Gynae Cancers Flashcards
What are the types of cervical cancer? What is the aetiology and RFs for it?
Cervical cancer = 80% squamous cell carcinoma (from CIN or cervical intraepithelial neoplasia) and 20% Adenocarcinoma (from CGIN or cervical glandular intra-epithelial neoplasia)
Aetiology =
-> HPV (types 16 and 18) in over 70% cases
RFs:
- > HPV = major
- > Minor = smoking, many sexual partners, early 1st intercourse, immunosuppression
How would cervical cancer present and in what age group?
Affects 45-50yo, 20% 65yo+
- 6% female malignancies
Sx:
- PV discharge, offensive or bloodstained e.g. PCB, IMB, PMB
- Deep dyspareunia
- Symptoms of late metastases e.g. SOB, DIC and FLAWS
- Metastasises to iliac LNs, not para-aortic
How is cervical cancer staged? How would you Ix suspected CC?
FIGO staging system
I = limited to cervix
II = extension to parametrical/uterus/vagina
III = extension to pelvic side wall and/or lower 1/3 vagina
IV = extension to adjacent organs or beyond true pelvis
Ix:
- > 2w urgent referral to cervical screening pathway
- > Bloods - FBC for anaemia, U&Es if obstructive picture, LFTs for metastasis, clotting, G&S
- > MRI scan (preferred over CT-CAP for CC but not for ovarian or endometrial)
How would you manage cervical cancer? [think stages]
Mx:
MDT approach
Stage Ia1 (micro invasive)
- Conservative
- LLETZ (large loop excision of the transformational zone), cone biopsy - follows smear pathway
Stage Ia2 to IIa (early stage)
- fertility sparing = radical trachelectomy (remove cervix) + bilateral pelvic node dissection
- Tumours less than and up to 4cm = radical hysterectomy + bilateral pelvic node dissection (Wertheim’s)
Stage IIb to IVa (locally advanced disease)
- Chemoradiation*
Stage IVb (metastatic disease)
- Combination chemotherapy (cisplatin-based)
- Single agent therapy and palliative care
*Radiotherapy can be external beam (10mins of delivery over 4w) or internal beam (brachytherapy - rods of radioactive selenium is inserted into the affected area)
What are complications of cervical cancer treatments?
Surgical risk e.g. in Wertheims hysterectomy
- Bladder dysfunction (atony) - common, may require intermittent self-catherisation
- Sexual dysfunction due tp vaginal shortening
- Lymphodema due to pelvic LN removal
Radiotherapy (used more than chemo)
- Lethargy, fatigue
- Infertility
- Skin erythema with external beam radiotherapy
- Incontinence, urgency, dyspareunia/vaginal stenosis
- Diarrhoea and malabsorption
What is the transformational zone and its significance?
Cervix = endocervix and ectocervix.
- > Endocervix (upper portion) has columnar epithelium
- > Ectocervix (lower portion) has squamous epithelium
Transformational zone is the area where the 2 epithelium join and where squamous cells change into columnar. Therefore, as it as an area for changing cells, it is where abnormal cells are most likely to occur
What is CIN and what are some risk factors for it, and who does it present in?
Cervical intraepithelial neoplasia = pre-malignant cellular atypia within squamous epithelium of the cervix
- > FIGO stage 0 - i.e. BEFORE cervical cancer
- > RFs = smoking, multiple sexual partners, HIV, early age of first sexual intercourse
- > Peak age = 25-29 whereas CC is 45-50y
How can CC be prevented or caught early? What are some reasons for inadequate smears?
HPV vaccine (Gardasil) - against strains 6, 11, 16 and 18
- > For boys and girls aged 12-13
- > If pregnant, delay until 3m/+ post partum
Smear testing:
- > Under 25y - once, <6m before 25th birthday
- > 25-49 - every 3y
- > 50-65 - every 5y
- > 65+ - only if one of the last 3 tests was abnormal
- > High risk e.g. HIV+
- > Pregnancy - if due a test, reschedule until at least 3m/+ postpartum
Reasons for inadequate results = inflammation, age-related atrophic change and blood on smear
How would someone with CIN present?
Sx:
- Sx of cervical cancer so PV bleeding (IMB, PCB, PMB)
- Found on routine screening
What dysplastic changes would you see in CIN? [3] How would you stage CIN? How would you follow these patients up/Mx?
Dysplastic changes:
- Increased nucleus to cytoplasmic ratio
- Abnormal nuclei shape, size and density (dyskaryosis)
- Reduced cytoplasm
Stages of CIN:
- low grade = mild dysplasia only in lower 1/3 of epithelium
- high grade = moderate dysplasia affecting 2/3 epithelial thickness
- high grade = severe dysplasia extending to upper 1/3 epithelium –> risk of Ia1 FIGO
Ix:
- > Smear screening; outcome f/u:
- > If CIN 1 then HPV test and if +ve then = colposcopy, -ve = routine recall
- > CIN 2 + CIN 3 require urgent colposcopy (<2w) and then treatment
- > Inadequate sample - repeat up to 2x, refer to colposcopy
What are the different management options for CIN? What are complications of CIN + Tx?
