Tumours of the lung and pleura Flashcards
What are the causes of lung cancer ?
Environmental (90%)
- tobacco smoking
- industrial exposures = asbestos, heavy metal, coal
- radiation
- pulmonary fibrosis = idiopathic, post-infectious
Genetic
- rare
- germline EGFR mutations
Sporadic
- uncommon
- typically - young, female
How is lung cancer diagnosed?
history
exam
imaging
tissue diagnosis
What are some important signs/symptoms to establish in history for lung cancer?
specific to lung cancer
- persistent cough
- haemoptysis
- breathlessness (increasing on little exertion)
- chest pain
General cancer symptoms
- unintentional weight loss
- fatigue
- lymphadenopathy
What does paraneoplastic mean?
syndrome that is the consequence of cancer in the body but unlike mass effect is not due to the local presence of cancer cells
What paraneoplastic syndromes have been associated with small cell carcinoma particularly?
cushing’s syndrome
syndrome of inappropriate ADH secretion
hypercalcaemia
What are the differential diagnoses for cough?
infection esp TB
foreign body
psychogenic
What are the differential diagnoses for haemoptysis?
Infection - esp TB
PE
What are the differential diagnoses for breathlessness?
infection foreign body PE pneumothorax COPD, asthma HF
What are the differential diagnoses for chest pain?
musculoskeletal
PE
pneumothorax
ischaemic heart disease
What are the different methods of tissue diagnosis?
sputum cytology = frail patients, low sensitivity
pleural cytology = reasonable sensitivity, diagnostic and therapeutic
bronchial washing/brushing cytology= tumours in larger airways, reasonable sensitivity
bronchial biopsy = tumours in the larger airways, good sensitivity
endobronchial us / fna = evidence of lymph node involvement, diagnostic and staging
transcutaneous biopsy= peripheral tumours, includes needle biopsy, open biopsy, VATS
How is lung cancer classified?
non-small cell carcinoma
=> adenocarcinoma
=> squamous cell carcinoma
=> others (uncommon)
small cell carcinoma
carcinoid tumours
metastases
What are the stages of making the correct diagnosis of lung cancer?
get extremely good idea from history and imaging
get better idea from morphology
clinch the diagnosis with immunohistochemistry
What is immunohistochemistry?
cells of different tumours express different antigens
primary antibodies specific to a desired antigen are applied then unbound antibodies washed off
secondary antibodies, specific to the primary antibodies and with attached peroxidase enzyme are applied
colourless substrate is added which becomes coloured when degraded by peroxidase
What are the following features of adenocarcinoma (non-small cell carcinoma)?
- imaging
- morphology
- immunohistochemistry
- management
imaging = classically peripheral
morphology = gland formation, intracellular mucin
immunohistochemistry = TTF1+
commonest type of lung cancer
weaker smoking association
management
- localised = resection/radiotherapy, adjuvant chemo
- metastatic= chemo, molecular targeted therapies, immunotherapy
What are the following features of squamous cell carcinoma (non-small cell carcinoma)?
- imaging
- morphology
- immunohistochemistry
- management
imaging = classically central, cavitating
morphology = keratinisation: extracellular and intracellular, intercellular bridges
immunohistochemistry = p63+, cytokeratin 5+
very strong association with smoking
management
- local = resection/radiotherapy adjuvant chemo
- metastatic= chemo, molecular targeted therapies, immunotherapy
probably better prognosis than adenocarcinoma
What are the following features of small cell carcinoma?
- imaging
- morphology
- immunohistochemistry
- management
much less common
imaging = usually massive mediastinal lymphadenopathy
morphology = very poorly differentiated, minimal cytoplasm, crushed appearance
immunohistochemistry = synpatophysin +, chromograinin+
strong smoking association
management
- local - extremely rare, sugery can be considered
- metastatic = chemo +/- radiotherapy
terrible prognosis
What are carcinoid tumours like?
well-differentiated, low grade malignancy
morphological features = orderly arrangements of uniform cells, well-circumscribed
immunohistochemistry = synaptophysin +, chromagranin +
treated usually by local resection
What are the commonest sources of metastatic lung cancer?
commonest tumours of the lungs
- breast, colon, stomach, pancreas, kidney
morphological features - usually multiple, more often peripheral
How are lung cancers reported?
provide info to assess
- adequacy of surgery - is all of the tumour out?
- whether pt needs further surgery
- what the pts likely prognosis
mostly encompassed by stage
also non-staging features e.g. tumour differentiation
What is encompassed in T-stage of TNM staging?
tumour size
distance from carina
extent of lung collapse caused by tumour
separate tumour nodules
invasion beyond lungs - pleura, chest wall, diaphragm, mediastinal pleura, parietal pericardium
What is encompassed in the N stage of the TNM staging?
involvement of intrapulmonary, hilar, peribronchial nodes
involvement of ipsilateral mediastinal or subcarinal nodes
involvement of contralateral nodes or scalene, supraclavicular nodes
What are the stage groups of TNM staging and why are they important?
stage group IA = t1, n0, m0
stage group IIB = t2b, n1, m0
stage group IV = any t, any n, m1
used for treatment decisions and prognostication
How is non-small cell carcinoma treated in general terms?
localised
- surgery and radiotherapy
advanced
- chemo
- immunotherapy
- targeted molecular therapy
- maybe radiotherapy
What are immunotherapy treatments?
drugs which modulate the immune response, triggering anti-tumour immune responses
extremely effective, relatively few SE
PD-L1 testing in non-small cell lung cancer is routine
- +ve in around 50% cases
- high levels expression predict good response to immunotherapy e.g. pembrolizumab
also used in melanoma and head and neck squamous cell carcinoma
What are targeted molecular therapies?
drugs targeted against specific mutations in tumour cells
- extremely effective and relatively few side effects
EGFR, ALK and ROS1 testing are now routine in non-small cell lung cancer
- EGFR mutations predict response to anti-EGFR tyrosine kinase inhibitors - gefitinib
- ALK translocations predict response to anti-ALK tyrosine kinase inhibitors - crizotinib
- ROS1 translocations predict response to same drugs as ALK
What is the management of non-small cell lung cancer?
all can be tested for EGFR mutations, ALK translocations and ROS1 translocations and PDL1 expression
>50% are now eligible for immunotherapy or targeted molecular therapy
much better prognosis for these patients:
- months - yrs of high quality life
well enough to return to normal activities
fewer admissions from side effects
What is mesothelioma?
tumours of the pleura are most commonly metastatic
rare derives from mesothelial lining of pleura
male>female
extremely poor prognosis
>90% caused by asbestos
usually present with SOB, chest pain
