Gynae - Gynaecological Malignancy

Question 1

Ovarian Cysts and Tumours

Risk Factors
Clinical Features
Risk of Malignancy Index

Answer 1

1. ) Risk Factors - surface epithelial irritation during ovulation so more ovulations –> ↑risk of malignancy
   - nulliparity, early menarche, late menopause, HRT (oestrogen-only), post-menopausal, smoking, obesity
   - genetic: BRCA1/2 mutations, HNPCC (Lynch II syn…)
   - protective factors: multiparity, breastfeeding, combined contraceptive methods
2. ) Clinical Features - size and pathology dependent
   - red flags (2WW referral): ascites OR a pelvic or abdo mass identified on examination (not obv fibroids)
   - persistent/frequent (>12x/month) sx esp if >50yrs: reduced appetite or early satiety, abdo distension, abdominal or pelvic pain, urinary urgency/frequency
   - unexplained fatigue, weight loss, bowel habit change
   - IBS sx in women >50 (rarely presents that late)
   - many simple ovarian cysts are asymptomatic and are incidental findings on scans for other reasons
   - acute pain: suggests rupture, torsion or bleeding
3. ) Risk of Malignancy Index - risk stratification tool in those patients with suspected ovarian cancer
   - RMI = CA-125 (U/ml) x M x U | M = 1 (premenopausal) OR 3 (postmenopausal) | U = 1 (1 feature on USS) OR 3 (2+ features on USS)
   - RMI >250 should be referred to a gynaecologist

Question 2

Classification of Ovarian Cysts/Tumours

Functional Non-Neoplastic
Pathological Non-Neoplastic
Benign Neoplastic Epithelial Tumours
Benign Neoplastic Germ Cell Tumours
Benign Neoplastic Sex-Cord Stromal Tumours
Malignant Tumours (Ovarian Cancer)

Answer 2

1. ) Functional Non-Neoplastic - these are normal
   - follicular cysts: <3cm, occur in the follicular phase
   - Corpus luteal cysts: <5cm, occur in the luteal phase
2. ) Pathological Non-Neoplastic
   - endometrioma: ‘chocolate cysts’ due to bleeding into the cyst in those with occurs in endometriosis
   - polycystic ovaries: not always due to PCOS
   - Theca lutein cyst: due to markedly raised hCG e.g. molar pregnancy, regresses upon resolution of ↑hCG
3. ) Benign Neoplastic Germ Cell Tumours - dermoid cysts (mature cystic teratoma), can be bilateral (10%)
   - can contain teeth, hair, skin and bone
   - occur in young women and during pregnancy
   - Rokitansky protuberance is a nodule sticking out consisting of hair, adipose, calcific, skin components
4. ) Benign Neoplastic Sex-Cord Stromal Tumours - a fibroma is the most common stromal tumour
   - up to 40% present with Meig’s syndrome: association between these tumours and ascites/pleural effusion
5. ) Benign Neoplastic Epithelial Tumours
   - serous cystadenoma: usually unilocular (one cavity) and can be bilateral, most common type
   - mucinous cystadenoma: multiloculated and unilateral
   - Brenner tumour: unilateral, appears solid grey/yellow
6. ) Malignant Tumours - most present late-stage
   - serous cystadenocarcinoma: Psammoma bodies
   - mucinous cystadenocarcinoma: mucin vacuoles

Question 3

Management of Ovarian Cysts/Tumours

Suspected Ovarian Cancer
Premenopausal Management of Ovarian Cysts
Postmenopausal Management of Ovarian Cysts
Management of Ovarian Cancer

Answer 3

1. ) Suspected Ovarian Cancer
   - refer red flags urgently (2WW) to gynaecology
   - Ca-125 blood test: if >35U/ml, arrange a pelvic USS
   - pelvic USS to calculate RMI, features inc: bilateral lesions, multilocular cyst, solid areas, ascites, mets
   - other bloods: FBC, U&Es, LFTs and albumin
2. ) Premenopausal Management of Ovarian Cysts - if the cyst is complex (solid mass or multiloculated)
   - measure serum markers: CA-125, β-hCG, αFP, LDH
   - if persistent after rescanning in 6wks, monitor with USS and CA-125 3-6monthly and calculate RMI
   - If persistent or over 5cm consider laparoscopic cystectomy or oophorectomy
3. ) Postmenopausal Management of Ovarian Cysts
   - depends on their calculated RMI:
   - low (<25): f/u in 1yr w/ USS and CA-125 if <5cm
   - mod (25-250): bilateral oophorectomy and if a malignancy is found, staging is required (w/ completion of hysterectomy, omentectomy +/- lymphadenectomy)
   - high (>250): referral for staging laparotomy
4. ) Management of Ovarian Cancer
   - surgery: staging laparotomy for those with a high RMI with an attempt to debulk the tumour
   - adjuvant chemotherapy: all patients except those w/ early, low-grade disease and use platinum compounds
   - follow up: clinical examination and monitoring of CA125 level for 5 years with intervals between visits becoming further apart according to risk of recurrence.

