Postmenopausal bleeding
119
Symptoms of endometrial cancer?
- Postmenopausal bleeding
- Postcoital bleeding
- Intermenstrual bleeding
- Unusually heavy menstrual bleeding
- Abnormal vaginal discharge
- Haematuria
- Anaemia
- Raised platelet count
- Pyometra --> a collection of pus in the uterine cavity
Advanced disease may present as pelvic pain, oedema, rectal bleeding, weight loss, and fatigue
Metastatic disease may present as cough, dyspnoea, haemoptysis, abdominal pain, jaundice, bone pain, hypercalcaemia, and pathological fractures
120
What is pyometra?
A collection of pus in the uterine cavity
121
Important areas to cover in potential endometrial cancer history?
Obstetric history: including parity and complications
Gynaecological history: including age at menarche, last menstrual period, menstrual cycle duration and pattern
Cervical smear history
Past medical or surgical history: including bleeding disorders, previous malignancy, polycystic kidney disease, type 2 diabetes mellitus, hypothyroidism, hypertension
Drug history: including use of COCP, HRT, tamoxifen, antihypertensives, or oral hypoglycaemics
Social history: smoking, alcohol, and recreational drug use
Family history: gynaecological or colorectal malignancies
Clinical examination
122
What are some typical clinical findings in endometrial cancer?
Uterine bleeding
Increased vaginal discharge
Pyometra
Oedema
In locally advanced disease the uterus may be enlarged or immobile on palpation
In advanced cases, there may be a palpable pelvic mass on bimanual examination of the abdomen
123
What are 3 differentials for endometrial cancer?
Uterine fibroids --> heavy menstrual bleeding, pelvic pressure or pain, frequent urination, and constipation.
Endometrial polyps --> symptoms may include irregular menstrual bleeding, bleeding between menstrual periods, excessively heavy menstrual periods, and vaginal bleeding after menopause.
Cervical cancer --> signs can include abnormal vaginal bleeding, postmenopausal bleeding, and pelvic pain.
124
What labs should be done in suspected endometrial cancer?
1) FBC
2) CA-125
125
What may an FBC show in endometrial cancer?
Low Hb and low platelets
126
What is a CA 125 test?
measures the amount of the protein CA 125 (cancer antigen 125) in the blood
127
What may an CA 125 test show in endometrial cancer?
may be elevated but not usually performed for cases of suspected endometrial cancer (as a high CA-125 does not always mean cancer is present)
128
What are 3 main investigations in endometrial cancer?
1. Endometrial (pipelle) biopsy (highly specific)
2. Hysteroscopy
3. Transvaginal US
129
What is the purpose of a transvaginal US?
to measure endometrial thickness (ET)
130
what is the normal ET post menopause?
<4mm
131
What ET on transvaginal US would be an indication for further investigations such as endometrial biopsy?
4mm or more
Endometrial biopsy is a quicker and less invasive alternative to hysteroscopy for excluding cancer in lower-risk women.
132
What is a hysteroscopy?
hysteroscopy is a procedure used to examine the inside of the uterus
133
Give some other potential imaging investigations in endometrial cancer
- Pelvic US --> to visualise the uterus, ovaries, and fallopian tubes
- CT scan of chest, abdomen, and pelvis --> may be used for preoperative staging
- MRI pelvis --> can be used to determine the local extent of the tumour and the presence of involved pelvic lymph nodes
134
What staging system is used to stage endometrial cancer?
FIGO --> International Federation of Gynaecology and Obstetrics
135
Grade vs stage of cancer?
Stage --> how large a cancer tumor is and how far the cancer has spread.
Grade --> how it looks under microscope (i.e. differentiation)
136
Describe stage 1 of endometrial cancer
Confined to the uterus
137
Describe stage 2 of endometrial cancer
Invades the cervix
138
Describe stage 3 of endometrial cancer
Invades the ovaries, fallopian tubes, vagina or lymph nodes
139
Describe stage 4 of endometrial cancer
Invades bladder, rectum or beyond the pelvis
140
What is the usual treatment for stage 1 and 2 endometrial cancer?
The usual treatment for stage 1 and 2 endometrial cancer is a total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO)
141
What is a bilateral salpingo-oophorectomy (BSO)?
surgical procedure to remove the ovaries and fallopian tubes.
142
Other management strategies of endometrial cancer in more advanced disease:
- Radiotherapy
- Chemotherapy
- Hormonal therapies e.g. progesterone
143
How can endometrial cancer lead to anaemia?
