Tumours of the lung and pleura

Question 1

What are the causes of lung cancer ?

Answer 1

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

Question 2

How is lung cancer diagnosed?

Answer 2

history
exam
imaging
tissue diagnosis

Question 3

What are some important signs/symptoms to establish in history for lung cancer?

Answer 3

specific to lung cancer

• persistent cough
• haemoptysis
• breathlessness (increasing on little exertion)
• chest pain

General cancer symptoms

• unintentional weight loss
• fatigue
• lymphadenopathy

Question 4

What does paraneoplastic mean?

Answer 4

syndrome that is the consequence of cancer in the body but unlike mass effect is not due to the local presence of cancer cells

Question 5

What paraneoplastic syndromes have been associated with small cell carcinoma particularly?

Answer 5

cushing’s syndrome
syndrome of inappropriate ADH secretion
hypercalcaemia

Question 6

What are the differential diagnoses for cough?

Answer 6

infection esp TB
foreign body
psychogenic

Question 7

What are the differential diagnoses for haemoptysis?

Answer 7

Infection - esp TB

PE

Question 8

What are the differential diagnoses for breathlessness?

Answer 8

infection 
foreign body 
PE
pneumothorax
COPD, asthma
HF

Question 9

What are the differential diagnoses for chest pain?

Answer 9

musculoskeletal
PE
pneumothorax
ischaemic heart disease

Question 10

What are the different methods of tissue diagnosis?

Answer 10

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

Question 11

How is lung cancer classified?

Answer 11

non-small cell carcinoma
=> adenocarcinoma
=> squamous cell carcinoma
=> others (uncommon)

small cell carcinoma
carcinoid tumours
metastases

Question 12

What are the stages of making the correct diagnosis of lung cancer?

Answer 12

get extremely good idea from history and imaging
get better idea from morphology
clinch the diagnosis with immunohistochemistry

Question 13

What is immunohistochemistry?

Answer 13

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

Question 14

What are the following features of adenocarcinoma (non-small cell carcinoma)?

• imaging
• morphology
• immunohistochemistry
• management

Answer 14

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

Question 15

What are the following features of squamous cell carcinoma (non-small cell carcinoma)?

• imaging
• morphology
• immunohistochemistry
• management

Answer 15

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

Question 16

What are the following features of small cell carcinoma?

• imaging
• morphology
• immunohistochemistry
• management

Answer 16

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

Question 17

What are carcinoid tumours like?

Answer 17

well-differentiated, low grade malignancy
morphological features = orderly arrangements of uniform cells, well-circumscribed
immunohistochemistry = synaptophysin +, chromagranin +
treated usually by local resection

Question 18

What are the commonest sources of metastatic lung cancer?

Answer 18

commonest tumours of the lungs
- breast, colon, stomach, pancreas, kidney

morphological features - usually multiple, more often peripheral

Question 19

How are lung cancers reported?

Answer 19

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

Question 20

What is encompassed in T-stage of TNM staging?

Answer 20

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

Question 21

What is encompassed in the N stage of the TNM staging?

Answer 21

involvement of intrapulmonary, hilar, peribronchial nodes
involvement of ipsilateral mediastinal or subcarinal nodes
involvement of contralateral nodes or scalene, supraclavicular nodes

Question 22

What are the stage groups of TNM staging and why are they important?

Answer 22

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

Question 23

How is non-small cell carcinoma treated in general terms?

Answer 23

localised
- surgery and radiotherapy

advanced

• chemo
• immunotherapy
• targeted molecular therapy
• maybe radiotherapy

Question 24

What are immunotherapy treatments?

Answer 24

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

Question 25

What are targeted molecular therapies?

Answer 25

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

Question 26

What is the management of non-small cell lung cancer?

Answer 26

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

Question 27

What is mesothelioma?

Answer 27

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