Oncology Flashcards
Diagnosis CRC
Clinical
- change in bowel habits
- > more common in left
- bleeding (haematochezia/malena)
- > more common in left
- anaemia
- > more common in right
- obstruction
- abdo pain
- > obstruction
- > peritoneal spread
- > perforation
- rectal or abdo mass
- rectal cancer
- > tenesmus
- > decreased stool caliber
- mets
- > liver
- > lungs
- > peritoneum
- > local lymph/supraclavicular nodes
Bloods:
- CBC
- LFTs
- > baseline
- > insensitive for mets
- EUCs
- > electrolytes
- > baseline
- > kidney function/contrast
- Iron studies
- Coags
- CEA
- > baseline, preop, post op decline and surveillance
Imaging
- Colonoscopy with biopsy
- CT colonography if colonoscopy unavailable
Risk factors CRC
Personal Hx (CRC or adenomatous polyps) Family Hx (CRC) Polyposis syndromes (FAP, MAP, Lynch) \+ SAAARRRCCOID -Smoking -Alcohol -Acromegaly -Androgen deprivation therapy -Radiation, pelvic (childhood cancer) -Renal transplant -Red/processed meat -Cholecystectomy -Cystic fibrosis -Obesity -IBD (UC) -Diabetes
management CRC
T1
-managed by local excision
Colon cancer
- hemicolectomy depending on site
- > 5cm proximal and distal margins
- lymphadenectomy
- > removal of mesentery to origin of named vessel
- > will contain paracolic and intermediate nodes
- neoadjuvant chemo
- > best evidence for stage III
- Surgical resection only curative option for local disease
- Decision as to presurgical radio/chemoradiation therapy. Best evidence for Stage III, disputed Stage II, certainly for rectal low lying
- post surgery chemo (oxaliplatin based) for 6 months. Treats micromets, decreases recurrence.
staging CRC
TNM system. Stage 0 = Tis. Invasion through lamina propria but not muscularis mucosae (as lamina does not contain lymph vessels) Stage 1: T1-2,N0,M0 -T1 = invasion into submucosa -T2 = invasion into muscularis propria Stage 2: T3-4,N0,M0 -T3 = invasion through muscularis -T4= locally invasive (4a= not adherent to local structures, 4b = adherent to local structures Stage 3: Tx,N1-2,M0 -N1 = 1-3 lymph nodes -N2 = 4 or more lymph nodes Stage 4: Tx,Nx,M1 M1 = distant metastases (usually liver, also lung, bone, brain)
Prognosis approx 95-90% for Stage 1 and 5% for stage 4.
pathogenesis CRC
CRC is thought to emerge from adenomatous polyps that become dysplastic. Adenomatous polyps occur when normal mechanisms regualting epithelial renewal are disrupted.
There are three broad modes of presentation, that likely represent different pathways along this adenoma-carcinoma sequence.
The first is sporadic which accounts for approx 70%. Here somatic mutations are accumulated in a stepwise manner due to environmental factors.
Truly inherited predispositions underlie approx 10% of CRC. Here, germline mutations predispose the individual to CRC, usually after acquiring further somatic mutations. There are polyposis syndromes such as FAP and MAP and non polyposis such as Lynch.
A third presentation, where there is a family history of CRC in the absence of one of the inherited conditions, is referred to as familial, which makes up about 25% of CRC. An example is Familial Colorectal Cancer Syndrome Type X. The mechanisms underlying this presentation are unclear.
pathophys CRC
There are three molecular pathways that lead to these presentations.
The first is the Chromosomal Instability Pathway, characterised by growth promoting mutations such as the oncogene RAS (kRAS; which becomes resistant to GTPase and is constitutively active as a growth signal transducer) and diminished activity of tumour suppressor genes such as APC, which regulates the Wnt pathway. Deletions in the long arm of chromosome 5, including the APC gene, underline FAP, but mutations in APC are thought to occur early in most sporadic presentations as well. Other tumor suppressor genes are p53 on chromosome 17, which occurs in the molecular sequence, and DCC on chromosome 18.
The second pathway is via defects in MMR. Though this can occur in sporadic disease, it is typical of Lynch syndrome in which there are mutations in hMSH 2 on chromosome 2 or hMLH1 on chromosome 3 that codes for the MMR enzyme. The resultant genetic signature has multiple stretches of incorrect nucleotide base pairs known as microsatelite instability.
The third pathway is largely epigenetic, which hypermethylation of CpG islands, including the promotor region for MMR enzymes such as hMLH1.