Question 4

Endometrial Cancer

Pathophysiology
Risk Factors
Clinical Features
Differentials for Post-Menopausal Bleeding

Answer 4

1. ) Pathophysiology - adenocarcinoma caused by the effects of unopposed oestrogen on the endometrium
   - long periods of anovulation is a significant risk factor as progesterone is produced after ovulation by the CL
   - unopposed oestrogen also causes endometrial hyperplasia which is a pre-cancerous state
2. ) Risk Factors
   - ↑oestrogen/↓progesterone: early menarche, late menopause, low parity, PCOS, HRT (oestrogen only), tamoxifen use
   - age: peaks between 65-75, rare in <45s
   - obesity: increased peripheral aromatisation of androgens to oestrogen in post-menopausal women
   - genetic: HNPCC (Lynch syndrome)
   - smoking is a PROTECTIVE FACTOR for endometrial cancer (risk factor cervical, vulval, breast cancer)
3. ) Clinical Features
   - majority present w/ post-menopausal bleeding (PMB) but it’s not specific as 90% of PMB is not cancer
   - irregular/intermenstrual bleeding in pre-menopausal
   - uncommonly presents with clear or white vaginal discharge, or with abnormal cervical smears
   - advanced/metastatic: abdo pain or weight loss
4. ) Differentials for Post-Menopausal Bleeding
   - endometrial: hyperplasia, atrophy, benign polyps
   - cervical: polyps, cervical cancer
   - vulval: atrophy, pre-malignant or malignant conditions

Question 5

Management of Endometrial Cancer

Investigations
FIGO Staging
Management of Endometrial Hyperplasia
Management of Endometrial Cancer

Answer 5

1. ) Investigations
   - transvaginal USS: endometrial thickness >4mm
   - endometrial pipelle biopsy: if thickness >4mm or if they continue to have abnormal bleeding
   - hysteroscopy w/ biopsy: if ‘high risk’ e.g. multiple risk factors, heavy bleeding, very thickened endometrium
   - confirmed malignancy: staging CT/MRI, baseline bloods (FBC, U+Es, LFTs, G+S)
2. ) FIGO Staging - depends on the carcinoma location
   - I: confined to within the uterine body
   - II: may extend to cervix, but not beyond the uterus
   - III: extends beyond the uterus, confined to the pelvis
   - IV: involves bladder/ bowel, mets to distant sites
3. ) Management of Endometrial Hyperplasia
   - non-malignant: high dose progestins to shed the lining –> COCP/LNG-IUS to prevent build up, patients are followed up every 6 months with biopsies
   - atypical: TAH for all women, additional BSO for post-menopausal women, if contraindicated, regular surveillance biopsies should be performed
4. ) Management of Endometrial Cancer - stages:
   - I: TAH + BSO with peritoneal washings (most present with stage 1 disease)
   - II: radical hysterectomy (vaginal tissue around cervix and ligaments also removed), lymphadenectomy, may also be offered adjuvant radiotherapy
   - III: maximal de-bulking surgery with additional chemo given prior to the radiotherapy
   - IV: maximal de-bulking surgery or palliative with low dose radiotherapy, or high dose oral progestogens

Question 6

Cervical Cancer

Pathophysiology
Human Papilloma Virus
Clinical Features
Examinations

Answer 6

1. ) Pathophysiology - the majority (70%) are SCCs, 15% adenocarcinoma, and 15% are mixed in type
   - majority of SCCs are caused by persistent HPV
   - often a progression of CIN occurring over 10-20yrs
   - invasive when basement membrane is breached
   - metastases common in lungs, liver, bone and bowel
   - young-onset: peak at 25-29, the second peak in 80s
   - risk factors: HPV, smoking, STIs, long-term COCP use, immunodeficiency e.g. HIV
2. ) Human Papilloma Virus - STI affecting the skin and mucous membranes, highly prevalent
   - majority of infections are cleared within 2 years but if not, they can go on to cause CIN and cervical cancer
   - HPV 6/11 cause warts, is unlikely to cause cancer
   - HPV 16/18 are high risk, inhibits protein p53 (TSG)
   - vaccination programme for HPV 16/18 and 6/11
3. ) Clinical Features
   - often asymptomatic, particularly in the early stages
   - bleeding: post-coital, intermenstrual, or PMB
   - other sx: pelvic pain, dyspareunia, discharge (blood-stained, foul-smelling), and weight loss
   - advanced (invading structures): oedema, loin pain, haematuria, rectal bleeding, radiculopathy
4. ) Examinations
   - bimanual: pelvic masses
   - speculum: bleeding, discharge, ulceration
   - GI exam: hydronephrosis, hepatomegaly
   - DRE: rectal bleeding, rectal masses

