lecture 7: pathology of lung cancer

Question 1

what are the initial clinical presentations?

Answer 1

• most patients are asymptomatic

- the clear symptoms are
coughing  
coughing up blood (haemoptysis) 
lots of infections 
chest wall pain

Question 2

what is cytology?

what is shown in cytology?

Answer 2

cytology is looking at the individual cells

• sputum
• bronchial washings
• pleural fluid

Question 3

what is histology ?

what does histology show?

Answer 3

• histology is looking at the tissues
• biopsy at bronchoscopy
• lymph node biopsy
• peripheral tumor biopsy

Question 4

what are the two types of tumour?

Answer 4

• benign tumours
  do not metastasise
  cause local complications
• malignant tumours
  have potential to metastasises
• involves the adjacent tissues

Question 5

what are the two types of tumour of the lung?

Answer 5

• non small cell
  adenocarcinoma
  squamous cell carcinoma
  large cell carcinoma
• small cell
  much worse prognosis than the non small cell
  grow rapidly
  and metastasise

Question 6

what types of lung cancer are increasing and what is decreasing?

Answer 6

• 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

Question 7

what is the most common malignant lung tumour?

Answer 7

• epithelial tissues

Question 8

what is the most common type of lung cancer of non smokers?

Answer 8

adenocarcinoma

Question 9

where are squamous cell carcinomas located ?

where are adenocarcinomas located?

Answer 9

• squamous cell carcinomas are located near the mediastinum

- adenocarcinomas are located in the periphery

Question 10

what is the main cause of lung cancer?

Answer 10

• smoking
  both passive and direct smoking
• asbestos
• radiation

Question 11

example of

• tumour initiator
• tumour promoter
• complete carcinogens

Answer 11

• hydrocarbons
• nicotine
• nickel

Question 12

how might a genetic predisposition arise?

Answer 12

• familial lung cancer is really rare
• there are some susceptible genes:
• nicotine addiction
• susceptibility to chromosome breaks and DNA damage

Question 13

what are the stages of development of a carcinoma?

Answer 13

• metaplasia
• dysplasia
• carcinoma in situ
• invasive carcinoma

a tumour is basically an accumulation of mutations

Question 14

what is the pathway of development of squamous cell carcinoma?

Answer 14

• 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

Question 15

what is the cytology of squamous cell carcinoma?

Answer 15

• large nuclei

- keratin in the cytoplasm

Question 16

what is the histology of squamous cell carcinomas?

Answer 16

• keratinisation
• intracellular prickles
• lots of subtypes

Question 17

what is the development of adenocarcinomas?

Answer 17

• 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

Question 18

what is the progression of an atypical adenomatous hyperplasia?

Answer 18

• 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

Question 19

what is the cytology of adenocarcinomas?

Answer 19

• shows glandular differentiation
• produces mucin
• a typical nuclei
• mucin globules present

Question 20

what is the histology of adenocarcinomas?

Answer 20

• peripheral
• glandular differentiation
• extracthoracic differentiation

Question 21

what are the two pathways for development of adenocarcinomas?

Answer 21

• smokers :
  k ras mutation
• non smokers :
  EGFR mutation

Question 22

why is it important to identify the specific pathway?

Answer 22

• 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

-

Question 23

what is large cell carcinoma?

Answer 23

• poorly differentiated tumours consisting of large cells

- they are just poorly differentiated versions of adenocarcinomas or squamous cell carcinoma

Question 24

what is the cytology of small cell carcinomas?

Answer 24

• this is the worst form of lung cancer

- just consists of nuclei and s tiny amount

Question 25

what is the histology of the small cell carcinoma?

Answer 25

- often central near the bronchi - associated with smoking - lots of mitosis - tumour often outgrows its blood supply and becomes necrotic

Question 26

what is the importance of the histological tumour type? | small cell or non small cell?

Answer 26

- small cell = use chemoradiotherapy | - non small cell = use surgery as it has not spread yet

Question 27

what are some predictors of response to conventional chemotherapy ? eg ERCC1

Answer 27

- 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

Question 28

how does the epidermal growth factor receptor help as a target of treatment?

Answer 28

- 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

Question 29

what are the local effects of a bronchogenic carcinoma ?

Answer 29

- causes bronchial obstruction - leads to collapse of the distal lung - impaired drainage of the bronchus

Question 30

what happens when the lung cancer invades local structures?

Answer 30

``` invasion of local airways - haemoptysis invasion around large vessels - oedema due to superior vena cava syndrome - ```

Question 31

what happens when the lung cancer invades the oesophagus

Answer 31

dysphagia

Question 32

what happens when the lung cancer invades the chest wall?

Answer 32

pain

Question 33

what happens when the lung cancer invades nerves?

Answer 33

horners syndrome

Question 34

what happens when the lung cancer extends through pleua or pericardium?

Answer 34

- breathlessness | - poor prognostic

Question 35

what are the systemic effects of bronchogenic carcinoma?

Answer 35

- brain (fits) - skin ( lumps) - liver ( liver pain) - bone ( bone pain and fracture)

Question 36

what is the paraneoplastic syndrome?

Answer 36

- it is the systemic effect of the tumour due to abnormal expression by tumour cells of factors (like hormones)

Question 37

what are paraneoplasmic syndromes that are endocrine?

Answer 37

- ADH - extra ADH = hyponatremia (low sodium) - ACTH = cushings - parathyroid issues = hypercalcemia

Question 38

what is the aetiology of malignant pleural tumours?

Answer 38

- due to asbestos

Question 39

what is the prognosis for malignant pleural tumours?

Answer 39

- very fatal - more common in men - long lag time