Oncology (NEW) Flashcards
Ovarian cancer background
Epidemiology
- 10th most common cancer in Aus women
- incidence by 85yrs is 1/85
- risk factors (BEEFALOS)
- > BRCA mutation
- > endometriosis
- > estrogen (nulliparity/HRT/menarche/menopause)
- > family hx (breast/ovaries/lynch/endometrial)
- > age
- > lynch syndrome
- > obesity
- > smoking
- protective factors
- > hysterectomy/tubal ligation/salpingoophorectomy
- > OCP
- > breast feeding
Histopath
- Epithelial (Some Epithelial Cancers Become Massive)
- > 70% of tumours/90% of cancers
- > named cystadenoma/carcinoma
- > serous (cystadenoma/carcinoma) = most common 75%
- > endometrioid
- > clear cell
- > Brenner tumour
- > mucinous
- Germ cell (TESTY minus seminoma)
- > teratoma (mature = dermoid/immature = rare)
- > embryonal carcinoma
- > trophoblastic (non GTD choriocarcinoma)
- > dysgerminoma (Don’t say seminoma)
- > yolk sac
- Sex chord/ stromal
- > estrogen producing (granulosa/thecoma)
- > progesterone producing (sertoli-leydig tumour)
- > fibroma (most common cause of meigs)
- Metastatic to ovaries
- > breast/colon/gastric
- > krukenberg tumours (mucin secreting signet ring)
Pathophys
- Invasion
- > only into superficial serosa
- > does not invade parenchyma
- Direct spread
- > uterus/fallopian tubes/ovaries
- > bladder
- > sigmoid colon
- Exfoliative spread
- > transported throughout peritoneum by fluid movement
- > liver capsule/sub diaphragmatic space/omentum
- Lymphatic spread
- > pelvic
- > para-aortic
- Vascular spread
- very rare
- late process
Ovarian cancer staging and grading
Staging
- stage 1
- > tumour confined to ovaries
- > 1c = local spill of malignant cells
- stage 2
- > local spread
- stage 3
- > spread to peritoneum outside pelvis
- > involvement of retroperitoneal lymph nodes
- stage 4
- > involvement of distant organs
- > involvement of lymph nodes outside of abdomen
Grading
- grade 1
- > well differentiated
- grade 2
- > moderately differentiated
- grade 3
- > poorly differentiated
Ovarian cancer management
Surgery
- definitive treatment and diagnosis
- indicated if high index of suspicion
- > risk factors
- > symptomatic
- > complex or progressing cyst/solid mass on US
- > raised CA 125
- method
- > laparotomy/laparoscopy
- > cystectomy/oophorectomy
Treatment principles
- approach based on tumour stage and grade
- maximal surgical debunking + adjuvant chemo
- intra-operative histology confirms ovarian carcinoma
- > surgical staging/biopsies required
Surgical staging
- > abdominal hysterectomy
- > bilateral salpingo-oophorectomy
- > appendectomy
- > omenectomy
- > pelvic and para-aortic lymph node dissection
Stage 1 (A/B) or grade 1 or 2
- favourable
- survival not improved by chemo post op
Stage 1C or grade 3
-require post operative carboplatin cycles
Stage II, III or IV
- maximal surgical effort for complete cytoreduction
- may involve
- > bowel resection
- > diaphragm peritoneum stripping
- > splenectomy
- optimal debulking
- > intraperitoneal cisplatin
- suboptimal debulking
- > adjuvant carboplatin cycles
Monitoring
- after remission
- > hx/exam/CA-125 every 3-4 months
Prognosis
- remission occurs in 80%
- treatment response to refractory disease 20%
Ovarian cysts background
Epidemiology
-approximately 10% lifetime prevalence
Aetiology
- Functional
- > follicular
- > corpus luteum
- > theca letum
- Non functional
- > endometrioma (chocolate cyst)
- > polycystic ovary
- Neoplastic
- > cystadenoma/cystadenocarcinoma
- > dermoid
- > granulosa
- > sertoli-leydig
- > krukenberg
Pathophys
- Follicular
- > graafian follicle fails to rupture
- > large, simple cyst
- > associated with endometrial hyperplasia
- Corpus luteum
- > corpus luteum fails to involute
- > often occurs during first 6 weeks of pregnancy
- > small/large, simple/complex/haemorrhagic
- > luteoma is solid corpus luteum cyst
- Theca lutein
- > overstimulation of theca interna cells of follicle
- > due to high levels of b HCG
- > molar or multiple pregnancy
- > multiple bilateral septated cysts
- Polycystic ovaries
- > may or may not be associated with PCOS
- Endometrioma
- > ectopic endometrial tissue bleeds within ovary
- > haematoma surrounded by parenchyma
- > complex cyst with internal echoes (ground glass)
clinical evaluation pelvic mass
Goal
- rule out ectopic!!
