Postmenopausal bleeding Flashcards
What is the definition of postmenopausal bleeding?
vaginal bleeding occurring after 12 months of amnoerrhoea, in women at the age where the menopause can be expected or women who have experienced premature ovarian failure or premature menopause
What is the most important thing to rule out in cases of postmenopausal bleeding?
endometrial malignancy
What is the most common cause of postmenopausal bleeding?
vaginal atrophy
What is vaginal atrophy?
thinning, drying and inflammation of the walls of the vagina due to a reduction in oestrogen following the menopause
What are 10 causes of postmenopausal bleeding?
- Vaginal atrophy
- HRT
- Endometrial hyperplasia
- Endometrial cancer
- Cervical cancer
- Ovarian cancer
- Vaginal cancer
- Trauma
- Vulval cancer
- Bleeding disorders
What can occur due to HRT causing PMB?
periods or spotting can continue in some women for many months with no pathological cause, or endometrial hyperplasia due to long-term oestrogen therapy may occur
What is a protective factor against endometrial hyperplasia?
use of the combined oral contraceptive pill
What proportion of patients with postmenopausal bleeding have endometrial cancer? What proportion of it presents with bleeding?
10%; 90% of it presents with PMB
Which type of ovarian cancer is particularly likely to cause postmenopausal bleeding?
oestrogen-secreting (theca cell) tumours
What is the management for all causes of postmenopausal bleeding?
all women over age of 55 with PMB must be investigation within 2 weeks by ultrasound for endometrial cancer - transvaginal ultrasound best
What are 9 things to ask about in the history for postmenopausal bleeding?
- Timing of bleeding
- Quantity of bleeding
- Consistency of bleeding
- Full gynaecological history
- Full obstetric history
- Risk factors for endometrial cancer
- Menstrual timeline from menarche to menopause
- Full drug history - including HRT
- Red flag symptoms for gynae cancer
What examination should be performed for postmenopausal cancer?
full vaginal and abdominal examination, looking for any masses or abnormalities within abdomen or felt from within the vagina, as well as speculum visualisation of walls of vagina and cervix
may see blood or discharge
What are 3 immediate tests that can be performed when a woman consults with PMB?
- Urine dipstick - haematuria or infection
- FBC - anaemia, bleeding disorder
- Ca-125 blood test
What is the type of ultrasound of choice for women referred on the 2 week cancer pathway who present with PMB?
transvaginal ultrasound
What is assessed on ultrasound of the uterus when women are referred on the 2 week pathway for PMB?
thickness of the endometrial lining; acceptable depth <5mm (sometimes said to be 4?)
this may miss some pathology so if clinical suspicion high, further testing required
How is a definitive diagnosis of endometrial cancer made?
- endometrial biopsy either during hysteroscopy or by aspiration (pipelle) biopsy as outpatient
- pipelle biopsy: thin flexible tube inserted into uterus via speculum to remove cells for testing
What imaging for gynaecological cancer may be performed?
CT or MRI of uterus, pelvis and abdomen, in secondary care
If a woman presents with PMB and is HRT what should be done?
still need to investigate for endometrial cancer with transvaginal ultrasound of endometrial thickness
What is the treatment for vaginal atrophy? 3 aspects
topical oestrogens, conservative measures like lubrication for symptoms, HRT
If a bleed is due to the type of HRT that a patient is on (and there is no endometrial hyperplasia/carcinoma) what is a management option?
different HRT preparations can be used to try and reduce it
What is the usual management of endometrial hyperplasia?
dilatation and curettage to remove excess endometrial tissue
What is the definition of endometrial hyperplasia?
abnormal proliferation of endometrium in excess of the normal proliferation that occurs during hte menstrual cycle
What are 4 types of endometrial hyperplasia?
- Simple
- Complex
- Simple atypical
- Complex atypical
What is the commonest type of endometrial tumour?
adenocarcinomas (arising from endometrial glands)
What are 11 risk factors for endometrial carcinoma?
- Obesity (especially upper body)
- Diabetes mellitus
- Nulliparity
- Late menopause
- Unopposed oestrogen therapy
- Tamoxifen
- Oesotrgen-secreting tumours (granulosa/theca cell ovarian tumours)
- Carbohydrate intolerance
- PCOS
- Personal history of breast or colon cancer
- Family history of breast, colon or endometrial cancer
What are 2 factors that decrease the risk of endometrial cancer?
