Gynaeoncology

Question 1

Cervical Cancer

Answer 1

Cervical screening program
	• From Dec 2017
	• HPV screening
		○ Then LBC done if HPV normal
	• Tests transformation zone
	• Every 5yrs from age 25 to 74yrs
	• From feb 1, if HPV other/LSIL on 2 occasions, can repeat in 12months without colposcopy UNLESS
		○ 2 or more years overdue
		○ >50yrs
		○ Indigenous

Treatment
• LSIL -> repeat HPV DNA in 12months
• HSIL -> LLETZ
○ If margins not involved and extends, then repeat cotest in 12 months

Pathophysiology
• TZ = where columnar cells transform into squamous cells
• Occurs at puberty
• If oncogenic HPV affects TZ, CIN may form instead of normal squamous tissue
• CIN 1,2,3 - depends on how much of epithelium is affected

HPV vaccine
• HPV 16 and 18 account for 70% of cervical cancers
• Introduced 2007, aimed girls and boys aged 12-13yrs
• 2 doses at 0 and 5-13 months; 3 doses if immunocompromised or over 15yrs at 0,2,6months
• Gardasil 9 protects against 90% of cervical cancers
• Can get vaccine females age 9-45yrs and males 9-26yrs
• Still need regular CST
• Not recommended in pregnancy but cases have not shown adverse effects in pregnancy

Vaginal screening after hysterectomy
• Hysterectomy for benign disease and normal CST history -> no screening
• Never had screening -> vaginal vault HPV test (not cotest) at 12months then annually until negative on 2 consecutive occasions then cease
• If HSIL and had test of cure (2 consecutive cotests) -> no screening
• If HSIL and no test of cure -> vaginal vault cotest 12months then annually until negative on 2 consecutive occasions then cease
• If unexpected LSIL or unexpected/known HSIL -> vaginal vault cotest 12months then annually until negative on 2 consecutive occasions then cease
• Adenocarcinoma -> vaginal vault cotest annually indefinitely
• Subtotal hysterectomy (cervix still insitu) -> 5-yearly HPV testing as per normal guidelines

If any of the above tests (cotest or HPV DNA) positive, refer for colposcopy

Trachelectomy = cervix, upper vagina, parametrium

STAGING FIGO 2018
STAGE 1 = cervix only
- 1A1 = stromal invasion <3mm; observation if fertility desired OR cone biopsy OR simple hysterectomy
- 1A2 = stromal invasion 3-5mm; pelvic lymphadenectomy or radical trachelectomy + pelvic lymphadenectomy if fertility desired OR modified radical hysterectomy +/- pelvic lymphadenectomy if fertility not desired
- 1B1 = >5mm to <2cm stromal invasion; radical hysterectomy + pelvic lymphadenectomy
- 1B2 = >2cm to <4cm stromal invasion; surgery + primary chemo/radio + neo-adjuvant chemo/radio
- 1B3 = >4cm
STAGE 2 = beyond uterus but not into lower third vagina or pelvic wall
- 2A1 = invasive <4cm
- 2A2 = invasive >4cm
- 2B = parametrium but not pelvic wall
STAGE 3 = lower third vagina, pelvic wall, hydronephrosis/pelvic LN
STAGE 4 = behind true pelvic into bladder/rectum

Treatment stage 2-4A = LN debulking if bulky retroperitoneal nodes + pelvic/para-aortic radiation + chemo + brachytherapy

If completed family:
- Always suggest radical or modified radical hysterectomy

Generally only recommend fertility sparing surgery if 1A1, 1A2 and 1B1
- Anything above 1B1, requiring radical surgery, chemo or radio risk is 30% -> so would not recommend fertility sparing surgery

Who would you recommend fertility sparing simple trachelectomy:

• Wanting fertility
• <40yrs
• Tumour 1B1 or less
• No LVSI
• No LN involved – negative PET/MRI (no parametrial involvement)

Ix:

• Rectal/pelvic exam
• Colposcopy
• Cystoscopy/proctoscopy
• CXR
• Cervical biopsy
• Pelvic MRI for local staging – check if extended into parametrium
• CT or PET for distant mets

Question 2

Cervical cancer questions

Answer 2

JULY 2015
Question 12 - Cervical malignancy
In both Australia and New Zealand, indigenous populations have significantly higher incidence of, and mortality from, cervical malignancy than non-indigenous populations.

a. Identify five (5) epidemiological factors which may account for this. (5marks)
Higher incidence:
- Underscreened population  late diagnosis and progress to higher grade change or malignancy before detection and treatment
- Geography – less access to medical care in form of screening and treatment
- Education – less education/health literacy surrounding importance and reason for screening
- Lack of access to HPV vaccination
- Increased rates of smoking – increased persistence of HPV infection
- Other medical comorbidities/immunosuppression  less clearance HPV infection
- Distrust in medical advice leading to poor follow-up or avoid treatment despite recommendations / lack of culturally sensitive facilities

Supuni’s additions:

• Lack of female doctors in remote areas – fear of embarrassment
• Higher rates STI including HPV
• Higher rates comorbidities making more susceptible to persistent HPV
• Lower socio-economic status
• ?Earlier age at first birth, earlier onset sexual activity, increasing parity

A 32 year old woman is diagnosed with cervical carcinoma Stage 1B.
b. According to the FIGO Staging system, list all the examinations and investigations that could have been included to establish the diagnosis and the stage of her cancer. (4 marks)

Stage 1B = confined to uterus with lesion bigger than 1A (depth invasion >5mm to 4cm)

Examination:

• Colposcopy – look for vaginal involvement
• EUA – parametrial involvement, extension beyond cervix/uterus to pelvic side wall, vagina, rectum
• Cystoscopy and proctoscopy – to exclude involvement bladder/rectum
• Histopathology of specimen – LLETZ/cone biopsy showing size of tumour, stromal invasion/parametrial involvement

Investigations:
- IVP – exclude hydronephrosis of kidney or extension to compress ureter
- CXR to exclude lung mets
Other possible useful imaging (but not required) MRI – good to show parametrial involvement; renal tract US/CT KUB – hydronephrosis or non-functioning kidney; CXR, CT or MRI to show distal spread – bladder, rectum, lungs, liver

Her tumour is a squamous cell carcinoma which is 2cm in size. Imaging studies do not suggest lymph node involvement.
(You may wish to use a table to answer the following.)
c. i) List her three (3) treatment options. (11⁄2 marks)

ii) Outline one (1) indication for each treatment option.(11⁄2marks)
iii) List two (2) long-term complications associated with each treatment option. (Use different complications for each treatment option). (3 marks)

Stage 1B1

• Radical hysterectomy + pelvic lymphadectomy
• > Indication: completed family, greatest likelihood of cure
• > Complications: increased surgical morbidity, lymphoedema, sexual/psychological dysfunction, bladder dysfunction
• Radical trachelectomy + pelvic lymphadenectomy
• > Indication: fertility sparing
• > Complications: increased risk of preterm birth/miscarriage, recurrence
• Chemoradiation
• > Indication: positive pelvic LN, positive surgical margins, not suitable for surgical management (obese, medical comorbidities)
• > Complication: radiation cystitis, vaginal stenosis / dyspareunia, hair loss

FEB 2015
Question 11 - HPV vaccination and prevention of cervical cancer
Both Australia and New Zealand have initiated National Human Papilloma virus (HPV) Vaccination Programs, which are endorsed by the RANZCOG. Two HPV vaccines, Gardasil and Cervarix, are available in both countries.

1. Describe the viral composition of Gardasil HPV vaccine. (2 marks)
   - Made from virus like proteins (VLP) that do NOT contain live, attenuated or killed virus (IM injection) induces Ab response which will protect from infection
   - Nanovalent (Gardasil 9) – 16, 18 - most oncogenic viruses and 6,11 that cause genital warts
2. Discuss four (4) benefits and three (3) limitations of Gardasil HPV vaccination in preventing genital tract dysplasia. (7 marks)
   Benefits:
   - Reduce incidence of CIN and cervical cancer
   - Reduces mortality from cervical cancer
   - Reduce incidence of VIN and VAIN
   - Freely available
   - Sperenza study: HPV vaccine reduced risk of recurrence in women with CIN2
   - Reduces recurrence of cervical cancer if vaccinated
   - Can be used in males - herd immunity, reduces rates of penile cancer

Limitations:

• Does not prevent against all HPV types (although some cross-reactivity); 15 oncogenic HPV types
• Less effective after sexual debut
• Not a treatment so doesn’t treat existing changes
• Not available in all countries - burden of disease of cervical cancer higher in those with limited access to HPV vaccine
• Doesn’t protect against other STI

3. Discuss one (1) benefit and one (1) limitation of Gardasil HPV vaccination in preventing genital warts. (2 marks)
   - Benefit: reduces genital warts - 90% caused by HPV 6,11 which are included in vaccine
   - Limitation: genital warts can be caused by other HPV strains, does not treat genital warts, does not protect against other STI

A 23 year old nulliparous woman who did not have HPV vaccination at school was vaccinated by her GP. A month after her first dose she discovers she is 9 weeks pregnant. She is seeing you because she wants to continue the pregnancy and is concerned about the effect of having inadvertently commenced the HPV vaccination program while pregnant.

