Flashcards in L74 – Lung Carcinoma Deck (76):
What is the incidence and mortality of lung carcinoma in male or female ?
Male = 1st in incidence, 1st in mortality
Female = 3rd in incidence, 1st in mortality
Name some carcinogens in tobacco smoke?
1. Polycyclic hydrocarbons
3. Aromatic amines
What is formed between carcinogen and DNA?
Carcinogens bind covalently to DNA >> form stable bulky
compounds (DNA adducts):
- DNA damage
- Steric hindrance during DNA repair in DNA replication > create mutations
How can tobacco smoke directly cause cancer?
directly cause oxidative stress, ROS >> cancer
What can lead to oxidative stress, increase risk of cancer?
Incomplete fuel combustion
Explain how chronic inflammation can cause cancer?
During inflammation, inflammatory cells and macrophages are activated
>> release inflammatory
mediators, reactive oxygen species (ROS), free radicals damage DNA
>> Damage lung epithelium and release more inflammatory factors
>> Induce persistent cell proliferation predisoposes to mistakes in DNA replication
Name some environment carcinogens?
Name some occupational carcinogens?
Heavy metals: chromium, nickel, cadmium, beryllium
Mustard gas, vinyl chloride
Asbestos fibers, crystalline silica particles
Explain the high incidence of lung cancer in females?
Females more sensitive than male to passive smoking
Higher estrogen receptor B levels affect cell proliferation
Susceptibility loci found GWAS
Explain the progression of cancer to strong carcinogen clones?
Genetic progression: cumulative damage to DNA (mutation) over many years > carcinogenesis
Genomic selection >> evolution of strong carcinogenic clones
What are the 5 stages in squamous cell carcinoma model?
metaplasia / hyperplasia
severe dysplasia/ carcinoma-in-situ (premalignant)
What are the 3 stages in the adenocarcinoma model?
carcinoma-in-situ (still premalignant)
adenocarcinoma (invades into stroma)
What are the 4 major histological types of primary lung carcinoma?
Squamous cell carcinoma (SCC)
Small cell carcinoma (SCLC)
Large cell carcinoma (LC)
Rank the 4 types of primary lung carcinoma in terms of prevalence?
from most to least prevalent:
AD > SCC > SCLC > LC
Which primary lung carcinomas are associated with smoker/ non-smokers?
AD = smokers and non-smokers
SCC = smoker
SCLC = smoker
What are the 4 different patterns of AD?
What is the morphorlogy in papillary predominant AD?
Stromal core contains fibroblasts, capillaries
Cancer cells proliferate on surface
What is the morphology of solid AD?
but still recognizable as glandular cells due to mucin production that stains red
How does Mucinous AD progress?
Tumor cells spread along alveolar wall, produce
large amounts of mucin
What are the symptoms of Mucinous AD?
Severe cough with sputum
Which type of pneumonia appears very similar to Mucinous AD?
On CXR, both appear diffuse and consolidated
- airspace in mucionous AD is filled with tumour masses;
- lobar pneu. airspace = filled with exudates and fluid
What are the 2 distinctive histopathological features of SCC?
1. Keratin formation >> intracellular / extracellular “pearls” (rounded structure stains pink / orange-red)
2. Intercellular bridges (fine hair-like lines/ slit in between cell junctions)
What is the morphology of SCLC?
Diffuse sheets of small tumor cells
Uniformly hyperchromatic nuclei (very dark blue), indistinct nucleoli, scanty cytoplasm
What does SCLC arise from? What can it produce?
Arise from neuroendocrine cells in airways
>> may produce hormone-like peptides in circulation in response to changes in environment
What is the morphology of LC?
Poor / little / no recognizable differentiation
No features of AD, SCC, SCLC by light microscope
What is the nature and prognosis of LC?
High grade, aggressive tumour, poor prognosis
Give 4 features of malignant lung cancer spread?
Infiltration of adjacent lung or pleura
Necrosis and haemorrhage
Solid mass obstruction of bronchial lumen
Explain the irregular edges of malignant lung cancer?
junction between normal lung and tumor not bound by basement membrane / fibrous capsule
Give one route that lung cancer can infiltrate adjacent lung or pleura?
(e.g. across interlobular fissure)
Explain how lung tumour can lead to hemorrhage?
Grow out of blood supply as tumour mass increases:
>> ischemia, infarction, necrosis, haemorrhage
What are the 4 locations that lung cancer can DIRECTLY spread to?
1) Brachial plexus
3) Pleura, pericardium
4) Chest wall
Consequences of lung cancer spread to Brachial plexus?
If tumor at apex: brachial plexus (nerves)
>> numbness, pain, atrophy / wasting of arm muscles
Consequences of lung cancer spread to Esophagus?
Narrowing of esophagus >> dysphagia ( difficulty in swallowing)
Consequences of lung cancer spread to Pleura and pericardium?
effusion >> press on heart >>
Apart from direct spread, what are 2 other routes for lung cancer spread? Which one is common for lung carcinoma?
