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1

State how cervical cancer is staged. (1 mark)

FIGO classification system Staging is clinical, using a combination of diagnostic tests to determine the local spread of cervical cancer during examination under anaesthesia

2

Outline the diagnostic tests which may be used to determine the stage using the International Federation of Gynaecology and Obstetrics (FIGO) staging system. (5 marks) (cervical ca)

• Colposcopy and biopsy- to assess the size of macroscopic tumours • Cone biopsy- to assess depth of invasion and size of microscopic tumours • EUA- examination of vulva, vagina and cervix under anaesthesia, bimanual and PR • Sigmoidoscopy- examination of invasion into the sigmoid colon • Cystoscopy- examination of invasion into the bladder • CXR- distant spread into the lungs • IVP- IV contrast given to image the renal tract and review if obstruction is present • Other modes of imaging- CT, MRI, PET CT are not part of formal FIGO staging but assist in surgical planning as they can help define node involvement

3

A 30 year old woman has a cervical biopsy showing cervical intraepithelial neoplasia Grade 3 (CIN 3). The histology of the large loop excision of the transformation zone (LLETZ) specimen is reported as “squamous cell carcinoma with invasion 6 mm deep and lateral spread of 9 mm”. Her last Pap smear, 5 years ago, was normal. She has no other significant past history and has one child delivered vaginally. After full assessment, diagnosis of cervical carcinoma Stage IB1 is made. b. Treatment options include surgery or chemoradiation. What factors influence the choice of treatment for this woman? (2 marks)

Patient factors • Current pregnancy status • Future plans for childbearing and fertility • Preference Tumour factors • If tumour is fully resectable • Any evidence of spread

4

Comprehensively outline the late complications of radiotherapy that could occur in this woman. (7 marks) (1b1 cervical ca)

1. Vaginal stenosis: Can occur with external beam and brachytherapy, Dyspareunia and interference with coitus- dilator therapy can help 2. Infertility and early menopause: Prevents further childbearing and if falls pregnancy high-risk pregnancy. Radiation to the ovaries raises the risk of early menopause and thus menopausal symptoms (VVA, VMS etc) and risks associated with early menopause (CVD, osteoporosis) 3. Bladder: Urinary incontinence and recurrent UTI 4. Chronic proctitis: Symptoms include rectal and abdominal pain, tenesmus, diarrhoea, rectal bleeding and dyschezia 5. Ileitis: Symptoms include severe abdominal pain, chronic constipation or diarrhoea, chronic PR bleeding Can result in stricture formation and bowel perforation 6. Fistula: Vesico-vaginal, ureterovaginal and rectovaginal fistula can all occur and be dehibilitating for women 7. Lymphoedema: Causes constant aching, difficulty with mobilising, predisposes to leg infections 8. Femoral head necrosis: Hip pain and immobility, necessitates hip replacement when severe 9. Pelvic malignancy: Risk of spontaneous pelvic malignancy increase eg leiomyosarcoma 10. Psychological symptoms: Anxiety, depression

5

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. (5 marks)

Increased incidence of smoking Lower age at commencing sexual intercourse Risker sexual behaviour ie multiple partners, less likely to use barrier contraception Barriers to cervical screening and colposcopy Barriers to appropriate medical care and follow up eg financial, psychosocial, transport issues Barriers to education regarding the importance of cervical screening, immunisation and treatment of CIN Lower Gardasil immunisation uptake Cultural barriers

6

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)

Physical examination- speculum, bimanual and rectovaginal examination for palpation and inspection of the primary tumour, uterus, vagina and parametria. Palpation of groin and supraclavicular LN to exclude metastatic cancer. Cystoscopy, Proctosigmoidoscopy EUA, hysteroscopy, endocervical curettage Colposcopic assessment- Colposcopy with directed cervical biopsy for visible cervical abnormalities/ lesion +/-Endocervical curettage, cone biopsy CXR Intravenous pyelogram (IVP) – Evaluation for urinary tract obstruction Imaging not part of FIGO staging but to help guide management: CT or MRI abdomen and pelvis to evaluate extra peritoneal or lymph node spread PET Barium enema

7

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. (1½ marks) ii) Outline one (1) indication for each treatment option. (1½ marks) iii) List two (2) long-term complications associated with each treatment option. (Use different complications for each treatment option). (3 marks)

