lecture 7: pathology of lung cancer Flashcards
what are the initial clinical presentations?
- most patients are asymptomatic
- the clear symptoms are coughing coughing up blood (haemoptysis) lots of infections chest wall pain
what is cytology?
what is shown in cytology?
cytology is looking at the individual cells
- sputum
- bronchial washings
- pleural fluid
what is histology ?
what does histology show?
- histology is looking at the tissues
- biopsy at bronchoscopy
- lymph node biopsy
- peripheral tumor biopsy
what are the two types of tumour?
- benign tumours
do not metastasise
cause local complications - malignant tumours
have potential to metastasises - involves the adjacent tissues
what are the two types of tumour of the lung?
- non small cell
adenocarcinoma
squamous cell carcinoma
large cell carcinoma - small cell
much worse prognosis than the non small cell
grow rapidly
and metastasise
what types of lung cancer are increasing and what is decreasing?
- the incidence of squamous cell carcinomas is decreasing
(due to a decreasing in the rates of smoking)
( also due to a change in the type of cigarettes smoked) - the proportion of lung cancer due to incidence of adenocarcinomas is inreasing
what is the most common malignant lung tumour?
- epithelial tissues
what is the most common type of lung cancer of non smokers?
adenocarcinoma
where are squamous cell carcinomas located ?
where are adenocarcinomas located?
- squamous cell carcinomas are located near the mediastinum
- adenocarcinomas are located in the periphery
what is the main cause of lung cancer?
- smoking
both passive and direct smoking - asbestos
- radiation
example of
- tumour initiator
- tumour promoter
- complete carcinogens
- hydrocarbons
- nicotine
- nickel
how might a genetic predisposition arise?
- familial lung cancer is really rare
- there are some susceptible genes:
- nicotine addiction
- susceptibility to chromosome breaks and DNA damage
what are the stages of development of a carcinoma?
- metaplasia
- dysplasia
- carcinoma in situ
- invasive carcinoma
a tumour is basically an accumulation of mutations
what is the pathway of development of squamous cell carcinoma?
- squamous cell carcinomas arise in the airways
- the airway reacts to the chronic irritation of the cigarette smoke
- the epithelium changes to a tougher epithelium
- if there are no cilia on the epithelium the mucus will stay in the lungs so you acquire smokers cough
- the squamous cells will acquire mutations so the normal pattern of growth is disrupted
- the dysplasia becomes more and more disordered
therefore becoming a carcinoma in situ - a further mutation will make it invasive
what is the cytology of squamous cell carcinoma?
- large nuclei
- keratin in the cytoplasm
what is the histology of squamous cell carcinomas?
- keratinisation
- intracellular prickles
- lots of subtypes
what is the development of adenocarcinomas?
- forms from glandular epithelium
- they develop in the periphery
- the pre cursor lesion is atypical adenomatous hyperplasia
- this is when the atypical cells lining the alveolar walls proliferate and eventually become invasive
what is the progression of an atypical adenomatous hyperplasia?
- alveolar walls are thickened
- and lined by atypical cells
- over time some of these cells will grow larger and larger
- at some point the cells mutate to produce enzymes that break down the stroma
- this forms fibrous scars and is accompanies by inflammation
- once the adenocarcinoma is invasive it might spread round the body
what is the cytology of adenocarcinomas?
- shows glandular differentiation
- produces mucin
- a typical nuclei
- mucin globules present
what is the histology of adenocarcinomas?
- peripheral
- glandular differentiation
- extracthoracic differentiation
what are the two pathways for development of adenocarcinomas?
- smokers :
k ras mutation - non smokers :
EGFR mutation
why is it important to identify the specific pathway?
- k ras mutation does not respond to targeted therapy
- EGFR mutation will respond to targeted therapy if it is a RESPONDER mutation
- it will not work with resistance mutations
-
what is large cell carcinoma?
- poorly differentiated tumours consisting of large cells
- they are just poorly differentiated versions of adenocarcinomas or squamous cell carcinoma
what is the cytology of small cell carcinomas?
- this is the worst form of lung cancer
- just consists of nuclei and s tiny amount
what is the histology of the small cell carcinoma?
- often central near the bronchi
- associated with smoking
- lots of mitosis
- tumour often outgrows its blood supply and becomes necrotic
what is the importance of the histological tumour type?
small cell or non small cell?
- small cell = use chemoradiotherapy
- non small cell = use surgery as it has not spread yet
what are some predictors of response to conventional chemotherapy ?
eg ERCC1
- this marker responds to cisplatin
- ERCC1 positive tumours have a poor response to cisplatin therapy
- so this can help us choose what drug to use
how does the epidermal growth factor receptor help as a target of treatment?
- EGFR
- makes the cells divide
- you can get a mutation of the EGFR
- EGFR is a type of membrane receptor tyrosine kinase
- it regulates angiotensin
- proliferation
- apoptosis
- migration
- EGFR is also the target of a tyrosine kinase inhibitor
what are the local effects of a bronchogenic carcinoma ?
- causes bronchial obstruction
- leads to collapse of the distal lung
- impaired drainage of the bronchus
what happens when the lung cancer invades local structures?
invasion of local airways - haemoptysis invasion around large vessels - oedema due to superior vena cava syndrome -
what happens when the lung cancer invades the oesophagus
dysphagia
what happens when the lung cancer invades the chest wall?
pain
what happens when the lung cancer invades nerves?
horners syndrome
what happens when the lung cancer extends through pleua or pericardium?
- breathlessness
- poor prognostic
what are the systemic effects of bronchogenic carcinoma?
- brain (fits)
- skin ( lumps)
- liver ( liver pain)
- bone ( bone pain and fracture)
what is the paraneoplastic syndrome?
- it is the systemic effect of the tumour due to abnormal expression by tumour cells of factors (like hormones)
what are paraneoplasmic syndromes that are endocrine?
- ADH - extra ADH = hyponatremia (low sodium)
- ACTH = cushings
- parathyroid issues = hypercalcemia
what is the aetiology of malignant pleural tumours?
- due to asbestos
what is the prognosis for malignant pleural tumours?
- very fatal
- more common in men
- long lag time
