1/30/25, 10:43 AM 8. Respiratory - Oxford University Laboratory Medicine Course Revision Not…
8. Respiratory
8.5 LUNG TUMOURS
• Understand the pathophysiology and clinical/histological features of lung tumours, to
include:
Non-small cell carcinoma
o Squamous carcinoma
o Adenocarcinoma
o Large cell carcinoma
Small cell carcinoma
Paraneoplastic syndromes
Mesothelioma
• To appreciate molecular testing in non-small cell lung cancer (EGFR, ROS-1, KRAS,
ALK, PDL-1)
Lung cancer – overview
- Common cause of cancer death worldwide
- Incidence mirrors cigarette use – main risk factor
- Incidence declining
- M:F converging (due to increased use of cigs by females)
- Other risk factors -> passive smoking, occupational exposure (e.g. asbestos),
pulmonary fibrosis (scar cancer), radiation
Presentation
- Systemic – weight loss,
malaise, poor appetite
- Local/direct – cough,
dyspnoea, haemoptysis
(coughing up blood),
wheeze, obstructive
pneumonia (due to lack of
clearance), pleural effusion
- Mediastinal involvement
- Metastases
- Paraneoplastic syndromes
- Haematological – DVT/PE,
anaemia
Local invasion – clinicopathological correlation:
- Hoarseness – recurrent laryngeal nerve
- Dyspnoea – obstruction/pleural effusion/phrenic nerve
- Dysphagia (trouble swallowing) – oesophagus
- Horners syndrome – apical tumour, sympathetic trunk, ipsilateral miosis, ptosis
- Pancoasts syndrome – apical tumours, brachial plexus
- SVC syndrome – SVC obstruction
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Non-small cell carcinoma
- Treatment options used to be the same – but now advances have split treatments to
more personalised medicine based on tumour
- Adenocarcinoma – EGFR, ALK, ROS1
- PD-L1 status assessed
Adenocarcinoma:
- Most common type of lung cancer
- Malignant epithelial tumour showing
glandular differentiation, mucin
production (mucin stain to identify) or
pneumocyte marker expression
- H&E stain allows assessment of morphology
- Usually peripheral
- Driven by oncotic mutations – EGFR
(epidermal growth factor receptor), KRAS,
ALK (v specific to adenocarcinomas)
- EGFR/ALK – preferentially seen in never
smokers
- KRAS – commonly seen in smokers
- Molecular testing advises treatment
- EGFR mutation (10%) – give tyrosine kinase inhibitors
- ALK rearrangement (2%) – ALK inhibitor
- PDL1 – programmed death ligand – binds to PD1 receptor on T cells allowing tumour
to escape immune response – give PDL1 inhibitors to allow host immune response to
attack the tumour
Squamous cell carcinoma:
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8. Respiratory
8.5 LUNG TUMOURS
• Understand the pathophysiology and clinical/histological features of lung tumours, to
include:
Non-small cell carcinoma
o Squamous carcinoma
o Adenocarcinoma
o Large cell carcinoma
Small cell carcinoma
Paraneoplastic syndromes
Mesothelioma
• To appreciate molecular testing in non-small cell lung cancer (EGFR, ROS-1, KRAS,
ALK, PDL-1)
Lung cancer – overview
- Common cause of cancer death worldwide
- Incidence mirrors cigarette use – main risk factor
- Incidence declining
- M:F converging (due to increased use of cigs by females)
- Other risk factors -> passive smoking, occupational exposure (e.g. asbestos),
pulmonary fibrosis (scar cancer), radiation
Presentation
- Systemic – weight loss,
malaise, poor appetite
- Local/direct – cough,
dyspnoea, haemoptysis
(coughing up blood),
wheeze, obstructive
pneumonia (due to lack of
clearance), pleural effusion
- Mediastinal involvement
- Metastases
- Paraneoplastic syndromes
- Haematological – DVT/PE,
anaemia
Local invasion – clinicopathological correlation:
- Hoarseness – recurrent laryngeal nerve
- Dyspnoea – obstruction/pleural effusion/phrenic nerve
- Dysphagia (trouble swallowing) – oesophagus
- Horners syndrome – apical tumour, sympathetic trunk, ipsilateral miosis, ptosis
- Pancoasts syndrome – apical tumours, brachial plexus
- SVC syndrome – SVC obstruction
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,1/30/25, 10:43 AM 8. Respiratory - Oxford University Laboratory Medicine Course Revision Not…
Non-small cell carcinoma
- Treatment options used to be the same – but now advances have split treatments to
more personalised medicine based on tumour
- Adenocarcinoma – EGFR, ALK, ROS1
- PD-L1 status assessed
Adenocarcinoma:
- Most common type of lung cancer
- Malignant epithelial tumour showing
glandular differentiation, mucin
production (mucin stain to identify) or
pneumocyte marker expression
- H&E stain allows assessment of morphology
- Usually peripheral
- Driven by oncotic mutations – EGFR
(epidermal growth factor receptor), KRAS,
ALK (v specific to adenocarcinomas)
- EGFR/ALK – preferentially seen in never
smokers
- KRAS – commonly seen in smokers
- Molecular testing advises treatment
- EGFR mutation (10%) – give tyrosine kinase inhibitors
- ALK rearrangement (2%) – ALK inhibitor
- PDL1 – programmed death ligand – binds to PD1 receptor on T cells allowing tumour
to escape immune response – give PDL1 inhibitors to allow host immune response to
attack the tumour
Squamous cell carcinoma:
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