- differentiate cyst from malignant neoplasm
- recognise rupture/torsion
Cyst clinical manifestations
- usually asymptomatic
- pain
- > rupture
- > haemorrhage creating pressure
- > torsion
- follicular
- > hyperestrogenism
- > breast tenderness/endometrial thickening
- corpus luteum
- > hyperprogesteronism
- > delayed menses
- theca lutein
- > virilisation/thyroid disease/hyperemesis/pre-eclampsia
- polycystic ovaries
- > hirsutism/acne/obesity/irregular and infrequent menses
- endometrioma
- > endometriosis symptoms
Neoplasia clinical manifestations
- abdo/pelvic/adnexal pain or pressure
- adnexal mass
- non specific symptoms
- > bloating/early satiety/post prandial fullness
- > anorexia/nausea/vomiting
- > urinary urgency/frequency
- metastatic disease
- > Meig’s syndrome (adnexal mass/pleural effusion/ascites)
- > bowel obstruction
- consider extraovarian primary
- > breast
- > GIT
- > endometrial
Rupture
- background
- > functional/endometrial/neoplastic cyst
- > more common in reproductive age
- > less common with oestrogen contraception
- adnexal mass
- lower quadrant pain
- > often sudden, severe and focal
- > often post exercise or sex
- may present with acute abdomen
- cervical motion tenderness
- massive haemorrhage
- > shoulder tip or upper abdo pain
- > tachycardia and hypotension
- > cullens signs
Torsion
- background
- > usually occurs with cysts/neoplasia
- > may occur with normal ovaries
- > pregnancy or reproductive age most common
- sudden, severe pelvic pain of variable character
- adnexal mass
- nausea and vomiting
- fever with necrosis
- signs of acute abdomen are unusual
pelvic mass investigations
- B HCG
- > if positive, ectopic pregnancy pathway
- First catch urine
- > chlamydia/gonorrhoea PID?
- FBC
- > anaemia?
- > thrombocytopaenia?
- > leukocytosis?
- Blood group and antibodies
Transvaginal ultrasound
- Normal findings
- > follicles (<25mm) in reproductive age
- > simple cyst 30-50mm
- Concerning for neoplasia
- > large (>10cm) simple cyst
- > complex cyst (solid components/septa/thick walled)
- > high flow on doppler
- > ascites
- > solid mass
- Concerning for torsion
- > enlarged ovary with cystic/solid mass
- > free fluid
- > diminished/absent blood flow on doppler
- Concerning for rupture
- > adnexal mass with free fluid
If concern for neoplasia
- CT abdo/pelvis/chest
- > metastatic disease
- CA-125
- > usually elevated in epithelial
- > aids in post treatment evaluation
- > most useful in post menopausal women
- > consider other germ cell markers in adolescents
- Consider synchronous endometrial neoplasia
- > occurs in approx 10%
- > endometrial biopsy if uterine bleeding/mass
ovarian cyst management
Simple cyst in premenopausal -almost always benign -non suspicious >expectant management ->serial ultrasounds every 2-3 months ->persists or enlarges = laparoscopy + histopath -suspicious ->laparotomy
Complex cyst in premenopausal
- non suspicious
- > expectant management
- > serial ultrasounds every 2-3 months
- > if persistent or >10cm = laparoscopy + histopath
- suspicious
- > laparotomy
Simple cyst in postmenopausal
- not suspicious and normal CA 125
- > expectant management
- > serial ultrasounds + CA 125 every 2-3 months
- > if persistent or >10cm = laparoscopy/laparotomy + histopath
- suspicious
- > laparotomy
Complex cyst post menopausal
-laparotomy
Solid mass in pre/postmenopausal
-first line laparotomy + histopath
Pregnant
- non symptomatic/not suspicious/small cyst
- > expectant management
- symptomatic/large cyst/not suspicious
- > laparoscopy + cystectomy
- suspicious
- > ideally delay laparotomy until post natal
- > consider in 2nd trimester if malignant
endometrial cancer background
Epidemiology
- most common gynaecological cancer
- 6th most common cancer in women
- lifetime risk approx 20/100,000
Aetiology
- Risk factors
