- Neoplasia : Pathology of Lung Cancers Flashcards
What is the most common cause of death by cancer worldwide?
Lung cancer
Lung cancer kills more than which 2 cancers combined?
Breast and prostate
Lung cancer accounts for what percentage of ALL deaths in Scotland?
6%
What is the 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 biggest cause of lung cancer?
85% of cases are attributed to tobacco
What percentage of smokers get lung cancer?
10%
How does the risk of smokers getting lung cancer differ in the sexes?
- Risk of cancer increased by 22x in males
- Risk of cancer increased by 12x in females
- However, females may be more susceptible per cigarette smoked
What is the risk of getting lung cancer related to in smoking?
Consumption- Inhalation and pack years
What risks does passive smoking pose?
- 50-100% increased risk
- Causes at least 25% of non-smoking lung cancers
How many chemicals are in tobacco?
Over 4000
How many carcinogens are in tobacco?
60 recognised carcinogens
What are 2 major classes of chemicals in tobacco?
- Polycyclic aromatic hydrocarbons
- N-nitrosamines
What are polycyclic aromatic hydrocarbons believed to be linked to?
Squamous small cell lung carcinoma
What are N-nitrosamines believed to be linked to?
Adenocarcinomas
What does tobacco smoke cause?
- Epithelial effects
- Multi-hit theory of carcinogenesis
- Host activation of pro-carcinogens
What can inherited polymorphisms predispose?
- Metabolism of pro-carcinogens
- Nicotine addiction
Where do adenocarcinomas normally from?
In the lung periphery when bronchioalveolar epithelial stem cells transform
Where do squamous cell carcinomas usually form?
In the central lung airways when bronchial epithelia stem cells transform
What are the states involved in the development of an invasive bronchogenic carcinoma?
- Squamous dysplasia
- Carcinoma-in-situ
- Invasive bronchogenic carcinoma
Process strongly associated with smoking
What are the states involved in the development of an invasive adenocarcinoma?
- Atypical adenomatous hyperplasia
- Adenocarcinoma-in-situ
- Invasive adenocarcinoma
Process associated with smoking, but also occurs in non-smokers
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What tumours can occur in the lung?
- Benign causes of mass lesion
- Carcinoid tumour
- Tumours of bronchial gland :VERY RARE
- Lymphoma
- Sarcoma
- Metastases to lung are common
What could be a benign cause of mass lesion?
Fibrous tissue formed during pneumonia
What are examples of bronchial gland tumours?
- Adenoid cystic carcinoma
- Mucoepidermoid carcinoma
- Benign adenoma
What are the 4 main types of carcinoma of the lung?
- Adenocarcinoma
- Squamous cell
- Small cell carcinoma
- Large cell carcinoma
What is bronchiolalveolar cell carcinoma now known as?
- It was a subtype of adenocarcinoma
- Now called adenocarcinoma in situ
What are the 2 histological types of lung carcinoma?
- Small cell carcinoma (SCLC)
- Non-small cell carcinomas (NSCLC)
What is included in NSCLC?
- Adenocarcinoma
- Squamous cell carcinoma
- Large cell carcinoma
- Others
Why is the term NSCLC used in diagnosis?
Sometimes the term is used as we cannot distinguish between particular types of non-small cell carcinomas on small biopsy samples
What is NSCLC not?
A single type of lung carcinoma
What is NSCLC?
A group of very biologically different diseases which have to be treated in very different ways
What is the main problem with primary lung cancer?
It grows clinically silent for many years and presents late in its natural history
What is a very important symptom in lung cancers
Haemoptysis
What are the local effects of lung cancer?
- Bronchial obstruction
- Pleural
- Direct invasion
- Lymph node metastasis
What can cause bronchial obstruction in cancer?
- Collapse
- Endogenous lipoid pneumonia
- Infection/abscess
- Bronchiectasis
What effects can cancer have on the pleura?
