Lung cancer Flashcards
Risk factors
main smoking - many carcinogens, if smoke cells will be exposed
radon
asbestos
mutational compensation
all cells have a tendency to become immortal
p53 gene prevents this by apoptosis
smoking stops this - process is unchecked in smoker
have genetic tendency too - oncogenes too.
smoking and prevalence of lung cancer
the curves of prevalence of cancer and smoking are out of phase by 10 years but match up
there is a significant risk of cancer in passive smokers, dose dependant effect of the number of cigarettes smoked
there is a commulative risk of smoking - still risk increases if continue smoking at age 60 - always worth stopping
Symptoms
haemoptysis - cough up blood symptoms that are unexplained that last >3 wks: cough shoulder/chest pain dyspnoea hoarseness finger clubbing - angle between nail and nail bed more obtuse, nail bed more boggy weight loss lethargy declining appetite
features seen on examination with lung cancer
clubbing of fingers
nicotine staining
cachexia - loss of appetite and weight
diminished air entry into R base
survival according to stage
related to suitability for surgery
considered in stage 1, 2 and 3a
need to detect early
5% overall risk and 10% major complications
prognosis
80% die in a year
5yr survical/cure rate <6%
where does lung cancer arise
large airway
terminal airway
alveoli
causes of lung cancer
smoking - 75% attributable - 25% attributed to passive smoking; tumour initiators, promoters and complete carninogens - polycyclic aromatic hydrocarbons, phenols, Nickle and arsenic
asbestos
radiation - radon exposure and therapeutics
genetic predisposition - rare
heavy metals - chromates, arsenic nickle
molecular abnormality
risks multiplicative
Development of carcinoma
multistep accumulation of mutations cause:
metastasis
disordered growth
loss of cell adhesion
invasion of tissue by tumour
stimulation of new vessel formation around tumours
mutations in epi cells and stem cells
pathways diff for diff tumour types - molecular therapies
early stages can be reversible
reflected in histology of tumours
benign lung tumours
don’t metastasise
local complications
chondroma - airway obstruction
malignant lung tumours
potential to met variable clinical behaviour commonest epithelial - carcinoma non-epi - sarcoma and lymphoma non-small cell 80% small cell 20% `
non-small cell carcinoma
squamous - 20-40%
adenocarcinoma 20-40%
large cell carcinoma - uncommon
small cell carcinoma
advance
aggressive
small survival
poor prognosis
presentation with lung cancer
asymptomatic symptoms vague: cough haemoptysis recurrent infection weight loss/malaise
local effects
bronchial obstruction - collapse of distal lung = shortness of breath or impaired drainage of bronchus - chest infection = pneumonia/abscess
invasion local structures - airways and vessels = haemoptysis and cough, large vessel = SVC syndrome - venous congestion of head arm oedema and upper circ collapse, oesophagus = dusphagia, chest wall = pain, nerves = horners syndrome
inflame/irritation/invasion of pleura/pericardium - pleuritus or pericarditis with effusion = breathlessness, cardiac compromise, fluid needs to be drained
systemic effects of bronchogenic carcinoma
don't present with primary cancer fits - brain met lumps on skin - stained to show primary lung liver pain/deranged LFTs - liver met bone pain/fracture - bones paraneoplastic syndromes
change in classification of tumour
used to be small lung cancer/non-lung small cancer
now more sub groups
immunotype the tumour
see if squamous cell carcinoma
adenocarcinoma
adenosquamos carcinoma
molecular phenotype - have different phenotypes
molecular phenotype of cancers
look at molecular fingertype
PDL-1 - death ligand - if >50% then the patients are suitable for immunotherapy
adenocarcinoma - tumour of EGFR gene for tyrosine kinase, ALK gene, ROS -1, kRAS - can give targeted treatment if mutations in these are present (crizotinib for AlK gene mutation)
Treatment
small cell cancer - rapidly dividing - chemo
non-small cell lung cancer - slow - cut out and can use chemo/radio after surgery
non-metastatic manifestations of lung cancer - eg wrist pain from tumour or increased Ca causing swelling - chemo/immunotherapy
death from malignant change of different types of cancer
squamous - 9.6
adenocarcinoma - 17.6
undifferentiated - 9.4
small cell - 3.2
squamous cell carcinoma development
squamous epithelium
not normally in lung
cilia irritated by carcinogens - metaplasia to squamous
more resistant to smoke
cant remove debris
chronic cough
dysplasia - disordered growth and differentiation
carcinoma in situ
mutation produce enzymes and MMP so invade stroma
metastasise
molecular and genetic changes in development of squamous cell carcinoma
3pLOH microsatellite alterations Myc overexpression and telomerase dysregulation neoangiogenesis gene methylation P16ink4 K-ras mutation
location of squamous cell carcinoma
previously in central airway
now smoke breathed more deeply
in lower airways SqCC - peripheral
squamnous cell carcinoma
25-40% pul carcinoma
smoking
local spread
met late
adenocarcinoma development
glamndular epi
periphery - around terminal airways and interstitium
precurser is atypical adenomatous hyperplasia - prolif in atypical cells lining alveolar walls - <5mm in size
become invasive or become fibrous scar