- > older age
- > obesity
- > PCOS/low parity/early menarche/late menopause
- > unopposed oestrogen/tamoxifen
- > family hx endometrial/breast/ovarian
- > family hx lynch/PTEN syndrome
- Endometrial hyperplasia
- > hyperplasia without atypia = >5 years to progress
- > atypical hyperplasia = 2.5 years to progress
Pathophys
- Type 1
- > most common (80%)
- > low grade (1 or 2) endometrioid/mucinous
- > stimulated by oestrogen
- > preceeded by endometrial hyperplasia
- > good prognosis
- Type 2
- > not oestrogen receptive/background atrophic
- > poor prognosis
- > grade 3 endometrioid/serous/clear cell/undifferentiated
Endometrial cancer evaluation and management
Clinical presentation
- AUB
- > post menopausal bleeding
- > premenopausal menorrhagia/inter menstrual bleeding
- pelvic/inguinal pain
- fatigue and weight loss
- diarrhoea/nausea/vomiting
- persistant cough/dyspnoea
- > neurological symptoms
- > exam is usually unrevealing
Transvaginal ultrasound
-abnormal thickening >4mm
Biopsy
- outpatient pipelle curette
- > often first line
- > caution if negative but high index suspicion
- D&C +/- hysteroscopy
- > most accurate
Cervical cytology
-sensitivity approx 60%
FBC -anaemia EUC -elevated creatinine? LFT -al phos?
- CT abdo/pelvis/chest
- > only if advanced disease suspected
- MRI pelvis
- > assess depth of invasion/surgical planning
- PET CT
- > non surgical candidates for monitoring
Management
- surgical staging
- hysterectomy(lap or abdo)/BSO/lymphadenectomy
- neo/adjuvant radiotherapy (brachytherapy or EBRT)
- adjuvant chemotherapy for advanced/palliative
- progestogen/GnRH/tamoxifen + progestogen for recurrent/resistant
Prognosis (5 year survival)
- Stage 1 = 85%
- Stage 2 = 75%
- Stage 3 = 65%
- Stage 4 = 20%
Cervical cancer staging
Evaluation
- Clinical
- > rectovaginal under anaesthesia
- > iliac/para-aortic/supra clavicular for lymphatic spread
- > palpate liver/spleen and balot kidneys for metastatic
- Scopes
- > hysteroscopy/cystoscopy/colonoscopy
- Imaging (if invasive cancer found)
- > CT abdo/pelvis/chest
- > MRI pelvis
- > PET scan (lymph node involvement)
- > US/CT guided ultrasound nodes if suspicious
Staging
- 1 (confined to cervix and uterine corpus)
- > 1A microscopic invasion (1A1 <3mm/1A2 <5mm)
- > 1B invasion >5mm
- 2 (invasion beyond uterus/not pelvic wall/not lower vagina)
- > 2A = upper 2/3rd vagina but not parametria
- > 2B = parametria involved
- 3
- > lower vagina
- > pelvic wall
- > hydronephrosis
- > pelvic/para-aortic lymph nodes
- 4
- > 4A = pelvic organs (bladder/rectum)
- > 4B = distant spread beyond true pelvis
Invasive cervical cancer treatment and prognosis
Stage 1A1 (micro invasive) -cone biopsy
Stage 1A2-2A (early stage)
- Radical abdominal hysterectomy + lymphadenectomy
- > adjuvant chemoradiation if large/nodes/+ive margins
- Chemoradiation
- > preferred if bulky disease
- > cisplatin + EBRT + brachytherapy
- Trachelectomy
- > if desiring fertility + small tumour
Stage 2B-4A (locally advanced)
- Chemoradiation
- > cisplatin + EBRT + brachytherapy
Stage 4B (metastatic)
- focal deposits
- > consider surgery/ablation/radiation
- chemotherapy +/- bevacizumab (VEGF MA)
- consider goals of care/palliation
Prognosis (5 year survival)
- Stage 1 = >90%
- Stage 2-3 = approx 50%
- Stage 4 = <20%
Cervical cancer background
Epidemiology
- 12th most common cancer in aus women
- > 5/100,000
- > ATSI rate x2
- Risk factors (HEMISPPACE)
- > HPV
- > early sexual debut
- > multiple sexual partners
- > immunosuppression
- > STI
- > parity
- > pill (OCP)
- > age (midlife)
- > cigarrettes (squamous)
- > economic (low SES)
Aetiology
- HPPV infection
- > 99% linked to oncogenic serotypes
- > 16 and 18 in up to 80%
Pathophys
- HPV infections
- > approx 80% lifetime prevalence
- > sexual activity (vaginal/oral/anal)
- HPV link to cancer