Question 7

Cervical Screening

Who and How Often?
Method
Inadequate Sample

Answer 7

1. ) Who and How Often?
   - 25-49 years: 3-yearly screening
   - 50-64 years: 5-yearly screening
   - cervical screening cannot be offered to women over 64 (no self-referrals like in breast cancer)
   - pregnancy: usually delayed until 3mths post-partum unless missed screening or previous abnormal smears
   - HIV positive patients require screening yearly
2. ) Method
   - first test for high risk strains of HPV (hrHPV)
   - negative hrHPV: returned to normal recall (3/5yrly)
   - positive hrHPV: samples examined cytologically
   - abnormal cytology: refer for colposcopy
   - normal cytology (w/ +ve hrHPV): repeat in 12mths:
   - negative hrHPV –> return to normal recall
   - positive hrHPV + normal cytology: repeat in 12mths
   - positive hrHPV at 24mths –> refer to colposcopy
3. ) Inadequate Sample
   - repeat sample in 3 months
   - 2 inadequate samples then refer for colposcopy

Question 8

Management of Cervical Cancer

Investigations
FIGO Staging
Surgical Management of Cervical Cancer
Radiotherapy 
Chemotherapy

Answer 8

1. ) Investigations
   - premenopausal: chlamydia test and treat infection, if negative or persists refer for colposcopy and biopsy
   - postmenopausal: urgent colposcopy and biopsy
   - confirmed cancer: baseline bloods, staging CT/MRI
2. ) FIGO Staging
   - 0: carcinoma in-situ, 1A: confined to cervix, only microscopically, 1B: gross lesions, clinically identifiable
   - 2A: beyond cervix but not pelvic sidewall, involves vagina but not lower 1/3 no parametrial involvement
   - 2B: obvious parametrial involvement
   - 3A: involves lower 1/3 vagina but not to sidewall
   - 3B: extension to the sidewall and/or hydronephrosis
   - 4A: involves bladder/rectum, 4B: distant organs
3. ) Surgical Management of Cervical Cancer - stages:
   - 1A: lap hysterectomy + pelvic lymphadenectomy, to preserve fertility, can do a cone biopsy or a radical trachelectomy (cervix and upper vagina)
   - 1B/2A: radical (Wertheim’s) hysterectomy (uterus, vaginal parametrial tissues) + lymphadenectomy
   - 4A/Recurrent: anterior/posterior/total pelvic exenteration, removal of all pelvic adnexa plus bladder (anterior)/rectum (posterior or both (total)
4. ) Radiotherapy - alternative to surgery in early disease
   - external beam therapy and intracavity brachytherapy. - 1B-3: used with chemo over a 5-8 week course
   - cervical smear testing is not valid after radiotherapy
5. ) Chemotherapy - cisplatin-based, neoadjuvant or adjuvant and is used in palliative care
   - follow-up: every 4 months for the first 2yrs, and every 6-12 months for the subsequent 3 years

Question 9

Vulval Cancer

Vulval Intraepithelial Neoplasia
Pathophysiology 
Clinical Features
Investigations 
Management

Answer 9

1. ) Vulval Intraepithelial Neoplasia - a premalignant condition affecting the squamous epithelium of the skin
   - high grade squamous intraepithelial lesion: associated with HPV, occurs in younger women (35-50)
   - differentiated VIN: associated with lichen sclerosis, occurs in older women (50-60)
   - biopsy is diagnostic, can be treated with W+W, wide local excision, imiquimod cream, or laser ablation
2. ) Pathophysiology - the majority (90%) are SCCs but less commonly, they can be malignant melanomas
   - risk factors: age (>75), HPV, lichen sclerosis, immunosuppression
3. ) Clinical Features - often affects the labia majora:
   - irregular mass, ulceration, bleeding, fungating lesion
   - can be painful, but can also be asymptomatic
   - inguinal lymphadenopathy
4. ) Investigations - 2WW cancer referral
   - biopsy: lesion and sentinel node
   - imaging for staging: e.g. CT-AP
5. ) Management - depends on staging
   - wide local excision to remove the cancer
   - groin lymph node dissection
   - chemotherapy and/or radiotherapy