Familial Adenomatous Polyposis
Inheritance
- autosomal dominant condition
- 30% have no family hx
- > de novo mutations
- deletion in long arm of chromosome 5
- > including adenomatous polyposis coli gene (APC) which ->tumor suppressor gene
Associated with
- > 100 (usually thousands) of adenomatous colonic polyps
- almost 100% get CRC
- represents only 1% of CRC
- mesenteric desmoid tumours and congenital retinal pigment hypertrophy
- > Gardners
- CNS tumours
- > Turcots
- Attenuated FAP
- > fewer polyps
Management
- surveillance (sigmoidoscopy) from 10-15
- require colectomy after first polyp
MUTYH Associated Polyposis
Inheritance
- autosomal recessive
- mutation in base excision repair gene MUT-4H
- > predisposes to APC mutations giving polyposis phenotype
Management
- 2 yearly colonoscopy from 18 years old
- yearly after first polyp
- if polyps cannot be adequately controlled
- > require colectomy
Lynch syndrome (Hereditary Nonpolyposis Colon Cancer)
Inheritance
- defined by amsterdam criteria (replaced by bethesda)
- > 3 family members with CRC
- > at least one under 50
- > across two generations
- mutations in mismatch repair genes
- > hMSH2 on chromosome 2
- > hMLH1 on chromosome 3
- generally have one germline mutation and a second somatic
Associated with
- CRC
- > approx 30% risk
- > mostly right sided
- polyps are rare
- > those that occur have high cancer risk
- other cancers
- > endometrial
- > ovarian
- > gastric
- > urothelial
- > small bowel
Management
- annual surveilence from age 25
- high rate of metachronous cancer
- risk reduced by
- > subtotal with ileosigmoidal anastamosis
- > total with ileorectal anastamosis
Screening for CRC
Average risk
- faecal occult
- every 2 years
- > from 50-74
- if positive
- > colonoscopy as soon as possible
Risk categories
- category 1
- > 2x risk
- > 1 family member above age 55
- category 2
- > 3-6x risk
- > first degree younger than 55
- > two first degrees of any age
- > 1 first and two second degree
- category 3
- > 7-10x risk
- > two second degree with one before 55
- > three first degree
Surveillance of categories
- category 1
- > doesn’t benefit from colonoscopy screening
- > faecal occult every 2 years from 45
- category 2
- > faecal occult every 2 from 40-50
- > colonscopy every 5 from 50-74
- > low dose aspirin
- category 3
- > faecal occult every 2 years from 35-45
- > colonoscopy every 5 years from 45-74
- > consider low dose aspirin
- > consider genetic counselling
Staging approach CRC
Colonoscopy
- visualise lesion
- > distance from anal verge
- > grossly more T2 or more?
- biopsy
- > tis or T1
- synchronous lesions
CT chest abdo pelvis
- M and N status
- T4 status can be determined
- MRI of liver more sensitive
PET CT
- only used when mets are found
- > to more accurately detect small distal mets
MRI pelvis
-more accurately examines locoregional involvement for rectal cancers
pancreatic cancer background
epidemiology
-age >65
risk factors
- modifiable
- > smoking
- > obesity
- genetic
- > lynch syndrome and FAP
- > peutz jeghers
- > BRCA1/2
- > hereditary pancreatitis
histology
- majority arise in head
- exocrine (>95%)
- > adenocarcinoma (most are ductal)
- > from epithelial cells
- endocrine (<5%)
- > neuroendocrine
pancreatic cancer stages and treatment options
staging
- stage 1
- > limited to pancreas
- > whipples with chemo
- stage 2
- > beyond pancreas
- > not involving coeliac or superior mesenteric
- > whipples with chemo
- stage 3
- > involves coeliac/superior mesenteric
- > inoperable
- > palliative chemo and radiation
- stage 4
- > mets
- > palliative chemo and radiation
pancreatic cancer prognosis
prognosis
- 80% have stage 3/4 at diagnosis
- > early metastasis
- no screening program
- adeno
- > stage 1 = 30% 5 year survival
- > stage 2 = 10% 5 year survival
- > stage 3/4 = median survival 6 months
- neuroendocrine
- > much more favourable
pancreatic cancer investigations
FBC -thrombocytopenia in DIC -anaemia LFTs -obstructive pattern Coags -DIC -Trousseau's syndrome Cancer antigen 19-9
non-invasive imaging
- abdominal ultrasound
- > mass/dilated ducts/liver mets
- > lower sensitivity for tail
- CT with contrast
- > mass and spread
consider
- biopsy
- > only necessary for decision to palliate, not for surgery
- > ultrasound guided endoscopic biopsy
- > ERCP
- ERCP or MRCP
- > when CT equivocal
- > better visualisation with ERCP and option for biopsy
GTD background
types (CHIPE)
- choriocarcinoma
- hydatiform mole
- > partial
- > complete
- invasive mole
- placental site trophoblastic tumour
- epithelioid trophoblastic tumour
choriocarcinoma
- occurs with
- > complete molar pregnancy
- > within 1 year of non molar abortion
- > after term pregnancy
- presentation
- > PV bleeding
- > pelvic mass
- > mets symptoms
- > HCH always elevated
hydatiform mole
- complete
- > fertilisation of chromosomally empty egg
- > 46XX or 46XY of only paternal DNA
- partial
- > fertilisation of normal ovum by two sperms
- > 69XXY or 69XXX
- presentation
- > fetal parts, circulation, RBCs in partial
- > higher HCG in complete
- > hyperemesis gravidarum, hyperthyroid, HTN
placental site trophoblastic tumour
- many years after
- > molar pregnancy
- > non molar abortion
- > term pregnancy
- presentation
- > mets less common
- > gynaecological symptoms
- > low HCG
epithelioid trophoblast tumour
- follows
- > long after normal pregnancy
- presentation
- > HCG low
- > mets less likely
investigations, management and complications GTD
