GONC Flashcards

Question

Typical ovarian tumour type based on age

Answer 1

Women <20y - Germ cell tumours 30s and 40s - Borderline tumours >50y - Epithelial tumours

Answer 2

Currently no evidence to support general population or high-risk group screening Studies using Ca125, USS and pelvic exam do not have an acceptable level of sensitivity and specificity Low prevalence of disease and lack of high quality screening methods make it more likely to obtain false positive results --> unnecessary interventions

Answer 3

90% epithelial Malignant GCT 3% Sex cord stromal cell tumours 1-2% 5% metastatic

Answer 4

``` High grade serous - 70% Endometrioid 10% Clear cell - 10% Mucinous 5% Low grade serous - 5% ```

Answer 5

If pre-op suspicion is of malignancy, laparotomy should be performed If no visible or palpable evidence of metastasis, perform the following to ensure adequate staging 1. Careful evaluation of all peritoneal surfaces 2. Retrieval of any peritoneal fluid or ascites - if none, washings should be performed 3. Infracolic omentectomy 4. +/- Selective lymphadenectomy of the pelvic and para-aortic LNs (No role for standard lymphadenectomy) 5. Biopsy or resection of any suspicious lesions, masses or adhesions 6. Random peritoneal biopsies of normal surfaces 7. TAH + BSO in most cases 8. Appendectomy for mucinous tumours Consider frozen section

Answer 6

HGSC - 60-80% arise from fimbrial ends, P53 / BRCA associated mutations. Typically aggressive Endometrioid and clear cell - arise from endometriosis LGSC - Typically younger age women than HGSC, Not a/w BRCA1/2 - Characterised by a relatively indolent behaviour and resistance to cytotoxic chemotherapy Mucinous carcinoma - A/w obesity and smoking. Need to exclude a GI primary. Cystic tumours with mucin secreting epithelium. Grow every large. 10% bilateral Confined to ovary in 95-98%

Answer 7

Peritoneum, including omentum and pelvic and abdominal viscera - Includes diaphragmatic and liver surfaces ``` Primarily through lymphatic and LN drainage - Para-aortic - External iliac - Common iliac - Hypogastric - Lateral sacral - Occasionally to the inguinal Peritoneal surfaces --> diaphragmatic lymphatics and hence to the major venous vessels above the diaphragm ``` Haematogenous spread is rare

Answer 8

``` Imaging - CT CAP - CXR can screen for pleural effusions - +/- PET Serum Ca125 If <40y, germ cell tumours more common - bHCG, AFP, LDH FHx - enquire about reproductive, breast or colon cancer ``` Definitive pathological diagnosis from tissue sample if suspect advanced - Biopsy (ascites, LN)

Answer 9

Nutritional assessment Optimise co-morbidities Anaesthetic review Genetics if HGSC Primary surgery via midline laparotomy, by GONC - staging - High correlation between optimal cytoreduction (debulking) and survival Neoadjuvant chemotherapy - Surgery deferred until after 3 cycles of chemotherapy, then interval debulking surgery, then followed by further 3 cycles. - c.f. primary surgery - median overall survival similar, more likely to achieve optimal debulking, less likely to die within 28 days of surgery and had fewer post-op complications vs. Adjuvant chemotherapy (given post-op)

Answer 10

Low chemosensitivity - LGSC, mucinous, CC Evidence that all patients other than stage 1 grade 1 may benefit from chemotherapy Standard: paclitaxel (taxane agent), followed by carboplatin (platinum-based) - 6 cycles Side effects paclitaxel - alopecia - neurotoxicity - arthralgia Side effects of carboplatin - nephrotoxicity - thrombocytopenia Both have - n/v - neutropenia - hypersensitivity reaction Almost 80% of women with advanced stage disease who respond to first line chemotherapy relapse

Answer 11

Patients with BRCA (germline and somatic) have the greatest benefit Frontline maintenance - for recurrence

Answer 12

Every 3-4 months in the first 2y 6 monthly to year 5 of treatment Then annual General clinical exam including pelvic exam Serum Ca125 - Studies show no change to survival benefit compared to monitoring symptoms Symptoms suggestive of recurrence --> imaging (usually CT)

Answer 13

Hereditary factors are implicated in ~20% of ovarian, fallopian tube and peritoneal cancers Approx 3-fold increase in relative risk to all first-degree relatives If first degree relative with epithelial ovarian cancer (EOC) and no known genetic susceptibility, lifetime risk of EOC is 2-3% If 2 relatives --> 8% (provided BRCA1/2 excluded)

Answer 14

Autosomal dominant pattern of inheritance Both are tumour suppressor genes that play a role in DNA repair Ashkenazi Jewish - 1 in 40 General population: 1 in 400 "60, 40, 40, 20" for breast and ovarian cancer risk for BRCA1/2 >15% of women with HGSC have BRCA1/2 mutation

Answer 15

Screen for in women with HGSC <70y Full pedigree analysis and genetics referral ACOG recommend TVS and Ca125 every 6 months for screening - TVS and Ca 125 - associated with high false positive rates and show no proven benefit Risk-reducing BSO once childbearing is complete - BRCA1: between 35-40y - BRCA2: between 40-45y Obtaining RRBSO by the recommended age may reduce the risk of breast cancer Risk reduction up to 95% for gynae cancer Risk of diagnosing occult tubal cancer - up to 6% of women undergoing RRBSO Residual lifetime risk of primary peritoneal cancer (1-2%) Use of HRT is generally consider safe - provided no personal Hx of breast cancer, or medical contraindications COCP reduces ovarian cancer risk of BRCA1, although significantly less effective than RRBSO Offer BS if declines BSO

Answer 16

Lynch syndrome accounts for ~3% of all endometrial cancers 50% of women with Lynch syndrome will present with a gynae cancer as their primary cancer Germline mutation in one of the DNA MMR genes Autosomal dominant Associated with cancer of the: - Colon - Stomach - Ovary - Lifetime risk 10-20% (EC or CCC) - Endometrium - Lifetime risk up to 60% - Prostate - Pancreas - Gallbladder - Brain - Skin - Ureter Discuss prophylactic hysterectomy and RR BSO once completed childbearing

Answer 17

Syndrome rather than pathological term Widespread deposit of mucin within the intra-abdominal cavity Primary appendiceal lesion Occasionally ovarian and other GIT sites

