Respiratory pathology - Lung cancer

Question 1

Describe the epidemiology of lung cancer?

Answer 1

• Third most common cause of death in UK
• 1/4 of cancer deaths
• 5 year survival is 5.5%

Question 2

What are some causes of lung cancer?

Answer 2

• tobacco
• asbestos
• radon

Question 3

What is the trend in smoking and how is it associated with mortality from lung cancer?

Answer 3

• Steady decline in smoking prevalence among men over the years
• The peak prevalence for women was about 15 years later
• Mirrors the mortality of lung cancer
• Mortality in men is declining over time

Question 4

What are some clinical features of lung cancer?

Answer 4

MANY HAVE NO SYMPTOMS
unexplained/persistant for over 3 weeks:
- cough
- shoulder/chest pain
- dyspnoea
- hoarseness
- finger clubbing - greater than 180 degrees

HAEMOPTYSIS - coughing blood

Question 5

What is done it if a patients presents with symptoms which could be due to lung cancer?

Answer 5

• X ray referral - URGENT

- If it shows a mass then a biopsy is taken

Question 6

How are tumours typed and staged?

Answer 6

• Small cell or non small cell?

- Tumour, nodes and metasteses (e.g. T1a - letters for each of 3 parts)

Question 7

What factors are considered in order to stage a tumour?

Answer 7

• Location of tumour indicated
• If closer to mediastinum/ chest wall/ spreads to lymph nodes in neck, has higher T staging
• Surgery impractical if spreads to lymph nodes
• Location, size and proximity to other organs
• Has it spread to other places

Question 8

How are PET scans done?

Answer 8

• Patients have to fast for 4 hours
• Given radioactive glucose
• Tumour much more metabolically active

Question 9

How is metastasis identified?

Answer 9

• Looking at scans, MRI, CT

Question 10

What are the stages involved in lung cancer diagnosis?

Answer 10

• Scan
• Biopsy
• Benign/Malignant
• Type?
• Staging
• Functional capacity of person
• Prognosis

Question 11

What is a trans-thoracic CT biopsy, advantages/disadvantages?

Answer 11

• Using CT guidance through thorax
• real time, sensitive
• risk of pneumothorax, small sample size, in case of bleeding no immediate therapy possible

Question 12

Why must the patients physical condition be assessed before considering a treatment plan?

Answer 12

• They may have other health conditions which affect treatment
• Are they fit to undergo treatment?

Question 13

What does prognosis of lung cancer depend on?

Answer 13

• Prognosis depends on the cell type and the extent of the spread

Question 14

How can cytology be done - where and how are specimens obtained?

Answer 14

Cytology:

• Sputum
• Bronchial washings and brushings
• Pleural fluid
• Endoscopic fine needle biopsy of tumour/lymph nodes

Question 15

How are biopsies obtained for histology (looking at tissues)?

Answer 15

Histology:

• Biopsy at bronchoscopy - central tumours
• Percutaneous CT guided biopsy - peripheral tumours
• Mediastinoscopy and lymph node biopsy - for staging
• Open biopsy at time of surgery

Question 16

Types of non-small cells carcinomas

Answer 16

• squamous cell carcinoma
• adenocarcinoma (glands)
• large cell carcinoma

Question 17

What is small cell carcinoma?

Answer 17

• They grow rapidly and metastasise early so it is unusual to find an early stage small cell carcinoma
• Worse than non-small cell

Question 18

What is squamous cell carcinoma and its features?

Answer 18

• develops by multi-step pathway
• changes from normal to squamous epithelium (found in skin)
• reversible at the start
• local spread, late metastasis
• arise centrally
• associated with smoking

Question 19

Adenocarcinoma

Answer 19

• common in non-smokers too
• atypical adenomatous hyperplasia - atypical cell proliferation lining alveolar walls
• different pathways in smokers and non-smokers
• metastise common and early

Question 20

What is large cell carcinoma and its features?

Answer 20

• anything doesn’t fit as adenocarcinoma or sqaumous
• poorly differentiated
• show some evidence of glandular, squamous or neuroendocrine differentiation on EM
• probably poorly differentiated adeno/squamous cell carcinomas
• poorer prognosis

Question 21

What is small cell carcinoma and its features?

Answer 21

• small cells
• not differentiated
• keep proliferating
• outgrow blood supply so become necrotic
• often near central bronchi
• smoking association
• most present with advanced diseasee
• bad prognosis
• paraneoplastic syndrome association

Question 22

What is the difference between small cell and non small cell carcinoma in terms of survival rate and treatment?

Answer 22

small cell - low survival rate, chemo-radiotherapy

non small cell - early stage has higher survival rate (60%). Some suitable for surgery. Less chemosensitive

Question 23

Why is it important to sub type non small cell carcinomas?

Answer 23

• Treatment depends on type

- Chemo better for adenocarcinoma

Question 24

Targetted therapy

Answer 24

• Looking at mutation type to target therapy

Question 25

What is a EGFR mutation? | common

Answer 25

- membrane receptor tyrosine kinase - regulates apoptosis, proliferation, migration, angiogenesis and migration - mutated in lung cancer so always on - more common in non-smokers, females, asian. - Common in adenocarcinoma - target of TKI

Question 26

What is ALK mutation? | not common

Answer 26

- mutations on downstream effects including tumour growth - non smokers may have it - Can use FISH

Question 27

What is immunemodulatory therapy?

Answer 27

- Tumours evade immune system | - PDL-1 made by tumours to inhibit cytotoxic T cells (drug target developed)

Question 28

What are the symptoms that may occur due to tumour invasion in other tissues

Answer 28

- bronchial obstruction = collapse of lung can cause shortness of breath, impaired bronchial drainage can cause chest infections - invasion of airway and vessels = cough, haemoptysis - oesophagus invasion = dysphagia (hard to swallow) - nerves = Horners syndrome - chest wall = pain - large vessel invasion = SVC congestion of head and arm, headache - invasion of pleura/pericardium = breathlessness, cardiac compromise

Question 29

What are the physical signs of distant spread of bronchogenic carcinoma?

Answer 29

- brain fits - skin lumps - liver pain - bones pain/fractures

Question 30

What is a paraneoplastic syndrome?

Answer 30

systemtic effect of tumour due to abnormal expression by tumour cells of factors like hormones not normally expressed. E.g. endrocine can cause syndrome of inappropriate ADH causing hyponatremia (low sodium)

Question 31

What are the different parts of TNM staging and give some examples

Answer 31

Primary tumour (T): TX can’t be assessed T0 no evidence T1 <3 cm + surrounded by lung or pleura + no bronchoscopic evidence of invasion into a main bronchus T2 >3 cm or involves main bronchus >2 cm from carina or invades visceral pleura T3 invades chest wall or diaphragm or mediastinal pleura or parietal pericardium or main bronchus <2 cm from carina T4 malignant pleural effusion or invades mediastinum or heart or great vessels or trachea or oesophagus or carina or vertebral body Lymph node (N) NX can’t be assessed N0 no regional lymph node metastasis N1 metastasis in ipsilateral peribronchial / hilar node N2 metastasis in ipsilateral mediastinal / subcarinal node N3 metastasis in contralateral mediastinal / hilar, ipsilateral / contralateral scalene, or supraclavicular node ``` Distant metastasis (M) MX can’t be assessed M0 no distant metastasis M1a metastasis within lung M1b metastasis outside lung ```