INVESTIGATIONS beta hCG -elevated FBC -anaemia from bleeding EUCs -chemo LFTS -chemo Coags -increased risk of bleeding with treatment Blood type with antibody screen TSH -hyperthyroidism
ultrasound -snowstorm appearance -absence of fetal cardiac activity CXR -mets
MANAGEMENT
- suction dilatation and evacuation
- hysterectomy
- all patients require contraception
COMPLICATIONS
- chorciocarcinoma
- invasive gestational trophoblastic neoplasia
- pre-eclampsia
- ashermans syndrome
types of lung cancer
Small cell (15%)
- neuroendocrine
- arising from major bronchi or lung periphery
- strongest association with smoking
- highly aggressive
- morphology
- > small
- > scant cytoplasm and nuceoli
- > granular chromatin
- immunophenotyping
- > CD56
- > neural cell adhesin molecule (NCAM)
- > synaptophysin
NSCC
- squamous and non squamous
- > squamous = p40 or 63 and mucin stains
- > adeno = thyroid transcription factor 1
- squamous
- > highly associated with smoking
- > resp epithelium of bronchi
- adenocarcinoma
- > glandular diff or mucin production
- > more peripheral than squamous
- > becoming most common
- > common in non smokers
- > adeno in situ, minimally invasive, invasive
- large cell carcinoma
- > least common of main
- > diagnosis of exclusion
- > lacks glandular or squamous or neuoendocrine differentiation (by light microscopy and immunophenotyping)
risk factors lung cancer
older age
COPD
family hx
smoking
- cigarrette
- > strong link
- > 30% in heavy user
- > risk proportional to use
- > declines but doesnt reach never smoker with cessation
- > cigars and pipes also
- > marijuana and ecigs less certain
- second hand
- air pollution
- indoor cooking
radon
- gaseous decay of uranium
- > miners
- > soil and housing
asbestos
-mainly occupational
diesel exhaust
paraneoplastic syndromes lung cancer
HAMCAN
- haematologic
- > anaemia
- > thrombocytopaenia
- > leukocytosis
- ADH (syndrome of inappropriate ADH secretion)
- > hyponatraemia
- musculoskeletal
- > hypertrophic osteoarthropathy
- > poly/dermatomyositis
- calcium (hyper)
- > lytic bone lesions
- > PTHrP
- Neurologic
- > Lambert Eaton syndrome (neuromuscular ACh release)
- > limbic encephalitis
- > ataxia
hx and exam lung cancer
Risk factors
Intrathoracic disease
- cough
- haemoptysis
- > represents cancer in up to 30% gen pop
- > bronchitis most common cause
- > pneumonia during red hepatization
- chest pain
- > dull and aching
- hoarseness
- > involvement of recurrent laryngeal
- pancoast syndrome
- > apical tumour
- > pain in C8, T1/2
- > hand and finger weakness
- > horners
- SVC syndrome
- > facial pleth
- > chest veins
- > widening mediastinum
- pleural effusion
Extrathoracic (mets)
- liver
- > al phos
- bone
- > pain
- > lytic lesions
- brain
- > headache, confusion, seizures etc
- adrenals
- > balot
Paraneoplastic (HAMCAN)
- fever
- anorexia
- fatigue, weakness
- weight loss
- nausea/vomitting
lung cancer complications of spread
Local spread:
- pleura
- > effusion
- chest wall
- > compression of intercostal nerves (neuropathic pain)
- brachial plexus (C8, T1,2)
- > pain in dermatomes and hand weakness
- pancoast syndrome
- > brachial plexus + inferior cervical ganglion/sympathetic chain
- SVC invasion
- > SVC syndrome
- recurrent laryngeal
- > hoarseness
Regional mets (lymphatic)
- hilar, mediastinal, supraclavicular nodes
- > oesophagus compression (dysphagia)
Distant mets (haematogenous)
- liver
- bone
- > pain
- > fractures
- > radiculopathy
- brain
- > seizures, confusion, headache
- adrenals
- > rarely symptomatic
small cell staging
Small cell
- limited
- > confined to ipsilateral hemithorax
- > disease within single radiation port
- extensive
- > bilateral involvement
- > mets
- > malignant effusion (can’t be encompassed within one port)
non small cell staging
Stage 1
-focal tumour
Stage II
- local spread
- > parietal pleura
- > chest wall
- > up to 2cm from carina
- nodes
- > hilar
- > mediastinum
Stage 3
- local spread with lymph nodes (hilar/mediastinal)
- local spread
- > great vessels
- > mediastinum
- > oesophagus
- > trachea
- nodes
- > contralateral
- > ipsilateral supraclavicular
Stage 4
-distant mets
bronchoscopy for lung cancer
flexible versus rigid
- flexible
- > conscious sedation
- > can visualise tertiary bronchi
- > diagnostic and therapeutic options
- rigid
- > larger
- > can only access proximal airways
- > requires general anaesthesia
- > used for interventions not available with flexible
flexible, conventional white light
- endobronchial brushing, washing or lavage
- > cytology
- > obvious lesions in airway
- transbronchial biopsy with forceps
- > peripheral, parenchyma lesions
- > not directly visualised
- > typically image guided (fluoscopy or ultrasound)
- > histology
- transbronchial needle aspirate
- > lesions and lymph nodes close to airways
- > guided by CT images in conventional
endobronchial ultrasound
- flexible bronchoscopy with hybrid scope
- > ultrasound probe attached
- real time ultrasound guidance
- > visualise anatomy
- > localise lymph nodes and peripheral lesions
- endobronchial needle aspirate or biopsy
- > cytology with aspirate
complications
- common
- > hypotension and hypoxia from sedation
- > bleeding
- > pneumothorax
- > nasal/throat pain
- > haemoptysis
- rarer but serious
- > broncho/laryngospasm
- > infection
- > cardiac arrthymias
lung cancer investigations
FBC -anaemia -leuko/thrombocytosis EUC -hyponatraemia -hypokalaemia (cushing/ACTH) CMP -hypercalcaemia LFTs -al phos Coags
