Gynae Cancers Flashcards

1
Q

What are the types of cervical cancer? What is the aetiology and RFs for it?

A

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
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2
Q

How would cervical cancer present and in what age group?

A

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
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3
Q

How is cervical cancer staged? How would you Ix suspected CC?

A

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)
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4
Q

How would you manage cervical cancer? [think stages]

A

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)

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5
Q

What are complications of cervical cancer treatments?

A

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
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6
Q

What is the transformational zone and its significance?

A

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

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7
Q

What is CIN and what are some risk factors for it, and who does it present in?

A

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
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8
Q

How can CC be prevented or caught early? What are some reasons for inadequate smears?

A

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

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9
Q

How would someone with CIN present?

A

Sx:

  • Sx of cervical cancer so PV bleeding (IMB, PCB, PMB)
  • Found on routine screening
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10
Q

What dysplastic changes would you see in CIN? [3] How would you stage CIN? How would you follow these patients up/Mx?

A

Dysplastic changes:

  • Increased nucleus to cytoplasmic ratio
  • Abnormal nuclei shape, size and density (dyskaryosis)
  • Reduced cytoplasm

Stages of CIN:

  1. low grade = mild dysplasia only in lower 1/3 of epithelium
  2. high grade = moderate dysplasia affecting 2/3 epithelial thickness
  3. 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
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11
Q

What are the different management options for CIN? What are complications of CIN + Tx?

A

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
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12
Q

What is endometrial hyperplasia and what are some RFs for it?

A

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
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13
Q

How may someone present with endometrial hyperplasia? How would you Ix them?

A

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
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14
Q

How would you manage patients with suspected EH? [After hysteroscopy and biopsy is carried out] + PACES counselling

A

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
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15
Q

What is endometrial cancer? Who does it affect and what are some RFs?

A

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
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16
Q

What are the different types of endometrial cancer and who do they affect? [2] What mutations are associated with these?

A

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)
17
Q

How may women with endometrial cancer present? When do most women present?

A

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

18
Q

What investigations would you consider for endometrial cancer?

A

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
19
Q

How would you manage endometrial cancer? What are non-surgical options?

A

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
20
Q

What is the prognosis for endometrial cancer? What are good and bad factors?

A

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)
21
Q

Why is ovarian cancer particularly dangerous and how common is it?

A

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)
22
Q

What are the different types of ovarian tumours? [4] State the subtypes and prevalence of each?

A

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&raquo_space;> clear cell and&raquo_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
23
Q

What are some risk factors (+mutations) and some protective factors for ovarian cancer?

A

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
24
Q

What are 2 associations/syndromes associated with ovarian tumours?

A

Associations:

  • > Peutz-Jegher’s syndrome (polyps in colon) - granulosa cell tumours
  • > Meig’s syndrome - ovarian fibroma (benign), ascites and right-sided pleural effusion
25
Q

How may patients present with ovarian tumours?

A

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
26
Q

What is the FIGO staging for ovarian cancers?

A

FIGO:

  1. Tumour confined to ovary
  2. Tumour outside ovary but within pelvis
  3. Tumour outside pelvis but within abdomen
  4. Distant metastases
27
Q

What Ix would you consider for w woman with suspected ovarian cancer?

A

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
28
Q

When else can Ca125 be raised?

A

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

29
Q

What is the RMI for ovarian cancer?

A

Risk of malignancy index (RMI) is calculated from

  • menopausal status
  • USS features
  • Ca125

= score >250 is considered high risk, <25 is low risk

30
Q

How is ovarian cancer managed? How would you counsel the patient?

A

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
31
Q

What is the prognosis of ovarian cancer?

A

Prognosis depends on residual disease following laparotomy

-> 5y survival is 46% (S1 = 90%, S3 = 30%)

32
Q

What is vulval cancer and the most common type?

A

Malignant neoplasm of the vulva

  • > Mainly SCC (95%) but less commonly malignant melanomas
  • > Rare
33
Q

What are some RFs and causes of vulval cancer?

A

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)
34
Q

How may women with vulval cancer or VIN present? What is VIN and 2 types+associations?

A

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
35
Q

How would you Ix and Mx vulval cancer?

A

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

36
Q

How would you manage VIN?

A

VIN:

  • > W+W with close follow up
  • > Wide local excision surgery to remove lesion
  • > Imiquimod cream
  • > Laser ablation
37
Q

What are some blood markers for particular ovarian cancers?

A

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