Pathology of Lung Cancer Flashcards
Describe the epidemiology of lung cancer
Current annual US death toll > 150,000 (more than breast, colon and prostate combined)
75.5 per 100,000 in Scotland
Two thirds of world smokers reside in China
Why are there less improvements in lung cancer mortality?
- Late presentation with advanced disease
- A disease of the elderly
- Extensive co-morbidities especially cardiac and respiratory
What are the causes of lung cancer?
- Smoking (>95%)= passive smoking effects difficult to quantify
- Occupational exposures (uranium mining, asbestos exposure)
- Environmental exposures= radon gas
- Genetic= Li-Fraumeni Syndrome (mutated p53 gene)
- Viral infection? = Retroviral infection in sheep leads to lung adenocarcinomas
What are the types of lung cancer?
- Squamous Carcinoma (30-40% and decreasing)
- Adenocarcinoma (40-50% and increasing)
- Small cell carcinoma (20%)
- Others (5%)= carcinoid tumours
What does a squamous carcinoma look like?
- Tumour cells are showing squamous differentiation
- Keratin production or ‘prickles’
What does Adenocarcinoma look like?
Evidence of a glandular growth pattern or mucin production
What does a small cell (undifferentiated) carcinoma look like?
Very poorly differentiated carcinoma showing variable evidence of neuroendocrine differentiation
What are the classifications of Carcinoid/ Neuroendocrine Tumours in the Lung?
- Typical (Classical) carcinoid
- Atypical carcinoid
What is Typical carcinoid?
- <2 mitoses per 2mm^2
- No necrosis
What is Atypical carcinoid?
- > 2 but <10 mitoses per 2mm^2
- Focal necrosis (may be very focal commedo like)
- > 10 mitoses per 2mm^2 with usually extensive necrosis then classified with LCNEC
What is the clinical significance of 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%
What is the clinical significance of atypical carcinoid?
- 40-50% have nodal metastases and 10% will have stage 4 disease at diagnosis
- 5 year survival 61-73%
- 10 year survival 35-59%
What are the mechanisms of Carcinogenesis?
Development of a malignant tumour is a multi-step genetic process requiring the accumulation of mutated genes
-adenoma carcinoma theory
What are oncogenes?
Mutated genes encoding growth-promoting proteins- these are overexpressed in neoplasia (k-Ras, cyclinD1)
What are oncosupressor genes?
Mutated genes encoding growth-inhibitory proteins= decreased expression can result in neoplasia (Rb)
Hoe is a malignant neoplasm formed?
- Clonal expansion
- Additional mutations
- Heterogeneity
Describe Pathogenesis of Squamous Carcinoma
Squamous metaplasia common in smokers, reversible
- Metaplastic squamous epithelium
- Squamous dysplasia
- Squamous carcinoma in-situ
- Invasive squamous carcinoma
Describe 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
What are the symptoms and signs of lung cancer?
- Cough
- Dyspnoea
- Haemoptysis
- Weight loss
- Chest/ shoulder pain
- Hoarseness
- Fatigue
- Slow to clear pneumonia
- Finger clubbing
- Cervical lymphadenopathy
- Liver, bone, brain metastases
- Pleural effusion
What are the initial investigations of lung cancer?
- Radiology= chest x-ray, CT scan
- Bloods= High Ca, abnormal liver function tests, low serum Na
How do we diagnose lung cancer?
- Biopsies
- Cytology
Describe biopsies
- Bronchial biopsies
- CT guided lung biopsies
- Biopsies of distant metastases e.g. pleura, liver, lymph node
Describe cytology
- Bronchial brushings and washings
- Sputum
- Pleural fluid aspiration
- Fine needle aspirates of metastases
How good are we at classifying lung cancer on small biopsies and cytology samples?
- Small cell carcinoma fairly robust >90% accuracy
- Squamous carcinoma and adenocarcinoma generally poor 50-60% accuracy= often classified as ‘non-small cell’ carcinomas in diagnostic specimens recognising the poor predictive value of small biopsies/ cytology samples
What can we do with the biopsies?
Immunohistochemistry
- Squamous markers= CK5, CK14, p63, 34betaE12
- Adenocarcinoma= CK7, TTF1 (c. 70-80% of primary lung tumours)
Describe the behaviour of lung cancer
- Intrapulmonary growth= Obstructive pneumonia, Lymphangitis carcinomatosis
- Invasion of adjacent structures= pleura (with associated effusion), chest wall, mediastinum (SVC, phrenic nerve, recurrant laryngeal nerve, atrium, aorta, oesophagus), Diaphragm
Where does the distant spread of lung cancer go via lymphatics and blood?
- Hilar and mediastinal nodes
- Liver
- Bones
- Adrenals
- Brain
Describe the process of Lung cancer staging
- Staging is assessing the extent of tumour growth and spread
- Allows patients to be grouped together for treatment schedules/ trials
- Predictor of prognosis
- TNM system
What is the TNM system?
- T= a measure of the growth of the primary tumour
- N= indication of the extent of local nodal disease
- M= presence or absence of distant metastases
What are the treatment modalities?
- Best supportive/ palliative care
- Chemotherapy
- Radiotherapy
- Surgery (around 15%, advanced disease at presentation, co-morbidities emphysema, ischaemic heart disease)
What drugs are being developed for lung cancer?
- Tyrosine kinase inhibitors (check mutations by pcr from specimens)
- Crizotinib (EML4-ALK Translocations)
What is immunotherapy?
Immune check point regulation
- Lung carcinomas may be associated with an inflammatory infiltrates
- Suggested for decades that a lymphoid infiltrate within these tumours may be associated with a better outcome
Hoe might personal medicine be used in lung cancer treatment?
- EGFR mutation and ALK fusion testing is the first of a growing list of mutation/ genetic factors that are potential targets
- Treatment not based on diagnosis but on specific characteristics any given tumour has in any given patient
What do we do in routine practice for lung cancer?
-Epidermal growth factor receptor mutations
-ALK fusion
-ROS-1 translocation
-PDL-1 expression
Small number of cases suitable for specific targeted therapies