CXR
-nodules, effusion, atelectasis, mediastinal mass
CT chest, neck, upper abdo with contrast
-tumour spread
-poor sensitivity for mediastinal staging
PET CT
-adjunct to CT (combination improves staging accuracy)
-more accurate evaluation of mediastinum and extrathoracic disease
-sometimes detects occult mets
-can guide biopsy
-not required if mets is already confirmed
Confirm diagnosis
- sputum cytology
- > high specificity, low sensitivity
- bronchoscopy
- > transbronchial needle aspirate most common
- > conventional or EBUS
- transthoracic needle aspiration
- > peripheral lesions unaccessible by bronchoscopy
- other lymph nodes
- > supraclavicular or neck
- thoracocentesis
- > if pleural effusion
- > presence of malignant cells
Pretreatment
- ECG
- pulmonary function tests
- staging scan (eg. MRI brain)
- genes (primary or metastatic lesion)
- > EGFR
- > ALK
- > ROS1
tumour genes lung cancer
epidermal growth factor receptor (EGFR)
- encoded by tyrosine kinase gene
- mainly adenocarcinoma
- never smokers
- detected by PCR
- benefit from EGFR kinase inhibitor therapy over chemo
anaplastic lymphoma kinase (ALK)
- rearrangements in gene
- adenocarcinoma in young non smokers
- detected by FISH
- benefit from ALK inhibitor therapy over chemo
ROS1
- receptor tyrosine kinase
- driver oncogene
- young, never smokers or light smokers
- adenocarcinoma
treatment workup lung cancer
division between surgical resection and inoperable (chemo/radiation)
- anatomic staging
- physiologic staging
- > patient’s ability to withstand treatment
- principally for NSCLC
- > small cell assumed to be systemic at time of diagnosis
anatomic staging
- inoperable
- > any criteria of stage 3 or 4
- > malignant pleural effusion
- > tamponade
- > within 2cm carina
- > phrenic and laryngeal nerve involvement
physiologic staging
- screen for comorbidities
- > basic bloods, ECG etc
- pulmonary function tests (COPD common)
- > FEV1 >2L or 80% predicted = pneumonectomy
- > FEV1 >1.5L = lobectomy
- cardiopulmonary exercise testing
- > for borderline lung function
- > maximal O2 consumption <15mL/kg = high post op complication risk
- secondary surgical options
- > wedge or anatomic segmental resection
- > higher rate of recurrence
- MI
- > within past 3 months = contraindication to thoracic surgery
- other major contraindications
- > uncontrolled arrhythmias
- > FEV1 <1L
- > PCO2 >45
- > DLco<40%
- > severe PHTN
treatment options lung cancer
NSCLC
- Stage 1A
- > surgery alone
- Stage 1B
- > surgery + adjuvant chemo
- Stage II or III with hilar or mediastinum nodes only
- > surgery + adjuvant chemo
- supraclavicular or contralateral nodes
- > no surgery
- > chemoradiation
- Stage 4
- > systemic therapy (chemo, immunotherapy)
- > pain management
- > radiotherapy
SCLC
- limited
- > surgically resection not usually recommended
- > can be performed with adjuvant chemo
- extensive
- > combined chemo + radiation preferable
- > alternate chemo/radiation if intolerable
DCIS and infiltrating ductal pathology
DCIS:
- presumably malignant lesion with no evidence of invasion
- comedo
- > large necrotic core
- > lots of calcification
- > degree of comedo necrosis correlates with prognosis
- cribiform
- > back to back glands without stroma in between
- micropapillary
- > tufts of cells without fibrovascular core
- papillarly
- > intraluminal projections
- > contains fibrovascular core
- solid
- > fill and distend involved spaces
- > no papillation or necrosis
INFILTRATING:
- macro
- > grey
- > gritty
- > invade in haphazard manner, creating stellate appearance
- micro
- > cords/nests of tumour cells
- > varying amounts of gland formation
- > induce fibrous change in parenchyma
grading infiltrating ductal carcinoma
divided into three grades (architecture and cytology)
-grade 1
->well differentiated
->infiltrate stroma as solid nests of glands
->uniform nuclei
-grade 2
->moderately differentiated
->infiltrate as solid nests with some glandular formation
->nuclear pleomorphism
->moderate mitotic rate
grade 3
->poorly differentiated
->solid nests of neoplastic cells with not gland formation
->marked nucelar atypia
->high mitotic rate
pathogenesis/phys breast cancer
OVERALL
arises from complex interactions of susceptibility genes and driver mutations resulting in uncontrolled expression of endogenous growth factors and signalling pathways
GENES
Familial/germline
- approx 10% are due to identifiable genes
- notable genes
- > BRCA1/2 (tumour suppressor/ DNA repair)
- > p53 (Li Fraumini syndrome)
- > PTEN (Cowen syndrome)
- BRCA1
- > approx 3/4 develop breast cancer
- > approx 1/3 develop ovarian cancer
- > almost always triple negative
- BRCA2
- > more likely to be ER positive
Sporardic
- thought to be due to risk factors
- > eg. estrogen exposure
- p53
- > occurs in 40% of breast cancer
- acquired mutations in PTEN
- > in 10%
HORMONES
Genetic/epigenetic changes (driver mutations)
- over express ER
- > gene is ESR1
- > 80% of all breast cancer
- amplification of erbB2
- > codes for HER2
- > 25% of breast cancer
OUTCOMES
final common pathway
- DCIS -> invasive cancer
- incompletely understood
- > majority of genetic/hormonal alterations already in place
- > may relate to similar remodelling events as occurs in pregnancy
pathways
- BRCA2 (luminal)
- > ER, HER2 positive
- > flat epithelial atypia -> atypical ductal hyperplasia -> DCIS
- HER2 positive (HER2 enriched)
- > either ER positive/negative
