Pathology of Lung Cancer Flashcards
What is the most common cancer to cause death?
Lung cancer
What is the aetiology of lung cancer?
Tobacco
Asbestos
Environmental radon
Other occupational exposure (chromates, hydrocarbons, nickel)
Air pollution and urban environment
Other radiation
Pulmonary fibrosis
What chemicals can lead to lung cancer?
Chromates
Hydrocarbons
Nickel
Asbestos
What percentage of lung cancer is due to smoking?
85%
What percentage of smokers get lung cancer?
10%
How does smoking affect the risk of getting lung cancer in males and females?
Males are 22x more at risk and females are 12x more at risk
What is the risk of smoking and causing lung cancer proportionate to?
Packs per day per year
How does passive smoke increase the risk of lung cancer?
50-100% increased risk
What percentage of non-smoking lung cancers does passive smoke cause?
25%
What is passive smoking?
Involuntary inhaling of smoke from other people’s cigarettes
How does stopping smoking change your risk of getting lung cancer?
Risk slowly decreases
What does abstinence mean?
Practice of restraining oneself from indulging in something
What percentage of males and females in the UK smoke?
33%
What percantage of males and females in the world smoke?
50% of men
12% of woman
What does tobacco smoke do that leads to lung cancer?
Epithelial effects
Multi-hit theory of carcinogenesis
Host activation of pro-carcinogens
What are the 2 main pathways of carcinogenesis in the lung?
Squamous cell carcinoma in the central lung airways
Adenocarcinoma in the lung periphery
Where does squamous cell carcinoma occur?
Central lung airways
Where does adenocarcinoma occur?
Lung periphery
What happens during adenocarcinoma?
Bronchioloalveolar epithelial stem cells transform
What happens during squamous cell carcinoma?
Bronchial epithelial stem cells transform
What is a squamous dysplasia becoming an invasive bronchogenic carcinoma strongly linked with?
Smoking
What are the key driver mutations for adenocarcinoma?
KRAS (35%)
EGFR (15%
BRAF, HER2 (1-2%)
ALK rearrangements (2%)
ROS1 gene rearrangements (1%)
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What mutational driver for lung cancer is smoking induced?
KRAS
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What mutations linked to adenocarcinomas has therapy been approved for targeting?
EGFR mutation
BRAF mutation
ALK rearrangement
ROS1 rearrangement
What therpies that target mutations linked to squamous cell carcinomas has been approved?
Very few suitable targets
Commonest alterations are inactivating mutations in tumour suppresor genes
What are some examples of tumours of the lungs>
Benign causes of mass lesion
Carcinoid tumour
Tumours of bronchial glands
Lymphoma
Sarcoma
What is a carcinoid tumour?
One originating in the neuroendocrine system
What are tumours originating in the neuroendocrine system called?
Carcinoid tumours
What is the malignancy of carcinoid tumours?
Low grade malignancy
What percentage of lung neoplasms are carcinoid tumours?
<5%
What are examples of tumours of the bronchial glands?
Adenoid cystic carcinoma
Mucoepidermoid carcinoma
Benign adenoma
How common are metastasis to the lung?
Common
What are the different kinds of lung cell carcinoma?
Squamous cell (40%)
Adenocarcinoma (41%)
Small cell carcinoma (15%)
Large cell carcinoma (4%)
What percentage of lung carcinomas are squamous cells?
40%
What percentage of lung carcinomas are adenocarcinomas?
41%
What percentage of lung carcinomas are small cell carcinomas?
15%
What percentage of lung carcinomas are large cell carcinomas?
4%
What is bronchioloalveolar cell carcinoma subtype of?
Adenocarcinoma
What is bronchioloalveolar cell carcinoma also called?
Alveolar cell carcinoma
Now called adenocarcinoma in situ
What does NSCLC stand up for?
Non-small cell carcinomas
What are examples of non-small cell carcinomas (NSCLC)?
Adenocarcinoma
Squamous cell carcinoma
Large cell carcinoma
How has the prevalance of squamous, small cell and adenocarinomas changed?
