Lung Cancer

Question 1

Identify smoking-related lung diseases.

Answer 1

1) COPD
- Emphysema
- Chronic bronchitis

Question 2

What is the common link between genetics and smoking in the development of lung disease ?

Answer 2

In cigarette smoking, there are different genetic predispositions to respond to cigarette smoke. Some patients, may activate more quickly leading to more reactive oxygen species, while others may be slow at detoxification (at removing toxic metabolites). Otherwise might be in the middle, better for them.
That’s why not every smoker gets lung disease, also if they do not at the same age

Question 3

Identify the main kinds of emphysema, from an anatomical POV. Identify their main anatomical features.

Answer 3

Centrilobular Emphysema
Panacinar Emphysema

1) Centrolobular emphysema: If particle is of a big size (i.e. cigarette smoke), tends to get deposited in branching point of bronchioles. Damage therefore typically happens at center of acinus, resulting in enlargement of airspaces because of damage tissue. Area for gas exchange reduced, so less gas exchange so hypoxia.
2) Panacinar emphysema: Permanent destruction of the airspaces (alveoli) distal to the respiratory bronchioles (whole of acinus is damaged). The pathogenesis relates to an intrinsic imbalance in the activity of protease/elastase released and an inhibitor of protease - alpha-1 antitrypsin.

E.g. smoking, get inflammation because smoking, neutrophils release proteases which damage tissue which causes holes (emphysema).
alpha-1 antitrypsin deficinency results in more protease activation so results may be more diffuse.

Question 4

Explain the delay in seeking medical advice in emphysema patients.

Answer 4

For symptoms to show at rest, requires 60% of lost lung tissue.
Before then, patient tend to adapt their lifestyles (e.g. stop sports or activities which cause symptoms).
As a result, patients tend to only present when symptoms are felt at rest or become a significant obstacle in daily life.

Question 5

Identify the main clinical features of chronic bronchitis.

Answer 5

• Cough
• Productive sputum (due to increased mucus production, since more mucus glands in bronchi, not due to infection)
• Possible reversible wheeze (hypersensitive muscle, may go into spasm if allergy or infection)
• Irreversible wheeze (due to thicker bronchi)
• Increased susceptibility to infection
• Edema

-Can still expand lungs fully, but takes time (more tissue, more mucus, possible edema)

Question 6

What are causes of chronic bronchitis ?

Answer 6

• Cigarette smoking mainly
• Industrial exposure and passive cigarette smoking
• E-cigarettes and vaping

Question 7

Define interstitial lung disease.

Answer 7

Pulmonary disorders characterized by interstitial inflammatory infiltrates, decreased lung volume and decreased oxygen-diffusing capacity on pulmonary function studies.

Question 8

Identify the main interstitial lung diseases.

Answer 8

• Hypersensitivity pneumonitis (extrinsic allergic alveolitis)
• Sarcoidosis
• Idiopathic Pulmonary Fibrosis

Question 9

Describe the main features of hypersensitivity pneumonitis (extrinsic allergic alveolitis).

Answer 9

♠ Inhaling antigen, and getting hypersensitivity reaction (type III and type IV)
♠ Extrinsic because antigens come from outside
♠ Acute or chronic interstitial inflammation in the lung
♠ In time, fibrosis and scarring occur, causing restriction to lungs
♠ Common types:
-Bird fancier (allergic to pigeons)
-Farmer’s lung (allergic to dust from moldy hay)

Question 10

Describe the main features of sarcoidosis. )

Answer 10

• Cell-mediated
• Granulomas are scattered in the interstitium of the lung
• The granulomatous phase of sarcoidosis can progress to a fibrotic phase (hence restriction)
• Hilar lymphadenopathy also occurs
• Raised angiotensin converting enzyme

Question 11

Is sarcoidosis specific to lungs ?

Answer 11

No, sarcoidosis is a systemic disease but typically presents in lungs

Question 12

Identify treatment for hypersensitivity pneumonitis and sarcoidosis.

Answer 12

1) Hypersensitivity pneumonitis: get away from allergen

2) Sarcoidosis: Steroids or immunosupressants

Question 13

Describe the main features of idiopathic pulmonary fibrosis.

Answer 13

• Etiology unknown (possibly partly post-viral)
• Scarring typically in lower lobes (hence restriction)
• Fibrosis is often patchy, with areas of dense scarring and honeycomb cystic change

Question 14

Is idiopathic pulmonary fibrosis specific to lungs ?

Answer 14

No, systemic disease

Question 15

What are the main types of tumors clinically ?

Answer 15

Benign

Malignant (primary and secondary)

Question 16

What are the characteristics of a benign lung tumor which could help you distinguish it from a malignant tumour ? What treatment would be required in such a situation ?

Answer 16

Lack of invasiveness
Clearly defined borders.
Slow growth from old CXR

In that situation, surgical excision

Question 17

Where can a primary malignant tumour grow in the lung ?

Answer 17

• Epithelium (most common)
• Vessels
• Muscle
• Cartilage
• Lymphoid
• Pleura

Question 18

What are the characteristics of a malignant lung tumor which could help you distinguish it from a benign tumour ? What treatment would be required in such a situation ?

Answer 18

Not well defined

Invasion pushing and invading lymph nodes

Question 19

Define metaplasia. How is it relevant in the lung ?

Answer 19

the change in the type of adult cells in a tissue to a form abnormal for that tissue. It is NOT pre-malignant.

In the lung, irritation (e.g. due to smoking) can result in metaplasia, from glandular columnar epithelium into squamous epithelium.

