Pathology of Lung Cancer

Question 1

What are the two main families of carcinogens in tobacco smoke

Answer 1

1. Polycyclic aromatic hydrocarbons

2. Nitrosamines

Question 2

How many carcinogens are present in tobacco smoke?

Answer 2

Over 60

Question 3

Which is the more prevalent family of carcinogens in modern cigarettes and which kind of lung cancer do they cause?

Answer 3

N-nitrosamines (more likely to cause adenocarcinoma)

Question 4

How many genomic alterations must occur in order to make a respiratory epithelial cell cancerous?

Answer 4

Around 3-12 key genomic alterations must be accumulated in a certain sequence to provide a cell with cancerous traits

Question 5

Explain why pro-carcinogens found in tobacco smoke are important in lung cancer aetiology

Answer 5

Pro-carcinogens which are metabolised into carcinogens by enzymes in the liver. These enzymes vary between individuals’ as we can inherit different iso-enzymes- therefore each individual has a different propensity for metabolising these pro-carcinogens into carcinogens (this directly impacts the risk of lung cancers).

Question 6

There are 2 principal stem cell populations in the lungs. Where are they located and which kind of cancer are they likely to differentiate into?

Answer 6

1. Stem cells of the bronchus become squamous cell carcinoma
2. peripheral epithelial stem cells become adenocarcinoma

Question 7

other than carcinoma, what other kinds of cancer can be found in the lungs?

Answer 7

Lymphoma
Sarcoma
Mets

Question 8

Is lung cancer usually diagnosed early or late?

Answer 8

Late- it is often asymptomatic for many years.

Symptomatic lung cancer tends to be fatal

Question 9

What happens when a tumour interferes with the phrenic nerve?

Answer 9

Diaphragmatic paralysis

Question 10

What happens when a tumour interferes with the left recurrent laryngeal nerve?

Answer 10

Hoarse voice & Bovine cough

Question 11

What happens when a tumour interferes with the brachial plexus?

Answer 11

Pancoast T1 damage

Question 12

What happens when a tumour interferes with the cervical sympathetic nerves?

Answer 12

Horner’s syndrome.

Horner’s syndrome is a rare condition characterized by miosis (constriction of the pupil), ptosis (drooping of the upper eyelid), and anhidrosis (absence of sweating of the face). It is caused by damage to the sympathetic nerves of the face.

Question 13

What do small cell carcinomas often secrete?

Answer 13

ADH

Question 14

Why do patients with squamous cell carcinoma often present with hypercalcaemia?

Answer 14

tumour often secretes a molecule similar to parathyroid hormone

Question 15

How is lung cancer investigated?

Answer 15

1. CXR
2. Bronchoscopy
3. Transthoracic fine needle biopsy
4. Transthoracic core biopsy
5. Pleural effusion cytology and biopsy
6. advanced imaging

Question 16

the 5 year survival of patients with lung cancer in scotland?

Answer 16

<9.8% (dreadful)

Question 17

What are the 5 year survival rates for stage I and stage II operable lung cancers?

Answer 17

Satge I = 6-%

Stage II = 35%

Question 18

What percentage of Scottish lung cancer patients are operable?

Answer 18

10-15%

Question 19

Which type of lung cancer is associated with the highest mortality?

Answer 19

Small cell carcinoma (5 year survival is 4%, median survival = 9 months)

Question 20

Are tumours caused by smoking molecularly simple or molecularly complex?

Answer 20

Complex

Question 21

Why is a molecularly complex tumour a bad thing?

Answer 21

it makes it harder to target with drugs

Question 22

List the 6 genetic alterations which can cause non-smoking related adenocarcinomas

Answer 22

EGFR alteration (15% in Aberdeen royal)

ALK gene rearrangement

ROS1 gene rearrangement

KRAS alteration

HER2 alteration

BRAF alteration

Question 23

explain how immunotherapy works

Answer 23

Lung cancers (especially those associated with tobacco) have very high numbers of gene mutations. These mutations potential cause the production of proteins which, according to the body, are “non self”

The immune response should then detect these foreign proteins and eliminate the cells before the tumour develops HOWEVER, the cancerous cells use molecules called Programme Death 1 & Programme Death Ligand 1 (PD1 & PDL2) to switch of immune cells and evade the immune response.

By therapeutically interrupting the interactions between PD1 (on the tumour cell) and PDL1 (on the immune cell), the immune cells will not be switched off and they should be able to destroy the cancer cells