Answer 18

40% of metastatic cancer to the ovaries Primary tumour in stomach, less commonly colon or appendix Mucin filled signet ring cells on histology Poor prognosis - most die within 1y

Answer 19

Breast Lower reproductive tract sites - cervix, uterine GIT - bowel, gastric (stomach most common), pancreatic Lymphoma

Answer 20

15-20% of all ovarian tumours 3% of all ovarian cancers Benign or malignant (1/3) Arise from primordial germ cells derived of the embryonal gonad Undergo defective meiosis Classified according to the type of cell that is produced ``` RISK FACTORS Higher in African, Asian, Hispanic Gonadal dysgenesis Abnormal karyotype Median age: 16-20y - Rare after 3rd decade No identifiable genetic link ```

Answer 21

DIFFERENTIATED Trophoblast --> choriocarcinoma (<1%) - HCG Yolk sac --> yolk sac tumour (20%) - aFP Embryo --> teratomas 20% (mature and immature) Whole blastocyst --> embryonal carcinoma (<5%) UNDIFFERENTIATED Dysgerminoma (45%) - LDH

Answer 22

Tend to present more acutely than epithelial ovarian cancer Rapidly enlarging mass Acute severe lower abdominal pain due to tumour rupture, haemorrhage or torsion Urinary symptoms - e.g. dysuria, frequency Rectal symptoms Menstrual irregularities Positive pregnancy test

Answer 23

aFP, hCG, LDH, Ca125 Karyotype in all premenarchal girls because these tumours can arise in dysgenetic gonads Adnexal masses that require surgical exploration: - >/=2cm in premenarchal girls - Complex masses >/=8cm in premenopausal patients Doppler USS and contrast-enhanced MRI of pelvis to look for adnexal masses and assess ease of operability Contrast-enhanced CT / MRI to evaluate abdomen / solid organs CXR - GCT can metastasise to the lungs or mediastinum MRI brain with contrast - If any woman with disease spread above the diaphragm or if otherwise clinically indicated

Answer 24

Fertility-preserving surgery via midline incision - Unilateral salpingo-oophorectomy - Surgical staging with omental and multiple peritoneal biopsies, peritoneal washings, biopsy of suspicious LN - Biopsy of contra-lateral normal appearing ovary not recommended Advanced stage disease - extensive surgery may delay chemotherapy administration, therefore chemotherapy is recommended as the primary treatment in the presence of metastatic disease ``` Very chemosensitive BEP chemotherapy - Bleomycin - Etoposide - Cisplatin (P for platinum) Offer for IB, recommend for IC + IA - chemo if recurrence (a/w 90% cure) ``` Most aggressive are endodermal sinus tumour and choriocarcinoma, but with combination chemotherapy are highly curable Dysgerminomas are exquisitely radiosensitive, but no longer forms a part of routine treatment algorithms due to long-term toxicities and effects

Answer 25

Previous publications have reported a successful pregnancy rate of 75% in those wishing to conceive following chemotherapy for GCTs No reports of an increased congenital abnormality rate following chemotherapy

Answer 26

Using close surveillance, chemotherapy is utilised only for those who relapse without compromising survival (IA +/- IB) Risk of relapse is relatively low - If relapses, can then salvage with curative chemotherapy Surveillance (10y total) - Tumour markers every 2 weeks for 6/12 - Monthly for 6/12 - 3 monthly spacing up to 6 monthly CXR on alternate visits MRI every third visit Advise against pregnancy during the first 2y

Answer 27

``` 10% of ovarian neoplasms in childhood and adolescents are SCST Cells that give risk to tumours: - Granulosa cell - Theca cell - Sertoli cell - Leydig cell - Fibroblast ``` Granulosa cell tumour - accounts for 70%

Answer 28

Most SCST are stage 1 at diagnosis, therefore curable with surgery alone Surgery: Fertility preserving - USO + washings + omental biopsy + careful inspection of contralateral ovary and all peritoneal surfaces

Answer 29

Two types: Juvenile (5%) - High estrogen production - Typically develops before puberty and presents with precocious puberty Adult types (95%) - May present with PMB - Usually present in middle-aged and older women (median 50-54y) - Excess estrogen --> endometrial hyperplasia (25-50%) or carcinoma (5-10%)

Answer 30

Tumour markers: - Inhibin B - AMH - CA 125 No evidence that adjuvant CT or RT improves results of surgery alone for stage I disease Stage at diagnosis - most important prognostic factor If elevated inhibin B and/or AMH at initial diagnosis, can use as reliable markers during f/u

Answer 31

SCST Benign Most common Originate from spindle cells, producing collagen Meigs syndrome - Fibroma + ascites +/- pleural effusion, due to VEGF

Answer 32

``` Post-menopausal Originate from spindle and theca cells Benign Produce excess estrogen - endometrial hyperplasia in 15% - carcinoma in 20-25% ```

Answer 33

3rd and 4th decades of life Benign or malignant Sertoli cells --> oestrogen Leydig cells --> androgens Clinical virilisation Management: USO Or TAH + BSO + staging if family complete 70-90% 5y survival for malignant disease

Answer 34

Heterogeneous group of lesions defined histologically by atypical epithelial proliferation without stromal invasion Behaviour that is intermediate between benign cystadenomas and invasive carcinomas Extensive sectioning of the tumour is necessary to rule out invasive cancer Invasive cancers that arise in borderline tumours are often indolent and generally have a low response to platinum-based chemotherapy Spontaneous regression of peritoneal implants has been observed

Answer 35

1.8 to 5.5 per 100,000 women per year Median age 45-48y - 1/3 of borderline ovarian tumours are diagnosed in women <40y 75% are stage I at diagnosis

Answer 36

Serous 45-60% Mucinous 30-50% Seromucinous, endometrioid, clear cell, Brenner (transitional cell) 5-10%