- Combined oral contraceptive pill
- Progestogens
What causes high levels of oestrogen in obesity?
aromatisation in body fat of peripheral androgens to oestrogens
What proportion of cases of endometrial cancer are thought to be related to obesity?
a third
What is thought to be the relationship of diabetes/hypertension and endometrial cancer?
possibly result of increased incidence of obesity in these groups, but role of insulin has been questioned
By what factor does unopposed HRT increase the risk of endometrial cancer?
4x (reduced to <1.0x with opposed HRT)
Why is the use of the COCP thought to reduce the risk of endometrial cancer?
probably because it administers progestogens throughout the cycle
Why do smokers have a lower incidence of endometrial cancer?
they are more likely to reach an earlier menopause
What are 2 broad types of endometrial cancer?
- Type I: seen around time of menopause or soon after, tumour cells have oestrogen and progesterone receptors
- Type II: not related to oestrogen production, seen in older women
How does the prognosis of type I endometrial cancer compare with type II and why?
much poorer prognosis for type II; type II progress more rapidly, not associated with hyperplastic or in situ phase whereas type I has premalignant change, slower growth
What is the cardinal symptom of endometrial carcinoma?
abnormal uterine bleeding - most commonly postmenopausal
any irregular uterine bleeding in those over 40 (especially if obese/ other risk factors) should be investigated
What are 4 symptoms of endometrial cancer?
- Postmenopausal bleeding
- Irregular uterine bleeding pre-menopause
- Vaginal discharge - blood stained, watery or purulent
- Can present with abnormal cells on a smear consistent with endometrial origin
What does pain in endometrial cancer usually indicate?
metastatic spread - rarely associated with early disease
What is the mode of spread of endometrial cancer?
principally direct spread, usually involves myometrium
cervix, fallopian tubes as well as local supporting tissues (parametrium) can also become involved with more locally advanced cases
lymphatic and haematogenous spread may also occur
What are the 4 main methods of investigation for endometrial cancer?
- Transvaginal ultrasound scanning
- Endometrial biopsy
- Dilatation and curettage
- Hysteroscopy
How is dilatation and curettage for endometrial cancer performed?
carried out under general anaesthesia, combined with hysteroscopy
cervix dilated to allow introduction of sharp curette, instrument that scrapes of endometrium for histological analysis
How commonly is dilatation and curettage now performed in suspected endometrial cancer?
used to be standard of care but rarely used alone now - combined with hysteroscopy in cases where additional investigations are required
What does hysteroscopy involve to investigate endometrial cancer?
visualising inside of uterine cavity directly using a hysteroscope (fine telescope), can be introduced with or without anaesthesia depending on the instrument and the local facilities
biopsy or curettage can be performed as same time
What is the gold standard investigation for endometrial cancer?
hysteroscopy with biopsy
What is endometrial hyperplasia?
increased number of endometrial cells due to proliferation and this results in a thicker endometrium
terms cystic glandular hyperplasia/simple hyperplasia/glandular hyperplasia/ endometrial hyperplasia are synonymous
What is the binary classification of endometrial hyperplasia?
with or without atypia
What might it be difficult to distinguish severe atypia in the hyperplastic state from?
well-differentiated carcinoma
What is needed for a diagnosis of endometrial hyperplasia?
should be increase in gland-to-stromal ratio
glands may vary in size and shape or may branch abnormally
What is seen on histology in hyperplasia with atypia? 3 things
- loss of polarity of cells within the glands
- increase in nuclear-cytoplasmic ratio
- nuclear irregularity with hyperchromatic changes, chromatin clumping and prominent nucleoli
How can benign endometrial lesions be differentiated from those with invasive potentia?
atypia - if prseent, likely to become invasive
What proportion of patients with endometrial hyperplasia with atypia will develop carcinoma?
10-20% will in 10 years
How is endometrial hyperplasia usually discovered?
endometrial biopsy as part of investigation of abnormal uterine bleeding
In which group of patients does simple endometrial hyperplasia typically occur?
anovulatory teenagers, and perimenopausal years
What is the treatment of simple endometrial hyperplasia?