1. Modified radical hysterectomy and lymph node dissection. Indication: Complete staging procedure- able to o provide histological specimen and information regarding lymph node spread Has completed famiy Other uterine pathology present- firboid Complication: Lymphadema, Chronic pelvic pain, Damage to bladder/ bowel, Pelvic floor prolapse, Sexual dysfuction, Haematoma 2. Trachelectomy Indication: Fertility sparing option for women in childbearing age Complication: Cervical incompetence Preterm birth Requires cervical suture and ELLSCS Stenosis/ impair fertility 3. Primary radiotherapy Indication: Reserved as primary treatment for women who are not candidates for surgery due to medical comorbidities or poor functional status/ declined surgery Complication: Ovarian failure, Vaginal stenosis, Radiation cystitis, Bladder dysfunction, Dyspareunia Bowel stenosis 4. Hysterectomy with ovarian conservation Indication: Provide treatment wihout casuing premature menopause Complication: Risk of disease spread to the adnexa or parametria Risk of lymphovascular invasion, 2-8%

8

What is CIN? What is metaplasia?

Cancer precursors Lack the features of invasive cancer (no invasion of the basement membrane) Severity of lesion is in thirds from the bottom (basement membrane) upwards. How does metaplasia occur? - rise in oestrogen at puberty - promotes growth of lactobacilli - lowers pH - exposure of low pH to columnar epithelium stimulates metaplasia  squamous - metaplasia most active during adolescence and pregnancy

9

Likelihood of developing cancer for CIN 1,2 and 3:

CIN1 = 1% proceed to cancer CIN2 = 5% CIN3 = 12+ % Only a third of CIN3 will regress.

10

Sensitivity and specificity of smear?

- 55-80% sensitivity for a single test. However very high specificity (98%) - Never evaluated in an RCT however countries using it in screening programmes have noted a dramatic decline in cervical cancer

11

How to take a smear?

Taking a pap smear - avoid menstruation or intercourse 48h prior. - Document date of last period, pregnancy or not, hormone use, IUCDs, menopausal status, past smear history Now Liquid based cytology used - put brush in a liquid transport medium - processed to produce a monolayer of cells on a glass slide. - Blood, mucus and cell overlap eliminated - Most of all collected cell material is available on glass slide - ? lower unsatisfactory smear rate however ? lower positive predictive value.

12

Colposcopy

- magnification 3 to 40 fold - high intensity light - green (red free) filter - normal saline- helps remove mucus - acetic acid (clumps nuclear chromatin) - Lugol (iodine) normal oestrogenised cells stain dark due to glycogen content. Dysplastic cells have lower glycogen content Reid Colposcopic index (each scored 0-2) - peripheral margin (feathery, smooth, rolled) - colour to ACW (shiney translucent, duller white, dull white/ gray) - vascular patterns (fine, absent, coarsed) - lugol solution (positive, partial, negative) Other things to note about abnormal vessels - punctuation (fine  coarse) - mosaicism (mosaic tiles with central punctuation = CIS) - atypical vessels o graded on o vessel calibre o intercapillary distance o uniformity

13

Advantages and disadvantages of LLETZ:

Advantages - can be done in clinic under local - ease of procedure - safety profile - low cost - good tissue specimen Disadvantages - training - bleeding - infection - cervical insufficiency - preterm birth - cervical stenosis

14

Mary Smith is a 54-year old woman presenting with recent onset of vaginal bleeding. Her last period was four years earlier. Mary is obese (BMI 33). She is otherwise well and has not been taking any medication or over-the-counter therapies. Bimanual pelvic examination is normal. Her last Pap smear was 18 months ago and was normal. a) Mary is concerned that she has cancer. What are you going to advise her in the outpatient setting? (3 marks)

• Cancer is not the most common cause of her symptoms (only 10%) but it is an important one to investigate • Potential cancers could include endometrial, cervical, vaginal, vulvar or ovarian (atypical presentation but possible) • Other potential causes for her PMB are: o Atrophy o Polyps o Hyperplasia o Infection • Suggest further investigation with imaging (TV USS) and endometrial biopsy.

15

Mary Smith is a 54-year old woman presenting with recent onset of vaginal bleeding. Her last period was four years earlier. Mary is obese (BMI 33). She is otherwise well and has not been taking any medication or over-the-counter therapies. Bimanual pelvic examination is normal. Her last Pap smear was 18 months ago and was normal. List and briefly compare three modalities of ultrasound evaluation of the endometrium in relation to this presentation. (3 marks)

• Grayscale USS – acceptable, cheap, TV gives best definition but TA may be more acceptable to some women • Sonohysterography – best for assessment of endometrial abnormalities e.g. polyps. More expensive • Doppler USS – helpful for assessing vascularity e.g. polyp. No additional cost (standard setting on most machines)

16

Briefly compare and contrast the role of outpatient endometrial sampling (such as Pipelle) versus formal hysteroscopy, dilatation and curettage with reference to the differential diagnosis of endometrial carcinoma in this presentation. (4 marks)

 

Pipelle

Hyst D&C

Cost

Cheap

Expensive

Need for GA

No

Sometimes 

Outpatient procedure

Yes

Sometimes office

Targetted biopsy

No

Yes

Visualise endometrial cavity

No

Yes

Can ‘see and treat’

No

Yes e.g. polyp, submucous fibroid

Risk perforation

No

Possible

Need for cervical dilation

No

Possible

Sensitivity for cancer

High

High

False negative

Possible (10%) – may miss polyp or may miss cancer if small area

Less likely

17

The histopathology of the endometrium shows “complex atypical endometrial hyperplasia”.

