8. Respiratory Pathology Flashcards
Lung cancer as a COD
3rd most common COD
6 Causes of lung cancer
Tobacco
Asbestos exposure
Radiation (radon exposure, therapeutic radiation)
Genetic predisposition
Familial (RARE)
Other (heavy metals (chromates, arsenic, nickel))
How does smoking cause lung cancer?
Smoking damages/ destroys p53 genes which usually regulate cell cycle
Uncontrollable cell division occurs
7 Clinical features of lung cancer
Haemoptysis (coughing up blood) Cough Chest/ Shoulder pain Dyspnoea Weight loss Finger clubbing Hoarseness
What is clubbing?
Angle between nail and nail bed becomes more obtuse
What are the local effects of bronchial obstruction in Lung cancer?
Cancerous tumour pushes on bronchus/ bronchiole, no air can get in/ out, anything past obstruction collapses: causes breathlessness
Impaired drainage of bronchus: Chest infection, Pneumonia, abscess
What are the effects of invasion of local structures in Lung cancer?
Invasion of local airways and vessels: Haemoptysis, cough
Invasion around large vessels: SVC syndrome: venous congestion, head and arm oedema, ultimately circulatory collapse
Oesophagus: Dysphagia
Chest wall: Pain
Nerves: Horners syndrome
What are the effects of inflammation/ irritation/ invasion of pleura or pericardium in Lung cancer?
Pleuritis or pericarditis, with effusions
=Breathlessness
=Cardiac compromise
Name 3 features of benign tumours and give an example
Grow more slowly
Do NOT metastasis
Do NOT invade adjacent tissues
E.g. Chrondroma
What are the 3 types of non-small cell carcinoma? What percentage of lung cancers are non-small cell?
Non-Small Cell = 80%
Squamous cell carcinoma (20-40%)
Adenocarcinoma (20-40%)
Large cell carcinoma (Rare)
How does cancer arise?
Multistep accumulation of mutations resulting in:
Disordered growth
Loss of cell adhesion
Invasion of tissue by tumour
Stimulation of new vessel formation around tumours
Name 2 features of malignant tumours and give an example
Potential to metastasise
Variable clinical behaviour from relatively indolent to aggressive
Commonest are epithelial tumours: “carcinomas”
4 Characteristics of small cell carcinoma
Undifferentiated
Aggressive
Paraneoplastic syndromes
Often outgrow blood supply and become necrotic
Presentation of small cell carcinoma
Close association with smoking
Often presenting in advanced stage
Often central near bronchi
Treatment and prognosis for small cell carcinoma
Chemotherapy only option
Poor survival and prognosis
Non-small cell cancer:
3 Characteristics of Squamous cell carcinoma
Local spread, metastasize late
Traditionally central, arising from bronchial epithelium, but recently increase in peripheral SqCC
Close association with smoking
Non-small cell cancer:
Arisal of Squamous cell carcinoma
In smokers, ciliated epithelium gets irritated and changes via metaplasia into squamous epithelium
Squamous epithelium is more resistant to irritants, but has no cilia so can’t clear mucus, causes cough
What are the 5 stages in the pathway to carcinoma?
Hyperplasia Metaplasia Dysplasia Carcinoma in situ Invasive Carcinoma
Non-small cell cancer:
Adenocarcinoma: What is it and where is it?
Cancer of glandular epithelium
Tends to develop in periphery of lung around terminal airways and in interstitium
What is the precursor stage of adenocarcinoma?
Atypical adenomatous hyperplasia: proliferation of atypical cells lining the alveolar walls.
Increases in size and eventually can become invasive
Which 2 mutations lead to adenocarcinomas in smokers and non-smokers?
Smokers: K ras mutation, DNA methylation p53
Non-smokers: EGFR mutation/ amplification
Which type of lung cancer is more common in non-smokers and females?
Adenocarcinoma
Non-small cell cancer:
Adenocarcinoma: metastasis
Extrathoracic metastases common and early
Non-small cell cancer:
Adenocarcinoma cytology
Malignant cells with large nucleoli and mucin vacuoles
How are the incidences of squamous cell carcinoma and adenocarcinoma changing?
Squamous cell carcinoma incidence is decreasing
Adenocarcinoma incidence is increasing
Non-small cell cancer:
Large cell carcinoma
Poorly differentiated tumours composed of large cells
Poorer prognosis
Small cell lung carcinoma survival
Untreated: 2-4 months
With current therapy: 10-20 months
=Chemoradiotherapy
(surgery very rarely undertaken as most have spread at time of diagnosis)
Non-small cell lung carcinoma survival
Depends on stage at diagnosis
Early Stage 1: 60% 5 yr survival
Late Stage 4: 5% 5 yr survival
20-30% have early stage tumours suitable for surgical resection.
Difficult to identify when at early stage
Less chemo-sensitive
Why is it important to differentiate between the different pathways leading to adenocarcinoma?
K ras mutation: unlikely to respond to targeted therapies
EGFR mutation: respond well to highly targeted therapy
What type of receptor is EGFR and what is used to block this receptor?
Tyrosine kinase receptor
Tyrosine kinase inhibitors work against this
What are paraneoplastic syndromes?
Systemic effect of tumour due to abnormal expression by tumour cells of factors (e.g. hormones) NOT normally expressed by the tissue from which the tumour arose
State some endocrine paraneoplastic syndromes.
SIADH (inappropriate ADH, causes hyponatremia)
Cushing’s Syndrome (producing ectopic ACTH)
Tumour cells can evade immune system through interaction with PD-l1 and PD-1, inhibiting cytotoxic T cells from targeting tumour cells
PD-L1 Inhibitors inhibit this action so our immune system can recognise tumour cells
How can samples be acquired for cytological analysis?
Bronchial brushing
Sputum
Pleural fluid
How can the tissue be examined for histological analysis?
Biopsy
Central tumour: bronchoscopy
Peripheral tumours: CT guided biopsy through skin
Surgical biopsy:
Mediastinal lymph node biopsy: for staging
How do we describe tumour spread (stage)?
T = Tumour (T1-4): tumour size or extent of local invasion N = Nodes (N0-3): No of lymph nodes involved M = Metastases (M0-1): presence of metastases
Systemic effects of bronchogenic carcinoma
Brain (fits)
Skin (lumps)
Liver (liver pain, deranged LFTs)
Bones (bone pain, fracture)
Non-endocrine example of paraneoplastic syndrome
Haematologic/coagulation defects
What is strongly associated with mesothelioma?
Asbestos