Mx:
- Conservative for CIN1 - smear in 12m
- LLETZ or loop diathermy - removal of cells with thin wire loop which is heated by electricity and done under LA. SE’s = increased risk of miscarriage, cervical stenosis and incontinence, f/u smear difficulties
- Cone biopsy - done under GA, less used than LLETZ but done if a large area of tissue needs to be removed
- Other therapies: cryotherapy, laser , hysterectomy (requires a vault smear 6m and 18m later)
- F/u test of cure 6m later of a smear and HPV test: if +ve then repeat colposcopy to find residual/untreated CIN, if -ve then recall in 3y
Complications:
- Miscarriage and PTL
- CIN can progress to CC but may also spontaneously regress, especially if young
What is endometrial hyperplasia and what are some RFs for it?
EH = excess endometrial growth which usually occurs after the menopause and can progress to cancer. May be:
- EH without atypic = cells normal
- EH + atypia = cells abnormal
RFs:
- Increased age
- OESTROGEN exposure
- -> early menarche, late menopause
- -> Tamoxifen, HRT
- -> Nulliparous
- -> Sex-cord stromal ovarian tumours e.g. Granulosa cell tumour which secrete oestrogen
- -> High insulin levels e.g. PCOS and T2DM
- -> Obesity, smoking
- -> FHx of ovarian, bowel cancer, HNPCC, Lynch syndrome
How may someone present with endometrial hyperplasia? How would you Ix them?
Sx:
- PV bleeding, usually post menopausal bleeding (PMB)
Ix:
- > Full Hx and exam
- > 1st line = TVUSS if PMB
- – if endometrial lining >4mm post-menopausal (>10 if not) then hysteroscopy +/- biopsy
- > 2nd line [GOLD-standard] = Hysteroscopy under LA +/- pipelle biopsy (i.e. showing complex hyperplasia with atypia = premalignant condition), but now sonohysterography is slowly replacing it as method of visualisation
How would you manage patients with suspected EH? [After hysteroscopy and biopsy is carried out] + PACES counselling
Mx:
- If EH and no atypia:
- > Reverse RFs e.g. obesity, HRT
- > <5% risk of becoming malignant in 20y
- > Endometrial surveillance every 6m, biopsies recommended in high risk women
- > 1st line = progestogens e.g. LNG-IUS for 5y or oral continuous progestogens for minimum 6m
- > Hysterectomy is an option also
- If EH + atypia:
- > If don’t require fertility sparing then total hysterectomy and BSO if post-menopausal
- > Fertility preserving = LNG-IUS or 2nd line: oral progestogens
- > Regular endometrial surveillance with biopsies every 3m
PACES:
- Explain Dx - abnormal thickening of the endometrial/lining of the womb
- We are worried/take concern as there is a risk it could progress to cancer
- Explain Mx - depending if atypia or not
What is endometrial cancer? Who does it affect and what are some RFs?
Malignancy of the endometrial tissue = most common gynae malignancy in the UK (1% lifetime risk)
- Mean age 54yo; uncommon in those under <40yo
- Unclear aetiology but involves unopposed oestrogen stimulation of the endometrium, either endogenous or exogenous
- RFs = same as endometrial hyperplasia:
- Increased age
- OESTROGEN exposure
- -> early menarche, late menopause
- -> Tamoxifen, HRT, COCP
- -> Nulliparous
- -> Sex-cord stromal ovarian tumours e.g. Granulosa cell tumour which secrete oestrogen
- -> High insulin levels e.g. PCOS and T2DM
- -> Obesity, smoking
- -> FHx of ovarian, bowel cancer, HNPCC, Lynch syndrome
What are the different types of endometrial cancer and who do they affect? [2] What mutations are associated with these?
90% are adenocarcinomas
Type 1 - SEM (secretory, endometrioid, mucinous carcinoma) = 85%
- -> younger patients, oestrogen dependent, superficially invade, low-grade
- -> requires at least 4 mutations (i.e. PTEN, PI3KCA, K-ras, P53, FGFR2, CTNNB1)
Type 2 - SC (uterine papillary serous carcinoma, clear cell carcinoma) = 15%
- -> Older patients, less oestrogen dependent, deeper invasion and higher grade
- -> associated mutations include p53 (90% in serous carcinomas) and PTEN (CCC)
How may women with endometrial cancer present? When do most women present?
Sx:
- PV bleeding (i.e. PMB is endometrial cancer until proven otherwise)
- Bulky uterus
- Metastasises to para-aortic LNs
note: most present in stage 1 disease (PV bleeding) so surgery is enough to treat
What investigations would you consider for endometrial cancer?