Answer 37

``` Typical USS features Multi-loculated ○ 30% of serous ○ 40% of mucinous Solid / cystic, internal papillations ○ 78% of serous ○ 40% of mucinous Thickened septae Bilateral ``` CA125 - similar to epithelial ovarian cancer - elevated in 80-90% advanced serous borderline tumours

Answer 38

Advise woman not a cancer MDT - Review pathology with expert pathologist - GONC, radiologist, med onc Complete staging vs. conservative surgery - should be individualised Completion surgery when fertility preservation no longer required is controversial Laparoscopy vs. laparotomy - Laparoscopy a/w increased chance of cyst rupture and under staging - Despite this, no difference in survival rates or treatment plan No adjuvant therapy recommended as no change to survival rates (regardless of stage)

Answer 39

Complete staging- TAH + BSO + peritoneal washings + omentectomy + resection of mets PROS - Detection of advanced stage disease Upstaging not uncommon after initial non-staging procedure Detection of occult invasion Better information for prognostic counselling CONS - Premature surgical menopause (1/3 <40y). Infertility. Procedure with higher surgical morbidity -------------------------------- Conservative treatment - conserve >1 ovary to preserve fertility, avoid premature menopause Cystectomy - 10-30% recurrence vs. oophorectomy - ~1% recurrence. PROS - Disease has a good prognosis. Recurrence does not affect survival (for USO vs, full staging) CONS - Will require second procedure if missed occult invasion on frozen section

Answer 40

Favourable prognosis a/w: - Early stage - Serous histology - Younger age at diagnosis Causes of death usually complications of disease (e.g. SBO) or complications of therapy - rarely malignant transformation

Answer 41

USS every 6 months +/- CA125 if elevated at diagnosis Total 10-15y surveillence Consider completion surgery when family complete

Answer 42

Conservative surgery (cystectomy) - recurrence rate of 15-50% - But survival unchanged Micropapillary features of serous BOT - A/w increased likelihood of both invasive peritoneal implants and recurrence Mucinous prognostic factors - Extra-ovarian tumour - Pseudomyxoma peritoneii

Answer 43

50% will become spontaneously pregnancy after conservative surgery Increased risk of infertility - reduced ovarian reserve, adhesions Large number of women already suffering from infertility before diagnosis

Answer 44

Postmenopausal ovaries are physiologically active, continue to produce oestradiol (at low levels) and testosterone. Modelling study, 2005 - "women <65y clearly benefit from ovarian conservation, and at no age is there a clear benefit from prophylactic oophorectomy" Nurses' Health Study - Median f/u 24y Bilateral oophorectomy at time of hysterectomy for benign disease a/w: - Decreased risk of breast and ovarian cancer - Increased risk of all-cause mortality, and fatal and non-fatal CHD At no age was oophorectomy a/w increased survival Oophorectomy not associated with decreased survival in women >55y at the time of hysterectomy + oophorectomy

Answer 45

Increased mortality due to coronary heart disease Increased morbidity and mortality due to osteoporosis related fracture Increased risk of cognitive dysfunction, including dementia Increased risk of depressive and anxiety symptoms In premenopausal women: - More severe and prolonged vasomotor symptoms than those seen following natural menopause - Reduction in libido and sexual dysfunction With the exception of osteoporosis related fracture, it is unclear whether the incidence and severity of the above conditions are ameliorated by oestrogen replacement therapy

Answer 46

Growing evidence that high-grade serous tumours of ovary and peritoneal surface epithelium may originate in the fallopian tubes Removal does not appear to increase surgical complications or impact ovarian function No population based data to quantify the risk-benefit profile

Answer 47

Irregular proliferation of glands of irregular size and shape, with an increase in the gland to stroma ratio when compared with proliferative endometrium Incidence age dependent - 1.3% in women <40y - Post-menopausal with AUB - 8-15%

Answer 48

``` Obesity - Peripheral aromatisation of fat tissue - androgens converted to oestrogen PCOS / anovulation Nulliparity Unopposed oestrogen - Oestrogen stimulating tumours (e.g. ovarian granulosa cell neoplasm) - Oestrogen therapy Tamoxifen Peri- and post-menopausal age groups FHx of breast, colon, or endometrial cancer Age >45y Late menopause Diabetes HTN ``` COCP and Mirena are protective

Answer 49

Increase in gland to stroma ratio, variation in size and shape of glands WITH ATYPIA Nuclear atypia and hyperplasia More related to cytological features rather than architectural criteria

Answer 50

``` Address reversible factors - Weight loss - Metformin Progesterone resolution rates up to 96% LNG-IUS = first-line - Higher disease regression rate - More favourable bleeding profile - Fewer adverse effects ``` Continuous oral progesterone - MPA 10-20mg/day - Norethisterone 10-15mg/day Resample at 6/12 and 12/12 At least 2 negative biopsies prior to discharge If high risk, annual sampling and f/u Consider hysterectomy if no regression, progression to atypia, relapse or high risk of progression (on tamoxifen, FHx

Answer 51

Hyperplasia without atypia - <5% over 20y - <1% of concomitant cancer - 80% regression Hyperplasia with atypia - 30% over 20y - 22-43% of concomitant cancer - <30% regression

Answer 52

Address reversible factors Standard management if not desiring fertility and medically feasible: hysterectomy +/- BSO Premenopausal - maybe BSO, individualise - Warn about possibility of second procedure pending final histology Fertility sparing: - MDT review - Need to rule out invasive Ca or co-existing ovarian Ca - 5-fold reduction in risk of progression with progestogen Rx - Regression rates up to 86% with LNG-IUS (1st line). Takes 3-10 months (mean 6 months) - Relapse rates variable (approx 25%) - LBR 26% Resample 6 months, then 12 months On completion of family, consider completion hysterectomy Malignancy risk 11% long term with cessation of treatment

Answer 53

Up to 1 in 45 Higher in high income countries because fat and inactive Majority are diagnosed early

Answer 54

Direct spread - Through the fallopian tubes onto the ovaries the peritoneal cavity Most common route - myometrial and eventually serosal involvement To parametrial, vaginal, pelvic and para-aortic nodes Primary modality of distant metastatic spread Haematogenous spread to liver, lungs, CNS, bone (rare)

Answer 55

``` Hyperplasia Obesity (34% attributed to obesity) Older age - Peak incidence 60-79y Unopposed oestrogen Tamoxifen (RR 2-3) Nulliparous (35-40% of endometrial cancers occur in women who are nulliparous) Early menarche Late menopause PCOS Diabetes Genetic syndrome - Lynch syndrome - Cowden syndrome FHx of ovarian, breast or colon cancer ```

