Week 6 - RESP Flashcards
Lung Cancers
What is the pathogenesis of lung cancer?
- smoking/carcinogens
- 3p/EGFR mutations
- dysplasia
- more mutations (Kras/C-myc)
- infiltration
- spread
- metastases (p53 mutation)
*normal –> hyperplasia –> metaplasia –> mild dysplasia –>severe dysplasia –> MALIGNANCY
What are the gross and microscopic features of small cell carcinomas?
Gross:
- grey/white, diffuse, infiltrating tumour at hilar region
- spread around bronchi
- infiltrative
- early/rapid spread
Micro:
- irregular, small, dark blue/hyperchromatic cells in sheets
- pleomorphic cells with irregular large nuclei
- scanty cytoplasm
- neuroendocrine cells –> paraneoplastic syndromes
- OAT CELLS
What are the gross and microscopic features of squamous cell carcinomas?
Gross:
- expanding tumour (NOT infiltrating)
- grey/white, nodular, central (hilum)
- spread to LNs/extrapulmonary structures
Micro:
- pleomorphic cells with irregular nuclei forming irregular clusters
- keratin pearl formation/keratinisation of cells
What are the gross and microscopic features of adenocarcinomas?
Gross:
- grey/white, nodular, peripheral tumours
- expanding (NOT infiltrating)
- increase in F/non-smokers
- central scar
- spread to LNs/extrapulmonary structures
Micro:
- pleomorphic cells with irregular dark nuclei forming irregular glands
- areas of necrosis
Which mutations are commonly seen in squamous cell carcinomas vs. adenocarcinomas?
SCC = 3p deletion (increase in males/smokers) Adeno. = EGFR mutation (increase in previous scar pts.)
Compare grade 1 vs. grade 4 cancers?
Grade 1:
- well differentiated
- slow growing
- still gland formation (some cells functioning normally)
Grade 4:
- poorly differentiated (very irregular/pleomorphic)
- fast growing
- NO gland formation
True or False?
3p deletion mutation is seen in normal bronchial epithelium of smokers
True
What are local and systemic clinical features of lung cancer?
Local:
- obstruction (effusions, pneumonias, atelectasis)
- hemoptysis
- bronchiectasis
- SVC obstruction/syndrome
- pancoast tumour
- horner’s syndrome
Systemic:
- cachexia
- paraneoplastic syndromes
- clubbing
- bone pain/epilepsy –> metastases
What is pancoast tumour?
- destructive lesions of thoracic inlet (destruction of ribs 1 + 2)
- involvement of brachial plexus + cervical sympathetic nerves –> severe shoulder pain radiating to axilla/scapulae, atrophy of hand/finger muscles, wrist tenderness, horner’s syndrome, SVC syndrome
What is horner’s syndrome?
- seen in pts. with pancoast tumours
- 3 features:
- Ptosis
- Meiosis
- Anhydrosis
What sign is seen in SVC syndrome? How do you test for it and what indicates a positive sign?
Pemberton’s Sign:
- raise patient’s arms above head for 30s
- a positive test will give rise to flushing/facial swelling, plethora, inspiratory stridor, raised JVP
What is the pathogenesis of hemoptysis in lung cancer?
Cancer proteases break down surrounding tissue and vessels causing haemorrhage
What are Ix. for lung cancer?
Imaging
-CXR, US, MRI, CT, PET scan
Cytology
- sputum
- bronchial lavage
Bronchoscopy/Thoracotomy
Biopsy
-needle/excision
Tumour markers
-epithelial; neuroendocrine
Outline lung cancer cytology for the “big 3”
Adenocarcinoma:
- gland formation
- mucin
Squamous cell carcinoma:
- pink cytoplasm
- keratin pearl formation
Small cell carcinoma:
- little cytoplasm
- nil glands/keratin
- oat cells
True or False?
Carcinoid tumours continuously produce hormones
True
-they have neuroendocrine cells which secrete serotonin and other hormones
What is carcinoid syndrome?
- intermittent diarrhoea
- facial flushing –> dry (no sweating)
- palpitations
- abdominal cramps
- SOB/wheezing
*result of carcinoid tumour
What is a lung hamartoma?