- > atypical apocrine adenosis -> DCIS
- BRCA1 (Basal)
- > triple negative
- > precursor lesion to DCIS not yet described
- > usually have p53 mutation
genetic testing breast cancer
availability
- funded by medicare if >10% chance of finding mutation
- strong hx
- > multiple relatives with breast/ovarian
- > younger age at diagnosis
- > bilateral breast
- > ashkenazi jew
options
- mutation search
- > in affected individual
- > determine if BRCA1/2 is present
- predictive test
- > in family member of affect individual
- > determine whether they have family mutation
- founder mutation testing
- > offered to populations with high rates
outcome
- surgery almost completely reduces risk
- > risk reducing salpingo-oopherectomy
- > risk reducing mastectomy
- increased life expectancy
- > chance of being alive by 70 goes from 50% to 80%
- alternative
- > surveillance
- > tamoxifen/raloxifen
imaging breast cancer
mammography
- high sensitivity and specificity
- > detects cancer years before it becomes clinically evident
- suspicious findings
- > spiculated focal mass
- > dense mass
- > clustered or linear branching microcalcifications
ultrasound
- utility
- > combined increased sensitivity and specificity
- > better sensitivity than mam in younger patients
- > differentiate cystic (benign), solid and complex masses
- > characterise lesion found on exam but not mammography
- > involvement of axilla and breast nodes
MRI
- highest sensitivity but poor specificity
- > hasnt been shown to improve outcomes
biopsy breast cancer
core needle biopsy
- prefered
- > still minimally invasive
- > differentiates pre-invasive and invasive
- > inadequate sampling less likely
- > assessment of receptor status
- image guided
- > ultrasound
- > stereotactic (xray)
- > tomosynthesis (3-D xray reconstruction)
- > MRI
fine needle aspirate -sensitivity >98% -specificity ->97% -utility ->rapid diagnosis of malignancy -negatives ->cannot distinguish between invasive/non-invasive ->higher false neg ->higher inadequate sampling ->often can't be used for receptor status
surgical biopsy
- not first line
- > performed when FNA or CNB impossible
- can be excisional/incisional
punch biopsy
-rarely used
sentinel lymph node biopsy
SLNB versus ALND
- SLNB
- > when clinically negative nodes
- ALND
- > palpable nodes
- > suspicious nodes on US
- > advanced disease
SLNB technique
- hypothesis
- > metastatic tumour spreads to one or a few lymph nodes before involving others
- > potentially avoid morbidity of ALND
- surgical levels
- > level 1 below pec minor
- > level 2 behind pec minor
- > level 3 medial and above pec minor
- inject tracer near tumour or into areolar plexus
- > blue dye
- > radioactive colloid
- identify sentinel nodes
- > after approx 5 mins
- > incision in axilla
- > identify bluest nodes or gamma probe
- > excise sentinel nodes
MORBIDITY ALND
- infection
- haematoma
- seroma
- arm lymphoedema
- > radical mastectomy
- > radiation therapy
- > ALND
- nerve injury
- > eg long thoracic = winging
- > rare
indicators of breast cancer prognosis
imaging
-detected by screening mam = better than clinical
path
- advanced stage = poor
- higher grade = poor
- lymphovascular invasion = poor
morphology
->ILC initially less recurrence than IDC, then more after 6 years
tissue marker
- ER/PR positive = good
- HER2 positive = bad
genomic profile
- luminal
- > luminal A = best prognosis of all
- 21 gene recurrence score
- > RT PCR
- > evaluates expression of 21 genes within tumour
- > provides risk score
- > useful in determining benefit of adjuvant chemo
breast cancer treatment
early disease and locally advanced
- breast conserving lumpectomy + radiation
- mastectomy
- lymph nodes
- > SLNB if clinically negative
- > ALND if mets present or positive exam
- consider
- > chemo
- > biology therapy
- > endocrine therapy
- neoadjuvant chemo for locally advanced
mets
- symptomatic relief is priority
- anti-oestrogen
- > tamoxifen
- radiotherapy
- > bone pain
- > prevent fractures
- surgery
- > focal control
risk factors laryngeal cancer
non modifiable
- age >40
- male
- black
- family history
- vocal cord dysplasia
modifiable
- smoking
- alcohol
- acid
- > GORD
- > achlohydria in gastrectomy
- radiation
- HPV
investigations laryngeal cancer
neck CT with contrast
->useful for evaluating lymph node mets
chest CT with contrast
- > lymphadenopathy
- > nodules not detected by xray
FNA neck mass
- > histology may reveal squamous cell
- > negative does not rule out diagnosis
flexible laryngoscopy
- > visualise lesion
- > assess airway patency
consider:
- rigid videostroboscopy
- > evaluate vocal cord movement
- > submucosal lesion
- rigid bronchoscopy
- > biopsy
- whole body CT PET
laryngeal cancer routes of spread
nodes of head and neck common
- waldeyes ring
- level 1
- > submandibular
- level 2-4
- > from angle of jaw to neck
- > understernoclidomastoid
- level 5
- > posterior triangle
- level 6
- > paramedia (tracheal and thyroid) area
haematogenous
- bone
- liver
- lung
pituitary mass ddx
Neoplasia
benign
- pituitary adenoma + CMP
- craniopharyngioma
- meningioma
- pituicytoma
malignant (primary = Good Luck Curing) -germ cell -lymphoma -chordoma (metastatic) -breast -lung
Hyperplasia
-eg. gonadotroph in congential hypogonadism
Cysts (RAD)
- rathke’s cleft
- arachnoid
- dermoid
Abscess
AV fistula
risk factors seminoma
- cryptorchidism
- personal history
- family history
- cannabis
- infection (mumps and HIV)/trauma
staging seminoma
Stage 1