Lymphatic (common for carcinoma)
Give the entire sequence of lymphatic drainage of the lungs from superficial lymph nodes to RA?
1) Superficial plexus / lymph nodes
2) >> deep plexus / lymph nodes (bronchopulmonary)
3) >> superior/ inferior tracheobronchial (carinal) nodes
4) >> right /left paratracheal nodes)
5) >> bronchomediastinal
6) >> (left) thoracic duct / right lymphatic duct
7) >> subclavian vein > brachiocephalic vein
8) >> superior vena cava > right atrium
Name 3 lymph nodes that lung cancer spread to?
Result of lung cancer spread via pleural lymphatics?
Name some organs that lung cancers can haematogenously spread to?
Which lung cancers spread via blood commonly?
What does the T in TNM assess?
2cm = Ia
3cm = Ib
5cm = II
7 cm or larger = III
Extent (e.g. pleura, rib cage, heart, mediastinum)
What does the N in TNM assess?
Site of lymph node (hilar, mediastinal, neck)
Same side as tumour? (ipsilateral / contralateral)
What does the M in TNM assess?
Metastasis: distant organs
Definition of paraneoplastic syndromes?
= symptoms / signs due to circulating tumour-derived factors acting on distant sites, but not directly
the physical presence of tumour
Name some clinical representations of lung cancer related to local disease?
cough, haemoptysis, obstruction, collapse
Name some clinical representations of lung cancer related to metastatic disease?
pleural effusion, enlarged lymph nodes, blood spread (stroke)
How to tell whether tumour progresses to pleural surface or intrapleural?
Pleural surface = pain
Intrapleural = no pain
Give an example of circulating tumour-derived factors causing para-neoplastic syndromes?
e.g. antibodies against lung tumor self-react with cerebellum tissue >> cerebellar signs
symptom e.g. unsteady gait/ cant walk properly
How to relieve para-neoplastic syndromes?
Removal of tumour > no more tumour factors in circulation
Name some general para-neoplastic syndromes?
e.g. TNFα, IL6 secreted by tumour
>> fever, fatigue, weight loss, loss of appetite, clubbing
What are the 3 categories of paraneoplastic syndromes?
Ectopic hormone effect
Which lung carcinoma shows ectopic hormone effects most? Why? Name some ectopic hormones?
arise from neuroendocrine cells > produce abnormal peptides and raise hormone levels
PTH, ADH, ACTH
Name some autoimmune paraneoplastic syndromes?
sensory impairment, muscle pain, muscle weakness, cerebellar signs
Bone pain, joint pain
Paraneoplastic signs appear before or after tumours present?
May present even earlier than the tumours
Metastatic or primary tumours are much more commone?
What are the sources of metastatic lung cancer?
Blood-borne from all organs (esp gastrointestinal, breast, ovary, uterus, kidneys)
What are the sources of metastatic pleura cancer?
Lymphatic / blood spread (e.g. lung, breast, ovary, pancreas, GI, etc.)
Name some primary cancers in the lungs?
Same a pleura primary cancer?
Compare the spread an aggression between SCLC and Non-SCLC (SCC, AD, LC)
Early blood spread
Initially local spread
What determines the outcome between SCLC and NSCLC?
Poor (3 months survival)
NSCLC: Depends on:
Stage of tumour at diagnosis
Fitness of patient
What is the standard treatment of SCLC?
Good response to chemotherapy, radiotherapy
Usually metastasized do not offer surgery
What is the standard treatment of NSCLC?
Early: surgical resection
Late: systemic therapy / chemotherapy
*but different drugs for AD, SCC*
What is the prognosis of lung cancer?
Average 5yr survival = 15%
What is EGFR and what is it associated with?
Epidermal Growth Factor Receptor
Associated with Adenocarcinome > 20% smoker, 70% Non-smoker
What is the MoA of EGFR normally?
Normal: ligand binding causes dimerization and ligand-dependent firing
regulated cell proliferation, survival, growth and tissue repair
What is the MoA of EGFR mutant?
Ligand- INDEPENDENT firing
Cause uncontrolled, autonomous cell proliferation
Increase survival, tumour properties
What is the response to EGFR treatment in wild type EGFR and mutant EGFR patients?
Wild type EGFR: chemotherapy has much better treatment response
Mutatn EGFR: EGFR medication has much better response than chemotherapy
Name some 1st gen and 2n d gen EGFR drugs?
1st gen: Erlotinib, Gefitinib (reversible binding)
2nd gen: afatinib (irreversible binding)
What is the MoA of Gefitinib?
tyrosine-kinase inhibitor (TKI) against EGFR: disrupt signaling of tumor cells
Compare the stimulus that activate EGFR vs ALK fusion gene?
EGFR stimulated by ligand
ALK gene activated by chromosome translocation
MoA of ALK fusion gene?
ALK gene activated by chromosome translocation >> combine with partner gene to induce cell proliferation and survival
What is ALK fusion gene associated with?
Overall 5%, esp. AD
What is the drug for anti-ALK fusion gene?
Name some SCC mutations?