 

d)        Briefly discuss the significance of this report and the likely pathogenesis in this patient. (2 marks)

  • Significance:
    •  This is a premalignant condition with a high (30%) chance of coexistent endometrial cancer
  • Pathogenesis:
    • Related to oestrogen exposure – obesity and/or other risk factors
    • Unopposed oestrogen leads to excessive stimulation/growth of endometrium
    • Progressive growth of endometrium can cause hyperplasia
    • Further progression can occur to atypia and malignancy

 

18

List the management options available for Mary. (3 marks)

(obese, endometrial hyperplasia with atypia)

  • Hysterectomy recommended with the presence of atypia
  • Can offer BSO and peritoneal washings at the same time, as if coexistent endometrial cancer diagnosed on histology after hysterectomy, will be recommended for staging surgery (reduces risk of needing subsequent surgery)
  • Progesterone therapy – PO or mirena and ongoing surveillance with repeat endometrial biopsy in 3-6 months
  • Possible if not fit for surgery (unlikely in this case) or unwilling
  • If persists try higher dose, if persists despite this recommend hysterectomy
  • If normalizes continue progesterone for minimum of 1 year with annual TVUSS

 

 

19

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)

Pre-operative:

Explain and counsel patient re diagnosis, treatment and possible prognosis

Gynaeoncology MDT referral (gynaeoncologists, medical and radation oncologists, radiologists, pathologists, nurse specialists) - to assess likely stage and grade after review of endometrial biopsy histology and imaging and plan primary surgeon and surgical approach

FBC, G&S, U&E, LFT – for medical pre-op workup

CXR – metastases

MRI – assess depth of invasion of tumour for surgical planning (PLND if >50% DOI) and for cervical involvement, lymph node involvement and metastases

CT chest/abdo/pelvis if high grade or high risk cancer eg sarcoma

Assess comorbidities, fitness for surgery, optimize health e.g. correct anaemia. Anaesthetic review.  

 

Intra-operative – staging laparotomy and treatment:

Consent

Midline laparotomy

TAH/BSO and washings for all women

PLND if - >50% DOI on MRI (stage 1b or above), high risk histological subtype or grade 3 tumour

Inspection/palpation of all peritoneal surfaces – include liver, omentum, pelvic sidewalls, para-arotic nodes, biopsy/cytoreduction of any suspicious lesions.  

VTE prophylaxis 

20

List eight main prognostic factors associated with a poor outcome in this condition. (4 marks)

(Endometrial adenocarcinoma)

Disease factors:

  • High stage disease
  • High grade tumour
  • High risk histological subtype e.g. papillary serous, clear cell
  • Lymphovascular space invasion
  • Tumour > 2cm
  • Hormone receptor status
  • Nuclear grade

 

Patient factors:

  • Age > 60
  • Medical comorbidities

Obesity

21

Describe the situations where radiotherapy can be used in the management of endometrial carcinoma. (5 marks)

Adjuvant therapy:

  • Stage 1b – 2
  • High grade tumour – grade 3 (any stage)
  • High risk histological subtype (any stage or grade)

2.  Primary therapy for women not fit for surgery (but poor outcomes)

3.  Palliation – advanced disease (usually in combination with chemotherapy)

4.  Treatment of local recurrence if not had previous radiotherapy

 

Can be given in the form of external beam radiation and/or vault brachytherapy

22

What are the problems associated with a population-based cervical screening?

