pathology of pulmonary neoplasia Flashcards
aetiology of lung cancer
TOBACCO asbestos environmental radon occupational exposure - chromates, hydrocarbons, nickel air pollution and urban environment other radiation pulmonary fibrosis
what is the predominant cause of 1y lung cancer
tobacco smoke
tobacco smoke and asbestos combined have a multiplicative effect in causing lung cancer
what % of lung cancers are attributable to tobacco
85
what % of smokers get lung cancer
10
increases in risk of lung cancer in smokers
22x in males
12x in females
females may be more susceptible to carcinogenic effects of tobacco smoke
risk related to consumption (inhalation and pack years)
NO safe smoking threshold
passive smoking
50-1005 increased risk
causes at least 25% of “non-smoking” lung cancers
how does risk reduce with abstinence from smoking
risk reduces but slowly due to persisting genomic damage
in what areas of the lung do adenocarcinoma and squamous/SCLC occur
adenocarcinoma - peripheal
squamous/SCLC - central parts arising from large airways
how does tobacco smoke result in lung cancer
epithelial effects
multi-hit theory
host activation of pro-carcinogens
host activation of pro-carcinogens
inherited polymorphisms predispose metabolism of pro-carcinogens and nicotine addiction
pathway of carcinogenesis in the lung periphery
bronchioalveolar epithelial stem cells transform
adenocarcinoma
less strongly but still associated with smoking, does occur in non-smokers
pathway of carcinogenesis in the central lung airways
bronchial epithelial stem cells transform
squamous cell carcinoma
strongly associated with smoking
molecular biology of adenocarcinogenesis
oncogene addiction - key driver mutations
KRAS ~ 35% - smoking induces
EGFR ~15%, BRAF/HER2 ~1-2% each, ROS1 gene rearrangements ~1%, ALK rearrangements ~2% - not related to tobacco carcinogenesis
what molecular aspects can be targeted with therapy
EGFR mutation
BRAF mutation
ALK rearrangement
ROS1 rearrangement
squamous cell targets and therapy
very few suitable targets - very few addictive oncogenes
the most common alterations are inactivating mutations in tumour suppressor genes
types of tumours of the lung
benign causes of mass lesion carcinoid tumour tumours of bronchial glands lymphoma sarcoma mets to the lung - common
carcinoid tumour
<5% of lung neoplasms
low grade malignancy
bronchial gland tumours
very rare
adenoid cystic carcinoma
mucoepidermoid carcinoma
benign adenomas
cell types in lung carcinoma
squamous cell 40%
adenocarcinoma 41%
small cell carcinoma ( heavy tobacco consumption) 15%
large cell carcinoma 5%
primary lung cancer
clinically silent for yrs
presents late in natural hx
few if any signs or symptoms until advanced disease
may be found incidentally
symptomatic lung cancer is generally fatal
local effects of lung cancer
bronchial obstruction pleural direct invasion mediastinum - SVC, pericardium lymph node mets
bronchial obstruction
collapse
endogenous lipoid pneumonia - not infection but retention of things that would normally be cleared
infection/abscess
bronchiectasis
pleural involvement
inflammatory or malignant
can result in effusion
direct invasion
chest wall
nerves - phrenic, L recurrent laryngeal, brachial plexus, cervical sympathetic
what would phrenic nerve involvement result in
diaphragmatic paralysis
what would L recurrent laryngeal nerve involvement result in
Hoarse, bovine cough
L vocal cord paralysis
what would brachial plexus involvement result from
T1 damage by pancoast tumour
what would cervical sympathetic involvement result in
Horner’s syndrome
lymph node metastases (local)
mass effect
lymphangitis carcinomatosa
lung cancer distant effects
distant mets
2y to local effects - neural, vascular
non-metastatic paraneoplastic effects
where does lung cancer commonly metastasise to
liver adrenals bone brain skin
non-metastatic paraneoplastic effects of lung cancer
skeletal endocrine neurological cutaneous haematologic cardiovascular renal
skeletal non-metastatic paraneoplastic effects of lung cancer
finger clubbing
hypertrophic pulmonary oesteoarthropathy (HPOA) - pain in wrists, knees, ankles
investigations for lung cancer
CXR bronchoscopy trans-thoracic FNA trans-thoracic core biopsy pleural effusion cytology and biopsy advanced imagint techniques - CT, MRI, PET
endocrine non-metastatic paraneoplastic effects of lung cancer
ACTH, SIADH - SCLC
PTH - squamous
carcinoid syndrome
gynecomastia
neurological non-metastatic paraneoplastic effects of lung cancer
polyneuropathy
encephalopathy
cerebellar degeneration
Myasthenia (Eaton-Lambert)
cutaneous non-metastatic paraneoplastic effects of lung cancer
acanthosis nigricans
dermatomyositis
haematologic non-metastatic paraneoplastic effects of lung cancer
granulocytosis
eosinophilia
DIC
cardiovascular non-metastatic paraneoplastic effects of lung cancer
thrombophlebitis migrans
renal non-metastatic paraneoplastic effects of lung cancer
nephrotic syndrome
prognostic factors in lung cancer
stage of disease
classification of disease
ALSO: markers/oncogenes/gene expression profile growth rate cell proliferation DNA aneuploidy immune cell infiltration
what is the prognosis for lung cancer
Generally very bad
<9.8% 5YS in scotland
operable lung cancer: (10-12% of pts in Scotland)
stage I >60% 5YS
stage II 35% 5YS
overal correlation w/ stage
5YS for non-small cell carcinomas
10-25%
small cell carcinoma 5YS
4%
median survival 9mths
what are predictive biomarkers used for in lung cancer
selection fo patients for therapy
adenocarcinoma - EGFR, ALK and ROS1 translocations can be targeted
squamous cell - little or no effective molecular targeted therapy
immunotherapy in NSCLC has transformed practice
therapeutic targets in NSCLC immunotherapy
PD/PD-L1 axis immune checkpoint
persuades the immune system to switch back on
can be curative
immune checkpoints
control immune reactions
adopted by tumours to avoid immune destruction
PD1, PD-L1, CTLA4