from adenocarcinoma in situ to mixe2d pattern adenoCa - need invasive phenotype
in situ
round
can remove
not in interstitium
mutations in adenoCa
mutually exclusive
precursor type 2 pneumocyte/club cell
smoker - K ras mutation, DNA methylation, p53
non-smoker - EGFR mutation/amplification, ALK, ROS
histology of adenocarcinoma
increasing incidence - 25-40% pul carcinomas
common in far east, females, non-smokers
peripheral
multicentriuc
extrathoracic met - common and early
glandular diff- capillaries produce mucin
multipke legions at different stages
large nuclei and mucin vacuoles in cytologyu
large cell carcinoma
poorly diff tumour
large cell
no histological evidence of glandular/squamous differentiation
electron microscopy = glandular/squamous/neuroendocrine diff
poor prognosis
histology of small cell carcinoma
20-25% central - near bronchi smoking 80% present with advanced disease chemosensitive abysmal prognosis - high and quick recurrence 18months with treatment 2months without paraneoplastic syndromes outgrow blood supply - necrotic
treatment of small cell lung cancer
chemoradiotherapy
surgery rare - already met
mon-small lung cancer prognosis and treatment
early stage 1 - 60% 5yr survival late stage 4- 5% year survival 20-30% have early stage tumours for surgical resection less chemoreceptive diagnosis - late in disease
treatment of squamous cell carcinoma
fatal haemorrhage from anti-angiogenic therapy Bevacizumab
give chemotherapeutic agent
treatment of adenoCa
some chemo works better in adenoCa- pemetrexed
molecular abnormalities provide targets only in adenoCa - ALK, ROS, EGFR, ret mutations
evolution of targeted therapy
non-small lung cancer - 1 disease
histology based subtyping: squamous and adenoCa
subdivided by mutations
adenoCa - main use of molecular therapy
EGFR
membrane receptor tyrosine kinase regulates: angiogenesis prolif apoptosis cellular migration
EGFR in NSCLC
always on from mutation = unregulated growth
non-smoker
female
asian
an inhibitor can act anywhere along the pathway
inhibitor = prolongued survival compared to chemo
ALK +ve adenoCa
gene rearrange protein test FISH show translocation male young non-smoker large response to treatment in 6months
basis behind immunomodulatory therapy
tumour express new antigens
PD-L1 from tumour interact with PD1
evade the immune system
inhibit cytotoxic T cell attacking tumour
immunomodulatory therapy
inhibit PDL1
dramatic response
immune system attack tumour
role of histopathologist
confirm diagnosis
determine histopathological type
determine stage - pleural involvement, lymph node involvement
molecular pathology
confirming the diagnosis
look at sputum
bronchial wash and blush
pleural fluid
endoscopic fine needle aspiration of tumour/nodes
next steps if adenoCa
molecular testing
next steps if adenoCa/squamoCa
PDL1 testing for immunotherapy
Bronchoscopy
camera down the airways
lung cancer = a lot of mucous secretion so can see mucous artefacts
use forceps to take biopsy of tumour so can see what pathology is
CT
when have cough for >4/6wks
screen people >55 who are heavy smoking - reduce their death by 25%
when there is spread to lymph nodes
look at the nodes
give staging and diagnosis at the same time
PET
only imaging give radiolabelled glucose taken up by highly active cells shouldn't be in lung additional specimen collection is required to confirm diagnosis
ultrasound
see gland in real time
needle in area - take sample
send sample to pathologist
stain with Ab
gives molecular fingerprint
Transthoracic CT biopsy
use scanner needle into lung tissue real time - quick sensitivity 70-100% 25-30% pneumothorax small sample size if bleed - no intrabronchial treatment possible
diagnostic strategy
non-specific symptoms chest xray - abnormal refer to respiratory pul func tests, CT scan of the thorax, exercise tests diagnosis and staging PET-CT, PFTS, MRI brain (cant use PET because always active) lung function see how fit discussed in MDT
biopsy
central tumour - bronchoscopy
peripheral -CT guided, through chest wall
surgical biopsy
mediastinal lymph node biopsy - staging
open biopsy during op - frozen section
resection specimen - confirm excision and staging
background of lung - predisposistion of cancer eg asbestos
look at size, if invaded pleura, subtype
how far from resection margin - ensure all removed
staging
TNM
tumour - size and where
node - lymph
metastasis
certain number for T but gets upstaged if touch chest wall, major vessels, heart, diaphragm
nodes - consider the contralateral lymph nodes - if nodes on the other side of the body, then the tumour has spread more
M - increased staging if spread to brain
how does staging affect treatment
how does staging affect treatment
staging - T
tumour T1-4 size invasion pleura invasion other structures
staging - N
lymph node met
N0-3
N0 - not invaded
N1-3 node involved by tumour
staging - M
distant met M0 or 1 in liver bone brain separate tumour nodule in different lobe of lung
what does staging do
give info on prognosis and operability
can be clinical, radiological or pathological
what is paraneoplastic syndrome
systemic effect of tumour
expression of hormones and other factors not normally expressed in tissue where tumour occurs
example of paraneoplastic syndrome
syndrome of inappropriate ADH = hyponatraemia in small cell cancer
expression of PTH in liver - high Ca
hematologic/coagulation defects
