Carcinoma of Bronchus Flashcards
Lung cancer is the 2nd most common cancer in the UK w/ a peak incidence in the 50-60yo age group. It’s the most common cause of cancer death in both men + women - bc of poor prognosis (<10% of pts remain alive 5 yrs from diagnosis).
What are the causes of lung cancer?
- 80-90% lung carcinomas attributed to cig smoking
- lung cancer only develops in ~10% heavy smokers
-
10-20% lung cancers occur in non-smokers, causes:
- industrial hazards eg. asbestos, arsenic, chromium, radiation
- env exposure eg. radon gas (cornwall)
- genetic factors eg. EGFR (epidermal growth factor receptor) gene mutations
How is lung cancer histologically classified?
- Small cell lung cancer vs non-small cell lung cancer
- Small cell lung cancer → 15% cases + worse prognosis
- Non-small cell lung cancer:
- adenocarcinoma → most common type, most non-smokers
- squamous cell
- large cell
- alveolar cell carcinoma → not related to smoking
- bronchial adenoma → mostly carcinoid
Differentiating is important due to different drugs available to treat different types
The majority of lung cancers are carcinomas. They can be subdivided into 4 main groups + a misc category.
What are the different types/groups?
- adenocarcinoma (40%)
- squamous cell carcinoma (25%)
- small cell carcinoma (15%)
- others (eg. carcinoid, large cell neuroendocrine carcinoma etc)
also, don’t forget that lung is most common site of metastatic tumour (both carcinomas and sarcomas arising anywhere in the body may spread to the lungs)
How does squamous cell carcinoma arise in the lung?
- strong association w/ smoking
- tends to arise in larger airways near hilum
- graded as: well, moderately or poorly differentiated
- well-defined ‘metaplasia-dysplasia-carcinoma’ sequence
What are characteristics of adenocarcinoma?
- increasing in incidence (uknown reason)
- most common type of lung cancer in non-smokers
- although majority of these pts are smokers
- associated w/ mutations in EGFR gene
- tends to arise in peripheral smaller airways
- graded as: well, moderately or poorly differentiated
- premalignant lesion is called atypical adenomatous hyperplasia (equiv to dysplasia)
- it is asymptomatic
What are characteristics of small cell carcinoma?
- strongest association w/ smoking
- usually arise in central location (APUD cells)
- highly aggressive tumour, notorious for rapid growth + early spread
- not graded (by definition, small cell carcinoma = high grade)
- no recognised precursor (premalignant) lesion
- associated w/ ectopic ADH + ACTH secretion → hyponatraemia, cushing’s, adrenal hyperplasia
What are large cell carcinomas?
- undifferentiated carcinomas, poor prognosis
- cannot be otherwise categories
- lack morphological features of other forms of lung cancer
- typically peripheral + anaplastic
In recent years there have been several important advances in understanding of the genomics of lung cancer. Some genetic mutations are targets for new therapies.
Use tyrosine kinase inhibitors as an example of this
- EGFR is a transmembrane tyrosine kinase that is mutated in between 10-50% of non-small cell carcinomas
- certain EGFR mutations are associated w/ response to tyrosine kinase inhibitors eg. gefitinib + erlotinib
- another genomic alteration seein in approx 2-5% of lung cancers is an inversion in the short arm of chromosome 2 -> results in fusion of EML4 gene w/ ALK gene -> results in EML4-ALK fusion tyrosine kinase - tumours with this mutation are associated w/ response to the TKI crizotinib
Obtaining a histological/cytological diagnosis of malignancy is important prior to tx.
One reason for this is bc certain non-malignant processes (benign tumours, certain infection) can result in a mass lesion in the lung. Also, important to know the histological type of cancer that the patient has for management purposes + prognosis.
What investigations are best for the following?
- central lesions
- peripheral lesions
-
central lesions (ie near hilum) -> bronchoscopy sampling
- biopsy (histology) and/or washings, brushings (cytology)
-
peripheral lesions -> CT-guided sampling
- biopsy (histology) and/or FNA (cytology)
How is immunotherapy in targeting genetic mutations for lung cancer?
- immune checkpoints affect immune system functioning
- can be stimulatory or inhibitory
- tumours can use checkpoints to protect themselves from immune attacks
-
PD-L1 is a key regulator of T cell function
- binds to PD1 on T cells + inhibits their activity
- PD-L1 expressed by some cancer cells
- enables them to inhibit T cells that might attack them
- PD1 and PDL1 inhibitors (monoclonal abs) eg pembrolizumab have been developed for non-small cell lung cancer
- the antibodies bind to either PD-1 or PD-L1 + therefore blocks the interaction
- therefore, immune system able to mount response to tumour cells + kill them
How is lung cancer staged?
- both small + non-small cell carcinoma staged using TNM
-
imaging has a very important role in staging lung cancer:
- CT good for T (tumour) staging - less sensitive for detection of involved lymph nodes + distant mets
- PET or PET-CT enables more accurate staging of N (nodes) + M (mets) prior to surgery
What is Pancoast’s tumour?
- in apex of lung
- involves 8th cervical + 1st and 2nd thoracic nerves
- may manifest as Pancoast’s syndrome
- shoulder pain radiating in an ulnar distribution down arm
- or Horner’s syndrome
What are local symptoms and signs of lung cancer?
- cough (involvement of central airways) - most common initial presenting symptoms
- haemoptysis (bleeding from tumour)
- stridor/wheeze (large airway obstruction)
- hoarse voice (invasion of left recurrent laryngeal nerve)
- breathlessness (large airway obstruction and/or development of associated pleural effusion)
- chest wall pain (chest wall involvement)
- non-resolving pneumonia (tumours may partially obstruct airways leading to infection)
What is the link with SVC obstruction and lung cancer?
- obstruction of SVC usually due to right-sided lung tumour (often small cell carcinoma)
- causes increased venous pressure
- results in interstitial oedema + retrograde collateral flow
- collateral venous return to heart from upper half of body is through azygos venous system, internal mammary venous system and long thoracic venous system
- despite collateral pathways, venous pressure is almost always elevated
- most common symptoms = SoB, facial swelling, head fullness, cough, arm swelling, chest pain, dysphagia, hoarseness, stridor
- SVC obstruction = oncological emergency bc may lead to laryngeal oedema, cerebral oedema or decreased CO
What is Horner’s syndrome characterised by?
- endopthalmos (eyeball depression)
- ptosis (droop) of upper eyelid
- miosis (pupil constriction)
- anhidrosis (absence of sweating)
Many causes of Horner’s syndrome, of which Pancoast’s tumour is one. Due to sympathetic nerve infiltration by tumour, particularly T1