- Inflammation
- Malignant
What can be directly invaded in lung cancer?
- The chest wall
- Nerves
- Mediastinum
What nerves can be affected by direct invasion in cancer?
- Phrenic: diaphragmatic paralysis
- L recurrent laryngeal: hoarse, bovine cough
- Brachial plexus: Pancoast T1 damage
- Cervical sympathetic: Horner’s syndrome
What can be affected by direct invasion in the mediastinum in cancer?
- Superior vena cava
- Pericardium
What can lymph node metastases lead to?
- Mass effect
- Lymphangitis carcinomatosa
Where can lung cancer metastasise to?
- Liver
- Adrenals
- Bone
- Brain
- Skin
What local effects can be secondary to lung cancer?
- Neural
- Vascular
What systems can non-metastatic paraneoplastic effects of lung cancer affect?
- Skeletal
- Endocrine
- Neurological
- Cutaneous
- Haematological
- Cardiovascular
- Renal
Non-metastatic paraneoplastic effects of lung cancer: Skeletal
- Clubbing
- HPOA
Non-metastatic paraneoplastic effects of lung cancer: Endocrine
- ACTH, SIADH, PTH
- Carcinoid syndrome
- Gynecomastia
Non-metastatic paraneoplastic effects of lung cancer: Neurological
- Polyneuropathy
- Encephalopathy
- Cerebellar degeneration
- Myasthenia
Non-metastatic paraneoplastic effects of lung cancer: Cutaneous
- Acanthosis nigricans
- Dermatomyositis
Non-metastatic paraneoplastic effects of lung cancer: Haematological
- Granulocytosis
- Eosinophilia
- DIC
Non-metastatic paraneoplastic effects of lung cancer: Cardiovascular
-Thrombophlebitis migrans
Non-metastatic paraneoplastic effects of lung cancer: Renal
Nephrotic syndrome
What Non-metastatic paraneoplastic effect of lung cancer is associated with small cell carcinoma?
Release of ACTH and SIADH by the endocrine system
What Non-metastatic paraneoplastic effect of lung cancer is associated with squamous cell carcinoma?
Release of PTH by the endocrine system
What does release of PTH lead to?
Hypercalcaemia
What does HPOA cause?
Sore ankles and wrists
What investigations are often carried out with lung cancer?
- Chest X-ray
- Sputum cytology is rarely used
- Bronchoscopy
- Trans-thoracic fine needle aspiration
- Trans-thoracic core biopsy
- Pleural effusion
What are the limitations of samples collected during investigations?
Often very small so not much material to work with
What advance imaging techniques can be used in the investigation of lung cancer?
- CT scanning
- MRI
- PET
- Other imaging
What type of bronchoscopies can be carried out?
- Bronchial biopsy
- Bronchial brushings and washings
- Endobronchial US guided aspiration
What prognostic factors are there in lung cancer?
- Stage of disease
- Classification/ type of disease
What might prognostic factors be used for in selection of patients?
To select patients for adjuvant therapy
What is the prognosis for operable lung cancer?
- Type I >60% 5YS
- Type II 35% 5YS
What is the 5YS rate for Non-small cell carcinomas?
- Anywhere between 10-25%
- Some cell types do badly
What is the 5YS for small cell carcinoma?
- 4%
- Medial survival 9 months
After diagnosis is made what predictive factors can be used to select patients for therapy?
Predictive biomarkers:
- Adenocarcinoma: EGFR, KRAS, HER2, BRAF mutations, ALK translocations
- Squamous cell: FGFR1 gene copy number, DDR2 and FGFR2 mutations
What do immune checkpoints do?
Control immune reactions
How do tumours use immune checkpoints?
To avoid immune destruction
What are examples of immune checkpoints?
- PD1
- PD-L1
- CTLA4
What are gaining use in cancers?
Drugs against immune checkpoints known as immune checkpoint inhibitors