- NOT a true tumour
- it is an embryonic disorganisation
- consists of normal lung tissue BUT in a hapazard arrangement
- round or nodular
- benign behaviour
What are the 2 types of embryonic disorganisation?
- Hamartoma:
- normal tissue in normal place (hapazard arrangement)
- e.g. lung hamartoma - Choristoma:
- normal tissue in abnormal place (ectopic)
- e.g. gastric tissue in appendix
True or False?
There is a latent period of roughly 25-40yrs for mesothelioma to manifest
True
- preceded by fibrous pleural plaques caused by asbestos bodies
- chronic pleural irritation
- encases lung from pleura (literally “squeezes” the lung)
What is broncho-alveolar carcinoma?
- in-situ adenocarcinoma (low grade)
- pneumonic spread –> NO invasion/tissue damage
- tumour cells line alveolar walls
- presents clinically like pneumonia
What is paraneoplastic syndrome?
Clinical symptoms due to “chemical product” released by tumour
*NOT as a result of the tumour itself
What % of lung cancers produce substances which cause paraneoplastic syndromes and which type are they commonest in?
3-10%
-common in small cell lung cancers
What substance can be released by some squamous cell carcinomas?
Parathyroid hormone related peptide (PTH-rp)
-results in paraneoplastic syndrome causing lysis of bone and hypercalcemia!
What paraneoplastic syndromes commonly occur in adenocarcinomas?
Haematologic syndromes
- mucin from tumour causes coagulation of blood
e.g. migratory thrombophlebitis, non-bacterial endocarditis
What paraneoplastic syndromes commonly occur in small cell lung cancer?
ACTH –> cushings syndrome
ADH –> hyponatremia, SIADH, Diabetes insipidus
Gastrin releasing peptide –> peptic ulcer
Calcitonin –> hypocalcemia
Myasthenic syndrome –> autoimmune damage
Compare NSCLC vs. SCLC
NSCLC:
- expansive tumours
- squamous + adeno.
- better prognosis
- later spread
- less paraneoplastic syndromes
- early –> surgical resection
SCLC:
- infiltrating tumours
- small cell/oat cell cancer
- poor prognosis
- early spread
- more paraneoplastic syndromes
- surgery NOT an option
What is the commonest type of lung cancer?
NSCLC
-adenocarcinoma
Why are cells so dark in small cell lung cancer?
- scanty cytoplasm
- increase nucleus size
Why do small cell cancers secrete increased hormones?
- cells involved are neuroendocrine cells
- increase chance of paraneoplastic syndromes
p53/Rb gene mutations are more commonly seen in?
small cell carcinomas
Multiple large, rounded tumours scattered all over lungs is likely?
metastases
What is the common route of spread of tumour –> lungs (metastases)?
- lungs = most common site of metastases
- haematogenous spread
- tumour invades veins –> R heart –> lungs
*veins increase risk of tumour invasion than arteries as they are thinner
What is silhouette sign?
- loss of normal silhouette of a structure
- due to change of differing densities to similar densities of 2 adjacent structures
What are air bronchograms?
- radiological feature of consolidation
- patent, air-filled airways within the opacity which stand out as dark, linear +/or branching structures against the opacified lung
What are the most common causes of consolidation?
- pneumonia
- neoplasm
What are the 2 types of atelectasis?
- Resorption:
- mucous
- tumour
- foreign body - Relaxation
- pleural effusion
- pneumothorax
- round atelectasis
Where do adenocarcinomas, squamous cell carcinomas and small cell carcinomas typically arise from?
Adenocarcinoma:
-peripheral tumour
Squamous:
-central tumour (hilum)
Small cell:
-central tumour (hilum)
What are the 2 types of bronchogenic carcinomas?
- SCLC (20%)
- NSCLC (80%)
- adenocarcinomas (50%)
- squamous cell carcinomas (30%)
What is the etiology of lung cancer?
- smoking
- occupational exposures (asbestos, fumes, etc.)
- fibrosis/scarring (TB, pneumoconioses, etc.)
- radioactive gases
- genetics
- idiopathic
What % of heavy smokers develop lung cancer?
11%
-BUT, 90% of lung cancer incidence is smokers
True or False?
95% of lung cancers in smokers is bronchogenic carcinoma
True
-5% = carcinoid, hamartoma, mesothelioma
What is the most common internal cancer?
Lung cancer
