Pathology of Lung cancers

Question 1

What is the most common cause of death by cancer ?

Answer 1

Lung Cancer

Question 2

What is the aetiology of lung cancer ?

Answer 2

Tobacco 
Asbestos
Environmental radon
Occupational exposures:
    - chromates
    - hydrocarbons
    - nickel
Air pollution and urban environment 
Other radiation
Pulmonary fibrosis

Question 3

How much of lung cancer is attributable to tobacco ?

Answer 3

> 85%

Question 4

What percentage of smokers get lung cancer ?

Answer 4

10%

Question 5

What gender is more susceptible to cancer ?

Answer 5

Females

Question 6

What percentage of non-smoking lung cancers are caused by passive smoking ?

Answer 6

At least 25%

Question 7

Why does tobacco smoke cause lung cancer ?

Answer 7

Epithelial effects Multi-hit theory in carcinogenesis Host activation of pro-carcinogens - Inherited polymorphisms predispose (metabolism of pro-carcinogens, nicotine addiction)

Question 8

How does adenocarcinoma arise in the lung ?

Answer 8

Bronchoalveolar epithelial stem cells transform

Question 9

How does squamous cell carcinoma arise from ?

Answer 9

Bronchial epithelial stem cells transform

Question 10

Where about do you see adenocarcinoma ?

Answer 10

In the lung periphery

Question 11

Where about do you see squamous cell carcinoma?

Answer 11

In the central lung airways

Question 12

Which oncogene is activated by smoking ?

Answer 12

KRAS

Question 13

What are the other important oncogenes that give rise to lung cancer ?

Answer 13

EGFR BRAF HER2 ALK rearrangements

Question 14

What are the common tumours of the lung ?

Answer 14

Carcinoid tumours:
    - <5% of lung neoplasms 
    - low grade malignancy 
Tumours of bronchial glands:
    - very rare 
    - adenoid cystic carcinoma 
    - mucoepidermoid carcinoma
    - benign adenomas
Lymphoma 
Sarcoma
Metastases

Question 15

What are the 4 main types of lung cancer ?

Answer 15

Squamous cell carcinoma
Adenocarcinoma
Small cell carcinoma
Large cell carcinoma

Question 16

What is an adenocarcinoma in situ ?

Answer 16

Bronchioalveolar cell carcinoma (subtype of adenocarcinoma)

Question 17

When does primary lung cancer present itself ?

Answer 17

Late in its natural history, grows clinically silent for many years

Question 18

What does symptomatic lung cancer indicate ?

Answer 18

Fatal

Question 19

What are the local effects of bronchial obstruction caused by lung cancer ?

Answer 19

Bronchial obstruction:

- collapse 
- endogenous lipoid pneumonia 
- infection/ abscess
- bronchiectasis

Question 20

What is endogenous lipoid pneumonia ?

Answer 20

When lipids enter the bronchial tree (the result of localised accumulation of lipid laden macrophages within alveolar spaces distal to an obstructed airway)

Question 21

What are the local pleural effects caused by lung cancer ?

Answer 21

Inflammation

Malignancy

Question 22

What are the direct invasions caused by lung cancer ?

Answer 22

Into the chest wall
Nerves
Mediastinum (superior vena cava and pericardium)
Lymph nodes

Question 23

What are the local effects of cancer on the nerves ?

Answer 23

Phrenic- diaphragmatic paralysis
L recurrent laryngeal- hoarse, Bovine cough
Brachial plexus- Pancoast T1 damage
Cervical sympathetic- Horner’s syndrome

Question 24

What is the outcome from lymph node metastasis ?

Answer 24

Lymphangitis carcinomatosa

Question 25

What are the distant effects of lung cancer ?

Answer 25

Distant metastases (liver, adrenals, bone, brain, skin) Secondary to local effects (neural, vascular)
Non- metastatic effects

Question 26

What are the non-metastatic paraneoplastic effects of lung cancer ?

Answer 26

Skeletal:
    - clubbing
    - HPOA
Endocrine:
    - ACTH, siADH, PTH
    - carcinoid syndrome
    - gynecomastia 
Neurological:
    - polyneuropathy 
    - encephalopathy 
    - cerebellar degeneration 
    - myasthenia 
Cutaneous:
    - acanthosis nigricans 
    - dermatomycosis
Hematologic:
    - granulocytosis
    - eosinophilia 
    - DIC
Cardiovascular:
    - thrombophlebitis migrans 
Renal:
    - nephrotic syndrome

Question 27

What are the non-metastatic paraneoplastic effects of lung cancer, that are endocrine and caused by small cell cancers ?

Answer 27

ACTH, siADH

Question 28

What are the non-metastatic paraneoplastic effects of lung cancer, that are endocrine and caused by squamous cell cancers ?

Answer 28

PTH

Question 29

What are the lung cancer investigations ?

Answer 29

CXR

Sputum cytology (rarely used)
Bronchoscopy:
    - bronchial biopsy
    - bronchial brushings and washings 
    - EBUS
Trans-thoracic fine needle aspiration
Trans-thoracic core biopsy 
Pleural effusion cytology and biopsy 

Advanced imaging techniques:

- CT
- MRI, PET

Question 30

What are the prognostic factors in lung cancer ?

Answer 30

Stage of disease
Classification: Type of Disease
Markers / Oncogenes / Gene expression profiles
Prognostic markers MIGHT be used to select patients for ADJUVANT therapy

Question 31

What percentage of patients in Scotland with Lung cancer get surgical treatment ?

Answer 31

10-12%

Question 32

What is 5 year survival rate for non-small cell carcinomas ?

Answer 32

Between 10-25%

Question 33

What is the 5 year survival rate of small cell carcinomas ?

Answer 33

4%

Question 34

What is the average survival rate for small cell carcinoma ?

Answer 34

9 months

Question 35

What is used after the diagnosis to select patients for therapy ?

Answer 35

Predictive biomarkers will increasingly be used to select pateints for therapy:

- adenocarcinoma:
      - EGRF, KRAS, HER2, BRAF mutations 
      - ALK translocations 
- squamous cell:
      - little or no effective molecular targeted therapy
- immunotherapy in NSCLC has transformed practise

Question 36

What is an immune checkpoint inhibitor ?

Answer 36

A drug which prevents passage past a checkpoint, immune checkpoints control immune reactions

Question 37

Give examples of how cancer cells avoid immune destruction ?

Answer 37

PD1, PD-L1