Due to excessive blood loss from the uterus
144
Symptoms of anaemia?
can present with symptoms including fatigue, weakness, and palpitations
145
Why is ovarian cancer a 'nightmare' cancer?
Its vague, insidious onset means that it tends not to present until it is too late, and there is currently no effective screening programme in place to detect it at an earlier stage
More than 70% of patients with ovarian cancer present after it has spread beyond the pelvis.
146
Function of the ovaries?
Gonads --> producing female germ cells called ova
Endocrine glands --> secrete the female sex hormones oestrogen and progesterone.
147
What are the 2 components of the ovaries?
- outer cortex (contains ovarian follicles)
- inner medulla (contains blood vessels, nerves and lymphatics)
148
The ovaries are usually located on the lateral wall of the pelvis in a depression known as the ovarian fossa.
What tends to lie
a) above
b) laterally
c) behind
a) external iliac vessels
b) obturator nerve
c) internal iliac vessels and ureter
However, their position can be extremely variable and they tend to move around a lot during and after pregnancy.
149
What 3 ligaments hold the ovaries in place?
1) broad ligament
2) suspensory ligament
3) ovarian ligament
150
Function of the broad ligament?
This is a sheet of peritoneum, associated with both the uterus and ovaries.
It extends from the lateral pelvic walls on both sides, and folds over the internal female genitalia, covering their surface anteriorly and posteriorly.
Three other ligaments of the female reproductive tract are located within the broad ligament:
- Ovarian ligament.
- Round ligament of uterus.
- Suspensory ligament of ovary (also known as the infundibulopelvic ligament).
151
Function of the ovarian ligament?
The ovarian ligament is attached to the ovary inferiorly. It connects the ovary to the side of the uterus.
152
Function of the suspensory ligament of the ovary?
The suspensory ligament of ovary extends outwards from the ovary to the lateral abdominal wall.
The function of this ligament is to contain the ovarian vessels and nerves (ovarian artery, ovarian vein, ovarian nerve plexus and lymphatic vessels).
153
What is the leading cause of death from gynaecological cancer in the UK?
Ovarian cancer
154
Who is ovarian cancer more common in?
it has a peak incidence in women in their 60s and 70s and is rare under the age of 40
ovarian cancer is almost twice as common in developed countries than in the developing world
155
What is the most common type of ovarian cancer?
Epithelial cell tumours (around 90%)
156
What are 5 subtypes of ovarian epithelial cell tumours
1. Serous tumours
2. Endometrioid carcinomas
3. Clear cell adenocarcinoma
4. Mucinous adenocarcinoma
5. Undifferentiated tumours
157
What is the most common type of ovarian epithelial cell tumours?
Serous tumours
158
Other types of ovarian cancer make up approx 10% of cases.
Who do they tend to affect? How do they progress?
Generally affect younger women and progress more quickly and aggressively
159
Give 3 examples of other types of ovarian cancer
1. Sex cord stromal tumours e.g. Sertoli-Leydig cell tumour, granulosa theca cell tumours
2. Germ cell tumours e.g. dysgerminoma, teratoma, choriocarcinoma
3. Metastases from other sites e.g. colorectal, breast, gastric (Krukenberg tumour)
160
What does a Sertoli-Leydig cell tumour produce?
The cancer cells produce and release a male sex hormone called testosterone.
161
What is a dermoid cyst/teratoma?
Teratomas are referred to as dermoid cysts when they occur at birth
They may contain various tissue types, such as skin, teeth, hair and bone
162
What condition are teratomas particularly associated with?
Ovarian torsion
163
Germ cell tumours may cause raised what?
alpha-fetoprotein (α-FP) and human chorionic gonadotrophin (hCG).
164
what is alpha-fetoprotein (α-FP)?
a tumour marker
165
why can a teratoma cause a positive pregnancy test?
can caused raised hCG
166
what is a krukenberg tumour?
refers to a metastasis in the ovary, usually from a gastrointestinal tract cancer, particularly the stomach
167
what is the characteristic sign of a krukenberg tumour in histology?
'signet ring' sign
168
Risk factors for ovarian cancer?
- Age (peaks age 60)
- BRCA1 and BRCA2 genes (consider the family history)
- Increased number of ovulations
- Obesity
- Smoking
- Recurrent use of clomifene
- Previous breast cancer or ovarian cancer
- Asbestos exposure
Risk factors linked to incessant ovulation:
- early menarche
- late menopause
- delayed childbearing
- nulliparity
- use of HRT >5 years
- use of fertility drugs to stimulate ovulation (clomiphene)
- increased age
169
What is the 'theory of incessant ovulation'?
