GONC Flashcards
Incidence of adnexal masses
Up to 10% of women will have some form of surgery for an ovarian mass during their lifetime
Pre-menopausal
- Almost all are benign and resolve in 2-3 menstrual cycles
- 0.1-0.3% of cysts are malignant
Post-menopausal:
Incidence of cysts is 5-17%
Incidence of ovarian cancer
Lifetime risk 1.5%
Mean age 61y
23% of gynae cancers are ovarian, but makes up 47% of deaths from gynae cancers
80% of cases present stage 2, 3, 4
Overall 5y survival 42%
Frozen section
Literature rates variable in terms of accuracy - 56-86%
Compared with final histological diagnosis
- Sensitivity 65-100%
- Specificity >99%
Factors that lower sensitivity
- Large neoplasm (>8cm)
- Mucinous tumours
- Borderline tumours
Adnexal torsion - aetiology
25% of adnexal torsions occur in children
- Only 50% a/w a mass
Dermoid most common aetiology - up to 10% of dermoids undergo torsion.
=/> 5cm –> risk of torsion
Cause:
- Postulated that occurs where there is an unusually long ovarian pedicle with a moderately large cyst
- No evidence more common in pregnancy
Disruption of venous return occurs but arterial supply is largely maintained
- That’s what causes congestion and oedema
USS findings of torsion
Sensitivity 46-75%
Ovary may be rounded, enlarged and have a heterogeneous appearance compared with the contralateral ovary due to oedema, engorgement, and/or haemorrhage
Ovary may be located anterior to the uterus, rather than in the normal lateral or posterior position
Multiple small follicles (string of pearls, peripheralisation of follicles) - due to displacement by oedema
Mass may be present
Doppler flow may be:
- Present / normal - Due to incomplete occlusion, intermittent torsion, collateral blood supply
- Decreased
- Absent
- Assess contralateral ovary doppler flow to compare
Whirlpool sign - round hyperechoic structure with concentric hypoechoic stripes or a tubular structure with internal heterogeneous echoes - Twisting of the vascular pedicle
Management of adnexal torsion
Surgical evaluation
- Ovarian necrosis is rare
- The vast majority of torsed ovaries can and should be salvaged, unless malignancy is suspected
- Studies had found that many patients (even those with black or blue ovary) retain ovarian function following detorsion - USS f/u - rate of follicular development >80%
Time (up to 36h) is more important than appearance
If premenopausal, benefits of ovarian conservation appear to outweigh theoretical risks
Post-menopausal, or suspicious looking –> USO
No high quality data to support oophoropexy
Cyst rupture / haemorrhage timing
Usually days 20-26 of cycle
Recurrent cyst rupture / haemorrhage can be prevented by ovulation suppression (e.g. COCP) - but won’t treat current cyst
Management of premenopausal simple cysts
Functional or simple ovarian cysts <50mm usually resolve over 2-3 menstrual cycles
50-70mm - yearly USS f/u
>70mm - consider further imaging (MRI) or surgical intervention
- Due to difficulties in examining the entire cyst adequately at time of USS
Recurrence rates after laparoscopic needle aspiration of simple cysts range from 53-84%
Complications of dermoid cysts
Avoid rupture as cannot exclude malignancy
Chemical peritonitis due to spillage occurs in less than 0.2% of cases
If spillage occurs, meticulous peritoneal lavage should be performed with warmed fluid
Post-menopausal - conservative management of cysts
Cystic lesions smaller than 1cm are clinically inconsequential
- At the discretion of the reporting clinician whether or not to describe them in the imaging report
Asymptomatic, simple, unilateral, unilocular ovarian cysts, <5cm
- Low risk of malignancy (<1%)
If normal Ca125, repeat evaluation in 4-6 months, if stable then discharge after 1y of follow if stable or reduces with normal Ca125
Post-menopausal - surgical management of cysts
Assess:
- Comorbidities
- Nutritional status
- Functional status
Indications:
- Symptomatic simple cyst
- Suspicious or persistent complex mass
Consider laparoscopy if:
- RMI <200
- Surgeon with suitable experience
Procedure: BSO
Avoid intraperitoneal spillage
Consider laparotomy if:
- RMI >200
- CT findings, clinical assessment or findings as laparoscopy require a full laparotomy and staging procedure
Work up of post-menopausal / complex cyst
Symptoms suggestive of malignancy?
- Protective factors - parity, COCP use
FHx of ovarian, bowel or breast cancer
Exam - ascites? LN?