d. Outline two (2) pieces of advice you will give to the patient and justify each with respect to HPV related issues. (4 marks)
- Not a live virus therefore no risk to fetus
- Less effective as already sexual active prior to vaccination
- Defer subsequent doses until after pregnancy
- Continue cervical screening program

JULY 2012 - Question 9
A 27 year old woman has been referred to the antenatal clinic at 13 weeks gestation. A cervical smear taken at booking was reported as follows: “Possible high grade squamous intra-epithelial neoplasia.”

a. Apart from high grade CIN what other conditions may be associated with such a report? (5 marks)
- Low grade CIN (CIN 1)
- Inflammatory/infective
- Cervical cancer – squamous cell carcinoma, cervical adenocarcinoma in situ (AIS)
- Normal cervix
- Endometrial cancer
- Endometrial hyperplasia
- Vaginal intraepithelial neoplasia
- Cervical polyp

You recommend colposcopy.

b. List four (4) issues as to how pregnancy might affect the colposcopic assessment of this patient? (2 marks)
- Altered appearance of transformation zone - increased squamous metaplasia which may make more concern for high grade appearance
- Altered location of transformation zone – more likely to have ectropion
- Increased patient anxiety – more concerned about how colposcopy may affect pregnancy
- Cervix may be more vascular with increased bleeding if biopsy taken
- Increase in cervical mucous making visualisation more difficult
- Unable to lie supine for long period time so positioning of patient important and may make examination more difficulty (risk aorto-caval compression - dizziness etc.)

Supuni answer:

• Laxity of vaginal walls - difficult visualisation cervix
• Difficult to take sample – risk bleeding
• Pregnancy triggers active squamous metaplasia which can make interpretation difficult (acetowhite changes etc.)
• Increased vascularity, hypertrophy makes difficult colposcopic assessment and interpretation
• Cervical ectropion may impair colposcopic assessment
• Reluctance and anxiety of patient
• Endocervical brush contraindication  can lead to inadequate sampling
• Stromal decidual changes can be misinterpreted

Colposcopic biopsy confirms CIN II. The management of this patient is complicated by the fact that she is now 15 weeks gestation.

c. Describe your counselling, management and follow up of this woman, and how this would compare with that of a non-pregnant woman. (8 marks)
- Counsel/educate re: HPV and effects on cervix
- Explain pre-malignant change and therefore not cancerous however usual management would be treatment of the abnormality to prevent progression to cancer
- Explain that diagnosis of this does not lead to recommend TOP and safe to continue pregnancy
- Explain process of LLETZ and importance of follow-up post-partum to arrange this
- Discuss possible implications on pregnancy – slightly higher risk pre-term labour, PPROM, however no change to usual pregnancy management unless a problem arises
- Should have repeat colposcopy in third trimester and then plan to follow-up 6 weeks post-partum with repeat colposcopy +/- LLETZ
- Not perform while pregnant

Compared to non-pregnant:

• Arrange for treatment with LLETZ
• Would counsel re: avoiding pregnancy until treatment completed
• Risk post-treatment in future pregnancy of pre-term labour, PPROM secondary to cervical incompetence

                   CIN 1	CIN 2	CIN 3 Regression	57%	        43%	        32% Persist      	32%	         35%	56% Progress	                         11%	        22%	 Cancer	          1%	         5%	       >12%

AUGUST 2011 - Question 2
1. State how cervical cancer is staged (1 mark)
Clinically
NOT surgically staged (ovarian and endometrial are)

2. Outline the diagnostic tests which may be used to determine the stage using the FIGO staging system (5 marks)
   - Cervical biopsy/LLETZ/cone biopsy/colposcopy – depth of invasion and widest diameter
   - EUA + colposcopy - determine tumour size; vaginal or parametrial involvement; bladder/rectum; excisional biopsies (cone vs. LLETZ)
   - CT KUB
   - CT CAP
   - Cystoscopy – look for extension to bladder
   - Protoscopy/colonscopy – direct extension to bowel
   In 3rd world countries where imaging not possible: CXR or CT KUB/IVP

A 30-year old woman has a cervical biopsy showing CIN 3. The histology of the LLETZ specimen is reported as “squamous cell carcinoma with invasion 6mm deep and lateral spread of 9mm”. Her last pap smear, 5 years ago was normal. She has no other significant past history and has one delivered vaginally. After full assessment, diagnosis of cervical carcinoma Stage 1B1 is made.

2. A) Treatment options including surgery or chemoradiation. What factors influence the choice of treatment for this woman? (2 marks)
   Patient – future fertility plans, comorbidities/surgical fitness
   ? Tumour – stage and size of tumour (positive lymph nodes = chemoradiation; IB2 or above cannot have fertility sparing)

B) Comprehensively outline the late complications of radiotherapy that could occur in this woman? (7 marks)

• Radiation cystitis
• Vesico-vaginal or vagino-rectal fistula
• Vaginal stenosis and dyspareunia
• Menopause
• Lymphoedema
• Other cancers due to radiation
• Fibrosis
• Radiation enteritis
• Radiation proctitis, bowel stricture or perforation
• Osteoporosis/reduced bone density

Question 3

Endometrial cancer notes

Answer 3

For endometrial hyperplasia WITHOUT atypia:
Follow up is 6monthly until 2x negative then cease
IF high risk (BMI>35 or using PO progesterone), for 6monthly for 2yrs then annually
Offer hysterectomy if progression, does not regress >12months, relapse, ongoing abnormal bleeding, difficult to follow up

For endometrial hyperplasia WITH atypia:
Hysterectomy is recommendation
Postmenopausal -> and BSO
Premenopausal -> discuss removing ovaries (though will need HRT) and recommend BS to reduce risk of ovarian cancer
No benefit of routine frozen section or lymphadenectomy
If wanting to preserve fertility, check for invasive endometrial cancer and ovarian cancer; review in MDT; treat with IUD (1) or PO progesterone (2) then offer hysterectomy once fertility no longer required due to high risk of relapse
Follow up if not having hysterectomy is 3monthly biopsies, then once 2x every 6-12months until hysterectomy

If wanting to conceive:
Need to see disease regression (with no atypia or with atypia) in at least one endometrial sample before attempting to conceive
Refer to fertility specialist
Consider ART as live birth rate is higher and may prevent relapse compared to natural conception

HRT and hyperplasia:
Review need for HRT
Change to continuous combined HRT or add IUD

Tamoxifen increases risk of endometrial hyperplasia and cancer but aromatase inhibitors (letrozole etc) do not

Sentinel LN biopsy:

• > Negative predictive value is 97-99% - same for endometrial, vulval
• > False negative rate – 5% for endometrial cancer, 2-3% for vulval

Question 4

Endometrial cancer - QUESTIONS + ANSWERS

Answer 4

February 2017

Question 9 - postmenopausal bleeding +/- endometrial cancer

A 63 year old woman presents after one episode of light vaginal bleeding over the last week. She has a BMI of 42, chronic hypertension and type 2 diabetes

A: List five possible causes for her bleeding. Identify the most common cause (3 marks)
Grade 1-3 – associated with degree of differentiation (grade 3 being worst)
80% endometrioid (adenocarcinoma, adenocarcinoma variant); 20% non endometrioid (clear cell, serous, sarcoma, squamous)

Endometrial hyperplasia, endometrial cancer, endometrial polyp, cervical cancer, oestrogen secreting tumours, cervical polyp – most common cause genital tract atrophy

B: i) List 4 risk factors for endometrial cancer not mentioned in the scenario that you should elicit from her history

a. Unopposed oestrogen, nulliparity, anovulation/PCOS, tamoxifen, family history, Lynch syndrome, early menarche/late menopause, endometrial hyperplasia

ii) Justify your initial management of this patient to assess her risk for endometrial cancer (3 marks)
b. Assess risk:
i. History – age of menopause, parity, history of bleeding – amount/frequency, CST, medical history
ii. Examination – abdominal exam for palpable uterus, pelvic and per vaginal exam for palpable masses; speculum for cervical lesion/CST, pipelle biopsy
iii. Investigations – TV US to assess endometrial thickness, FBC/UEC/LFT, Ca125, hysteroscopy/dilation and curettage

This patient underwent hysteroscopy and endometrial biopsy. The histology report showed a grade 1 endometrial adenocarcinoma.