Basically states that the more a woman ovulates in her lifetime, the higher her risk of ovarian cancer, due to the increased cumulative damage to the epithelium and the increased risk of mutations during its subsequent repair and regeneration
Risk factors are linked to incessant ovulation
170
Protective factors for ovarian cancer?
Factors that stop ovulation or reduce the number of lifetime ovulations, reduce the risk:
- Combined contraceptive pill
- Breastfeeding
- Pregnancy
- Multiparity (>3 pregnancies)
- Hysterectomy
- Tubal ligation
- Exercise
- Aspirin
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Where do sex cord stromal tumours arise from?
connective tissue
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Symptoms of ovarian cancer?
Its insidious onset and non specific symptoms means that up to 75% of patients present with symptoms of advanced disease due to the mass effects of the tumour
- non-specific GI symptoms such as bloating or indigestion (often misdiagnosed as IBS), early satiety, loss of appetite
- gradually increasing abdominal distension (often misdiagnosed as “middle-aged spread”)
- increasing tumour size results in pressure effects causing chronic abdominal, pelvic or back pain, urinary frequency/urgency (pressure on the bladder), constipation/altered bowel habit/bowel obstruction (pressure on bowel), leg swelling and DVT/PE (pressure on pelvic veins)
- abnormal vaginal bleeding
- symptoms of metastatic disease include pleural effusion, ascites, weight loss and fatigue
- less commonly, sudden torsion, rupture or infection of the tumour in early disease can present with acute abdominal or pelvic pain – this is a blessing in disguise as it can lead to early diagnosis
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Why can ovarian cancer sometimes present with hip or groin pain?
An ovarian mass may press on the obturator nerve and cause referred hip or groin pain
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Where does the obturator nerve pass?
The obturator nerve passes along the inside of the pelvic, lateral to the ovaries, where an ovarian mass can compress it.
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Clinical signs in ovarian cancer?
general examination – cachexia, lymphadenopathy, signs of pleural effusion
abdominal examination – distension, ascites, palpable pelvic mass, “omental cake” metastasis
Cusco speculum examination – usually normal
bimanual palpation – palpable adnexal/pelvic mass which may be fixed and immobile
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Differentials of a pelvic mass?
ovarian pathology – ovarian cyst/benign tumour, ovarian cancer
tubal pathology – tubo-ovarian abscess, tubal malignancy (treat as ovarian)
uterine pathology – pregnancy, fibroids/benign tumour, uterine cancer
urological pathology – distended bladder, pelvic kidney, transplanted kidney
GI pathology – the 6 Fs: fat, fluid, flatus, faeces, fetus, filthy big tumour
other abdominal pathology – primary peritoneal cancer, retroperitoneal sarcoma.
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Differentials for ovarian cancer:
Gastrointestinal conditions (e.g., irritable bowel syndrome) --> Characterised by abdominal pain, bloating, and changes in bowel habits
Fibroids --> May cause heavy menstrual bleeding, pelvic pressure or pain, frequent urination, and constipation
Ovarian cysts --> Can cause pelvic pain, fullness or heaviness in the abdomen, and bloating
Other cancers (e.g., bladder, endometrial) --> May present with symptoms such as abnormal bleeding, pelvic pain, and urinary symptoms
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What are the red flags in potential ovarian cancer that require a 2-week-wait referral?
If the clinical exam reveals:
- Ascites
- Pelvic mass (unless clearly due to fibroids)
- Abdominal mass
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Carry out further investigations before referral in women presenting with symptoms of possible ovarian cancer such as:
New symptoms of IBS / change in bowel habit
Abdominal bloating
Early satiety
Pelvic pain
Urinary frequency or urgency
Weight loss
This is particularly important in women over 50 years
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What investigation should always be done in suspected ovarian cancer (or any gynaecological symptom) in women of reproductive age?
pregnancy test
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What are the 2 main investigations in suspected ovarian cancer?
1) blood test for CA-125
2) pelvic and abdominal US
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How is CA-125 effective in ovarian cancer?
It is very sensitive for ovarian cancer but not particularly specific – it can also be raised in other gynaecological cancers, GI cancers, benign abdominal and pelvic disorders, breast cancer and diseases affecting the pleura, pericardium or peritoneum.
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What is the risk of malignancy index (RMI) in ovarian cancer?
The risk of malignancy index (RMI) estimates the risk of an ovarian mass being malignant
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What 3 things does the RMI take into account in ovarian cancer?
1) menopausal status
2) US findings
3) CA125 level
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What RMI score indicates a prompt referral to a specialist gynae-oncology centre?