Answer 56

OCP and smoking are protective Physical activity High coffee drinkers

Answer 57

Endometrial thickness on US (post-menopausal) - =4mm - risk of malignancy is <0.5%, >99% NPV - >10mm - risk of malignancy is 10-20% PIPELLE - Failure rate: ~7% - Inadequate samples 13-15% - Potentially >90% sensitivity for endometrial Ca if good sample HYST D&C - PPV 100%, NPV 99.5%

Answer 58

Grade 1 and 2 endometroid carcinoma Most common May arise from complex atypical hyperplasia Linked to excess estrogen (unopposed by progesterone) Usually diagnosed early Relatively good prognosis

Answer 59

Grade 3 endometrioid tumours, non-endometrioid tumours - Typically serous cancers (molecular pathogenesis driven by p53 mutation) Develop from atrophic endometrium Less hormone sensitive Diagnosed later, generally more aggressive

Answer 60

I - confined to uterus - A <50% myometrial invasion - B >/=50% II - invades cervical stroma III - local or regional spread - A - serosa or adnexa - B vaginal or parametrial - C1 - pelvic LN - C2 - para-aortic LN IV - invasion of bladder, bowel, distant sites - A bladder or bowel - B - distant mets (incl abdominal mets, inguinal LN)

Answer 61

Australia tend to do CT abdo pelvis, NZ MRI - MRI no medicare funded in Australia - MRI is less accessible - Similar in detection of nodal metastases and extrauterine spread MRI - Optimal method for assessing degree of myometrial invasion in endometrioid tumours CXR +/- Ca125 (associated with advanced stage, peritoneal involvement, ovarian mets)

Answer 62

``` Grade of tumour (G3 - poorly differentiated) Depth of invasion (myometrial) Histologic subtype - non-endometroid histology (papillary serous and clear cell) LVSI (lympho-vascular space invasion) Cervical stromal involvement Increasing age (>65y) Stage (>IB) Tumour extension beyond fundus Tumour >2cm Positive peritoneal cytology Comorbidities ```

Answer 63

``` Surgical Conservative - For surgically unfit - Desiring fertility Medical - Can consider up front in some scenarios Palliative ```

Answer 64

Standard primary treatment is surgery Complete staging may confer some benefit but no evidence of survival advantage Hysterectomy + BSO - Tubes and ovaries may contain micro-metastases therefore recommend removal +/- peritoneal washings +/- Move to sentinel node rather than extensive lymphadenectomy (unless high risk features) Sentinel LN - NPV 99.6% Full surgical staging is not required for low risk tumours - grade 1-2, stage IA - can be operated on by general gynae (TLH+BSO)

Answer 65

Intraoperative - Vessel injury - Nerve damage (obturator, genitofemoral) - VTE Post-op - Lymphocele 20% (symptomatic in 6%) - Lymphoedema (1.5-28%) but 60% report affect on ADLs - Infection

Answer 66

Stage I-II disease - reduces pelvic recurrence with no change in survival Indications: - To treat recurrence - Palliative setting - bleeding - Rx in non-surgically resectable disease - Stage I disease - if patients have high-intermediate risk factors then vaginal brachytherapy, >2 of: age >60y, deep myometrial invasion, grade 3, serous or CC, LVSI - stage II + disease

Answer 67

``` Progesterone Indications: - Fertility sparing treatment desired - Inoperable (co-morbidities) - Recurrent disease ``` LNG IUS or oral progesterone 100mg bd Response rate: 50-95% Recurrence rates: up to 66% Pregnancy outcomes similar to those of atypical hyperplasia Treat underlying co-morbidities - bariatric surgery

Answer 68

``` Overall cure rate 75-80% Recurrence - Classically at the vault - 75% within 12 months Treatment of recurrence: - If no previous RT, then pelvic RT appropriate - If prior radiation with isolated central pelvic recurrence with no evidence of LN involvement - consider exenterative surgery - Hormonal Rx - Chemotherapy ```

Answer 69

Role of f/u is controversial - Unlikely to find recurrence in absence of symptoms 75% of recurrences symptomatic NCCN guidelines: - Physical exam every 3-6 months for 2-3y, then 6 monthly or annually - Imaging as clinically indicated - Patient education - Symptoms of recurrence - Treatment of recurrence - MDT

Answer 70

Theoretical risk of stimulating the tumour cells - Evidence is unclear about this risk Treat on individual basis depending on the symptoms and prognostic risk factors Consider alternative treatments

Answer 71

Selective estrogen receptor modulator (SERM) - Anti-oestrogen effects in the breast - Oestrogenic effects in other tissues including blood (VTE risk), bone and endometrium Indications for tamoxifen: - ER positive breast cancer - Risk reduction in pre-menopausal women with a high inherited risk of breast cancer

Answer 72

Oestrogen-like changes in the vaginal epithelium of some patients Stimulation of endometriosis --> worsening Sx Stimulation of growth of benign fibroids ``` ENDOMETRIUM Benign cystic hyperplasia Increased incidence of: - Benign endometrial polyps - Endometrial proliferation - Hyperplasia If endometrial pathology prior to starting tamoxifen, statistically significantly higher risk of developing lesions at 2y compared to patients without Increased risk of endometrial adenocarcinoma in post-menopausal women (RR = 4.01) only ``` Can induce ovulation May be teratogenic

Answer 73

Routine screening with TVS or endometrial biopsy is not recommended No clear evidence that LNG-IUS prevents endometrial cancer in those with breast cancer on tamoxifen Investigate if symptomatic

Answer 74

Arise from the myometrium or the connective tissue elements of the endometrium <10% of cancers of the uterine corpus Often behave aggressively