C: Discuss the rationale for your management plan for this patient (5 marks)

Management plan:

a. Inform patient of results
b. Refer to Gynaeoncology for MDT
c. Further investigations to aid in staging
i. FBC/UEC/LFT – anaemia, extension into kidneys/liver
ii. CT/MRI staging
iii. CXR
iv. Ca 125
d. Treatment
i. Pre-operative risk assessment / anaesthetic review / endocrine review for T2DM
ii. Optimising risk factor pre-op
1. Weight loss
2. BSL control
iii. Ask other specialties if needed
iv. Bowel prep
v. DVT prophylaxis
vi. Counselling on treatment options – staging is surgical:
1. Progesterone (intrauterine or oral) – not first line, if risk of surgery too high
2. TLH + BSO (lap or abdominal) – first line
a. Oophorectomy as postmenopausal and reduces risk of ovarian cancer
b. Salpingectomy as reduces risk of ovarian cancer
3. LN – controversial
a. Facilitate staging but no survival benefit
4. Intraoperative frozen section of uterus
5. Perineal fluid cytology
6. +/- cystoscopy (if extension to bladder suspected)
7. +/- proctoscopy (if extension to colon suspected)
8. Chemo/radio depending on surgical staging
9. Omentectomy if clear cell or serous
vii. Follow up
1. Depends on stage
2. Vault smears annually

D: Discuss the aspects in her history that would alert you to the possibility of her having Lynch syndrome (2 marks)
Also has ovarian tumour, previous colorectal cancer, strong family history of endometrial/ovarian/colorectal cancer, endometrial cancer <50yrs, younger age of presentation, other cancers stomach/intestinal/pancreas/kidney/brain

 
July 2015

Endometrial hyperplasia is a common cause of postmenopausal bleeding. List 4 other common causes of postmenopausal bleeding, starting with the most common cause. (3 marks)
Endometrial cancer, endometrial polyp, cervical cancer, oestrogen secreting tumours, cervical polyp – most common cause genital tract atrophy

An obese (BMI 42) 60 year old woman presents with recurrent postmenopausal bleeding. She has never used hormone replacement therapy. Examinations, including a speculum exam and a pap smear, are normal. Histopathology diagnoses complex endometrial hyperplasia with atypia following hysteroscopy and curettage.

A) Discuss your options for treatment in this patient, with justification(s) for each option (10 marks)
Options:
- Progesterone – oral or IUD
i. If wanting to preserve fertility
ii. If wanting to avoid surgery or too high risk for surgery
- TLH + BS
i. Salpingectomy reduces risk of ovarian cancer
- TLH + BSO
i. Oophorectomy if postmenopausal – discuss with patient
- Weight loss
- Optimise medical risk factors
- Follow up 3 monthly then if 2x negative then 6monthly for 2yrs – annual follow up if high risk (BMI>35 or abnormal bleeding)

B) If histopathology did not show “atypia”, how would it alter your approach to her treatment? Give your reason (2 marks)
Treatment:
- Progesterone (IUD >PO) is first line
- Hysterectomy only if progression, no regression >12months, persistent bleeding, patient not following up, patient request
- Follow up 6monthly and if 2x negative then cease follow up

 
February 2012

Question 7
A 60 year old woman presented to you with a history of postmenopausal bleeding. An endometrial biopsy demonstrates endometrial adenocarcinoma.
a. Describe the main pre-operative and intra-operative management principles for staging and treatment in this case. (6 marks)
Preoperative
• Multidisciplinary approach in management involving gynaecologist at a tertiary referral centre and anaesthetic review
• Assess preoperative fitness and optimise for surgery
• Investigations
o Bloods
o Imaging to help plan operative extent
 Cxr - look for metastasis
 CT abdo/pelvis – lymph node involvement
 Can consider MRI – look at depth of myometrial involvement or cervical involvement
o DVT prophylaxis, Antibiotic prophylaxis and bowel prep
o consent
Intraoperative
• Midline laparotomy
o Peritoneal fluid for cytology
o Total abdominal hysterectomy with bilateral salpingo-opherectomy
 Bisect uterus and inspect depth of invasion
o Palpate Lymph nodes for sampling and suspicious LN, radical lymphadenectomy is rarely indicated
o Pelvic lymphadenectomy
 Radical lymphadenectomy allows for completed staging of disease  may avoid radiotherapy if nodes confirmed to be negative
 Decision to perform lymphadenectomy depends on depth of invasion (identified at frozen section taken intra-operatively)
• Palpate para-aortic lymph nodes and remove nodes suspicious for macroscopic disease
• Exploration of intra-abdominal contents: omentum, liver, peritoneal cul-de-sac, adnexal surfaces
• Stage disease based on histopathological and surgical findings  plan subsequent management  radiotherapy for high grade tumour, etc
• Omentectomy is clear cell/serous
• Palpate upper abdomen for any lesions is suspicious
• Closure in layers
• Review in tumour board with pathology to determine further management

b. List eight main prognostic factors associated with a poor outcome in this condition. (4 marks)
•	Tumour
o	Grade >2
o	Lymphovascular space invasion
o	Cervical stromal invasion
o	Histological subtypes (non endometrioid)– clear cell, serous
o	>50% of myometrial involvement
o	Higher stage >1B
o	Hormone receptor status
o	Cancers with p53 mutation
•	Patient
o	Age
o	Other medical comorbidities

c. Describe the situations where radiotherapy can be used in the management of endometrial carcinoma. (5 marks)
Can be used in the form of EBRT or brachytherapy (often vaginally)

Primary radiotherapy – if surgically unfit for primary treatment
• Advanced stage disease or inoperable disease

Adjuvant radiotherapy
o If more that stage I Endometrial cancer
o Metastasis – LN involvement
o Presence of any poor prognostic factors
 Other histological subtypes
 Cx involvement or extension more than 50% of uterus
 High grade >3

Palliative treatment
• Pain
• Intractable bleeding
• Debulking

Radiotherapy for recurrence – if intent is to cure

Question 5

Vulval table

Answer 5

VIN 1 (LSIL or differentiated)= flat condylomata or HPV effect
VIN 2 or 3 (HSIL or undifferentiated) = warty type, basaloid type, mixed type

Dermatitis or LSC

• Irritant triggers
• Treat with environmental modifications, topical methylpred
• Commonly recur

Chronic vulvovaginal candidiasis

• Likely hypersensitivity to candida
• Affects pre-menopausal women (need oestrogen)
• Itchy, burning, dysuria, dypareunia, does not need to have discharge
• Thrush worsened premenstrually and after antibiotics
• Vaginal erythema and oedema
• Treat with oral fluconazole 150mg every 2-3 days then weekly for weeks to suppress symptoms then wean to avoid recurrence
• For non albicans candida, boric acid pessary 600mg daily

Lichen sclerosus

• More common peri and post menopausal and prepubertal girls
• Itch, dysuria, dyspareunia
• Atrophic pale papules and plaques and later sclerotic plaques in figure of 8 distribution; loss of architecture; obliteration of clitoral hood; adhesions on labia minora and introital stenosis
• Does not involve vagina
• Diagnose on biopsy
• Potent topical steroids (bethamethasine 0.05%) BD for 4 weeks, then daily for 4 weeks; maintenance treatment with weaker topical steroids (methylpred 0.1%)
• 5% risk SCC
• Can have surgery to divide adhesions with post op potent topical steroids to prevent recurrence

Lichen planus

• Lymphocytic infiltrate in upper dermis
• Erythematous papules and plaques
• Can involve vagina
• Topical steroids or calcineurin inhibitors (tacrolimus 0.1% ointment)
• Can have surgery to divide adhesions with post op potent topical steroids to prevent recurrence

Vulval cancer:
The reason for LN dissection is depth of invasion >1mm (does not depend on size)
If <4cm, negative imaging, only 1 site of disease -> need to do just sentinel LN dissection (never do frozen second on LN)
- If positive imaging or more sites of disease or >1mm -> need to do LN dissection

If sentinel LN is positive, need to do full ipsilateral groin LN dissection +/- contralateral groin LN dissection

Question 6

Vulval questions

Answer 6

2017 Question 12 – Benign vulval dermatoses
A 60 year old woman presents with a 12- month history of vulval itch and insertional dyspareunia. On examination, the labia minora are absent and there is a thickened white area at the posterior introitus. Speculum examination shows that the vagina is normal. You suspect lichen sclerosus (LS) and perform a biopsy. The histology report comments: “the epidermis is atrophic with hydropic degeneration of basal cells and an homogenous pale zone in the upper dermis. There is a lichenoid infiltrate of mainly mononuclear cells in the dermis”.

a. Identify all the particular features presented in the scenario (history, examination and histology) that explain why the diagnoses of each of the following two conditions is unlikely:
i) Lichen planus (LP) (3 marks)
- Involves vagina
- LP is lymphocytic infiltrate/basal cell liquefaction/sawtooth akanthosis and LS is thinned epidermis and inflammatory infiltrates
- Younger age in LP (average age 37) whereas in LS is often postmenopausal
- LS is thickened white area
- Loss of architecture and loss of labia minora is LS

ii) Lichenified dermatitis (lichen simplex chronicus [LSC]) (3 marks)
- LSC usually has environmental factors like heat/rubbing
- This stem has no clear trigger like allergic reaction or related to psychiatric disorders of OCD/depression
- LSC no atrophic changes or loss of labia minora
- LSC is thickened plaques due to years of itchiness not white areas
- LSC affects all ages, LS is mostly postmenopausal women
- Years of symptoms in LSC
- LSC usually affects labia majora, in LS labia minora is absent
- Histology shows hyperkeratinised cells

b. Outline your first-line management following confirmation of the diagnosis of lichen sclerosus with a punch biopsy. (7 marks)