Tumour markers
- Ca125 - should not be used in isolation to determine if a cyst is malignant, not specific
- Ca199, CEA = epithelial tumour markers
If under 40y - LDH, aFP, hCG
DON’T FORGET TO EXCLUDE PREGNANCY
Imaging
- USS first line
- MRI if need further cyst characterisation
- CT if RMI >200
Assess:
- Comorbidities
- Nutritional status
- Functional status
RMI
Menopausal status (M)
- 1 = premenopausal
- 3 = postmenopausal
Presence / absence of suspicious ultrasound features (U) 1 point for each of the following: - Multilocular cysts - Solid areas - Metastases - Ascites - Bilateral lesions U = 0 for ultrasound score of 0 U = 1 for score of 1 U = 3 for a score of 2-5
Serum Ca125 in IU/ml
RMI = U x M x CA-125
RMI I score >200
- 78% sensitivity and 87% specificity for cancer
- If post-menopausal, PPV 96% for malignancy
IOTA simple rules
- Benign features
Unilocular cyst Solid components present but <7mm Acoustic shadows Smooth multilocular lesion with largest diameter <10cm No blood flow
IOTA simple rules
- Malignant features
Irregular solid lesions
Ascites (fluid above the top of the uterus)
=/>4 papillary structures
Irregular multilocular-solid tumour with largest diameter >10cm
Abundant blood flow
Utility of IOTA simple rules
Sensitivity 95%, specificity 91%
25% of unclassifiable lesions can be sent for second opinion or have ADNEX model applied
Ovarian torsion in pregnant women
Most common cyst to affect pregnant women is a dermoid cyst
Torsion most commonly occurs in the first trimester or post-partum
Tumour markers for specific ovarian cancer types
Epithelial CA125 CEA Ca19-9 HE4
Germ cell
LDH
aFP
B-hCG
Sex cord stromal E2 FSH Inhibin Testosterone
CA125
Sensitive but not specific
Elevated in 80% of non-mucinous ovarian cancers
Elevated in only 50% stage I cancers
In premenopausal women, can be elevated if:
- Taken when menstruating
- Active endometriosis
- Pregnancy
- Infection
Better predictive value in post-menopausal women
CA 19-9
Non-specific Elevated in - Mucinous borderline tumours - Pancreatic - Gastric
Ovarian cancer
- 76% of mucinous carcinomas of the ovary
- 27% of serous carcinomas of the ovary
CEA
Elevated in
- Metastatic bowel cancer
- Mucinous borderline tumours
- Other cancers - lung, breast, liver, pancreas, thyroid, stomach
- Non cancerous conditions - e.g. UC, smoking
Elevated 37% of mucinous carcinomas of the ovary
Outline FIGO staging for ovarian cancer
I - Tumour confirmed to ovaries or fallopian tubes
- A - one ovary, capsule intact
- B - both ovaries, capsule intact
- C1 - surgical spill
- C2 - capsule rupture before surgery
- C3 - positive washings
II - pelvic extension
- A - uterus or tube or ovary
- B - other pelvic structures
III - spread to peritoneum outside of pelvis or retroperitoneal LN
- A1 - LN (i or ii)
- A2 - micro peritoneal mets
- B - macro peritoneal mets
- C - capsule of liver or spleen
IV - distant mets (excluding peritoneal mets)
- A - pleural effusion
- B parenchymal mets and mets beyond abdomen
Risk factors for ovarian cancer
Increasing age - Incidence increases rapidly after menopause Nulliparity (2x increased risk) Infertility Use of perineal talc Obesity HRT BRCA Lynch syndrome FHx of ovarian cancer
Protective factors for ovarian cancer
COCP - If on for >5y then reduce risk of ovarian or endometrial cancer by 50%
Breastfeeding - Cumulative total of 18 months –> reduced risk 1.5
Sterilisation / tubal ligation
Hysterectomy
First pregnancy at an early age
Early menopause
Typical ovarian tumour type based on age
Women <20y
- Germ cell tumours
30s and 40s
- Borderline tumours
> 50y
- Epithelial tumours
Screening for ovarian cancer
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
Types of ovarian cancer
90% epithelial
Malignant GCT 3%
Sex cord stromal cell tumours 1-2%
5% metastatic
Types of epithelial ovarian cancer
High grade serous - 70% Endometrioid 10% Clear cell - 10% Mucinous 5% Low grade serous - 5%
Staging laparotomy for ovarian cancer
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
Pathophysiology of epithelial cancers
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%
Spread of ovarian cancer
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
Diagnostic work up before MDM for ovarian cancer
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)
Principles of treatment for ovarian cancer
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)
Chemotherapy for epithelial ovarian cancer
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
What are PARP inhibitors?
Patients with BRCA (germline and somatic) have the greatest benefit
Frontline maintenance - for recurrence
Follow up after ovarian cancer treatment
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)
Family history of ovarian cancer
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)
About BRCA
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
BRCA management
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
Lynch syndrome
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
PSEUDOMYXOMA
Syndrome rather than pathological term
Widespread deposit of mucin within the intra-abdominal cavity
Primary appendiceal lesion
Occasionally ovarian and other GIT sites
Krukenburg tumour
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
Primary sites of mets to ovary
Breast
Lower reproductive tract sites - cervix, uterine
GIT - bowel, gastric (stomach most common), pancreatic
Lymphoma
Aetiology of germ cell tumours
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
Which germ cells cause with GCT
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
Clinical presentation of GCT
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
Investigation of GCT
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
Management of GCT
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
Fertility for GCT post-treatment
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
Follow up of GCT
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
Aetiology of SCST
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%
Management of SCST
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
Granulosa cell tumours - types
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%)
Granulosa cell tumours - investigation and management
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
About fibroma
SCST
Benign
Most common
Originate from spindle cells, producing collagen
Meigs syndrome - Fibroma + ascites +/- pleural effusion, due to VEGF
About thecoma
Post-menopausal Originate from spindle and theca cells Benign Produce excess estrogen - endometrial hyperplasia in 15% - carcinoma in 20-25%
About Sertoli-Leydig cells
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
Define borderline tumours
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
Incidence of BOT
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
Histology of BOT
Serous 45-60%
Mucinous 30-50%
Seromucinous, endometrioid, clear cell, Brenner (transitional cell) 5-10%
Investigations of BOT
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
Management of BOT
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)
Surgical options for BOT
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
Prognosis of BOT
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
Follow up of BOT
USS every 6 months +/- CA125 if elevated at diagnosis
Total 10-15y surveillence
Consider completion surgery when family complete
Features of BOT associated with increased risk of recurrence
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
Counselling of fertility with BOT
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
Evidence to guide management of adnexa at benign hysterectomy
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
Potential risks of oophorectomy at time of hysterectomy for benign disease
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
Removal of the tubes at time of hysterectomy for benign disease
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
