8. Lung Cancer Pathology Flashcards by Yash Kapoor

What are the symptoms of lung cancer?

• Most patients are asymptomatic
• Symptomatic
- cough
- haemoptysis
- recurrent infections
- chest wall pain

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What can pathologists look at when determining lung cancer, in terms of cytology?

(study of individual cells)
• sputum
• bronchial washings and brushings
• pleural fluid
• endoscopic fine needle aspiration

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What can pathologists look at when determining lung cancer, in terms of histology?

(study of tissues)
• Biopsy at bronchoscopy - central tymours
• Percutaneous CT guided biopsy - peripheral tumours
• Mediastinoscopy and lymph node biopsy - staging
• Open biopsy at time of surgery
• Resection specimen

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What are the characteristics of a benign lung tumour?

Don’t metastasise

* Local complications e.g. obstruction of airways

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What are the characteristics of a malignant lung tumour?

Potential to metastasise
Invade adjacent tissues
Most common: epithelial tumours (carcinomas)

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What are the 3 types of Non-Small Cell Carcinoma

Squamous Cell Carcinoma
Adenocarcinoma (most common lung cancer among non-smokers)
Large Cell Carcinoma

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How is Small Cell Carcinoma different to Non-small Cell Carcinoma?

• Worst form of lung cancer
(• Worse prognosis than non-small cell)
• Unusual to find early stage - rapid and more aggressive

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What are the trends in the incidence of Non-Small Cell Carcinoma?

Incidence of Squamous Cell Carcinoma is decreasing (association with smoking)
Incidence of adenocarcinoma is increasing (as incidence of smoking is decreasing, or less tar in cigarettes)

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Where do squamous cell carcinomas and adenocarcinomas tend to arise?

Squamous - near the mediastinum, in airways (there has been an increase in peripheral)
Adenocarcinoma - periphery

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What are the main causes of lung cancer?

• Smoking
- 75% of smokers and 25% of non smokers (passive smoking)
- Tumour initiators: polycyclic aromatic hydrocarbons
- Tumour promoters: N Nitrosamines, Nicotine, Phenols
- Complete carcinogens: Nickel, Arsenic
• Asbestos Exposure
• Radiation
• Rare metals

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How do genes affect lung cancer?

• Familial lung cancers are very rare
• Susceptibility genes:
- Nicotine addiction
- Chemical modification of carcinogens (Cytochrome P450 enzymes and Glutathione S transferases)
• Susceptibility to chromosome breaks and DNA damage

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How does a carcinoma generally develop?

Disordered growth
Loss of cell adhesion
Invasion of tissue
Stimulation of new vessel formation

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How does a Squamous Cell Carcinoma develop?

Airway epithelium toughens after irritation by cigarette smoke (hyperplasia)
Repeated exposure - squamous metaplasia
No cilia => mucus stays => carcinogens accumulate
Squamous cells acquire mutations - dyplasia
More disordered => carcinoma in sity
Further mutations => invasive

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Is Squamous Cell Carcinoma reversible?

Remove exposure to the irritant up to the metaplastic squamous cell stage
Can revert back to ciliated epithelial cells
Further along the pathway, mutations are irreversible

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Describe the cytology of Squamous Cancer Cells

Large nuclei

* Keratin in the cytoplasm

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Describe the histology of Squamous Cancer tissues

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Keratinisation

* Intracellular ‘prickles’ represent desmosomes

Describe the development of adenocarcinomas

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• Forms from glandular epithelium
• Increasing in incidence because of deeper inhalation
• Precursor lesion - atypical adenomatous hyperplasia
- proliferation of atypical cells lining the alveolar walls
• Walls thicken
• Cells grow larger
• Cells form enzymes that break down the stroma (connective tissue)
• Inflammation
• Invasion

Describe the cytology of an adenocarcinoma

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Produces mucin
Big atypical nuclei
Rest of cytoplasm filled with mucin globule

Describe the histology of adenocarcinoma

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Multi-focal in the lungs
Tends to spread early
Glandular differentiation

What are the molecular pathways in adenocarcinoma?

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• Smoker - K ras mutation (DNA methylation + P53)
- can’t respond to targeted therapy
• Non-Smoker - EGFR mutation/amplification
- responder mutation: almost complete regression to targeted therapy
- resistance mutation

Describe the histology of large cell carcinoma

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• Poorly differentiated tumours
• No evidence of glandular, squamous or neuroendocrine differentiation
- apart from on electron microscopy
• Probably poorly differentiated adenocarcinoma or squamous cell carcinoma
• Poorer prognosis

Describe the cytology of small cell carcinoma

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Small cells
Nuclei with a small amount of cytoplasm
Look like lymphocytes

Describe the histology of small cell carcinoma

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Central near the bronchi
80% of cases present with advanced disease
Lot of paraneoplastic syndromes (involves altered immune response)
Lots of mitoses
Often outgrows its blood supply and becomes necrotic

What is the prognosis like for small cell carcinoma?