Progestogens - Mirena IUS often used to manage abnormal uterine bleeding in premenopausal women
What is the recommended management for atypical hyperplasia?
hysterectomy
What is the histological appearance of endometrial carcinoma?
- can have variety of histological appearances depending on if purely glandular or has areas of squamous differentiation (may appear malignant or benign)
- or whether demonstrates papillary or clear cell pattern
- latter 2 associated with poorer prognosis
Which 2 histological appearances of endometrial carcinoma are associated with a poorer prognosis?
- papillary
- clear cell pattern
What is another type of endometrial cancer in addition to the most common, adenocarcinoma?
endometrial sarcoma - locally agressive tumour that metastasizes early, genearlly poor prognosis
What is the key indicator of prognosis of endometrial cancer?
the stage, based on FIGO 2009 scheme (International Federation of Gynaecology and Obstetrics)
What are 7 factors which all affect the prognosis of endometrial cancer?
- Histological type
- Histological differentiation
- Stage of disease
- Myometrial invasion
- Peritoneal cytology
- Lymph node metastasis
- Adnexal metastasis
What is the staging system for endometrial cancer?
FIGO staging
- I
- IA: Tumour confined to the uterus, no or <50% myometrial invasion
- IB: Tumour confined to the uterus, >50% myometrial invasion
- II
- II: Cervical stromal invasion, but not beyond uterus
- III
- IIIA: Tumour invades serosa or adnexa
- IIIB: Vaginal and/or parametrial involvement
- IIIC1: Pelvic node involvement
- IIIC2: Para-aortic involvement
- IV
- IVA: Tumour invasion bladder and/or bowel mucosa
- IVB: Distant metastases including abdominal metastases and/or inguinal lymph nodes
How are endometrial sarcomas staged?
new corpus sarcoma staging system based on criteria used in other soft tissue sarcomas
Before management of endometrial carcinoma is performed, what investigation is done first?
MRI scan before operating to determine degree of involvement of local tissues and allow assessment of lymph nodes
sometimes CT but MRI better to look at local infiltration
What is the mainstay of treatment for endometrial carcinoma?
surgical management: hysterectomy and bilateral salpingo-oophorectomy
often performed laparoscopically (reduces length of stay, recovery time etc.)
peritoneal cytology usually also sent
Which part of the management of endometrial cancer is there debate about?
whether pelvic lymph nodes should be removed - trade off between complications and additional information (positive or negative) that each option brings
certainty of negative lymph nodes can redue/limit adjuvant radiotherapy
What is the management of endometrial cancer if it has spread beyond the uterus?
individualised treatment, often focused on gaining control of local tumour
surgery if in fallopian tubes followed by adjuvant treatment
if more widespread, should be managed depending on degree and location of spread + condition of patient
What is the treatment of endometrial cancer after surgery?
- related to stage of disease
- radiotherapy may be used as adjuvant (postoperative) if tumour invades myometrium deeply - higher risk of extrauterine disease
- local radiotherapy to vault of vagina (brachytherapy) may prevent recurrence developing in this area
- radiotherapy to whole pelvis (external beam radiotherapy) will also prevent local disease recurring but doesn’t improve survival
What treatment of endometrial cancer may be used if the patient is medically unfit for major surgery? 2 things
- radiotherapy - but becoming less common as most patients’ comorbidity can be optimised for surger
- high dose progestogens can be used to slow progression (but less commonly used now
If endometrial cancer is very widespread what treatment amy be considered?
chemotherapy - cisplatinum and doxorubicin most helpful (controversial effect on response rate)
What is the recurrence of edometrial cancer like?
for most treated patients, will not recur and prognosis good
When and where does recurrence of endometrial cancer typically occur?
usually within first 2 years of primary treatment
most commonly in vault of vagina
also in lymph node chains, lungs, bone, liver
If recurrence of endometrial cancer occurs at a distance site what is the management and why?
should aim to maximise quality of life rather than subject to treatment with high morbidity and slim chance of success
this is because 80% with distant recurrent disease will die wihtin 2 years
What are 3 options for management of recurrence of endometrial cancer in the vaginal vault?