Answer 75

``` Age (usually >40y) - Mean age of diagnosis: 60y Menopausal status African American ethnic background Current or prior tamoxifen exposure Hx of pelvic irradiation Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome Survivors of childhood retinoblastoma ```

Answer 76

Endometrial stromal sarcoma - low grade, best prognosis Adenosarcoma - low grade Undifferentiated endometrial sarcoma - high grade Leiomyosarcoma - high grade

Answer 77

Tumour stage = most important High grade tumour Adnexal spread LN metastasis

Answer 78

TAH + BSO Pelvic and/or para-aortic lymphadenectomy - Mainly indicated in carcinosarcoma - Not in leiomyosarcoma or undifferentiated sarcoma Adjuvant pelvic RT - Reduces risk of local recurrence but has little influence on overall survival rates

Answer 79

Incidence of 0.02-0.3% Malignant transformation occurs in <1% of fibroids Approx 1/3 of uterine sarcomas Arises from the smooth muscle of the uterine wall Leiomyomas do not appear to be the precursor to leiomyosarcomas

Answer 80

Rapidly expanding mass PMB or variants of AUB (if premenopausal) Ascites Lymphadenopathy Evidence of secondary spread No established tumour markers for LMS, but may be an elevation in LDH related to increased cell turnover Typically large (>10cm)

Answer 81

Often behave aggressively Have a poorer prognosis than EAC 70% of stage I and II tumours recur - Often in the form of distant mets

Answer 82

Urinary - Radiation cystitis - irritative voiding symptoms and bladder spasms GI - Enteritis / colitis - nausea and vomiting, watery diarrhoea, cramping, urgency - Proctitis - rectal discomfort, tenesmus Vaginal - Ulceration - Erythema - Discharge - Infection Skin - Erythema - Moist desquamation

Answer 83

Urinary - Bladder fibrosis, reduced capacity, haematuria, ulceration, pain - UV and VV fistula GI - Chronic enteropathy - chronic diarrhoea and malabsorption - Fibrosis - dysmotility or obstruction / ileus - Ulcerations Vaginal - Sexual dysfunction - Stenosis - Vaginismus - Adhesions Ovaries - Early menopause Bone and bone marrow - Insufficiency fractures Skin - Fibrosis - Hyperpigmentation - Telangiectasia

Answer 84

Lifetime risk 1 in 9 | 15% diagnosed before age of 45y

Answer 85

Pregnancy itself does not appear to worsen prognosis for women diagnosed in pregnancy However, pregnancy-associated breast Ca occurs in a younger population who may have features that carry a higher risk of metastases

Answer 86

If presents with breast lump during pregnancy, refer to breast specialist team Diagnosis can be difficult when pregnant or lactating USS first line for discrete lump Tissue diagnosis through US-guided biopsy for histology - Cytology (FNA) inconclusive in pregnancy due to proliferative changes Staging for metastases is conducted only if there is high clinical suspicion - CXR - Liver USS - Gadolinium-enhanced MRI - limited safety evidence, therefore avoid in pregnancy - Bone scanning and pelvic CT are not recommended in pregnancy Tumour markers not helpful

Answer 87

``` MDT Consider TOP Surgical treatment - Including loco-regional clearance - Can be done in all trimesters Radiotherapy - Contraindicated until delivery ``` Chemotherapy - Contraindicated in first trimester - Safe from second trimester - Tamoxifen and trastuzumab are contraindicated in pregnancy Most women can go to full term and have a normal or induced delivery Following Rx, can breastfeed from the unaffected breast May depend on surgery and whether major ducts have been excised - No evidence breastfeeding increases the risk of recurrence RT --> fibrosis - makes lactation unlikely Not advised while on chemotherapy Non-hormonal contraception

Answer 88

Chemotherapy induced gonadotoxicity may cause permanent amenorrhoea with complete loss of germ cells, transient amenorrhoea, menstrual irregularity and subfertility Dependent on specific agents used, cumulative dose, women's age Tamoxifen - can cause menstrual irregularity but doesn't appear to affect fertility

Answer 89

MDT input Long-term survival after breast cancer is not adversely affected by pregnancy Stop tamoxifen for at least 3/12 prior to trying to conceive - If ER + disease, tamoxifen is usually given for 5 years Most women should wait at least 2y after treatment before conceiving - as this is when the risk of cancer recurrence is highest Outcome of pregnancy - May be an increased risk of miscarriage No evidence of increase in congenital malformations or stillbirth

Answer 90

Double stranded DNA virus single ring genome Starts with sexual activity, introduces viral particles Virus infects the parabasal cells of metaplasia epithelium (via microabrasions) Then enters the cytoplasm, where hard to detect At some point HPV DNA enters nucleus --> low grade squamous changes Koilocyte - characteristic cells of HPV infection, occurs when HPV enters cell and replicates. At the end of the life cycle, cells lyse, releases infective particles into genital tract In 10-20% HPV genomes integrates into host genome --> HG changes E6 and E7 proteins (viral oncogenes) are over-expressed --> inactivation of p53 and pRB (growth regulatory proteins) --> uncontrolled cell division and no apoptosis

Answer 91

Viral lifecycle takes place entirely within epithelium No viraemia No cell death No inflammation Local immunosuppression caused by viral proteins

Answer 92

~70-80% of sexually active women worldwide become infected at some stage of their life - in 80% - infection will be transient, asymptomatic and resolve spontaneously - in 10% will develop cervical dysplasia 10-20y latency between HPV infection and development of cervical cancer