 

  • Acceptability – may not be acceptable to all patients to have a smear
  • Reliability – some false positive and false negatives, some missed cases and some unnecessary colposcopy/treatment/anxiety
  • Cost/facilities – advertising campaigns to increase participation, places to have smear taken, pathology labs to interpret results, colposcopy clinics to followup abnormalities, quality control and assessment/audit
  • Some cultural/language barriers and lack of education regarding importance

23

  1. What is necessary for a successful population based cervical screening program?

 

  • Nationwide program for recall and recording of results
  • Availability of skilled smear takers in primary practice in close proximity for all women
  • Low cost appointments for smear taking
  • Education programme to emphasise the importance of smears and screening interval
  • System of notification and explanation of smear results
  • Clear guidelines for smear takers on when to refer for colposcopy
  • Adequate colposcopy services in all regions
  • Skilled and accredited colposcopists
  • Skilled and accredited labs for cytology and histology
  • MDT meetings for complex cases and discrepancies between smear/colposcopy/biopsy
  • Clear guidelines on followup
  • Gynaeoncology teams to refer patients with cervical cancer

24

  1. What are the indications for cone biopsy?

 

  • Suspicion of early microinvasive SCC or known stage 1a1 SCC – fertility sparing option
  • Inability to visualise upper limit of lesion or transformation zone with HSIL referral
  • Suspicion of concurrent significant glandular abnormality

25

  1. HPV testing for women with treated HSIL – what are the sensitivity and PPV for residual/recurrent disease?

  • Sens 96%
  • Spec 81%
  • PPV 46%
  • NPV 99%

 

26

A 63 year old woman presents after one episode of light vaginal bleeding over the last week. She has a BMI of 42 kg/m2, chronic hypertension and Type 2 diabetes.

 

a.  List five (5) possible causes for her bleeding. Identify the most common cause. (3 marks)

 

  • Vulvo-vaginal atrophy (most common cause)
  • Endometrial hyperplasia (endogenous or exogenous oestrogen)
  • Endometrial polyp
  • Cervical polyp
  • Cervical cancer
  • Trauma
  • Anti-coagulants
  • STIs

27

A 63 year old woman presents after one episode of light vaginal bleeding over the last week. She has a BMI of 42 kg/m2, chronic hypertension and Type 2 diabetes.

 

i)  List four (4) risk factors for endometrial cancer not mentioned in the scenario that you

should elicit from her .history. (2 marks)

  • Early menarche and late menopause
  • Nulliparity
  • Unopposed oestrogen Rx
  • Tamoxifen
  • PCOS
  • Familial cancer syndrome

 

28

ii)  Justify your initial management of this patient to assess her risk for endometrial cancer. (3

marks)

Management

Justification

Pelvic examination

Will reveal vulvovaginal atrophy, cervical polyps or masses

Assess the size and mobility of the uterus

Swabs + cervical smear

Important for screening for cervical pre-malignancy, not sensitive for invasive cervical cancer, may see atypical endometrial cells on smear test

Rule out STI as contributory to bleeding

Pelvic ultrasound

Review pelvic anatomy, endometrial thickness (ET <5 usually excludes endometrial cancer and >20 is highly suggestive), presence of polyps, fibroids, or other masses

Endometrial sampling

Office endometrial biopsy has a good sensitivity for endometrial cancer- 95-99% if the cancer/hyperplasia is >50% of the cavity, in women with a high suspicion of cancer, formal sampling under GA will be needed

Hysteroscopy

Reviews the structure of the endometrium, can identify polyps and thickened endometrium.

Can be done as an office procedure or under GA.

29

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)

  • Explain results to patient and counsel regarding surgery, next steps, ensure support person present, give written information
  • MRI pelvis: in New Zealand, surgery for superficial endometrial cancer is performed by general gynaecologists, rather than gynae-oncologists, so an MRI needs to be done before a gynae onc MDM referral to review degree of invasion and any obvious nodal metastases
  • CT chest/abdo/pelvis: used to exclude other masses or metastases
    • Consider PET scan where lymph node metastases are suspected
  • Refer to gynae onc MDM: review of imaging, pathology and decision about when/where/who will do the operation
  • TAH/TLH, BSO, and washings as recommended treatment
    • Intraoperative frozen section or inspection of the myometrium to determine the degree of myometrial invasion can be done at the same time
    • Pelvic LN dissection recommendation depends on the unit internationally- in low-risk women with small tumours it may not be necessary, should be done if >50% myometrium involved 
    • Explain further treatment may be needed if the intra-operative findings are different from the findings on imaging
  • Pre-op planning
    • Pre-operative bloods: group and hold, full blood count, renal function and electrolytes
    • Anaesthetic assessment: ensure anaesthetic is safe
    • Optimisation of medical conditions pre-op

 

30

d.  Discuss the aspects in her history that would alert you to the possibility of her having Lynch

syndrome. (2 marks)

  • Personal history of ovarian, urinary tract, or colorectal cancer (right colon)
  • Family history (Amsterdam criteria) (3, 2, 1 rule):
    • 3 affected family members with histologically verified lynch-syndrome associated cancers, one of whom is a first degree relative of the other two and in whom familial adenomatous polyposis has been excluded
    • 2 generations of affected family members
    • 1 or more cancers diagnosed before the age of 50