Ix:
- Speculum + Bimanual
- Bloods - FBC
- TVUSS = 1st line
- -> thickness of endometrial lining >4mm warrants 2nd line investigations:
- Hysteroscopy +/- pipelle biopsy performed under LA as an OP
- CT-CAP for FIGO staging
How would you manage endometrial cancer? What are non-surgical options?
Mx:
FIGO staging where CT-CAP is preferred over MRI
-> Stage 1 requires total abdominal hysterectomy and bilateral salpingo-oopherectomy + peritoneal washings
-> Stage 2 requires a radical hysterectomy (includes cervix) and radiotherapy adjunct
Others:
- Chemo has limited use, i.e. when cancer isn’t amenable to radiotherapy
- Hormone therapy such as high dose oral/intrauterise progestins such as the LNG-IUS may be indicated with women with complex typical hyperplasia + low grade stage 1A endometrial tumours. Relapse rates are high but can be suitable for those not fit for surgery or fertility reasons
What is the prognosis for endometrial cancer? What are good and bad factors?
80% 5y survival
- Bad prognostic factors = age, grade 3 tumours, distant metastasis, deep invasion, nodal involvement
- Hormone receptor expression may influence a better prognosis/treatment (Her2)
Why is ovarian cancer particularly dangerous and how common is it?
Cancer of the ovaries
- -> Presents late due to non-specific symptoms and therefore worse prognosis
- ->70% present after cancer has spread beyond pelvis
- -> 5% female cancers (5th most common malignancy in females)
What are the different types of ovarian tumours? [4] State the subtypes and prevalence of each?
Types of ovarian cancer:
EPITHELIAL CELL TUMOURS
- -> Commonest (70%)
- -> Post-menopausal women
- -> Arise from ovarian epithelial cells
- -> Subtypes include: serous tumours (commonest), endometroid carcinomas, clear cell tumours, mucinous tumours and undifferentiated tumours
- -> Endometriosis associated with»_space;> clear cell and»_space; endometroid ovarian carcinoma
- -> Mostly benign apart from high-grade serous epithelial tumours (95% of malignant ovarian tumours are epithelial)
DERMOID CYSTS/GERM CELL TUMOURS
- -> Benign ovarian tumours
- -> 15-20%
- -> Teratomas (originate from germ cells) = contain various tissue types such as skin, teeth, hair and bone
- -> Young women (20s) and older women (70s)
- -> Particularly associated with ovarian torsion
- -> May cause raises aFP and hCG
SEX CORD-STROMAL TUMOURS
- -> Rare (5-10%)
- -> All ages
- -> Malignant (usually immature) or benign (usually mature)
- -> Arise from connective tissue (stroma) or sex cords (embryonic structures associated with the follicles)
- -> Several types including: sertoli-leydig cell tumours and granulose cell tumours
METASTASES
- -> Secondary tumours in ovaries
- -> E.g. Krukenberg tumour refers to ovarian metastasis, usually from GIT (or breast) cancers, especially the stomach. They show a characteristic ‘signet-ring’ on histology and are mucin-producing
What are some risk factors (+mutations) and some protective factors for ovarian cancer?
RFs:
- > Age (peaks at 60y)
- > BRCA1+2 genes (see FHx) and MLH1 and MSH2 (Lynch syndrome/HNPCC)
- > Increased ovulations (early menarche, late menopause, nulliparity)
- > Obesity
- > Smoking
- > Recurrent clomifene use
Protective factors:
- > COCP use
- > Pregnancy + breastfeeding
What are 2 associations/syndromes associated with ovarian tumours?
Associations:
- > Peutz-Jegher’s syndrome (polyps in colon) - granulosa cell tumours
- > Meig’s syndrome - ovarian fibroma (benign), ascites and right-sided pleural effusion
How may patients present with ovarian tumours?
Sx:
- > Increased age (if v young, consider germ cell)
- > Late presentation (75% present at stage 3)
- > Bloating, distension
- > Pelvic pain (referred hip or groin pain due to obturator nerve compression by mass)
- > Abdominal or pelvic mass
- > Early satiety, loss of appetite
- > Urinary symptoms (frequency, urgency)
- > Weight loss
- > Ascites
- > O/E: Adnexal mass and NO PV bleeding
What is the FIGO staging for ovarian cancers?
FIGO:
- Tumour confined to ovary
- Tumour outside ovary but within pelvis
- Tumour outside pelvis but within abdomen
- Distant metastases
What Ix would you consider for w woman with suspected ovarian cancer?