- if have not received radiotherapy should be considered for this treatment
- for the remainder, choice is between hormonal therapy and chemotherapy
- main hormonal option is high-dose progestogens, which may give a response (slowing disease) in 30%
- chemotherapy can produce tumour shrinkage in some cases but toxicity is considerable
What type of cancer are the vast majority of vulval cancers?
squamous cell carcinoma
In what age group do most cases of vulval carcinoma occur?
over age of 65 years
What are 5 risk factors for vulval carcinoma?
- Age >65years
- HPV infection
- Vulval intraepithelial neoplasia (VIN)
- Immunosuppression
- Lichen sclerosus
What is the typical presentation of vulval carcinoma?
lump or ulcer on labia majora; may be associated with itching, irritation
What is lichen sclerosus?
inflammatory condition which usually affects the genitalia and is more common in elderly females; leads to atrophy of epidermis with white plaques forming
What is the key clinical feature of lichen sclerosus?
itch is prominent
How is a diagnosis of lichen sclerosus usually made?
usually on clinical grounds, but biopsy may be performed if atypical features are present
What is the management of lichen sclerosus?
topical steroids and emollients
What are 4 situations when you should consider biopsy of lichen sclerosus?
- Suspicion of neoplastic change i.e. persistent area of hyperkeratosis, erosion or erythema, new warty or papular lesions
- Disease fails to respond to adequate treatent
- Extragenital lichen sclerosus, with features suggesting overlap with morphoea
- Pigmented areas in order to exclude abnormal melanocytic proliferation
What are the 4 groups that benign ovarian cysts can be divided into?
- physiological cysts (follicular cysts and corpus luteum cyst)
- benign germ cell tumours (dermoid cyst)
- benign epithelial tumours (serous cystadenoma, mucinous cystadenoma)
- sex cord stromal tumours
When should you perform a biopsy on an ovarian cyst?
if they are complex i.e. multi-loculated
What is the commonest type of ovarian cyst?
follicular cysts
What are 2 types of physiological ovarian cysts?
- follicular cysts
- corpus luteum cyst
What causes a follicular cyst in the ovary?
due to non-rupture of the dominant follicle or failure of atresia in a non-dominant follicle
What is the usual prognosis for follicular cysts of the ovary?
commonly regress after several menstrual cycles
What causes a corpus luteum cyst of the ovary?
during the menstrual cycle if pregnancy doesn’t occur the corpus luteum usually breaks down and disappears. if this doesn’t occur, the corpus luteum may fill with blood or fluid and form a corpus luteal cyst
How are corpus luteum cysts likely to present?
more likely to present with intraperitoneal bleeding (than follicular cysts)
What is the key type of benign germ cell tumour affecting the ovary to know about?
dermoid cyst
What is another name for dermoid cysts and what are they?
also called mature cystic teratomas
usually lined with epithelial tissue and hence may contain skin appendages, hair and teeth
What is the median age of diagnosis of dermoid cysts?
30 years old (most common benign ovarian tumour in woman under 30)
How commonly are dermoid cysts bilateral?
10-20% of cases
What is the usual presentation of dermoid cysts?
usually asymptomatic; torsion more likely than with other ovarian tumours
What are the 2 key ypes of benign epithelial tumours of the ovary?
- Serous cystadenoma (first most common)
- Mucinous cystadenoma (second most common)
What are benign epithelial tumours of the ovary?
arise from the ovarian surface epithelium
What do serous cystadenomas of the ovary bear a resemblane to?
the most common type of ovarian cancer - serous carcinoma
What proportion of serous cystadenomas of the ovary are bilateral?
20%
What is the typical morphology of mucinous cystadenomas?
typically large, may become massive
What is a possible complication of mucinous cystadenomas?
if rupture, may cause pseudomyxoma peritonei - presence of mucin in the peritoneal cavity (commonest cause is appendix cancer)
How do the cysts of PCOS appear on ultrasound?
bulky ovaries with multiple small follicles, fibrotic capsule, smooth surface - ring of pearls sign on TVUSS
What are sex cord-stromal tumours?
rare ovarian tumours composed of granulosa cells, theca cells, Sertoli cells, Leydig cells, and fibroblasts of stromal origin, singly or in various combinations
What are 4 examples of sex cord stromal tumours of the ovary?