- no evidence of metastatic spread on chest/abdo/pelvis imaging
- if pre-orchiectomy hCG levels elevated, decline post surgery
- can be locally invasive through albuginea, with or without lymphovascular invasion
Stage 2
- abdo node involvement
- stratified further by size
Stage 3
-distant (non-retroperitoneal) mets
seminoma routes of spread
Lymphatic
- initial route
- retroperitoneal nodes
- left sided –> left para-aortic nodes inferior to left renal vessel
- right sided –> aortocaval nodes inferior to right renal vessels
- inguinal if scrotal violation has occured
- later = retrocrural, mediastinal and suprclavicular
Haematogenous
- lung most common
- liver, brain and bone
testicular cancer types
Germ cell (TESTY) = 95%
- teratoma/carcinoma
- embryonal carcinoma
- seminoma
- trophoblastic (choriocarcinoma)
- yolk sac
Sex chord stromal
- leydig
- sertoli
- granulosa
Gonadoblastoma (mixed seminoma with sertoli)
Paratesticular
- mesothelial
- epithelial
Non-hodgkins lymphoma
urothelial carcinoma risk factors
Smoking Occupational -paints, metals, hair dyes, leather work, cement Water -low intake -chlorine -arsenic Chronic cystitis HPV infection Upper UT urothelial cancer Iatrogenic -radiation Drugs -cyclophosphamide -phenacitin -thiazelidediones Family Hx
prostate cancer treatment options
Varies by risk category
Observation
-monitoring course of disease with aim to provide palliative treatment when signs or symptoms arise
Active surveillance
- PSA 6-12 monthly
- DRE 6/12 monthly
- biopsy >12 monthly
- treat with curative intent when detected
External beam radiotherapy
- focused radiation
- every day for 2 months
- 20% risk bowel dysfunction
- 70% risk erectile dysfuntion
Brachytherapy
-transperineal implantation of radioactive sources into prostate without incision
Radical prostatectomy
- when localised to prostate
- lymph nodes can be resected
- reduces recurrence but does not improve mortality
- 70% risk erectile dysfunction
ADT
- LHRH agonist or antagonist plus NSAID initially
- bilateral orchiectomy
- mainly for metastatic disease
- 70% erectile dysfunction
cervical cancer ddx
AEEIoU
-adenosis (columnar surrounding fibromuscular)
-ectropian
-endometriosis
-infection (herpes, syphilis, STI)
other
-ulcerative (nabothian, leiomyoma, polyp)
Abnormal uterine bleeding FIGO (POLICEMAN)
- polyps (uterine/cervical)
- ovulatory dysfunction
- leiomyoma
- iatrogenic (drugs, contraceptive device)
- coagulopathy (vWD)
- endometrial dysfunction
- malignancy (cervical, leiomyosarcoma, endometrial carcinoma
- adenomyosis
- not otherwise classified
Vaginal/Vulva bleeding BAIT
- benign (polyp)
- atrophy
- infection
- trauma (sex, foreign body, pelvic)
investigations urothelial carcinoma
Urinalysis
Urine cytology
FBC
EUC
LFTs
-alphos
CT contrast/non con -locally invasive -nodes MRI with gadolinium -same or more sensitive as CT IVP -largely replaced by CT
Flexible cystoscopy
- narrow band imaging
- fluroscene staining
Consider
- urinary markers
- CXR/ chest CT
- Pelvis CT
staging urothelial carcinoma
T
- Ta = papillary (restricted to urothelium)
- Tis = carcinoma in situ (usually flat, restricted by basement membrane)
- T1 = through BM, not into MP
- T2 = into MP
- T3 = through MP (adventitia/perivesicle fat)
- T4 = invasion into prostate, vagina, uterus or bowel; invasion into pelvic/abdo wall
N
- N1 = single lymph node in pelvis
- N2 = multiple lymph nodes in pelvis
- N3 = involvement of common iliac nodes
M
- Nodes beyond common iliac
- distant mets
Stage 1 -T1 Stage 2 -T2 Stage 3 -T3/4 -Any T with any N Stage 4 -any M -T4b with any N
Urothelial carcinoma complications
Local spread
- irritative voiding symptoms (urgency, frequency etc)
- obstructive voiding symptoms (straining, incomplete voiding)
- retention (clot formation or outlet obstruction)
- hydronephrosis (tumour of the trigone and ureteral orifice)
Lymphatic spread
-iliace nodes –> para-aortic
Haematogenous
-bone, brain, liver, lung
Prostatic urothelial carcinoma
-up to 25%
Upper UT urothelial carcinoma (ureter/pelvis)
- up to 25%
- high mortality
staging prostate cancer
Stage 1 -T1 (not palpable)/T2 (confined to prostate) -and PSA <10 -and GG 1 Stage 2 -combinations of T1/2 with PSA >10<20 and GG 1-4 Stage 3 -T3/4 -PSA >20 -GG 5 Stage 4 -N1 -M1
seminoma extra-testicular manifestations
Gynecomastia
-production of hCG by foci of choriocarcinoma or trophoblastic cells
Hyperthyroidism
-alpha and beta subunit homology between TSH and hCG
Paraneoplastic limbic encephalitis
-mood/behavioural changes
-short term memory problems and cognitive difficulty
-focal seizures (impaired awareness)
-hypothalamic = hyperthermia, somnolence, endocrine
-anti-Ma2 antibodies (selectively expressed in neuronal nucleoli and tumour cells)
paraneoplastic syndrome RCC
CATFACES
- cachexia
- anaemia (chronic disease)
- thrombocytosis
- fever (night sweats, weight loss)
- amyloidosis (secondary, inflammation)
- calcium (hypercalcaemia: lytic mets, bone turnover prostaglandins, PTHrP)
- erythrocytosis (EPO)
- Stauffer syndrome (IL-6, GM-CSF)
staging RCC
T1
- limited to kidney
- <7cm
T2
- limited to kidney
- > 7cm
T3
- into perinephric tissue
- limited by Gerota’s fascia
- a = renal vein
- b= vena cava below diaphragm
- c = vena cava above diaphragm
Nodes
-N1 or N0
Mets
- M1 or M0
- multiple lymph nodes, adjacent organs, distant
Stage 1 -T1, N0, M0 Stage 2 -T2, N0, M0 Stage 3 -T3, N0/1, M0 -T1/2, N1, M0 Stage 4 -M1
investigations seminoma
Urinalysis
Urine culture/PCR?
