Pathology of Lung Cancer Flashcards
What are the two main families of carcinogens in tobacco smoke
- Polycyclic aromatic hydrocarbons
2. Nitrosamines
How many carcinogens are present in tobacco smoke?
Over 60
Which is the more prevalent family of carcinogens in modern cigarettes and which kind of lung cancer do they cause?
N-nitrosamines (more likely to cause adenocarcinoma)
How many genomic alterations must occur in order to make a respiratory epithelial cell cancerous?
Around 3-12 key genomic alterations must be accumulated in a certain sequence to provide a cell with cancerous traits
Explain why pro-carcinogens found in tobacco smoke are important in lung cancer aetiology
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).
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?
- Stem cells of the bronchus become squamous cell carcinoma
- peripheral epithelial stem cells become adenocarcinoma
other than carcinoma, what other kinds of cancer can be found in the lungs?
Lymphoma
Sarcoma
Mets
Is lung cancer usually diagnosed early or late?
Late- it is often asymptomatic for many years.
Symptomatic lung cancer tends to be fatal
What happens when a tumour interferes with the phrenic nerve?
Diaphragmatic paralysis
What happens when a tumour interferes with the left recurrent laryngeal nerve?
Hoarse voice & Bovine cough
What happens when a tumour interferes with the brachial plexus?
Pancoast T1 damage
What happens when a tumour interferes with the cervical sympathetic nerves?
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.
What do small cell carcinomas often secrete?
ADH
Why do patients with squamous cell carcinoma often present with hypercalcaemia?
tumour often secretes a molecule similar to parathyroid hormone
How is lung cancer investigated?
- CXR
- Bronchoscopy
- Transthoracic fine needle biopsy
- Transthoracic core biopsy
- Pleural effusion cytology and biopsy
- advanced imaging
the 5 year survival of patients with lung cancer in scotland?
<9.8% (dreadful)
What are the 5 year survival rates for stage I and stage II operable lung cancers?
Satge I = 6-%
Stage II = 35%
What percentage of Scottish lung cancer patients are operable?
10-15%
Which type of lung cancer is associated with the highest mortality?
Small cell carcinoma (5 year survival is 4%, median survival = 9 months)
Are tumours caused by smoking molecularly simple or molecularly complex?
Complex
Why is a molecularly complex tumour a bad thing?
it makes it harder to target with drugs
List the 6 genetic alterations which can cause non-smoking related adenocarcinomas
EGFR alteration (15% in Aberdeen royal)
ALK gene rearrangement
ROS1 gene rearrangement
KRAS alteration
HER2 alteration
BRAF alteration
explain how immunotherapy works
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
