Pathology of lung cancer Flashcards
State the risk factors of lung cancer
- tobacco
- asbestos
- enironmental radon
- polycyclic aromatic hydrocarbons; found in tobacco smoke but also occupational risk of exposure ( road paving, aluminium production)
- other occupational exposures chromatex, nickel
- air pollution + urban environement
- other radiation
- pulmonary fibrosis
- inherited polymorphism predispose ( certain inherited enzyme metabolise substances in tobacco smoke which makes them more carcinogenic + Nicotine addiction)
Describe the effect of smoking and lung cancer
- multi hit theory of carcinogenesis
- host activation of pro-carcinogens
- SCLC mostly associated
State the 2 main pathways of carcinogenesis in the lung
NSCLC
Adenocarcinoma:
-located in lung periphery (brionchioles/alveolar wall)
-transformed from bronchioalveolar stem cells
Sqamous:
- located in central airways
- transformed from bronchial epithelial cells
Describe the formation of an adenocarcinoma in smokers
Atypical adenomatous hyperplasia>Adenocarcinoma in situ > invasive adenocarcinoma
(Same sequence as non smokers so less assoc with smoking. Adenocarcinoma in situ is a subtype of adenocarcinoma)
Describe the formation of an invasive bronchogenic carcinoma in smokers
Squamous dysplasia/Carcinoma in-situ(CIS)»_space; Invasive bronchogenic carcinoma
What mutations/rearrangements can therapies target (ADENOCARCINOMAS)
- BRAF, HER2 EGFR mutations
- ALK, ROS1 rearrangements
What is targeted in squamous cell carcinomas?
-inactivating mutations in tumour suppressor genes
Types of tumours of the lung
- benign causes of mass lesion
- carcinoid tumour( lung neoplasms/low grade malignancy. NSCLC)
- tumours of bronchial glands ( adenoid cystic carcionoma, mucoepidermoid carcinoma, benign adenomas)
- lymphoma
- sarcoma
- metastases
State the cell types of lung carcinomas
- adenocarcinomas : 41%
- squamous cell: 40%
- small cell carcinoma: 15%
- large cell carcinoma: 4%
(all organised according to most common)
What is non-small cell carcinoma (NSCLC)?
- common
- squamous, adenocarcinomas, large cell carcinomas + carcinoid tumour(others)
State features of primary lung cancer
- presents late in its natural history
- asymptomatic until disease is advanced
- incidentally found during investigation of something unrelated
Local effects of lung cancer
- bronchial obstruction:
- collapse
- endogenous lipid pneumonia
- bronchiectasis
- infection/abscess formation
- pleural(inflammation/malignancy)
- direct invasion(chest wall)
- lymph node metastases
Lung cancer - direct invasion of chest wall
Nerves:
- Phrenic > diapgramatic paralysis
- Left recurrent larngeal > hoarse, bovine cough
- Brachial plexus(C5-T1) > pancoast T1 damage
- cervical sympathetic > horner’s syndrome
- mediastinum ( SVC, pericardium)
- lymph node metastases
Lung cancer - Lymph node metastases + symptom
- lymphangitis carcinomatosa
- presented as dull ache on chest
Lung cancer - distant effects
- Distant metastases: Liver, adrenals, bone, brain, skin (LABBS)
- Secondary to local effects: neural, vascular
- non metastic effects
State the non-metastic paraneoplastic effects of lung cancer
- Skeletal
- Endocrine
- Neurological
- Cutaenous
- haematologic
- Cardiovascular
- Renal
Non-metastic paraneoplastic effects of lung cancer - Skeletal
-clubbing, HPOA
Non-metastic paraneoplastic effects of lung cancer - Endocrine
- ACTH, SIADH, PTH
- Carcinoid syndrome
- gynecomastia
Non-metastic paraneoplastic effects of lung cancer - Neurological
- polyneuropathy
- encephalopathy
- cerebellar degeneration
- myasthenia ( eaton-lambert)
Non-metastic paraneoplastic effects of lung cancer - Cutaneous
- Acanthosis nigricans
- dermatomyositis
Non-metastic paraneoplastic effects of lung cancer - Haematologic
- Granulocytosis
- Eosinophillia
- DIC
Non-metastic paraneoplastic effects of lung cancer - Cardiovascular
-Thromboplebitis migrans
Non-metastic paraneoplastic effects of lung cancer - Renal
-Nephrotic syndrome
Non-metastic paraneoplastic effects of lung cancer - Endocrine ( lung cell types of cancer)
ACTH + SIADH (small cell)
PTH (squamous)
State the non-metastatic effects of lung cancer
- Finger clubbing
- Hypertrophic pulmonary osteoarthropathy (HPOA)
Lung cancer - investigations
Chest X-Ray
Sputum Cytology rarely used Bronchoscopy Bronchial biopsy Bronchial 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
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
Lung cancer 5 year survival by histiological cell type
Non-cell carcinomas ( 10-25%)
Small cell carcinoma ( 4%) ; median survival is 9 months
Predicitive biomarkers used to select patients for therapy - Adenocarcinoma
EGFR, KRAS, HER2, BRAF mutations,
ALK translocations, ROS1 translocations
Predicitive biomarkers used to select patients for therapy - Squamous cell
-little/no effective molecular targeted therapy
Predicitive biomarkers used to select patients for therapy - NSCLC
-immunotherapy
The PD1/PD-L1 axis immune checkpoint in NSCLC
-therapeutic target + imp biomarker
If there is an immune response, how does the tumour evade it?
- inhibitory immune checkpoints
- most cancers are not immunogenic, hence will determine effectivenessof tumour directed immune
- Immune checkpoints control immune reactions and are adopted by tumours to avoid immune destructionresponse
What checkpoints are targeted by drugs?
-PD-1, PD-L1, CTLA4
What is small cell carcinomas associated with?
- Polycyclic aromatic hydrocarbons
- siADH ( syndrome of inappopriate ADH prod)
- ACTH ( adrenocortitropic hormone
- Lambert - Eaton Syndrome ( muscle weakness)
What are adenocarcinomas associated with?
- Nitrosamines
- less associated with smoking
- likely to occur in non-smokers than squamous cell carcinomas
- mostly women
- Oncogene addiction -KRAS(smoking induced), EGFR, BRAF, HER2 mutations ROS1+ ALK rearrangments ( not smoking induced)
What is paraneoplastic effect of squamous cell carcinomas
-Hypercalcaemia - PTH