Answer 93

``` Made from Virus Like Proteins (VPL) - Does not contain live, attenuated or killed viruses, therefore are not infectious IM infection Induces antibody response Do not treat existing lesions ``` Gardasil 9 - contains HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58 - Potentially prevents 90% of cervical cancers - Trials demonstrated 95-100% efficacy against HPV types in the vaccine 75% decline in HSIL in young women since introduction of vaccine (Victoria) 59% reduction in genital warts Some studies that show if vaccinate women who were previously unvaccinated, after their treatment for CIN/HPV, significantly reduce their risk of recurrence

Answer 94

Cervix (99.7%) - Types 16 and 18 account for ~71% of cervical cancers (16 >18) - 31, 33, 45, 52 and 58 - account for ~19% - Non-oncogenic types 6 and 11 cause genital warts Vulva, vagina (40%) Anus (90%) - HPV 16 Penis Some head and neck cancers

Answer 95

OK when breastfeeding Not recommended during pregnancy (note no adverse effects reported) Anaphylaxis rate: 1-3 in every million doses No other serious responses have been identified Minor adverse reactions - injection site reactions, fever, headaches, dizziness, muscle pain Immune response may be smaller in the immunocompromised patient Effectiveness is optimal when given <15y and prior to onset of sex

Answer 96

Registered for use in females 9-45y and males 9-26y Funded for males and females 9-26y (inclusive) 9-14 get 2 dose schedule (0 and 5-13 months) 15-26y get 3 dose schedule (0, 2, and 6 months)

Answer 97

Higher sensitivity and NPV (99%) Allows extended screening intervals Expected to have cost reductions long term Thought to result in 30% reduction in incidence of cervical cancer over time (more sensitive and detects higher grade lesions earlier) Initially result in increase colposcopy by 36% but will be reduced by 7% due to HPV vaccine 6% increase in treatments for CIN2 in unvaccinated population, decrease for those that are vaccinated

Answer 98

5 yearly HPV screening with reflex liquid-based cytology 25-74y Exit test age 70-74 Primary HPV test with partial HPV genotyping and reflex liquid based cytology triage Self-testing - For under-screened or never-screened women - Facilitated by a medical or nurse practitioner If hrHPV --> colp If oncogenic HPV that isn't 16 or 18, conventional smear - if normal smear or LSIL, repeat HPV in 1/12 - if HSIL --> colp

Answer 99

3 yearly If 'first ever' or >5y since the previous test, second test 12 months later 25-69 for any person who is sexually active Liquid based cytology If unsatisfactory, repeat after 4-6 weeks - If 3 consecutive --> colp - If post-menopausal, PN or breastfeeding, give Ovestin nightly for 2-3 weeks prior to repeating cytology

Answer 100

If no abnormal cytology within the last 5y and 25-29, repeat in 12 months If at 12 months: - Negative - repeat in 12 months, then return to 3y - If abnormal - refer colp - Don't test HPV as positivity rate is too high in this age group If prev abn cytology in last 5y, refer straight to colp >30y then reflex hrHPV test added - If negative - repeat cytology in 12 months - If positive - refer colp

Answer 101

Satisfactory and normal - Refer back to smear taker for 2 annual cytology tests Satisfactory and abnormal --> target biopsy. Histologically confirmed LSIL - refer back to smear taker for two annual smears Unsatisfactory - Review cytology - if concerned LG, repeat colp, cytology and hrHPV in 12 months

Answer 102

Satisfactory and abnormal colp --> targeted biopsy - If CIN 1 - MDM review - If HSIL on biopsy --> Rx Satisfactory and normal colp / negative biopsy: Review cytology - If confirms HG, repeat colp + cytology within 3 months - normal, repeat at 12/12 - LSIL --> MDM - HSIL --> Rx HPV testing should be used to assist with the management of people with discordant results Unsatisfactory colp - Review cytology - if confirms ASC-H/HSIL - type 3 excision is recommended. Otherwise MDM. If colp shows no abnormality, need careful inspection and colposcopy of the entire lower genital tract

Answer 103

Ensure HPV + cytology co-testing at 6 and 18 months post-treatment If negative x2, they can return to 3 yearly screening If positive, then re-refer to colp

Answer 104

Refer any one with glandular abnormalities on cytology for colp AIS on smear --> type 3 excision to exclude cancer Colp Hysteroscopy D&C Type 3 excision Even when margins clear, AIS risk of recurrence up to 20%

Answer 105

Can be taken at any time during pregnancy Particularly if never screened, overdue, abnormal screening history After delivery, delay screening until 3/12 PP to allow the pregnancy-associated changes to resolve If screening PN and/or breastfeeding, PV oestrogen cream nightly for 2-3 weeks is recommended Colp is safe Unlikely that biopsy or Rx would be undertaken during pregnancy Risk of progression of HSIL to invasive cancer during pregnancy is low Biopsy if invasion suspected - If not suspected, delay until after delivery

Answer 106

Normal endometrial cells in cervical cytology - Pre-menopausal - If asymptomatic, no further evaluation is recommended - >40y - rarely can be a/w endometrial pathology. If symptoms --> investigation. Correlate with symptoms and histology specimens where possible Atypical endometrial cells- at any age, refer to gynae

Answer 107

Normal cytology - Annual screening and indefinite Abnormal cytology - Refer for colp, even for LSIL Evaluate whole of lower genital tract Treatment of the cervix should be excisional methods F/u should include colposcopy + cytology

Answer 108

Diethylstilboestrol prior to 18/40 --> increased risk of clear cell adenocarcinoma of the vagina and cervix, and some increased risk of HSIL and cervical cancer Normal cytology - Offer annual screening and colp - Continue indefinitely Abnormal cytology - Refer colp

Answer 109

Subtotal hyst, HSIL regular screening Do single screen if no screening if 5y prior to hyst LSIL in past 5y, or LSIL in specimen - 2 vault smears 12 months apart, then stop Surveillance under/guided by GONC if hyst for malignancy

Answer 110

Subjective method of examining the cervix with a low power microscope to identify areas of pre-invasive disease in asymptomatic women with abnormal cervical screening Limitations (colp vs. 4 quadrant biopsy) - Sensitivity 81% for CIN2 - 91% for CIN3 - 100% for cancer

Answer 111

Ectocervix (intravaginal) - Lined by squamous epithelium Endocervical canal - Lined by columnar epithelium The squamocolumnar junction (SCJ) = - the junction between the two When the cervix grows (influence of oestrogen - puberty, pregnancy), the cervix elongates and everts slightly, pushing columnar epithelium into the acidic vaginal environment - Columnar epithelium replaced by squamous (metaplasia) - When columnar epithelium extends to the ectocervix, it forms an ectropion - New SCJ forms close to the ectocervix - Following menopause, moves towards and into the cervical canal - may be invisible on visual examination ``` Transformation zone (TZ) = the area between the original SCJ and the current SCJ - Almost all CIN and carcinoma develops in the TZ ```

Answer 112

Type 1 - Completely on the ectocervix and visible to colposcopic assessment Type 2 - Partially extending into the endocervical canal, but completely visible to colposcopic assessment Type 3 - Partially or completely extending into the endocervical canal, and not completely visible to colposcopic assessment

Answer 113

Surface contour - flat = normal - Micropapillary, hyperkeratosis, ulcerated Vascular pattern - abnormal vessels - appear to stop and start (punctation), variable calibre (mosaic) Acetic acid 5% changes - dehydrates cells and reversibly coagulates the nuclear proteins - More rapidly dividing = more nuclear protein / nuclear activity = more white Topography - describe lesions and TZ, how many quadrants, use clock face to describe location Iodine uptake - stains deeply brown in mature squamous epithelium containing glycogen, dysplastic epithelium contains little to no glycogen so does NOT take up iodine Columnar epithelium does not stain at all

Answer 114

Enlarged pleiomorphic nuclei - irregular in size and shape Relatively reduced cytoplasm (halo cells) - Increased nucleus : cytoplasm ratio Large irregular cells Irregular chromatin formation with clumping

Answer 115

Increased nuclear material Reduction in cellular differentiation Increased mitotic figures Involves entire thickness of epithelium but does not breach basement membrane

Answer 116

Changes in lower third of epithelium

Answer 117

Progression to cervical cancer 30-50% at 30y | Reduces 0.7% with treatment

Answer 118

Aim is to remove, or destroy, a cone shaped block of tissue, down to a minimum depth of 6mm, aiming to remove the entire TZ 6mm is the depth to which cervical glands (and therefore potential dysplastic cells) may extend Most surgeons aim for 8mm

Answer 119

Adequate colp exam with pathologic / colposcopic diagnosis agreement Must have a fully visible TZ / entire lesion can be visualised Must have no evidence of invasive disease or glandular disease (on cytology, colposcopy or histology) Must have biopsies taken Usually for women who want to have children Any recurrence after ablative treatment should be treated by excision

Answer 120

Minimal pain Blood-stained vaginal discharge for 2-3 weeks Some short term disturbance of menstrual periods (variable) No intercourse, tampons for 4-6 weeks No swimming for 2-4 weeks Follow up

Answer 121

Excision > ablative treatment methods are a/w a small but real increase in long-term adverse obstetric outcomes Excision depth >10mm --> significantly increased risk However PTL is increased in women with untreated CIN If younger, uncompleted family - laser If older, completed family - LLETZ

Answer 122

TZ if not fully visible Suspicion of invasive disease or glandular disease (on cytology, histology or colposcopy) Cytological evidence of high grade disease but no evidence of this on colposcopy / biopsy

Answer 123

Lifetime risk <1 in 250 - And falling 90% of cases in LMIC - 18x higher mortality than high income countries HPV found in virtually all cases of squamous cell cervical cancer Most glandular lesions also contain HPV 70% are squamous lesions 20% are adenocarcinomas

Answer 124