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Chemosensitive due to high growth rate

* However, awful prognosis - can relapse after treatment

Compare the survival rate of small cell carcinoma with non-small cell carcinoma

Small cell carcinoma • General survival of 2-4 months untreated • General survival of 10-20 months with current treatment (• Chemoradiotherapy) ``` Non-small cell carcinoma • Early Stage 1: 60% 5 year survival • Late Stage 4: 5% 5 year survival • 20-30% have early stage tumours suitable for surgical resection (• Less chemosensitive) ```

Why is it important to subtype Non-small cell carcinoma in terms of treatment?

* If treated with Bevacizumab and actually have squamous cell carcinoma - may develop fatal haemorrhage * Some chemo e.g. Pemetrexed, works better in adenocarcinoma instead due to specific characteristics e.g. EGFR, ALK, ros, ret mutations

Give an example of a way you can predict the response to conventional chemotherapy

• Excision Repair Cross-Complimentation Group 1 Protein (ERCC1) • This marker determines response to cisplatin • Advanced stage non-small cell lung cancer: - ERCC1 positive tumours have a poor response to cisplatin based chemotherpy - ERCC1 protein removes drug-DNA adducts

How can EGFR (Epidermal Growth Factor Receptor) be used as a target for treatment?

* Membrane receptor Tyrosine Kinase * Regulates angiogenesis, proliferation, apoptosis and migration * Mutation/amplification of EGFR => adenocarcinoma (mainly non-smokers) * Target of a Tyrosine Kinase Inhibitor

What is the ALK gene and what does a mutation in it lead to + treatment?

* Gene with instructions for production of ALK receptor tyrosine kinase (regulating cell growth) * Mutation in the gene occurs in a small number of adenocarcinomas * Stain to look for mutations * Treated with anti-ALK mediation

What is PDL-1?

* Protein expressed by tumour cells * Hides the tumour from cytotoxic T-cells * Immunotherapy - medication can be used to block PDL-1 so the T-cell can recognise the tumour cells

Which of the following tumour staging is the gold standard: • clinical • radiological • pathological

Pathological

What are the local effects of a bronchogenic carcinoma?

• Proximal tumour - squamous cell or small cell carcinoma • Bronchial obstruction - collapse of distal lung => shortness of breath - impaired drainage of the bronchus => chest infection • Invasion of local airways and vessels => haemoptysis • Invasion around large vessels - Superior Vena Cava syndrome => venous congestion of the head and arm, oedema and ultimately circulatory collapse • Dysphagia - difficulty swalling • Horner's syndrome - tumour on sympathetic nervous system => miosis (constricted pupil) and ptosis (weak, droopy eyelid)

What are the effects when bronchogenic carcinoma extends through the pleura/pericardium?

* Pleuritis or pericarditis with effusions => breathlessness * Cardiac compromise => effusion can affect cardiac function * Diffuse lymphatic spread within lung => shortness of breath, poor prognostic features

What are the systemic effects of bronchogenic carcinoma?

* Brain => fits * Skin => lumps * Liver => pain, deranged function tests * Bone => pain, fracture * Paraneoplastic Syndrome => abnormal expression of factors by tumour cells, not normally expressed by the tissue it came from

Give examples of endocrine paraneoplastic syndromes

* Anti-diuretic hormone (ADH) => SIADH (high ADH) - hyponatremia * Low adrenocorticotropic hormone (ACTH) => Cushing's Syndrome (especially small cell carcinoma) * Parathyroid hormone-related peptides => hypercalcaemia (especially squamous cell carcinoma) * Calcitonin => Hypocalcaemia * Gonadotrophins => Gynaecomastia * Seratonin => Carcinoid Syndrome

What do non-endocrine paraneoplastic syndromes affect?

* Haematologic/coagulation defects * Skin * Muscular * Miscellaneous

What is the cause of mesothelioma (a malignant pleural tumour) and how does it present?

* Asbestos * Currently a peak in incidence * Fatal * Long lag time (develops decades after exposure) * More common in males * Shortness of breath, chest pain * Awful prognosis

8. Lung Cancer Pathology Flashcards

(37 cards)