• Patient education about disease and counselling
• 5% progression to VIN/vulval SCC – which can be reduced with treatment
• Conservative
  Vulval hygiene
  Avoid irritants/tight clothing/hot showers
  Wear cotton underwear
• Medical
  Topical steroid cream – betamethasone, methylprednisolone, clobetasone
  Use daily for 4 weeks, then 2nd daily for 4 weeks then twice weekly for 4 weeks then review
  Use minimal effective dose to manage for maintenance therapy
  Topical oestrogen and lubricant
• Second line
  Topical calcineurin inhibitors
  Tacrolimus or clobetasol
  UVA phototherapy
• Surgery (laser, cryotherapy, vulvectomy) reserved for those that affect lifestyle and not responding to other treatment e.g. severe vaginal stenosis prohibiting intercourse
• Follow up after 4-6 weeks to see improvement then reduce dose
• Once stable, for annual follow up
• If not improving or worsening, consider re-biopsy for VIN or vulval cancer
• Educate patient if worsening/bleeding, re-present due to risk of malignant transformation

The patient presents for her 6-week follow-up visit, and reports that her dyspareunia is reduced, but not eliminated. Examination shows that the LS lesions are no longer visible, but there is substantial spasm of the pubococcygeus muscles, causing a reduction in the introital dimensions.

c. What is the correct management? (2 marks)
Vaginismus
- Physio
	Vaginal dilators
	PFE
- Review by psychologist 
- Confounding contributor
Check for marital discourse
History of sexual abuse
- Sexual education
	Foreplay
Lubricant
Stimulation
 

February 2016

A 68 year old woman presents with a 6 month history of vulval pruritus and irritation. A grey white partially ulcerated lesion is noted on the left labia majora. A key punch biopsy shows VIN3.

a. i) Name the two (2) different types of VIN3 she could have. (2 marks)
ii) Discuss the aetiology of each type. (2 marks)

Undifferentiated or usual (warty, basaloid, mixed)

• Related to HPV infection
• Also associated with cigarette smoking, immunocompromised status
• May co-exist with CIN
• Usually in younger women

Differentiated

• Associated with lichen sclerosis and/or squamous hyperplasia
• Usually in older women

b. i) Identify three (3) treatment options for her VIN3. (3 marks)
ii) List two (2) indications or advantages for each option. (3 marks)

Superficial local excision of the vulvar epithelium with a 0.5 – 1cm margin (WLE)

• Histopathological diagnosis achieved as sample excised
• For lesions on lateral aspect of vulva
• Risk of recurrence less compared to laser vaporisation

Laser vaporisation

• If involving labia minora, clitoral, perianal lesions – difficult to excise
• If invasive disease not suspected
• Preserves anatomy

Topical immune response modifier: Imiquimod (Aldara)

• If not suitable for surgery due to medical co-morbidities
• Complete response rate of 35 – 81%
• Avoid surgical destruction of clitoris, urethra if close
• If multi-focal disease

 
An excision biopsy is performed which shows an early invasive squamous cell carcinoma of the vulva. Excision margins are well clear but the depth of invasion is 3 mm. A sentinel node biopsy is considered rather than a formal groin dissection.

c. With respect to sentinel node biopsy compared to formal groin dissection in this patient:
i) Identify three (3) advantages. (3 marks)
• If sentinel node negative  avoids complete node dissection
• Reduce risk of lower limb oedema
• Less invasive surgery: less risk of wound breakdown, infection/cellulitis
• Does not increase the risk of recurrence; high sensitivity ~95%

ii) Identify two (2) disadvantages. (2 marks)
• Risk a false negative sentinel lymph node (3% risk false negative  95% mortality)
• Greatest single factor in reducing mortality is appropriate groin node dissection (necessary for all except Stage 1A)
• Contraindicated if allergic to blue dye (1% risk anaphylaxis)
• Not suitable for patients with lesion > 4cm, infected tumour, palpable enlarged groin nodes
• Learning curve to reduce false negative; rate influenced by experience of surgeon

 
2014 July SAQ
Question 10 – vulval dermatosis

A physically active 23 year old woman presents with vulval dermatitis.

a. List 4 other conditions that present with vulval itch and a rash. (4 marks)

• Lichen sclerosis
• Lichen planus
• Lichen simplex chronicus
• Vulval psoriasis
• Eczema
• VIN (vulval intraepithelial neoplasia)
• Folliculitis
• Vulval candidiasis
• Extra-mammary Paget’s disease

b. Describe 5 features of the medical history that are important in making a diagnosis of vulval dermatitis in this patient. Justify your responses. (5 marks)

• Assess likelihood of dermatitis
- exacerbating factors: perineal hygiene, wearing tight clothing, use of irritating soaps
- timing of onset of dermatitis  ? related to change in hygiene practice, ? worsened during summer months when more sweaty
• Assess tendency to atopy
- ? history of eczema, asthma
• Exclude other causes of itch and rash
- ? rash elsewhere on body suggestive of psoriasis (scalp, elbows, knees, nails)
- ? signs of lichen planus in the mouth
- ? associated symptoms: vaginal discharge  ? candida
- ? bleeding
- ? history of shaving  ? folliculitis
- ? urinary or faecal incontinence  potentially irritating
• Assess risk of infection
- PMHx: ? history of poorly controlled diabetes
- Medication: ? on regular steroids
• Assess risk for VIN
- Review pap smear history
- ? smoker
• Family history
• Assess risk for lichen sclerosis – presence of other autoimmune conditions
- Thyroid disorders, alopecia areata, pernicious anaemia, T1DM, vitiligo
• ? History of iron deficiency anaemia
- Correction of iron deficiency anaemia or low serum ferritin can relieve vulval symptoms

 
c. List 8 environmental modifications that may assist in the treatment of vulval dermatitis. (4 marks)

• Wearing loose cotton underwear
• Sleep without underwear
• Wear loose fitting clothing, rather than tight pants
• Avoiding irritating soaps
• Avoid excessive washing of vulval region; shower rather than bathe
• Dry area well (eg: using a hairdryer on cool setting)
• Pat dry rather than rubbing
• Avoid excessive exposure to synthetic panty liners
• Assess for and manage any incontinence  avoid prolonged exposure of vulva to urine and faeces
• Tampons rather than pads
• Changing pads regularly
• Changing underwear regularly

d. Discuss the medical management of vulval dermatitis. (2 marks)

• Consider use of topical steroids if unresponsive to environmental modifications
• Emollients play a key role in protecting the skin and restoring skin barrier function
- Use emollients with soap substitutes  maintain symptom relief; may reduce use of topical corticosteroids
• Correction of iron deficiency can reduce symptoms of vulval itch
• Consider oral antihistamines
• Treat coexisting infections – BV, thrush
• If not responsive to environmental and medical management, consider biopsy + referral to specialist vulval clinic

Question 7

Gestational trophoblastic disease

Answer 7

GTD:
• Group of disorders including partial mole, complete mole, invasive mole, choriocarcoma and placental site trophoblastic tumour (PSTT)
• Persistence of GTD (persistent elevation of bHCCG) is GTN (gestational trophoblastic neoplasia)

Pathogenesis:
• Paternal genes control placental growth, maternal genes control fetal growth
• Excess paternal genes causing excessive placental or trophoblastic proliferation

Partial molar:
	• Triploid (90%)
		○ Two sets of paternal haploid genes + one set of maternal haploid genes
	• 69XXY
	• Some fetal tissue
	• Dispermic fertilisation of normal ovum
	• 0.5% of GTN
	• Stains p57 positive

Complete molar:
• Diploid
• Paternal origin 46XX / male genetic material
• No fetal tissue
• Duplication of single sperm fertility empty ovum (75%) or dispermic fertilisation of empty ovum (25%)
• 15% of persistent GTD

Histopathology:
• Marked proliferation of villous trophoblast
• Hydropic chorionic villi
• Gross villous vesicles
• Partial molar has less and smaller villi but chorionic villi still present

Clinical presentation:
• Irregular vaginal bleeding (most common symptom)
• Hyperemesis
• Excessive uterine enlargement
• Early failed pregnancy
• Rarer - hyperthyroidism, early onset PET, acute respiratory failure (mets), seizures (mets)

Investigations:
• bhCG - rapid increases, >2x multiples of median for GA
• Ultrasound - cystic spaces in placenta, ratio of transverse to AP dimension of gestational sac >1.5, snowstorm appearance
• G+H
• FBC/UEC/TFT
• CXR - to exclude pulmonary mets

Management:
• SUCTION CURETTAGE - GOLD STANDARD FOR DIAGNOSIS
○ Karyotype
○ P57 studies
○ Consider ultrasound guided
○ Senior doctor present
○ Valid G+H due to risk of bleeding
○ Can give misoprostol prior to procedure
○ Be careful with oxytocin infusions during procedure due to risk of tumour embolisation and dissemination of trophoblastic tissue
• Anti D
• If medical management of miscarriage occurs and products not sent to histopath, need urine bHCG 3 weeks post
• Limited data for mifepristone and misoprostol
• Register with GTD database
• P57 staining