FBC beta HCG -20% seminomas -all choriocarcinoma AFP -no pure seminomas or choriocarcinoma -elevated in rest LDH -prognostic/staging Placental al phos -advanced disease LFTs -mets -GGT raised in seminoma
Ultrasound
- extrinsic vs intrinsic
- pure seminoma = non cystic/fluid filled (NSGCT’s may be hetergeneous and cystic)
- microcalcification (common but non-specific)
- cannot determine spread through albuginea
CT abdo/pelvis
- retroperitoneal node involvment
- high false negative
CXR
-lung mets
CT chest
-if CXR shows lesion or nodes on abdo CT
PET CT
-controversial utility
Radical inguinal orchiectomy
-histologic evaluation and local control
Consider
- retroperitoneal lymph node dissection for subset of NSGCT identified after orchiectomy
- contralateral biopsy (controversial) due to rate of testicular germ cell tumour in situ
gleeson scoring
- based solely on architectural features
- correlates closely with clinical behaviour
- based on growth pattern and degree of differentiation, scored 1-5 with worse being 5
- 2 most common scores are reported and summed (tertiary score for group 3 when <5% are higher grade)
gleason group (risk of recurrence and mortality increases)
- Group 1 = 6 or less
- Group 2 = 7 (3+4)
- Group 3 = 7 (4+3)
- Group 4 = 8
- Group 5 = 9 or 10
investigations RCC
urinalysis -haematuria -leuks/nitrites -WCC urine culture
FBC -anaemai/erythrocytosis -thrombocytosis (Stauffer) Iron studies EUC -GFR -electrolytes -contrast CMP -hypercalcaemia LFTs -mets -stauffer Coags -PT in stauffer LDH -prognostic marker
CT abdo
-coticomedullary/nephrogenic/delayed/non con
MRI abdo
Ultrasound (can be initial to exclude cysts)
consider
- chest/pelvic CT (mets)
- MRI brain (mets)
- bone scan (bone pain/al phos)
- core biopsy
investigations prostate cancer
Urinalysis
PSA FBC -anaemia -baseline for ADT EUC -UTO -baseline for ADT CMP -hypocalcaemia LFT -baseline for ADT (risk of hepatitis) -al phos in mets Testosterone -baseline for ADT
Bone scan with T99 -symptomatic -supplemented with plain xray Pelvic CT/MRI -lymph nodes MRI spine -with and without contrast -ESCC/LSS
Needle Biopsy
- ultrasound guided
- at least 12 biopsies (equal each side)
ovarian cancer ddx
adnexal mass in menopause (LAUNCH)
- leiomyoma
- abscess (tubo-ovarian, abdomino-pelvic)
- urinary tract (eg. bladder diverticulitis)
- neoplasia (ovarian most common primary; mets from endometrium, breast, GI)
- cysts (ovarian)
- hydrosalpinx
uterine bleeding (CRAP Ovaries)
- other (bladder cancer, urethritis, diverticulitis etc)
- coagulopathy (vWD)
- replacement therapy
- atrophy
- polyps
ddx of brain mass
Primary brain tumour:
- low grade glioma (no uptake)
- high grade glioma (heterogeneous uptake)
- meningioma (homogeneous uptake)
- primary CNS lymphoma (homogeneous)
Metastatic tumour (homogenous):
- breast
- lung
- melanoma
Vascular: infarct -cortical emboli -venous thrombus (bleeding, oedema) haemorrhage (subacute intraparenchymal) anamoly -cavernous malformation -AV malformation -posterior reversible leukoencephalopathy syndrome
Infection:
- granuloma
- progressive multifocal leukoencephalopathy (JC virus)
- abscess
Inflammatory:
- demyelination (MS)
- autoimmune encephalitis (para/non neoplastic)
PSA screening benefits and harms
Benefits
- to accurately detect cancer in early stage so that treatment can be given to reduce morbidity and mortality
- PSA testing is associated with greater detection of cancer
- PSA testing reduces rate of detection of metastatic disease
- Inconsistent evidence as to whether this reduces mortality (slow growing, most almost 3/4 men over 75% die with it rather than from it)
- Inconsistent evidence as to whether early detection improves or reduces quality of life
Harms
- over-diagnosis by PSA approx 20-40%
- no way of knowing which are require treatment, so all much receive investigations
- investigations = anxiety, inconvenience, adverse outcomes (biopsy = 2% infection, pain, bleeding etc)
- false positive
- urinary incontinence = 15% radical prostatectomy
- erectile dysfunction = 70% radical prostatectomy/radiotherapy/androgen deprivation
- bowel problems = 20% external beam radiation
prostate cancer epidemiology and risk factors
Epidemiology
- prostate cancer second most common cancer in aus men
- prostate cancer second most common cause of cancer death in aus men
Risk factors
- family hx
- first degree relative = 2x incidence
- higher = multiple members, younger diagnosis, BRAC1/2
- overweight and obesity
- first degree relative = 2-3 x mortality rate
- higher = multiple family members, died from prostate cancer
PSA screening recommendation
Recommendation
-shared decision making as cannot offer definitive recommendation
-men >50 with average risk and knowledge of risk/benefits who want to be screened should receive PSA every 2 years til 69
-men <50 concerned about risks, offer PSA every 2 years until 69
(if initial <75th % for age, cease till 50)
(if initial <95 but >75 % keep screening)
(if initial >95%, repeat etc.)