Question 20

Define dysplasia. How is it relevant in the lung ?

Answer 20

an abnormality of development. It IS pre-malignant.

If metaplasia occurred due to cigarette smoking, and continue to expose epithelium it to carcinogens, squamous epithelium will become dysplasic. Either dysplasia superimposes original glandular (giving you adenocarcinoma) or superimposes squamous (giving you squamous carcinoma, which is likely to be central because airways larger so more likely to get direct trauma).

Question 21

Identify the main tumours which cause secondary malignant tumours in the lung. How does it reach the lungs ?

Answer 21

• Renal carcinoma: via lymph nodes, and along renal veins

- Osteosarcoma: by blood (not lymph nodes)

Question 22

What are the main types of primary epithelial malignant tumours ?

Answer 22

• Squamous cell carcinoma (=NSCLC)
• Adenocarcinoma
• Small cell undifferentiated carcinoma
• Carcinoid tumours

Question 23

Describe the main causes, and features of small cell undifferentiated carcinoma of the lung.

Answer 23

-Causes: smoking, asbestos, air pollution.
From neuro-endocrine stem cells, primitive. May have Paraneoplasticeffects: can produce bioactive amines or peptide such as parathromone (so may present with hyperparathryoidiism, increased Calcium). Can produce ADH, so patient does not pass urine (presenting as high sodium, edema, confusion).
Patients can also present with demyelination due to immune mediated reaction to tumor .

Question 24

What are different ways of diagnosing a lung cancer ?

Answer 24

• Radiology – size change
• Cytology
• EBUS
• Biopsy
• Circulating DNA (find evidence of particular mutation, typically in EGFR, and non-invasive way to monitor if disease is responding to treatment)

Question 25

Define and identify paraneoplastic syndromes.

Answer 25

A set of signs and symptoms not directly caused by the cancer, but may be related to factors produced, and may be immunological.

• Connective Tissue/Bone: Finger Clubbing
• Haematological: Erythropoeitin production
• Skin: acanthosis nigricans (EGF)
• Kidney: immune complex glomerulonephritis

Question 26

Describe the main features of squamous cell carcinoma in the lungs:

• Cause
• Histological features
• Percentage of all lung cancers

Answer 26

• Causes: smoking, asbestos, air pollution
• Histological features: After injury to the bronchial epithelium, such as occurs with cigarette smoking, squamous metaplasia occurs. The metaplastic squamous mucosa follows the sequence of dysplasia, carcinoma in situ and invasive tumor. Well-differentiated tumors have keratin “pearls,” small round nests of brightly eosinophilic aggregates of keratin surrounded by concentric (“onion skin”) layers of squamous cells
• Percentage of all lung cancers: 40%

Question 27

What method can we use to classify different cancers by extent of cancer development ?

Answer 27

TNM staging (stage I to IV)

Question 28

Describe the main features of adenocarcinomas in the lungs:

• Cause
• Histological features
• Percentage of all lung cancers

Answer 28

• Causes: smoking, asbestos, air pollution
• Histological features: = neoplasia of epithelial tissue that has glandular origin and/or characteristics. Tends to arise in the periphery and is often associated with pleural fibrosis and subpleural scar. Once thought to arise in scars left by old tuberculosis or healed infarcts.
• Percentage of all lung cancers: 40%

Question 29

Do adenocarcinomas affect any demographics in particular ?

Answer 29

Women slightly more affected than men

Question 30

Describe the main causes, and features of carcinoid tumors of the lung.

Answer 30

-Arise from the resident neuroendocrine cells in the bronchial epithelium.

• “Typical”- towards less aggressive end of spectrum (not so related to smoking)
• “Atypical”–smoking related, tends towards malignant end of spectrum

Question 31

Identify commonly mutated oncogenes, and the cancers they result in.
Why is it important to know the molecular basis of different cancers ?

Answer 31

Mutated: 
EGFR
BRAF (melanomas and brain cancers)
RAS (colon cancer)
ALK 
Because the specific mutation will dictate treatment.

Question 32

Define PD-1 and PD-L1 and explain their significance in the context of lung disease.

Answer 32

Cancer express PD-L1 (Programmed death-ligand 1)/PD-1 (Programmed cell death protein 1) which ligate PD receptors on lymphocytes. If tumor cell has lots of those, by binding lymphocyte, tells lymphocyte not to kill it, so has potential to resist effect of immune response.

Treatment target PDL1 or PD1 (typically with antibodies) trying to interrupt that communication preventing lymphocyte from killing cancer cell.

Question 33

Describe the main features of mesothelioma:

• Causes
• Incidence
• Lag period
• Demographics
• Histology
• Treatment

Answer 33

• Causes: asbestos, crocidolite
• Incidence: Rising
• Lag period: 20-40 years (long)
• Demographics: More males affected than females
• Histology: Grows along pleural surface, and encase and compress the lung
• Treatment: Mainly untreatable

Question 34

What is the link between pleural plaque and mesothelioma ?

Answer 34

Pleural plaque (thickened pleura with accumulation of material) and mesothelioma are both caused by exposure to asbestos.

However, having pleural plaques does not mean that patients have, or will go on to get, a more serious disease.

Question 35

How can mesothelioma lead to death ?

Answer 35

Restricted lungs, cannot expand, accumulate fluid, death

Question 36

Define TNM.

Answer 36

“Standard for classifying the extent of spread of cancer
T (size of OF tumor and invasion, Tx, Tis, T0 to T4)
N (lymph node involvement, Nx, N0 to N3)
M (distant metastasis, M0 or M1)”

Can be classified from stage I to stage IV.