>200 --> indicates 75% cancer risk
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If there is a high RMI score, what further invesigations can be done?
- CT scan to 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
- Blood tests –-> FBC (for anaemia), U+E (for renal function), LFTs (for metastases)
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CA125 is a tumour marker for epithelial cell ovarian cancer. It is not very specific, and there are many non-malignant causes of a raised CA125.
Give some examples of non-malignant causes of a raised CA125.
- Endometriosis
- Fibroids
- Adenomyosis
- Pelvic infection
- Liver disease
- Pregnancy
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What staging system is used to stage ovarian cancer?
FIGO
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Describe stage 1 FIGO of ovarian cancer
Confined to the ovary
Ia) one ovary
Ib) both ovaries
Ic) ruptured capsule, surface tumour, or positive peritoneal washings/ascites
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Describe stage 2 FIGO of ovarian cancer
Spread past the ovary but limited to the pelvis
IIa) uterus, tubes
IIb) other pelvic structures
IIc) the above plus positive peritoneal washings/ascites
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Describe stage 3 FIGO of ovarian cancer
Spread past the pelvis but limited to the abdomen
IIIa) microscopic metastases
IIIb) macroscopic metastases <2cm
IIIc) macroscopic metastases >2cm, regional lymph nodes
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Describe stage 4 FIGO of ovarian cancer
Spread outside the abdomen (distant metastasis)
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What is generally the mainstay of treatment of ovarian cancer?
Surgery and chemotherapy
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What genes are generally tested for in ovarian cancer genetic screening?
BRCA1, BRCA2, and/or HNPCC
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Next steps for patients who test positive for a mutation for ovarian cancer?
CA-125 levels and TVUSS (transvaginal ultrasound), or may choose to undergo prophylactic interventions such as BSO +/- hysterectomy.
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What is CA125?
CA-125 (cancer antigen 125) is a glycoprotein shed by epithelial tumours.
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What is the normal range of CA125?
<35IU/L
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What is the most common type of vulval cancer?
Squamous cell carcinoma
Less commonly, they can be malignant melanomas.
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Risk factors for vulval cancer?
- Advanced age (particularly over 75 years)
- Immunosuppression
- Human papillomavirus (HPV) infection
- Lichen sclerosus (around 5% of women with this get vulval cancer)
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what is lichen sclerosus?
Lichen sclerosus is a long-term (chronic) skin condition that causes itchy and painful patches of thin, white, wrinkled-looking skin.
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What premalignant conditions precipitates vulval cancer?
Vulval intraepithelial neoplasia (VIN)
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What is culval intraepithelial neoplasia (VIN)?
A premalignant condition affecting the squamous epithelium of the skin that can precede vulval cancer.
(VIN is similar to the premalignant condition that comes before cervical cancer (cervical intraepithelial neoplasia)).
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What type of VIN is associated with HPV infection and typically occurs in YOUNGER women (35-50s)?
High grade squamous intraepithelial lesion
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What type of VIN is associated with lichen sclerosus and typically occurs in older women (aged 50 – 60 years)?
Differentiated VIN
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What is required to diagnose VIN?
Biopsy
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Management options for VIN?
- Watch and wait with close followup
- Wide local excision (surgery) to remove the lesion
- Imiquimod cream
- Laser ablation
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What area does vulval cancer most frequently affect?
Labia majora
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Presentation of vulval cancer?
Vulval cancer may present with symptoms of:
- Vulval lump
- Ulceration
- Bleeding or discharge (not related to menstrual cycle)
- Pain
- Itching or discomfort
- Lymphadenopathy in the groin
- Skin changes e.g. thickening or changes in colour
Vulval cancer most frequently affects the labia majora, giving an appearance of:
- Irregular mass
- Fungating lesion
- Ulceration
- Bleeding
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Differentials for vulval cancer?
Vulval intraepithelial neoplasia: This precancerous condition can cause itching, burning, skin changes, and discomfort.
Lichen sclerosus: This condition can cause itching, pain, and white patches on the vulva.
Bartholin's cyst: This may present as a lump or swelling on the vulva, and can cause discomfort or pain.
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Investigations in vulval cancer?
Suspected vulval cancer should be referred on a 2-week-wait urgent cancer referral.
1) Biopsy of the lesion
2) Sentinel node biopsy to demonstrate lymph node spread
3) Further imaging for staging (e.g. CT abdomen and pelvis)
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What staging system is used in vulval cancer?
FIGO
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Managemnt of vulval cancer?
- Wide local excision to remove the cancer
- Groin lymph node dissection
- Chemotherapy
- Radiotherapy
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