Respiratory Histopathology (Cancer) Flashcards
What are the characteristics of benign lung tumours?
Do not metastasise
Can cause local complications
Airway obstruction
E.g. chondroma
What are the characteristics of malignant lung tumours?
Potential to metastasise, but variable clinical behaviour from indolent to aggressive
Commonest are epithelial tumours, and of these main types (90-95%)
What are the non small cell carcinomas and how much of total lung cancer burden do each of these make up?
Squamous cell carcinoma (30%)
Adenocarcinoma (30%)
Large cell carcinoma (20%)
What % of the lung cancer burden does small cell lung cancer make up?
20%
What are the common sites of lung cancer?
Left main bronchus
Bronchioles
Lung base
Pleura
What is the epidemiology of lung cancer?
1 in 7 new cancer cases
Almost 40,000 cases lung cancer in 2007
Men:women 4:3, but increasing numbers of women (1960’s ratio 6:1)
Men – second commonest to prostate cancer
Women – third commonest after breast and bowel cancer
Global cancer
What causes lung cancer?
Smoking - small cell and squamous cell
What does smoke contain?
Tumour initiators: Polycyclic aromatic hydrocarbons
Tumour promotors: N Nitrosamines, Nicotine, Phenols
Complete carcinogens: Nickel, Arsenic
25% of lung ca in non-smokers attributed to passive smoking
25% of lung ca in non-smokers attributed to passive smoking
Does stopping cigarette smoking decrease you risk of lung cancer?
Yes
What are non smoking risk factors of lung cancer?
Environment:
- Asbestos exposure (Asbestos + smoking = 50 fold increase risk)
- Radiation (Radon exposure, theraputic radiation, uranium miners)
- Air pollution
- Other: Heavy metals (Chromates, arsenic, nickel)
Genetics: Familial lung cancers rare, 1st degree relative (young age, non-smoking cases), Susceptibility genes
Which susceptibility genes exist for lung cancer?
Chemical modification of carcinogens
Polymorphisms in genes for cytochrome p450 (CYP1A1) and glutathione S transferases which play a role in eliminating carcinogens
Susceptibility to chromosome breaks and DNA damage
Nicotine addiction
How does lung cancer develop?
Multistep pathways:
metaplasia, dysplasia, carcinoma-in-situ to invasive carcinoma.
Associated with accumulation of gene mutations leading to disordered unregulated growth, tissue invasion, angiogenesis
Pathways different for different tumour types
For some lung tumours a precursor lesion is not identifiable e.g. small cell carcinoma
Which Mutation confers the most risk of SCC?
Gene methylation (p16ink4)
3pLOH, microsatellite alterations (50-80% of SCC)
Summarise Invasive Squamous Cell Carcinoma
Frequency
35% pulmonary carcinoma
Risk factor
Closely associated with smoking
Site
Traditionally centrally located arising from bronchial epithelium, however increasing number of peripheral squamous cell carcinomas
Behaviour
Local spread, metastasise late.
What is the precursor lesion to Adenocarcinoma (AC)
Precursor lesion: Atypical adenomatous hyperplasia
Proliferation of atypical cells lining the alveolar walls.
Increases in size and eventually can become invasive.
How does AAH progress to AC?
AAH
Non mucinous BAC
Mixed pattern adrenocarcinoma
What are the molecular pathways to adenocarcinoma?
Stem cells identified in TRU mice
in mice with kras mutation - serial changes from aah to bac to adenocarcinoma
Other pathways TRU - non ras non EGFR (motoi 0/7 egfr, 2/7 ras)
Other pathways - mucinous BAC from bronchial mucus cells, CCAM
BCD?
How frequent is an invasive adenocarcinoma?
Increasing incidence: 27% pulmonary carcinomas
What are the risk factors for an invasive adenocarcinoma?
Smoking + other
Commoner in far east, females and non-smokers
What is the site and behaviour of an invasive adenocarcinoma?
Site
Peripheral and more often multicentric
Behaviour
Extrathoracic metastases common and early (80% present with mets)
What is the histology of an invasive adenocarcinoma?
Histology shows evidence of glandular differentiation
What is a large cell carcinoma?
Peripheral or central 10% of tumours
Poorly differentiated tumours composed of large cells
No histological evidence of glandular or squamous differentiation
Poorer prognosis
What does electron microscopy of a large cell carcinoma show?
BUT on electron microscopy many show some evidence of glandular, squamous or neuroendocrine differentiation
i.e are probably very poorly differentiated adeno/squamous cell carcinomas
When and where are small cell carcinomas?
When: 20% of tumours, smokers
Where: Near bronchi (central)
How do small cell carcinomas act?
80% present with advanced disease
Although very chemosensitive, have an abysmal prognosis
Paraneoplastic syndromes
Small poorly differentiated cells
p53 and RB1 mutations common
Which non small cell lung cancer currently has the highest incidence?
Adenocarcinoma
How is survival different between small cell and non small cell lung cancers?
SC: Survival 2-4 months untreated, 10-20 months with current therapy
NSC: Early Stage 1: 60% 5 yr survival
Late Stage 4: 5% 5 yr survival
Which type of lung cancer is more chemosensitive?
Small cell lung cancer
Which NSCLC are important to differentiate for treatment?
Particularly : Adenocarcinoma vs squamous cell carcinoma
Some adenocarcinomas show a variety molecular changes which can be targeted by specific therapies.
EFGR mutation
ALK translocation
Ros1 translocation
In contrast some patients with squamous cell carcinoma develop fatal haemorrhage with some new chemotherapeutic drugs (Bevacizumab)
What can you look at in cytology?
Cytology - looking at cells Sputum Bronchial washings and brushings Pleural fluid Endoscopic fine needle aspiration of tumour/enlarged lymph nodes
What can you look at in histology?
Histology - looking at tissue
Biopsy at bronchoscopy - central tumours
Percutaneous CT guided biopsy - peripheral tumours
Mediastinoscopy and lymph node biopsy - for staging
Open biopsy at time of surgery if lesion not accessible otherwise - frozen section
Resection specimen - confirm excision and staging
What treatment pathway aims to be curative?
Curative: Surgery +/- radical chemoradiotherapy +/- immunemodulatory therapy
Which treatment pathway aims to be palliative?
Palliative: Chemoradiotherapy, immunemodulatory, targeted therapy
What do you look for in molecular testing?
EGFR mutation
Responder mutation
Resistance mutation
Alk translocation
Ros1 translocation
What are the types of molecular testing?
ALK, immunohistochemistry and FISH
What is a mesothelioma?
Malignant tumour of pleura (lining of the lung and chest wall)
Summarise a malignant mesothelioma
Frequency
<1% of cancer deaths, but increasing incidence
? Peak in incidence in about 2010.
Aetiology
asbestos exposure
Behaviour
Essentially a fatal disease
Medicolegal implications of diagnosis
compensation
Who gets mesothelioma?
Most patients have history of asbestos exposure
Long lag time: Tumour develops decades after exposure
males>females, approx 3:1
50-70 years of age
Present with shortness of breath, chest pain
Dismal prognosis
What can help in ALK translocation in cancers?
Crizotinib
What can be used to treat lung cancer?
mAbs
Immunotherapy
What % of lung cancers in the UK develop in non smokers?
10-20%
Stopping at any point reduces risk of lung cancer
Stopping at any point reduces risk of lung cancer