Follow up:
• Partial
○ Weekly until 3x negative
• Complete
○ Weekly until 3x negative then monthly for 6 months (complete)
○ If normal within 8weeks, follow up for 6months post D&C
○ If not normal within 8weeks, follow up for 6months post normal level
○ If plateauing or rising, refer to Gynaecology for persistent GTD
• Risk of another molar pregnancy is 1:80
• No impact on future fertility
• Always measure hCG levels 6 weeks post any future viable pregnancy
• Send placenta of future pregnancies or histopath of future miscarriages to check for recurrence of molar pregnancy
• If a further molar pregnancy does occur, in the majority (68-80%) of cases it will be of the same histological type
• Contraception
○ GTN - not to conceive until 1yr after chemotherapy
○ Not to conceive 3months post methotrexate
○ Barrier until bHCG normal then can use COCP (low risk of developing GTN if COCP used when bhCG levels not yet normal)
○ NO IUD until bhGC normal due to risk of uterine perforation
• HRT can be used after bHCG levels normal
• If <10% drop or rising bHCG, for gynae onc referral for persistent GTN

Long term outcomes:
• Women who receive chemotherapy for GTN are likely to have an earlier menopause
• Women with high risk GTN who require multi-agent chemotherapy which includes etoposide should be advised that they may be at increased risk of developing secondary cancers (AML, colorectal cancer, melanoma, breast cancer
• If chemotherapy is limited to <6mo then there is no increased risk of secondary cancers

With viable pregnancy:
• Seek MFM guidance
• 25% of live birth, 40% risk of early fetal loss, risk of PET
• Consider prenatal invasive testing to confirm coexisting molar pregnancy

GTN:
• Definition is same as persistent GTD
• Can develop after molar pregnancy, non-molar pregnancy or live birth
• Any woman who develops persistent vaginal bleeding after a pregnancy event is at risk of having GTN
• 15% risk after complete molar pregnancy
• Risk factors: older age, higher bHCG levels, complete molar
• 75% invasive moles, 25% choriocarcinoma
• All require:
○ Gynaeonc referral
○ CT/MRI
○ FIGO staging for treatment
• Single (methotrexate + folic acid) or multiagent chemotherapy based on FIGO 2000 scoring system (if <7 for single, if =7 or more then multi and consider hysterectomy and increased risk for secondary mets)
○ Low risk = 100% cure rate
○ High risk = 95% cure rate
○ High risk for premature menopause

Invasive mole:
• A molar pregnancy characterised by the presence of enlarged hydropic villi invading in to the myometrium, into vascular spaces or into extrauterine sites

Choriocarcinoma:
• Highly malignant epithelial tumour
• Can arise from any type of trophoblastic tissue, but only rarely from partial mole
§ Eg ectopic, abortion, term pregnancy etc
• Histology: sheets of anaplastic cytotrophoblasts and syncytiotrophoblasts without chorionic villi; extensive necrosis, haemorrhage and vascular invasion is common
§ Strong staining for hcg, inhibin, cytokeratin, Ki-67
• Metastatic sites: lung, brain, liver, pelvis, vagina, spleen, intestine, kidney

Placental Site Trophoblastic Tumours (PSTT)
• Rare, potentially malignant neoplasm originating from extravillous trophoblast cells
• Most commonly develop after a term gestation; usually female (46XX)
• ~70% act in a benign manner
• 30% metastasis and may result in death
§ More likely with age, advanced stage, longer interval from previous pregnancy, higher serum hcg, higher mitotic rate, coagulative tumour necrosis, clear cytoplasm
• When malignant, PSTT is fairly resistant to chemotherapy so treated with surgery

Question 8

GTD questions

Answer 8

2013 July SAQ
Question 8 – Gestational trophoblastic disease

A 19 year old woman is referred by the GP with vaginal bleeding in her first pregnancy. The pregnancy is unplanned and of uncertain gestation. Examination shows a 14 week size uterus. An ultrasound arranged by the GP is strongly suggestive of a complete molar pregnancy.

a. Outline the investigations required for this patient. (3 marks)
• FBC/UEC/LFT/TFT/G+H
Quantitative bHCG – significantly elevated in complete molar pregnancy
• CXR – to exclude pulmonary metastases
• Blood group and rhesus status – if rhesus negative, requires Anti-D
• Dilation of cervix + curettage of uterus – to obtain histology and confirm diagnosis (also forms part of treatment of molar pregnancy)
• Consider repeat tertiary level USS

b. Describe the initial management and follow up you would put in place for her. (5 marks)

• Explain diagnosis, counsel regarding follow up importance
• Dilation of cervix + curettage of uterus
• To be performed under ultrasound guided to assist with complete emptying of uterus
• p57 staining
• To be performed by appropriately trained senior gynaecologist
• Anaesthetics to be aware of risk of bleeding (relative to a routine D&C for a missed miscarriage) - have blood group and hold on system; large bore IV cannula in place; can consider use of syntometrine once uterine cavity emptied
• Avoid oxytocin until complete evacuation
• Misoprostol safe
  • Confirm no evidence of metastatic disease
• CXR
• Consider CT brain if symptomatic for brain lesions
  • Follow up histopathology in dedicated gynaecology clinic
  • Arrange follow up of quantitative bHCG to confirm resolution of disease
• Weekly until negative for three consecutive readings
• Monthly for 6 months
• If bHCG plateau (4 consecutive with < 10% drop) or rising (> 3 consecutive> 10%) - persistent mole - refer to gynae-oncology
  • Advise against pregnancy until bHCG follow up complete
• Arrange reliable contraception (eg: Implanon)
  • Advise risk of recurrence following other pregnancies 1:70 - need repeat bHCG following any pregnancy regardless of outcome

 

c. Histology confirms a complete molar pregnancy.
i) How would you explain the cause of molar pregnancy to this woman? (1 mark)
- Type of hydatiform mole
- 2 sperm fertilising empty ovum or 1 sperm splitting and fertilising empty ovum
- Paternal tissue, no fetal tissue

ii) What are the characteristic histopathological features? (1 mark)
- Gross villous vesicles
- Hydropic chorionic villi
- Marked proliferation of villous trophoblast
- Absent staining of p57

d. What is the long term risk associated with molar pregnancy? Outline the principles of its management. (3 marks)

• Persistent gestational trophoblastic disease - GTN
- 15% of complete molar pregnancy progress to GTN
• Management of GTN
- Referral to gynae-oncology + MDT involvement
- Metastatic sceen: CT C/A/P, CT brain +/- MRI brain
- Assess FIGO risk
- If score < 7 - low risk protocol
- Methotrexate + folinic acid rescue therapy
- If score > 7 - high risk protocol
- total hysterectomy
• Risk recurrence in future pregnancies
- Risk 1:80 overall
- Check bHCG after each subsequent pregnancy at 6 weeks post partum

e. Her ß‐hCG levels completely resolve after the affected pregnancy. What are the implications of a molar pregnancy for future pregnancies? (2 marks)
• Risk of recurrence
- Advise placenta to be sent for histopathology with each subsequent pregnancy and/or miscarriage to confirm nil evidence of recurrent molar pregnancy
• Has no impact on future fertility
• If has received methotrexate, advise to avoid pregnancy until at least 3 months post completion of methotrexate treatment

Question 9

Benign ovarian mass

Answer 9

1:25 women will have symptomatic cyst in their lifetime
30% ovarian masses >50yrs malignant

Clinical presentation:

• Asymptomatic
• Palpable
• Signs of rupture/torsion/haemorrhage
• Pain
• Bowel/urinary Sx
• Consider symptoms of endometriosis or symptoms of malignancy (bloating, loss of appetite, weight change, urinary changes)
• Consider Hx of other malignancies (breast, ovarian, bowel, endometrial)

DDx of adnexal mass:

• Gynae - ovarian, fallopian tube, TOA, ectopic pregnancy
• Non-gynae - appendiceal, bowel

Ix:

• History for risk factors
• Abdo exam/vaginal exam
• TV US
• bHCG
• Tumour markers - Ca125 does not need to be done if appears like simple ovarian cyst on US; AFP, HCG, LDH should be done <40yrs with complex ovarian mass
• RMI >200 high risk of malignancy

Treatment (pre-menopausal):

• <5cm → no follow up, likely to resolve in 2 to 3 menstrual cycles
• 5-7cm → annual follow up
• > 7cm or persistent or increase in size → consider surgery or further imaging (MRI) or tumour markers

Treatment (post-menopausal):

• If RMI <25 (<5cm + Ca125 normal) → reassess in 4-6 months and consider surgery or surveillance (US + Ca125) if persistent
• If RMI 25-250 → laparoscopic oophorectomy in a cancer unit
• If RMI >250 → full surgical staging laparotomy in cancer unit
• If any change in features or symptomatic, consider surgery
• Aspiration if only unfit for surgery due to risk of seeding

Surgery:

• Any cysts that persist or increase in size are unlikely to be functional and may warrant surgery
• Laparoscopy > open but cyst more likely to rupture if >7cm
• Consider open to avoid spillage and seeding
• If spilled, for meticulous washings with warm fluid
• Prefer removing masses via umbilical port for decreased post-op pain, decreased hernia risk, quicker retrieval time, better cosmetic outcome
• If postmenopausal, recommend BSO rather than cystectomy
• COCP does not promote resolution of functional ovarian cysts
• High recurrence rate of simple cyst after needle aspiration