- Fibroma (commonest)
- Sertoli-Leydig cell tumour (produce androgens)
- Thecoma (produce oestrogens)
- Lipoma
When would you consider non-conservative management of ovarian cysts?
if persists (most resolve spontaneously) or if >5cm
What is the prognosis of ovarian cancer usually like and why?
poor prognosis due to late diagnosis
What is the commonest type of ovarian cancer?
90% epithelial in origin, 70-80% od cases due to serous carcinomas
What has now been recognised is often the site of what is considered an ‘ovarian’ cancer?
distal end of fallopian tube
What are 4 risk factors for ovarian cancer?
- Family history: mutations of the BRCA1 or the BRCA2 gene
- Early menarche
- Late menopause
- Nulliparity (many ovulations)
What are 5 clinical features of ovarian cancer?
- Abdominal distension and bloating
- Abdominal and pelvic pain
- Urinary symptoms e.g. urgency
- Early satiety
- Diarrhoea
notoriously vague
What is the recommended investigation for suspected ovarian cancer?
-
CA-125
- if raised (>35 IU/ml) then urgent USS of abdomen and pelvis
- ultrasound
What is the normal range for CA125?
<35 IU/mL
When should you not use CA-125 measurement as screening for ovarian cancer?
in asymptomatic women
What is the definitive diagnosis for ovarian cancer?
diagnostic laparotomy usually
What does the management of ovarian cancer usually involve?
combination of surgery and platinum-based chemotherapy
What is the prognosis of ovarian cancer?
80% of women have advanced disease at presentation; 5-year survival is 46% (across all stages)
In which age group is vulval intraepithelial neoplasia (VIN) more common?
postmenopausal women, but may occur in any age group
What has been the trend in VIN in recent years and why is this thought to be?
increased; probably reflects changes in sexual practice and increased recognition
What proportion of VIN will progress to vulval cancer?
up to 9%
What is VIN and what is thought to cause it?
dysplastic lesion of the squamous epithelium of vulva; as with CIN, associated with persistent infection with HPV in >90% of cases. smoking also associated with it
What type of HPV is VIN particularly associated with?
HPV 16
What symptoms may be associaed with VIN?
- primarily itch, also pain and ulceration
- over 20% may be asymptomatic
- lesions may appear raised, hyperkeratotic, and warty or flat and erythematous
- frequently found at multiple sites on the vulva (50%)
How is a diagnosis of VIN made?
punch or excision biopsy
What condition should also be investigated for if a diagnosis of VIN is made?
CIN - should have regular cervical smears as HPV can cause multifocal disease
What are 3 aspects of management of vulval intra-epithelial neoplasia?
- Surveillance - careful follow up, biopsy suspicious lesions
- Surgery - excision of painful/rritating lesions can be performed
- Immunotherapy - imiquimod can be help with clearance of genital warts
What is the mainstay of treatment for vulval cancer?
surgery both for curative intent and for palliation
What is the cause of most vaginal cancer?
most are metastases from either above (cervical cancer or uterine) or below (vulval)
What is the comonest true vaginal malignant tumour?
squamous cell carcinomas
What are 5 predisposing factors for vaginal cancer?
- Previous hisory of intraepithelial neoplasia
- Invasive carcinoma of vulva, vagina, cervix
- Pelvic radiotherapy
- Long-term inflammation due to vaginal pessary or procidential
- Squamous cell carcinoma commonly HPV-related
What is the key predisposing factor to the vaginal clear cell adenocarcinoma type of tumour?
DES (diethylstilbestrol) exposure in utero - DES was administered to milllions of pregnant women at risk of miscarriage or premature delivery between 1940 and 1971
daughters of these women at risk of this cancer
What are the 3 things involved in the risk-malignancy index (RMI) for ovarian cancer?
CA-125, USS findings, menopausal status
What is the purpose of the risk malignancy status for ovarian cancer?
predicts prognosis
What are 3 things that can cause a raised CA-125 in addition to ovarian cancer?
- Endometriosis
- Menstruation
- Benign ovarian cysts
