Pathology of Pulmonary Neoplasia COPY Flashcards
What is the most common cause of death by cancer?
Lung Cancer
What are the Aetiologies for lung cancer?
- Tobacco
- passive smoking
- Asbestos
- other occupational exposure (chromates, hydrocarbons, Nickel)
- air pollution
- Radiation (environmental radon
- Diesel exhaust
- pulmonary fibrosis
How much of lung cancer is attritable to tobacco?
Over 85%
What percentage of smokers get lung cancer?
10%
What percentage of non-smoking lung cancers are caused by passive smoking?
At least 25%
Why does tobacco smoke cause lung cancer?
- Epithelial effects
- Multi-hit theory in carcinogenesis
- Host activation of pro-carcinogens
- Inherited polymorphisms predispose to metabolism of pro-carcinogens, nicotine addiction
How does adenocarcinoma arise in the lung?
Bronchoalveolar epithelial stem cells transform
How does squamous cell carcinoma arise from?
Bronchial epithelial stem cells transform
Where about do you see adenocarcinoma and squamous cell carcinoma?
Adenocarcinoma - Lung periphery
Squamous cell carcinoma - Central lung airways
Which oncogene is activated by smoking?
KRAS
What are the other important oncogenes that give rise to lung cancer?
EGFR BRAF HER2 ALK rearrangements
What are the common tumours of the lung?
- Carcinoid tumour (less than 5% of lung neoplasms, low grade malignancy)
- Benign causes of mass lesion
- Tumours of bronchial glands (V RARE, adenoid cystic carcinoma, mucoepidermoid carcinoma, benign adenomas)
- Lymphoma
- Sarcoma
- Metastesis to lung are common
What are the 4 main types of lung cancer?
- Squamous cell
- Adenocarcinoma
- Small cell carcinoma
- Large cell carcinoma
What is an adenocarcinoma in situ?
Bronchioalveolar cell carcinoma (subtype of adenocarcinoma)
What are carcinoid tumours?
Rare cancer of neuroendocrine system (system that produces hormones)
Tumour usually grows in bowels or appendix, can be found in stomach, pancreas, lung, breast, kidney, ovaries, testicles.
Grows very slowly
What is the difference in incidence between Small cell carcinoma and Non-small cell carcinoma
Small cell carcinoma - 15%
Non-small cell carcinoma - 85%
(Non-small cell carcinoma - adenocarcinoma, squamous cell carcinoma, large cell carcinoma)
What does symptomatic lung cancer indicate?
Late presentation, if symptomatic Usually fatal
When does primary lung cancer present itself?
Late in natural history, grows clinically silent for many years
What are the local effects of bronchial obstruction caused by lung cancer?
- Lung Collapse
- Endogenous lipoid pneumonia
- Infection / abscess
- Bronchiestasis
What is endogenous lipoid pneumonia?
Lipids enter bronchial tree (result of localised accumulation of lipid laden macrophages within alveolar spaces distal to an obstructed airway)
What are the local pleural effects caused by lung cancer?
- Inflammation (fibrosis, irritation, effusion)
- Malignant invasion
What are the direct invasions caused by lung cancer?
- Into chest wall
- Nerves
- Madiastinum (superior vena cava and pericardium)
- Lymph nodes
What are the local effects of cancer on the nerves?
- Phrenic – diaphragmatic paralysis
- L Recurrent laryngeal – Hoarse, Bovine cough
- Brachial plexus – Pancoast T1 damage
- Cervical Sympathetic - Horner’s syndrome
- Phrenic n. (C3-C5)-> diaphragm paralysis
- Left recurrent laryngeal nerve in left central lung cancer – hoarseness
- Brachial plexus (C5-T1) in Pancoast tumour- apices- hand symptoms
- Cervical sympathetic ganglia – Horner’s syndrome (anhidrosis, ptosis, miosis)
What is Horner’s syndrome?
Disruption of nerve pathway from brain to face and eye on one side of body
Decreases pupil size, drooping eyelid, decreased sweating on affected side
What are the local effects of cancer on the mediastinum?
- SVC obstruction- veins in upper limb engorged when raised above heart height- risk of cerebral oedema
- Pericardium
What is the outcome from lymph node metastasis?
Lymphangitis carcinomatosa
(hilar, Bronchial LN)
What are the distant effects of lung cancer?
Distant metastases (liver, adrenals, bone, brain, skin)
Secondary to local effects (neural, vascular)
Non- metastatic effects
What are the symptoms of paraneoplastic syndromes?
- Chronic cough (> 3 weeks)
- Wheeze
- Sob
- Hoarseness
- Haemoptysis
- Difficulty swallowing
- Chest/bone pain (hypertrophic pulmonary osteoarthropathy)
- Unexplained weight loss
- Nail clubbing
What are the signs of paraneoplastic syndromes
- Clubbing
- Supraclavicular lymphadenopathy
- Horner’s syndrome
- SVC obstruction
- Hepatomegaly
- Skin nodules
What are the non-metastaic paraneoplastic effects of lung cancer?
What are the non-metastatic paraneoplastic effects of lung cancer, that are endocrine and caused by small cell cancers?
ACTH
siADH
What are the non-metastatic paraneoplastic effects of lung cancer, that are endocrine and caused by squamous cell cancers?
PTH
What are the lung cancer investigations?
- CXR
- Sputum Cytology (rarely used)
- Bronchoscopy - Bronchial biopsy, brushings and Washings–Endobronchial US-guided aspiration (EBUS)
- Trans-thoracic Fine Needle Aspiration
- Trans-thoracic Core Biopsy
- Pleural effusion cytology and Biopsy
- Advanced Imaging Techniques - CT scanning, MRI, PET scanning, Other imaging
What are the proognostic factors in lung cancer?
Stage of disease
Classification: Type of Disease
- Markers / Oncogenes / Gene expression profiles
Prognostic markers MIGHT be used to select patients for ADJUVANT therapy
What percentage of patients in Scotland with Lung cancer get surgical treatment?
10%
What is 5 year survival rate for non-small cell carcinomas?
10-25%
What is the 5 year survival rate of small cell carcinomas?
4%
What is the average survival rate for small cell carcinoma?
9 months
What is used after the diagnosis to select patients for therapy?
Predictive biomarkers:
- Adenocarcinoma
- EGFR, KRAS, HER2, BRAF mutations
- ALK translocations, ROS1 translocations
Squamous Cell
- Little or no effective molecular targeted therapy
What is an immune checkpoint inhibitor?
Drug that prevents passage past checkpoint, immune checkpoints control immune reactions
Give examples of how cancer cells avoid immune destruction
PD1, PD-L1