Functional cyst (2.6%):

• Follicle that grows usually <3cm can be up to 10cm
• May become haemorrhagic
• Asymptomatic unless haemorrhagic/rupture/torsion
• Usually resolves spontaneously in 6-12weeks
• Smooth, thin walled, unilocular, round/oval shaped, anechoic fluid, no septations/nodules

Corpus luteal cyst:

• Corpus luteum that doesn’t involute and enlarges
• May become haemorrhagic
• Asymptomatic unless rupture/haemorrhage/torsion
• Complex or simple, thick walled, up to 8cm
• Usually resolved spontaneously in 6-12weeks

Endometrioma (17%):

• Ectopic growth of endometrial tissue
• Complex mass with homogenous internal echoes, “ground glass” appearance

Serous cystadenoma:

• Thin walled, usually unilocular
• Similar to fallopian tube epithelium

Mucinous cystadenoma:

• Thin walled, usually multi locular, smooth
• Similar to GI epithelium
• Usually unilateral, filled with mucin
• Can be up to 30cm (but does not correlate with malignancy)
• Less likely bilateral than serous
• 80% benign, 10% borderline, 10% malignancy

Dermoid/mature cystic teratoma (11%):

• Benign germ cell tumour so shows elements from germ cell layers (skin, hair, glands)
• Complex, unilocular, cystic, hyperechoic, fluid, acoustic shadowing
• Most common mass 10-30yo

Paraovarian/paratubal cysts (6%):

• From remnants of paramesonephrtic or mesonephric ducts
• Rare to be malignant

Question 10

Borderline ovarian tumours

Answer 10

Definition: heterogenous lesion with atypical epithelial proliferation without invasion into ovarian stroma (like malignant tumours); grow slower than malignant

15% of ovarian neoplasms
Diagnosed 20-40yrs

Type:

• Serous (65-70%) - most at stage 1 at Dx, 50% bilateral, more likely to recur if micropapillary structures present or stromal microinvasion
• Mucinous (10-15%) - >95% stage 1
• Others - endometriod, clear cell, Brenner

Sx:

• Often asymptomatic
• Pelvic pain/pressure/mass
• Dyspareunia

Ix:

• TVUS - have solid and fluid components, papillary structures common
• Ca125 not useful for borderline
• Surgical staging

Treatment - surgery:

• Ideally frozen section obtained intraop
• Surgical staging - if postmenopausal TSH/BSO + peritoneal washings + omentectomy +/- appendicectomy (if mucinous)
• No role for LN biopsy if borderline
• Consider fertility/menopausal status - can consider unilateral salpino-oopohorectomy than cystectomy due to reduced recurrence rate
• Chemotherapy not indicated in stage 1
• If found to be borderline after removing tumour, check histopath, check op report, monitor for residual disease, monitor with tumour markers and pelvic US
• If did cystectomy and it came back borderline, don’t need to do oophorectomy – can just monitor and remove if it recurs

Complications:

• <2% ovarian carcinoma from transformation, new ovarian cancer or peritoneal cancer
• Risk of malignant transformation – mucinous 5%, serous 2%

Recurrence:

• Recurrence rate in cystectomy (20-30%), oophorectomy then in opposite ovary (10%)
• If recurred, then 95% will be same type (serous or mucinous) as before
• 7-30%
• If it occurs after conservative Mx, consider more advanced surgery TAHBSO
• Pregnancy DOES NOT increase rate of recurrence
• Safe to undergo fertility treatment/ovulation induction
• Can still have HRT in future - recommended if they have had TAHBSO less than 45yrs until age 50
• Consider hysterectomy + BSO after family complete
• Still risk of peritoneal recurrence

Follow up:

• Same as ovarian cancer
• 2-4monthly for 2yrs, 3-6monthly for 3yrs then annually - tumour markers with each review
• No evidence for routine imaging or tumour markers however often done for conservative Mx

Question 11

Ovarian cancer

Answer 11

Background: highest mortality of gynaecological cancers, 70% diagnosed stage 3, peak 60-64yrs; 1% lifetime risk; 10% hereditary

Types:
1. Epithelial cell tumours (90%)
- High grade serous (70%) - 80% advanced, Ca125 elevated, associated with BRCA, very chemosensitive, thought to originate from fallopian tube
- Endometriod (10%) - assoc with Lynch syndrome, arise from endometriotic cysts, 15% also have endometrial cancer
- Clear cell (10%) - unilateral, Bx endometriosis
- Mucinous (3%) - GIT primary, CEA elevated
- Low grade serous (<5%) - borderline component
Pathogenesis:
- Incessant ovulation, persistent exposure to gonadotrophins

2. Germ cell tumours (5%)
   - From primordial germ cells of ovary
   - More common in younger women
   - Grow rapidly
   - 100% cure rate in early stage
   - Types: dysgerminomas (high LDH), yolk sac tumours (high AFP), immature teratomas, choriocarcinoma (high bHCG), embryonal/polyembryoma (high bHCG>AFP)
   - Do karyotype on patient
3. Ovarian stromal/sex cord tumours (<5%)
   - Adults or children
   - Present as precocious puberty in children as tumour produces sex hormones
   - Often diagnosed in early stage
   - Increased aFP and inhibin
   - Granulosa cell tumours (70%) - secrete oestrogen, age 50-59yrs
   - Sertoli-Leydig tumours - present with virilisation (acne, hirsutism, deepening voice, clitoromegaly)
4. Krukenberg tumour
   - Secondary ovarian tumour metastsises from primary site usually GIT
   - 75% bilateral
   - Median age 48yrs Dx, median survival 16months
   - Mucin-secreting signet ring cell carcinoma in the dense fibroblastic stroma of the ovary
5. Lynch syndrome / HNPCC
   - Autosomal dominant
   - Assoc with colorectal/endometrial/ovarian/urogenital/other GIT cancer
   - Age 40-50yrs
6. BRCA
   - BRCA 1 = 40% lifetime risk by age 70
   - BRCA 2 = 20% lifetime risk

Risk factors: *strongest risk factors

• Infertility
• Obesity
• PCOS
• Endometriosis
• Smoking
• Age
• Genetic (BRCA1* -40%, BRCA2 -20%, Lynch syndrome - ovarian 10%, endometrial 30%, bowel 60%)

Protective factors:

• Ovulation suppression - COCP, pregnancy, lactation >6months
• Salpingectomy / oophorectomy
• Hysterectomy
• NSAIDs
• Aspirin

Clinical presentation:

• Abdominal distention
• Nausea, reduced appetite
• Pelvic pain
• Ascites - shifting dullness
• Pouch of douglas nodularity
• Weight loss
• Change in urinary and bowel habits
• FHx of breast/colorectal/ovarian cancer

Tumour markers (picture):

• Ca 125 -> marker for epithelial ovarian, only raised in 50% of early disease, false positive with fibroids/endometriosis/adenomyosis/pelvic infection, >200 likely malignancy, if rising rapidly on serial measurements then more likely malignancy
• aFP -> in germ cell/stromal
• bHCG -> germ cell
• CEA -> Lynch syndrome (mucinous), colorectal cancer
• Ca 19.9 -> dermoid cysts, gastric/pancreatic/GB cancer
• LDH -> germ cell
• Inhibin B -> stromal granulosa

Imaging (picture):
- TVUS
- IOTA rules for benign vs malignant - sensitivity 95%, specificity 91%
B (benign) = unilocular cyst, solid component <7mm, acoustic shadowing, smooth multilocular diameter <10cm, no blood flow
M (malignant) = irregular solid tumour, ascites, 4 or more papillary structures, irregular multilocular solid diameter >10cm, very strong blood flow
Any M findings should be referred to gynae onc
- RMI - most effective with suspected ovarian cancer
U (multilocular/solid/mets/ascites/bilat) x M (pre or post menopausal) x Ca125 -> If >200 high risk for malignancy; sensitivity 78%, specificity 87%
RMI 0-25: 3% risk of malignancy
RMI 25-250: 20% risk of malignancy
RMI >250: 75% risk of malignancy

• CT C/A/P for staging
• CXR
• US>CT for image guided biopsy
• Cytology of ascitic or pleural fluid is informative but not diagnostic

Surgical staging:

• TAH+BSO (USO if fertility sparing stage 1A)
• Ascites/peritoneal washing
• Infracolic omentectomy
• Peritoneal biopsy/excision of disease
• LN dissection
• FIGO staging (picture)
• High grade ovarian/fallopian tube/peritoneal

Cytoreductive surgery/debulking:

• Volume of residual disease remains correlates inversely with survival
• Adv: removes space occupying effect, eliminates hypoxic areas of tumour which improves perfusion to residual nodules
• Disadv: delays start to chemo by 6wks or more, intraop complications, postop complications
• Can consider after a few rounds of chemo

Treatment for epithelial cell:

• 1A = surgery only
• 1B if grade 1 or 2 = surgery only (no benefit in chemotherapy)
• 1B if grade 3 (poorly differentiated) = surgery + chemotherapy
• 1C to 4B = surgery + chemotherapy
• 3C/4 consider chemo + interval debulking surgery which decreasing postop M&M

Treatment for germ cell:
- Surgery + chemo for all stages

Treatment for stromal:

• 1A + 1B = surgery only
• 1C = surgery + chemo
• 2A to 3B = surgery + chemo + radiotherapy

Chemotherapy agent:
- Carboplatin/paclitaxel - platinum based doublet

Complications:

• Bowel obstruction - often signal end of life
• Pain
• Nausea/vomiting due to poor SI absorption

Follow up:

• Same as borderline - 3-6monthly for 2yrs, 3-6monthly for 3yrs then yearly
• BUT with repeat tumour markers and US - however no evidence that regular Ca125 or regular US/CT improves survival

Risk reduction for BRCA/Lynch:
Surgery: - aim is to remove 5yrs earlier than youngest age in family member
- Lynch: BSO + TAH from 35yrs
- BRCA1: BSO between 35-40yrs
- BRCA2: BSO from 45yrs
BSO
- Adv: reduces risk of ovarian and breast cancer (50% in BRCA) and reduces mortality, reduces risk of high grade serous tumours of ovary that originate from fallopian tubes
- Disadv: major surgery, surgical menopause, CV/bone density risks, risk of primary peritoneal Ca remains
COCP:
- Adv: risk reduction for ovarian (by 30-50%) /endometrial/colorectal cancer, decreases benign breast disease and PID, decreases benign ovarian cysts, contraception, no surgery
- Disadv: has SE (IMB/bloating, VTE), controversial if it increases risk of breast or cervical cancer
Note: mastectomy does not reduce risk of ovarian cancer BUT BSO reduces risk of breast cancer
NOTE: BS alone does not reduce ovarian cancer or improve overall survival
HRT after surgical menopause does not increase risk of breast cancer (but is 80% risk anyway in BRCA1,2)

Screening:

• No screening yet for ovarian cancer - no benefit in routine Ca125 or annual pelvic US as do not detect ovarian cancer in early stages and no reduction in mortality, increase in morbidity due to false positives
• If high risk (BRCA/Lynch), offer risk reducing surgery
• From a gynae point of view, no screening technique has been shown to reduce risk of cancer or overall survival. However, other screening for other diseases do make a difference (E.g. breast screening, bowel screening)

Question 12

Ovarian cancer questions

Answer 12

Oct 2020

1. 4 US findings suggestive of ovarian malignancy
   - 4 or more papillary projections
   - Strong blood flow
   - Ascites
   - Irregular, multilocular solid >10cm diameter
2. TV US for screening in low risk woman (4 marks) ? discuss
   - Not recommended
   - Several trials show no benefit in mortality in screening with pelvic US and Ca125 - low sensitivity/specificity in early cancer, false positive with fibroids/endometriosis/PID etc
   - Increases morbidity with unnecessary surgery and psychological distress
3. CA125 for screening in low risk woman (2 marks)
   - Not recommended
   - False positives - lacks specificity
   - Increases morbidity with unnecessary surgery and psychological distress
4. Primary chemotherapy choice for ovarian epithelial cancer
   - Carboplatin/paclitaxel - platinum based doublet
5. What are their side effects
   - Nausea/vomiting, hair loss, diarrhoea, bruising, bleeding, cardiomyopathy, DVT
6. What is the efficacy rate
   - Depends on stage

Jan 2018
Question 8 – Benign Ovarian Cysts
A 22yo woman presents with a large ovarian cyst. 
a. According to the IOTA cyst rules, what features of this cyst would make you think it's benign?
- Unilocular
- Solid components <7mm
- Smooth multilocular <10cm
- Absence of blood flow
- Acoustic shadowing

b. The cyst looks a bit malignant. Justify your investigations (I think it was why do what investigations for which types of ovarian ca?)
- Germ cell tumour markers - aFP, bhCG, LDH, Ca 125
- Sex cord stromal - inhibin
- Calculate RMI
- TVUS
- CT staging

c. How would you manage her?
- Calculate RMI and likelihood of malignancy
- Discussion about fertility
- Refer to gynaeonc
- Counsel patient about risk of malignancy
- Surgical staging - frozen section intraop, counsel about USO, peritoneal washing, omental biopsy
- +/- chemo depending on stage
- Follow up (2-4monthly for 2yrs, 3-6monthly for 3yrs then annually) with relevant tumour markers and ultrasound

July 2017

Question 12 – borderline ovarian tumour

You see a 37 year old woman in the Gynaecology Outpatient Clinic. Three weeks ago, while on holiday, she developed acute appendicitis and had an uncomplicated laparoscopic appendicectomy. An incidental 8cm left ovarian cyst was found at the time of surgery and a laparoscopic ovarian cystectomy was performed.
Her recovery was uneventful and she attends with a letter from the hospital that advised she had a borderline ovarian tumour (BOT).

a) i. After initial history and examination, outline your immediate management plan with regard to her BOT (5 marks)
- Follow up histopath to ensure it was correct, and not benign or a malignancy
- Check op report whether the surgery was appropriate, was there spillage and washouts, was a frozen section sent
- Refer to gynaeonc
- Counsel patient
- Monitor for disease recurrence with tumour markers and pelvic US - as oophorectomy not performed so chance of recurrence

ii. Provider one (1) justification for each management action (5 marks)
- As above

A table may be used to set out your answers to part i and ii

b) List two (2) features of the tumour that would be associated with an increased risk of BOT recurrence in this woman (1 mark)
- Microinvasion of stoma
- Micropapillary structures present
- Focal area of malignancy
- Mucinous
- Higher grade

c) Following your initial management the oncology team decide to perform another laparoscopy. Describe and justify two (2) operations that reduce her oncological risk and enable her to have a family in the future (4marks). A table may be used to set out your answer.
- USO - compared to cystectomy will reduce risk of recurrence, unilateral maintains fertility, BS will reduce risk of high grade serous cancers
- BSO - reduces risk bilaterally, need IVF with donor egg, surgical menopause
- TLH once family complete
- Also do washings and omental biopsy

July 2016
Question 12 – Borderline ovarian tumour
You see a 37 year old woman in the Gynaecology Outpatient Clinic. Two months ago she developed acute appendicitis on holiday and had an uncomplicated laparoscopic appendicectomy at a rural hospital. An incidental finding of an 8cm left ovarian cyst was made at the time of surgery and a laparoscopic ovarian cystectomy was performed. Her recovery was uneventful and she attends with a letter from the rural hospital that advised her that she had a borderline ovarian tumour (BOT).

a. i) After initial history and examination, outline your immediate management plan with regard to her BOT. (4 marks)
- Same as above

ii) Justify each of your management points. (4 marks)
Use a table for your answer in part a. b.
- Same as above

What histological findings are associated with an increased risk of recurrence of a borderline ovarian tumour? (2 marks)
- Same as above

The woman has not yet had a family but intends to in the future. Assuming that she has no high-risk histological findings. c. Evaluate her current management considerations to reduce her long-term health risks but enable her to have a family and her future management considerations. (5 marks)
- Surgical and non surgical options
Surgical:
- As above
Non surgical:
- COCP reduces risk of ovarian cancer by 30-50% but confers risk of undetected recurrence and invasive spread
- Surveillance alone - however higher risk of recurrence
- TLH+BSO once family complete
- Can have HRT
- Note risk of peritoneal recurrence

July 2014 Question 8
A 44 year old pre-menopausal woman asks you whether bilateral salpingo-oophorectomy (BSO) should be performed at her planned hysterectomy for a benign condition. She has no family history of breast or ovarian cancer.
a i) State her background risk of developing ovarian cancer and describe how this risk is affected by BSO. (2 marks)
- Lifetime risk 1.5%
- Risk reduced significantly with BSO as tumours can originate from ovaries and fallopian tubes (high grade serous)

ii) Outline 2 relevant pieces of information that should be obtained from this patient prior to the informed consent process. Indicate as well, the significance of this information. (2 marks)
- Menopausal status - more likely to perform BSO and can start HRT
- Obtain information about contraindications to oestrogen therapy e.g. previous breast cancer
- Family Hx of ovarian/breast/endometrial/colorectal cancer - more likely to perform BSO

b) List 2 possible benefits of elective BSO in the scenario above. (2 marks)
- Reduces risk of ovarian cancer
- Reduces risk of breast cancer
- Avoids needs for secondary procedure in the future if she develops an adnexal mass

c) List 5 possible complications of elective BSO in this woman – include in your answer 2 complications that have been proven to be effectively treated with exogenous oestrogen. (6 marks)
- Severe vasomotor symptoms - improved with oestrogen
- Osteoporotic fracture risk - improved with oestrogen
- Cognitive decline including dementia
- Reduction in libido and sexual dysfunction
- Depression and anxiety symptoms
- Increase in coronary heart disease

d) Name an alternative procedure the patient could consider instead of BSO. Outline the advantage and disadvantage of this procedure. (3 marks)
- Bilateral salpingectomy alone
Adv: reduces risk of high grade serous (80% originate from fallopian tubes), maintain hormonal benefits of oestrogen from ovaries (prevent vasomotor Sx and osteoporotic risk), avoid surgical menopause
Disadv: risk of ovarian cancer arising from ovaries present, may need another procedure to remove ovaries