-men >70 advise risks likely greater than benefits
-life expectancy <7 years precludes screening
-if base rate risk higher, start 40/45 and follow above algorithm
PSA ranges and elevation causes
Normal ranges
- 40’s = 2.5ng/mL
- add 1ng/mL for every decade after
Causes elevated PSA
- cancer
- BPH
- prostatitis
- trauma (investigations, DRE, sexual activity)
PSA algorithm
IF 2-3ng/mL
- repeat in 1-3 months with free:total
- if now 5.5, offer biopsy
- if not 5.5 but free:total <25%, offer biopsy
Types of breast cancer
Non-invasive
- DCIS
- LCIS
- > rare
Invasive
- infiltrating ductal carcinoma
- > accounts for approx 3/4 invasive disease
- infiltrating lobular
- > approx 15%
- > incidence is increasing with HRT
- > occurs in older women
- > better differentiated
- > estrogen receptor positive
- > more commonly bilaterally
- > appear to have better prognosis
- > metastasis later (to meninges and peritoneum)
other
- mucinous
- tubular
- medullary
benign breast disease
non-proliferative (CAF)
- not associated with increased risk of breast cancer
- cysts
- > very common
- > 30-50 year olds
- apocrine change
- > apocrine differentiation of ductal cells after insult
- fibrosis
- > can occur with rupture of simple cyst
proliferative without atypia (I SURF)
- small increased risk 1.5-2 x
- Intraductal papilloma
- > array of papillary cells growing from cyst into lumen
- > can harbour DCIS
- Sclerosing adenosis
- > increased fibrosis tissue interspersed with glandular cells
- Usual ductal hyperplasia
- > increased cells within ductal space but normal cytology
- Radial scar
- > fibroelastic core with radiating ducts and lobules
- Fibroadenoma
- > most common
- > well defined, mobile mass on exam
- > benign solid tumour with fibrosis and glandular tissue
atypical hyperplasia
- increased risk of breast cancer (3.5-5.5x)
- some but not all features of DCIS/LCIS
- > atypical ductal hyperplasia
- > atypical lobular hyperplasia
risk factors breast cancer
personal hx family hx genetic FACEBARS -female -age -caucasian -estrogen exposure ->menarche/menopause ->nulliparity ->pill -benign breast disease ->proliferative without atypia ->atypical hyperplasia -alcohol -radiation -socioeconomic status (high)
hx and exam breast cancer
hx:
- risk factors
- mass
- > onset
- > evolution
- > relation to menstrual cycle
- skin
- > erythema
- > dimpling
- nipple
- > asymmetry
- > inversion
- > unilateral, bloody, serous, discharge
- pain
- trauma to breast
- mets
- > SOB, cough etc
- > bone pain
- > nausea, vom, anorexia
exam: -breast ->fixed, firm, irregular borders ->asymmetry skin ->peu d'orange ->erythema ->thickening -nipple ->asymmetry ->inversion -lymph nodes ->axillary ->supra/infra clavicular ->cervical -mets ->effusion ->boney tenderness ->jaundice
breast mass ddx
Breast cancer ..... CALMING Feel -cyst -abscess -lipoma -mastitis -ISURF (proliferative without atypia) -necrosis (fat) -galactocele -fibroadenoma
investigations breast cancer
FBC CMP -calcium LFTs -al phos
imaging
- mammography
- ultrasound
- consider MRI
- > in high risk
- > eg BRCA1/2 mutations
biopsy
- CNB preferred
- FNA
pre-treatment
- ER and RR
- > immunohistochemistry
- > positive if >1% positive tumour nuclei
- HER2
- > positive if 3+ on immunohistochemistry
- > confirm with FISH (amplification of erbB2)
with mets
- CXR
- > effusion
- CT staging scan (chest abdo)
- bone scan
- MRI spine
- > if neuro symptoms
- consider
- > PET scan
- > CEA
triple assessment breast cancer
three components
- hx and breast exam
- imaging
- > mammography
- > ultrasound
- biopys
- > CNB
- > FNA
performed in sequence
-allows accurate interpretation of result
outcome
- positive if any component is suspicious/malignant/indeterminate
- sensitivity
- > greatest when combined
- positive
- > 99% sensitive
- > further investigations
- > refer to surgeon
- negative
- > false negative= <1%
- > safe to cease investigations
