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23 Cards in this Set
- Front
- Back
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Why do improvements in lung cancer mortality |
Late presentation with advanced disease A disease of the elderlyl Extensive comordities especially cardiac and respiratory |
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Causes of Lung Cancer |
Smoking - passive smoking (effects difficult to quantify) Occupation exposures - uranium mining, asbestos exposure Environmental exposures - Radon gas Genetic - Li-Faumeni Syndrome (mutated p53 gene) Viral infection - retroviral infection in sheep leads to lung adenocarcinomas |
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Types of Lung Cancer |
Squamous Carcinoma (30-40% and decreasing) Adenocarcinoma (40-50% and increasing) Small cell carcinoma (20%) Others (5%) - carcinoid tumours |
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What does microscopy of squamous carcinoma? |
Tumour cells are showing squamous differentiation - keratin production or "prickles" |
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What does microscopical image of adenocarcinoma? |
Evidence of a glandular growth pattern or mucin production |
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Small cell (undifferentiated) Carcinoma microscopy |
Very poorly differentiated carcinoma showing variable evidence of neuroendocrine differentiation |
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Classification of carcinoid / neuroendocrine tumours in the lung |
Typical (classical) carcinoid - <2 mitoses per 2mm^2, no necrosis Atypical carcinoid - >2 but < 10 mitoses per 2mm focal necrosis > 10 mitoses per 2mm2 w/ usually extensive necrosis then classified w/ LCNEC |
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Clinical significance of classical carcinoid and atypical carcinoid |
Classical carcinoid - 10-15% have hilar nodal involvement at diagnosis - 5-10% will eventually develop distant sites - 5 year survival 90-98% - 10 year survival 82-95% Atypical carcinoid - 40-50% have nodal metastases and 10% will hae stage IV disease at diagnosis - 5 year survival l61-73% - 10 year survival 35-59% |
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Mechanisms of Carcinogenesis |
Development of malignant tumour is a multistep genetic process requiring accumulation of mutated genes "Adenoma carcinoma" theory |
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What genes are mutated in carcinogenesis? |
Oncogenes - mutated genes encoding growth promoting proteins - eg k-Ras, cylinD1 are overexpressed Oncosuppresor genes - mutated genes encoding growth inhibitory proteins - decreased expression can result in neoplasia eg retinoblastoma gene Rb Gene regulating apoptosis may also be mutated eg p53 Genes regulating DNA repair may be mutated |
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Pathogenesis of Squamous Carcinoma |
Squamous metaplasia - common finding in smokers and reversible metaplastic squamoous epithelium --> squamous dysplasia --> squamous carcinoma in situ --> invasive squamous carcinoma |
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Pathogenesis of Adenocarcinoma |
Central tumours may arise in a similar manner to squamous carcinoma but pre malignant states not really recognised Peripheral tumours now believed to arise through a sequence of step wise changes normal alveolar walls --> atypical adenomatous hyperplasia --> adenocarcinoma in situ --> invasive adenocarcinoma |
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Symptoms and signs of lung cancer |
Cough Dyspnoea Haemoptysis Weight loss Chest/shoulder pain Hoarseness Fatigue Slow to clear pneumonia Finger clubing Cervical lymphadenopathy Liver, bone, brain metastases Pleural effusion |
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Initial investigations |
Radiology - chest xray and ct Bloods - high ca, abnormal liver function tests, low serum na |
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How do we diagnose lung cancer? |
Biopsies - bronchial biopsies - CT guided lung biopsies - biopsies of distant metastases eg pleura, liver, lymph node Cytology - bronchial brushings and washings -sputum - pleural fluid aspiration -fine needle aspirates of metastases |
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How Good are we at classifying lung cancer on small biopsies and cytology samples? |
Small cell carcinoma - 90% accuracy squamous carcinoma and adenocarinoma generally poor 50-60% accuracy |
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Squamous markers |
CK5 CK14 p63 34BE12 |
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Adenocarcinoma |
CK7 TTF1 - 70-80% of primary lung tumours |
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Behaviour of Lung Cancer |
Intrapulmonary Growth - obstructive pneumonia, lymphangitis carcinomatosis Invasion of adjacent structures - pleura - chest wall - mediastinum - diaphragm |
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Staging Lung Cancer |
Predictor of prongosis T - measure of growth of primary tumour N - extent of local nodal disease M - presence of absence of distant metastases |
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Give an example of a designer drug |
Tyrosine kinase inhibitors |
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Immunotherapy |
Immune check point regulation - lung carcinomas may be assoicated w/ an inflammatory infiltrate lymphoid infiltrate w/n these tumours may be associated w/ a better outcome |
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What can we do ie test for? |
EGFR mutation ALK fusion testing ROS-1 translocation PDL-1 expression PERSONALISED CANCER THERAPY |