Ix:
- Abdo + Bi/Sp exam
- 2WW referral if red flags/you see ascites, pelvic mass or abdominal mass (NOT due to fibroids) on examination
- Ca125 = if 35IU/+ then refer via 2WW to O+G and TVUSS (aFP, bHCG if young pt)
- TVUSS by gynaecologist
- —-> Risk of malignancy index (RMI) calculated
Other:
- > Staging with CT-CAP
- > Histology using CT-guided biopsy, laparoscopy or laparotomy or paracentesis to test ascitic fluid for cancer cells
- > Woman under 40y with complex ovarian mass require tumour markers aFP and HCG to be checked for germ-cell tumours
When else can Ca125 be raised?
Ca125 is a tumour marker for epithelial ovarian cancer BUT is actually an indicator of stretch and therefore can be raised in pregnancy, endometriosis and alcoholic liver disease also
What is the RMI for ovarian cancer?
Risk of malignancy index (RMI) is calculated from
- menopausal status
- USS features
- Ca125
= score >250 is considered high risk, <25 is low risk
How is ovarian cancer managed? How would you counsel the patient?
Mx:
- > Mix of surgery and chemotherapy (2nd line is chemo alone)
- > Neoadjuvant/2nd line adjuvant chemotherapy = Platinum compound + Paclitaxel:
- –> Platinum compounds e.g. Carboplatin commonly used (less nephrotoxic and nauseating than cisplatin); act by cross-linking DNA and cell cycle arrest; dose as per pt GFR
- –> Paclitaxel causes micro-tubular damage, preventing cell division. Causes total loss of body hair. Pre-emptive steroids given to reduce hypersensitive reaction and Res (peripheral neuropathy, neutropenia, myalgia)
- –> Bevacizumab is a anti-VEGF antibody, inhibiting angiogenesis. Expensive, therefore not routinely used but available for recurrent disease treatment
- > Surgery = Laparotomy
- -> TAH+BSO + omentectomy + extra-debulking
- -> Consider fertility sparing in young women
- -> Chemotherapy is NOT useful in sex-cord stromal tumours, surgery is mainstay!
PACES:
- > Breaking bad news! ‘SPIKES’ - gauge perception and invitation
- > Explain what tests show and cancer Dx
- > Explain Mx if known/otherwise explain further tests may be necessary to see how far it has progressed
- > Explain Mx will be surgical +/- chemotherapy
- > RFs
What is the prognosis of ovarian cancer?
Prognosis depends on residual disease following laparotomy
-> 5y survival is 46% (S1 = 90%, S3 = 30%)
What is vulval cancer and the most common type?
Malignant neoplasm of the vulva
- > Mainly SCC (95%) but less commonly malignant melanomas
- > Rare
What are some RFs and causes of vulval cancer?
RFs:
- > Advanced age (especially 75+)
- > Immunosuppression
- > HPV infection* (HPV 16 can cause VIN)
- > Smoking
- > Lichen sclerosus (5% of women with LS get vulval cancer = differentiated type i.e. keratinised SCC)
How may women with vulval cancer or VIN present? What is VIN and 2 types+associations?
VIN = vulval intraepithelial neoplasia
- > Pre-malignant condition affecting squamous epithelium of skin, preceding vulval cancer
- > High-grade squamous intraepithelial lesion (HSIL) is a type of VIN associated with HPV* infection, typically occurring in woman aged 35-50y
- > Differentiated VIN (dVIN) is associated with lichen sclerosis and typically occurs in older women (50-60y)
Sx:
- > Vulval swelling/ulcer, itching, pain + dyspareunia, bleeding and discharge
- > Nodule/ulcer visible on vulva, commonly labia majora
- > Inguinal lymphadenopathy
- > May be incidental finding e.g. catheterisation in a woman with dementia
How would you Ix and Mx vulval cancer?
Ix:
- > Tissue diagnosis - biopsy
- > Sentinel node biopsy to demonstrate spread
- > Further imaging e.g. CT-AP for staging (FIGO)
- 2 WW urgent referral if suspected vulval cancer **
Vulval cancer Mx:
= Vulvectomy
-> If stage 1a = Wide local excision to remove cancer OR if stage 1a+ = radical vulvectomy + bilateral inguinal lymphadenectomy
-> Groin LN dissection
-> Chemo neo-adjuvantly may be considered
-> Radiotherapy if unsuitable for surgery
How would you manage VIN?
VIN:
- > W+W with close follow up
- > Wide local excision surgery to remove lesion
- > Imiquimod cream
- > Laser ablation
What are some blood markers for particular ovarian cancers?
Ca125 = serous epithelial ovarian cancer
Ca19-9 = mucinous epithelial ovarian cancer (+pancreatic cancer)
Inhibin = Granulosa cell tumours
CEA = Bowel cancer (i.e. metastases)
AFP = Teratoma, endodermal yolk sac tumour (+HCC)
HER2 = Breast cancer
LDH = Dysgerminoma
b-HCG = Dysgerminoma, choriocarcinoma