2013 July Question 7 – Ovarian cancer

a. With respect to the epidemiology of ovarian cancer in Australia and New Zealand:
i) Of 1000 women, approximately how many will develop ovarian cancer in their life? (1 mark)
• 1.5% lifetime risk = 15 women out of 1000

ii) Of these women who develop ovarian cancer, approximately how many will develop cancer because of a genetic predisposition? (1 mark)
• 15-20% of epithelial ovarian carcinomas are hereditary (RCOG)
- Hereditary breast and ovarian cancer, Lynch syndrome mostly
- Also Cowden, Peutz-Jeghers, Li-Fraumeni

iii) What is the strongest risk factor for developing ovarian cancer? (1 mark)
• Carrying hereditary high risk genetic mutation

iv) Describe two epidemiological factors which are most protective against developing ovarian cancer. (2 marks)
• Multiparous
• Use of COCP
• History of breastfeeding for > 6 months
• Younger age

A 36 year old G3P3 with a strong family history of ovarian and breast cancer consults you for advice regarding her risk of developing ovarian cancer. She has tested positive for the BRCA1 gene mutation.
b. Evaluate the use of regular screening in this woman. (3 marks)
• Screening (with Ca125, USS) is unlikely to alter her prognosis – has no impact on survival
• Risk false positives with associated anxiety
• Unlikely to detect ovarian cancer at an earlier stage – hence screening not justified as is unlikely to change the type of treatment required or prognosis
• Screening should not be recommended but should undergo risk reducing surgery
- UKFOCCS trial not shown any benefit
 
c. Describe two proven risk‐reduction strategies for this woman. State two advantages and two disadvantages for each strategy. (7 marks)
- BSO - adv: reduces risk of high grade serous, reduces risk of ovarian; disadv: surgical menopause, increase osteoporotic risk facture, increase cardiovascular risk, severe vasomotor symptoms, still has risk of primary peritoneal
- BS - adv: reduces risk of high grade serous, no menopause; disadv: risk of cancer arising from ovaries present, may need 2nd surgery
- COCP - adv: contraception, no surgery, reduces risk of ovarian, endometrial, colorectal; disadv: risk of high grade serous, side effects, increases risk of breast and cervical cancer

2013 February SAQ

Question 1
A 25 year old woman is undergoing a caesarean section for an abnormal CTG. After delivery of the baby you find an enlarged ovary that is cystic and solid in nature with a few papillary excrescences on the surface. You suspect this could be a borderline tumour.

a. Describe the intra-operative options available to confirm the diagnosis and assess the disease in this setting? (6 marks)
- Intra-operative opinion from gynae-oncologists
- Open disclosure to patient (possibly awake) – discuss suspicious and options for management
- Examine other ovary, fallopian tubes, uterus, omentum - +/- appendicectomy (if mucinous) (could be primary GIT tumour)
- Frozen section biopsy for preliminary diagnosis
- Take omental biopsy, peritoneal washings (contaminated)
- Avoid spillage
- Review patient history and risk factors, review recent USS
- Problems associated with immediate surgery (more so if higher grade malignancy suspected)
 Unable to perform tumour markers
 Unable to perform imaging for staging (USS, CT C/A/P)
 Complete staging procedure may be optimal
 Dissemination of malignant cells may be likely if removal attempted
- Assess future fertility plans
• Consider cystectomy or unilateral salpingo-oophorectomy but be wary there is no formal consent
• Document findings carefully including follow up plan if confirmed borderline

 
b. Initial biopsy confirms a serous borderline tumour. How would you counsel the patient about this condition, her treatment and follow up? (9 marks)
- Counselling re borderline tumours
- Refer to Gynaeonc
- Explain ovarian tumour with low malignant potential and usually limited to ovary
• Explain tumour: atypical epithelial proliferation and no stromal invasion
• Implications of diagnosis: benign with malignant potential (<2% of ovarian cancer)
- Management based on fertility preferences
- Incomplete staging - USO - adv and disadv - 2% chance of recurrence as invasive cancer, 15% chance of recurrence as borderline tumour
- Complete staging is hys/BSO/peritoneal washings/omentectomy/appendicectomy if biopsy shows mucinous - adv and disadv; to have complete staging after finishing family
- No chemo as no advantage unless malignant
- Risk of recurrence and malignancy and metastases
- Pregnancy does not increase risk of recurrence
- HRT is safe
- Fertility treatment safe
- Document and debrief post-operatively
- Follow up for results in Gynae clinic in 2 – 4 weeks
- Refer to gynae-oncology with follow up planned if histopathology confirmed
- Does not need surveillance with US or tumour markers

Question 11 Feb 2010
A 55 year old woman wishes to discuss her concerns after a relative of hers is diagnosed with ovarian cancer. She has no other significant history.
a. Outline your approach in identifying her risk and advising whether she should be tested for familial ovarian cancer. (6 Marks)
Medical history:
• Clinical features including any current symptoms
- OCP use
- Parity, breastfeeding
- Smoking
• Gynaecological history
o Assess for ovarian cancer risk factors (infertility, endometriosis)
o Assess for ovarian cancer protective factors (parity, breast feeding, OCP, tubal ligation)
o Determine pap smear history, breast USS/mammograms
• Family history of malignancy including breast and ovarian cancer, colon ca
o Degree of relatedness to affected relatives
o Number of affected relatives, age of diagnosis
• Past medical/surgical history including medications to determine performance status & assist surgical planning

Clinical examination:
• Lymphadenopathy
• Breast exam (lumps, masses)
• Abdominal examination (masses, ascites)
• Pelvic examination (adnexal masses)
• Pap smear if required

Referral to clinical geneticist for BRCA1 and BRCA2 gene mutation assessment if:
• One 1st degree relative with EOC in family of Ashkenazi Jewish descent
• Two 1st or 2nd degree relatives on same side of family with EOC, especially if
o Additional relative with breast or ovarian cancer
o Breast cancer diagnosed <40 years
o Bilateral breast cancer
o Breast and ovarian cancer in same women
o Breast cancer in male relative
• Three or more 1st or 2nd degree relatives on same side of family with any cancers consistent with HNPCC
• Member of a family in which the presence of a BRCA gene mutation has been established

She has heard that some symptoms are more suggestive of ovarian cancer than others.
b. What symptoms should you advise her to look out for? (3 Marks)
Symptoms of early stage disease:
• bloating
• increased abdominal size
• urinary urgency or frequency
• change in bowel habit
• difficulty eating or feeling full, nausea, anorexia
• abdominal/pelvic pain
• vaginal bleeding
• Fatigue

After assessing her risk you examine her and palpate a 7cm left adnexal mass.

c. Evaluate the advantages and disadvantages of each of the investigations that are available for her preoperative work up (6 marks)
- Ca125 - adv: if increased highly sensitive of malignancy; disadv: if low, doesn’t exclude malignancy
- TVUS - adv: look for sinister features that increase suspicion of malignancy, can see ascites; disadv: doesn’t exclude malignancy even if appears benign, can’t see metastases
- CT staging - adv: can look for metastatic spread; disadv: radiation

Question 13

Vaginal cancer

Answer 13

Background: mostly SCC (90%), can be adenocarcinoma (younger approx. age 20), sarcoma, melanoma; rare primary, common to have mets to vagina; usually >60yrs age group for SCC

RF (same as cervical cancer): HPV, first smoker, early age first intercourse, multiple sexual partners, DES exposure

Clinical presentation:

• Vaginal bleeding (most common)
• Vaginal mass
• Urinary or bowel symptoms
• Pelvic pain

Ix:

• Spec, bimanual exam, palpate LN
• > The posterior wall of the upper one-third of the vagina is the most common site of the tumour
• EUA +/- vaginoscopy +/- vaginal biopsy
• Cystoscopy
• Proctoscopy
• CXR, CTAP

Stages:

• Stage 1: vagina
• Stage 2: vaginal wall but not pelvis
• Stage 3: extends to pelvis
• Stage 4: extends to bladder/distal mets

Treatment:
- Radiation is mainstay
- If fistula, then exenteration
- Stage 2-4 -> chemoradiation
- Primary treatment with surgery for stage 1
Stage 1:
- If lower vagina: radical wide local excision, LN dissection
- If upper vagina: surgery usually radical hysterectomy, upper vaginectomy, and bilateral pelvic lymphadenectomy
- Radiotherapy - can be used alone in early stage

Complications of treatment:

• Rectovaginal fistulas
• Radiation cystitis or proctitis
• Vaginal stenosis -> can use vaginal dilators

Follow up:

• Low risk disease - every 6months for 2yrs then annually
• High risk disease (mets, needing adjuvant therapy) - for 3months for 2yrs, then 6monthly for another 3yrs then annually
• Vaginal or cervical cytology annually