``` HPV types Early onset of sexual activity Multiple sexual partners Family Hx COCP Diethylstilbestrol (in utero exposure) HIV Low SES, remote access, being indigenous Under screening ``` SCC - smoking - parity - younger age at first giving birth

Answer 125

I - confirm to cervix - A - microscopic disease - A1 stromal invasion <3mm - A2 3-5mm - B1 <2cm - B2 2-4cm - B3 >4cm II - A - upper 2/3 of vagina without parametrial (1 <4cm, 2 >4mcm) B - with parametrial involvement III - A lower 1/3 of vagina - B pelvic wall, hydronephrosis or non-functioning kidney - C 1. pelvic LN, 2. para-aortic LN IV - - A - growth to bladder or rectum - B - distant organs

Answer 126

Previously clinical staging preferred to surgical staging as accessible in LMIC Allow use of any imaging modality and/or pathological findings No recommendations for routine investigations, which are to be decided on the basis of clinical findings and standard of care MRI is superior to CT and clinical exam in determining the size, site and extent of cervical tumours No imaging for microinvasive disease PET-CT - More accurate than CT and MRI for nodal mets >10mm

Answer 127

- Colposcopy of the cervix - EUA - Endocervical curettage - Hysteroscopy - Cystoscopy - Proctoscopy

Answer 128

Overall 5-yr survival is 68% - LVSI is a poor prognostic factor - Age and performance status of the individual patient - Tumour type - Size of tumour (tumour volume) - Metastases to pelvic or para-aortic nodes Recurrence - survival closely related to tumour size and LN involvement

Answer 129

Surgery - Preserves sexual function, although vagina may be shortened - Conserves ovarian function (if patient doesn't opt for removal) - Treatment short with hospital stay ~1/52 - Few long-term problems - May require radiotherapy post-op pending histology Chemo-radiotherapy - Low immediate risk - Avoids major surgery - Prolonged Rx (6 weeks) - Sexual function difficult, dilators may help - Loss of ovarian function - N/v with CT - Long-term bowel and bladder problems including fistula formation (uncommon, but may be difficult to treat)

Answer 130

IA1 - diagnosed on cone - If completed fam, simple hyst - If LVSI +/- LN IA2 - type 2 rad hyst + pelvic LN - if desires fertility, cone or rad trachelectomy + pelvic LN IB1 - type C rad hyst + pelvic LN - if <2cm and want fertility, rad trach - If surgical margins close, or LN involved, consider adjuvant RT IB2 / IIA1 - Surgical or RT can be chosen as the primary treatment depending on other patient factors and local resources IB3 / IIA2 - Concurrent platinum-based chemoradiation = preferred Rx - Surgery not encouraged as first line IIB - IV A - Concurrent chemoradiation IVB - chemotherapy

Answer 131

Most recurrences are within 3y Prognosis is poor - Most patients die from progressive disease with uraemia being the most common terminal event Most common site of recurrence = pelvis - Potentially curable - if isolated, no pelvic side wall recurrence, <3cm - If follows surgery, usually treat with radical chemoradiation - If isolated central pelvic recurrence, consider pelvic exenteration Following radiotherapy, it is often difficult to perform anything other than a total exenteration in recurrent disease PET-CT scan - most sensitive non-invasive test to determine sites of distant disease

Answer 132

Stage IA - Smears q3/12 for 2y, then q6/12 for 3y - Normal at 5y --> routine screening Routine f/u visits: - Every 3-4 months for the first 2-3 years - Then 6 monthly until 5y - Then annual for life Consider HRT if <50y and lost ovarian function

Answer 133

VIN warty type - Surface is undulating or spiking --> condylomatous appearance - Marked cellular proliferation with numerous mitotic figures and abnormal maturation VIN basaloid type - Thickened epithelium with a relatively flat, smooth surface - Atypical immature parabasal type cells with numerous mitotic figures and enlarged hyperchromatic nuclei VIN mixed Typically occurs in younger, premenopausal women Risk factors - HPV infection - Smoking - Immunodeficiency Multifocal VIN and multicentric VIN are most often associated with HPV 16, 18, and 31 Risk of progression of HSIL is 9-16% if untreated (3% in treated cases)

Answer 134

<5% of preneoplastic lesions of the vulva Usually occur in postmenopausal women Usually unifocal and unicentric Often a/w lichen sclerosis (not HPV) Progresses in 30% Commonly found adjacent to keratinising squamous cell carcinoma or in patients with a Hx of vulvar cancer Appearance: - Epithelium is thickened and parakeratotic with elongated and anastomising rete ridges - Abnormal cells are confined to the parabasal and basal portion of the rete pegs with little or no atypia above the basal or parabasal layers - Basal cells usually stain positively for p53