Squamous and small cell has plateued or fallen
Adenocarcinomas has risen
What can be said about the years before a lung cancer diagnosis?
Lung cancer grows clinically silent for many years
When does a lung cancer clinically present in its history?
Late
What are the symptoms of lung cancer like as it progresses?
Initially may have few if any symptoms until the disease is very advanced
Generally speaking, what is symptomatic lung cancer?
Fatal
What local effects does lung cancer have?
Bronchial obstruction
Pleural
Direct invasion
Lymph node metastasis
What effects may lung cancer have on bronchial obstruction?
Collapse
Endogenous lipid pneumonia
Infection/abscess
Bronchiectasis
What effect may lung cancer have on the pleura?
Inflammatory
Malignant
What may lung cancer directly invade?
Chest wall
Nerves
Mediastinum
What nerves may lung cancer directly invade?
Phrenic
L recurrent laryngeal
Brachial plexus
Cervical sympathetic
What does lung cancer invading the phrenic nerve cause?
Diaphragmatic paralysis
What does lung cancer invading the L recurrent laryngeal nerve cause?
Hoarse
Boving cough
What does lung cancer invading the brachial plexus cause?
Pancoast T1 damage
What does lung cancer invading the cervical sympathetic nerves cause?
Horner’s syndrome
What effects can lung cancer have on lymph nodes?
Mass effect
Lymphangitis carcinomatosa
What distant effects does lung cancer have?
Distant metastasis
Secondary to local effects
Non-metastatic effects
What distant metastasis can lung cancer cause?
Liver
Adrenals
Bone
Brain
Skin
What distant effects can be secondary to local effects?
Neural
Vascular
What systems can lung cancer have non-metastatic effects on?
Skeletal
Endocrine
Neurological
Cutaneous
Haemoatologic
Cardiovascular
Renal
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What are some examples of non-metastatic effects that lung cancer can have?
Finger clubbing
Hypertrophic pulmonary osteoarthropathy (HPOA)
What investigations can be done for lung cancer?
Chest X-ray
Sputum cytology rarely used
Bronchoscopy
Trans-thoracic fine needle aspiration
Trans-thoracic core biopsy
Pleural effusion cytology and biopsy
Advanced imaging techniques
What are examples of advanced imaging techniques?
CT
MRI
PET
What are examples of bronchoscopy?
Bronchial biopsy
Bronchial brushings and washings
Endobronchial US-guided aspiration (EBUS)
What are prognostic factors in lung cancer?
Stage of disease
Classification (type of disease)
Markers/oncogenes/gene expression profiles
Growth rate
Cell proliferation
DNA aneuploidy
Immune cell infiltration
How would you describe the prognosis of lung cancer?
Generally terrible
What percentage of people with lung cancer surcive 5 years in Scotland?
<9.8% (>15% in USA)
What percentage of people with stage 1 lung cancer survive more than 5 years?
>60%
What percentage of people with stage 2 lung cancer survive more than 5 years?
35%
In Scotland, what percentage of people with lung cancer get surgical treatment?
10-12%
What percentage of people with non-small cell carcinomas survive more than 5 years?
10-25% (some types do badly)
What percentage of people with small cell carcinoma survive more than 5 years?
4%
What is the median survival time for people with small cell carinomas?
9 months
Do non-small cell or small cell carinomas have a better prognosis?
Non-small cell carinomas
What can be used after the diagnosis to select patients for therapy?
Predictive biomarkers
What has transormed practice in non-small cell carcinomas?
Immunotherapy
What does immunotherapy do?
Target immune checkpoints such as PD1/PD-L1 in NSCLC
What immune checkpoint is targeted in non-small cell carcinomas?
PD1/PD-L1
What do immune checkpoints do?
Control immune reactions
What can tumours do to immune checkpoints?
Adapt them to avoid immune destruction
What can target immune checkpoints to help treat cancer?
Immune checkpoint inhibitors