- > usually benign, 95% cleared within 3 years
- > if cleared, risk returns to baseline
- > carcinoma develops about 10-15 years post infection
- Disease progression
- > infection->persistance to LSIL or clearance
- > LSIL -> progression to HSIL
- > HSIL -> regression to LSIL or progress to carcinoma
- > approx 30% HSIL progress to carcinoma (annual 1.4%)
- Local invasion
- > initial corpus
- > vagina/peritoneum/bladder/rectum
- Haematogenous spread
- > lung/liver/bone most common
- > bowel/brain/adrenals/spleen
- Lymphatic
- > obturator and iliac are sentinel
- > parametrial/para-aortic/pre-sacral
cervical cancer evaluation
Hx
- PC
- > bleeding (intermenstrual/post coital/menorrhagia)
- > pain (pelvic/back/dyspareunia)
- > mucopurulent discharge
- Advanced disease
- > obstructive nephropathy
- > haematuria/haematochezia
- > vaginal passage urine or stool
- Menstrual hx
- > abnormal bleeding
- Sexual hx
- > debut/multiple partners
- > barrier protection/previous STD’s
- > use of OCP
- HPV
- > vaccination
- > last test/previous results
- Obstetric
- > previous children/plans for children
- Psychosocial
- > smoking
Exam
- Abdo
- > tenderness or masses?
- Speculum
- > cervical bleeding
- > ulceration/exophytic mass/barrel shaped endophytic
- Bimanual
- > consider PID
- > evidence of local invasion
Initial investigations
- cervical screening if asymptomatic
- colposcopy if symptomatic or visible lesion
- endocervical swabs if suspicious for cervicitis
Colposcopy
- General assessment
- > TZ type 1 (ectropian)/2 (normal)/3(not visible)
- > obvious masses/lesions
- > atypical vessels
- Apply acetic acid
- > abnormal = dense white/coarse mosaic/coarse punctation
- Lugol iodine
- > homogenous uptake = normal
- > reduced uptake by neoplastic cells
- Punch biopsies (pain + bleeding)
- > provides histopath
- > approx 2
- Consider endocervical curette
Preop evaluation
- Urinalysis
- > kidney dysfunction
- FBC
- > anaemia
- EUCs
- > obstructive nephropathy
- LFTs
- > alphas in liver/bone mets
cervical cancer screening pathway
Screening procedure
- all women who have been sexually active and 25-74yrs
- > vaccinated and unvaccinated
- > can stop at 70 if previous 2 normal
- routine screening every 5 years
- invitation, reminder letters
CST pathway
- first HPV partial genotypical
- > 16/18
- > other
- if positive for any HPV DNA
- > reflex liquid based cytology on same sample
- Low risk result
- > HPV not detected
- > continue 5 years screening
- Non 16/18 detected + pLSIL/LSIL
- > HPV again in 12 months (intermediate risk)
- ->if -ive = continue 5 year screening (low risk)
- ->if +ive for any HPV=reflex LBC + colposcopy (high risk)
- Non 16/18 detected + pHSIL/HSIL
- > colposcopy (high risk)
- 16/18 detected
- > LBC + colposcopy (high risk)
- Any glandular abnormalities detected
- > refer to colposcopy (high risk)
- Hysterectomy
- > normal screening/benign disease/no path = no testing
- > treated for HSIL with test of cure = no testing
- > AIS = 12 month testing indefinitely
- > subtotal = like general population
cervical cancer histopath
- Carcinoma classification
- > squamous cell carcinoma (80%)
- > adenocarcinoma/adenosquamous (15%)
- > other rare forms (neuroendocrine)
Squamous lesions
- LSIL
- > acute HPV infection
- > increased mitoses/C:N
- pLSIL
- > possibly LSIL
- HSIL
- > persistent HPV infection
- > loss of differentiation
- > CIN2 = p16 positive, not fitting CIN3 criteria
- > CIN3 = dysplasia in >2/3 thickness but no invasion
- pHSIL
- > possibly HSIL
- Squamous cell carcinoma
- > invasive epithelial tumour with squamous differentiation
- Superficial invasive squamous cell carcinoma
- > favourable prognosis
Glandular lesions
- Adenocarcinoma in situ
- > mucosal pre-invasive lesions
- Invasive adenocarcinoma
- > invasive epithelial tumour with glandular differentiation