Answer 135

``` Pruritis - most common complaint Visible lesion Palpable abnormality Perineal pain or burning Dysuria 50% asymptomatic ```

Answer 136

Tissue biopsy Colposcopy Inspection and palpation of the vulva and groin for masses, ulceration or colour changes - Most VIN lesions are multifocal and located in the non hairy part of the vulva

Answer 137

prevent development of invasive vulvar cancer and relieve symptoms, while preserving normal vulvar anatomy and function Individualise Rx Options: - WLE - Laser ablation - Topical Rx

Answer 138

Advantages: occult invasive SCC present in many women, especially >50y Preferred Rx for dVIN as unifocal nature and high malignant potential 1cm margins Excision can be performed with knife, electrosurgery, or CO2 laser

Answer 139

Useful if multifocal disease, especially multiple small lesions Disadvantages - Tissue is ablated, therefore liberal colposcopy directed biopsies required to rule out invasive cancer Colposcopy used to control the depth of tissue destruction to <1mm - Ablates intraepithelial lesion and allows for rapid healing - 1mm - sufficient for hair free epithelial - 3mm required for hairy areas because the hair root sheath tends to extend as deep as 2.5mm and significant risk of harbouring VIN Superficial laser vaporisation may offer cosmetic advantages Deep results in destruction of the skin appendage - Leads to hypertrophic scar formation, negating cosmetic advantages over excisional surgery

Answer 140

Aimed at preserving anatomy, useful in younger patients Careful colp exam with biopsies to exclude invasive disease Imiquimod (Aldara) - Topical immune response modifier - Antiviral and antitumour effects mediated through the stimulation of local cytokine production and cell-mediated immunity - Appears to be effective therapy for HGIL - need more data

Answer 141

Unusual kind of skin cancer that arises from glandular cells Rare Lesions may appear as eczematoid with a scaly surface but vague margins Or may be sharply bordered with a red and velvety texture with areas and islands of hyperkeratosis Vulval adenocarcinoma may be present in 4-8% Achieving clear margins is difficult Recurrence: 50% or more

Answer 142

0.3% lifetime risk Mean age 65y Keratinising SCC - Differentiated vulvar intraepithelial neoplasia - Usually occurs in a background of lichen sclerosus Warty / basaloid SCC - High risk HPV - particularly 16, 18, 31, 33 - 25-30% of all vulvar SCC - Precursor: HSIL or usual type VIN

Answer 143

``` Squamous carcinomas 90% Malignant melanoma 3% Basal cell carcinoma 2-4% Adenocarcinoma <1% Verrucous carcinoma <1% Sarcomas 1-2% ```

Answer 144

Biopsy including area of skin where there is a transition from normal to abnormal epithelium - Keyes biopsy instrument (3 or 4mm) - Depth >1mm Presence or absence of enlarged groin LN If HPV related aetiology suspected, perform colposcopy of cervix and vagina FBC, U&E, LFTs Consider HIV screening Pre-op imaging - CT AP or MRI - for LN or distant mets - USS groin - CXR or CT for chest imaging

Answer 145

Inguinofemoral LN metastases - Most important factor determining survival - negative --> 92% 5y survival - positive nodes --> varies, 30-75% FIGO stage Histological grade of the tumour Depth of invasion - Most important factor for predicting nodal involvement - 1-2mm --> positive nodes in 8% - 3-5mm --> 30% Age and performance status of the patient Centrally localised tumours have a worse prognosis than lateral tumours - Propensity to metastasise to both groins

Answer 146

I - tumour confined to vulva A - <2cm size, stromal invasion <1mm B - >2cm, or >1mm II - extension to 1/3 lower vagina, urethra or anus III - positive inguinofemoral LN A and B related to number and size of LN C - extracapcular spread of LN mets IV - 2/3 upper vagina, urethra or distant mets

Answer 147

Mainstay of Rx Tumour-free margin of >8mm in the fixed histopathological specimen (2cm macro) Stage IA - WLE alone Otherwise radical WLE with groin LN dissection (sentinel or lymphectomy) - triple incision technique to reduce morbidity Radical WLE is as effective as radical vulvectomy in preventing local recurrence, but substantially decreases the psychosexual morbidity of treatment

Answer 148

Radio-labelled technetium and blue dye Unifocal tumours confined to the vulva <4cm in diameter Stromal invasion >1mm Clinically negative groin nodes If ipsilateral sentinel LN is not detected, complete lymphadenectomy should be done If positive sentinel LN, then bilateral inguinofemoral lymphadenectomy is recommended Disadvantages - False negative rate up to 4% - If false negative associated with 90% mortality - If positive, need repeat procedure for full LN dissection

Answer 149

``` Wound dehiscence Infection Lymphocyst formation Lymphoedema 30% Immobility Prolonged hospitalisation ```

Answer 150

Adjuvant radiotherapy a/w improved survival in patients who have >1 or grossly positive LN Indications for adjuvant RT to the pelvic and groin: - Presence of extracapsular spread in the involved groin node - 2+ positive groin nodes Radiation fields should include LNs in: - Inguinofemoral - External and internal iliac Shown to improve survival if positive margins If node positive, shown to benefit from chemo in addition to R

Answer 151

Treatment decisions depend on patient wishes and performance status Ultra-radical surgery - Radical vulval excision with partial or total exenteration and groin lymphadenectomy with plastic reconstruction - Post-op mortality 0-20% Pre-op RT and CT may shrink the tumour to allow less destructive surgery - Combination Rx is a/w significantly more morbidity than either Rx alone Primary RT +/- CT Palliative treatment

Answer 152

Up to 1/3 Vulva is the commonest site of recurrence (70%) - many "recurrent" vulvar cancers are probably new tumours If small local vulval recurrence --> WLE, better prognosis - Or consider RT Groin recurrence --> surgery or RT - Poorer prognosis Pelvic recurrence --> chemo RT

Answer 153

No evidence for best schedule ``` Clinical exam of vulva and groin No evidence for routine imaging European society of gynae onc: - 3-4 monthly for first 2y - 6 monthly for years 3 and 4 - Annual thereafter ```

GONC Flashcards

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