L74 – Lung Carcinoma Flashcards by Max Kam

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

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Name some carcinogens in tobacco smoke?

Polycyclic hydrocarbons
Nitrosamines
Aromatic amines

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What is formed between carcinogen and DNA?

Carcinogens bind covalently to DNA&raquo_space; form stable bulky
compounds (DNA adducts):

DNA damage
Steric hindrance during DNA repair in DNA replication > create mutations

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How can tobacco smoke directly cause cancer?

directly cause oxidative stress, ROS&raquo_space; cancer

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What can lead to oxidative stress, increase risk of cancer?

Occupational carcinogens

Environmental carcinogens

Chronic inflammation

Incomplete fuel combustion

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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

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Name some environment carcinogens?

benzo[a]pyrene

radon

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Name some occupational carcinogens?

 Heavy metals: chromium, nickel, cadmium, beryllium
 Mustard gas, vinyl chloride
 Asbestos fibers, crystalline silica particles

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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

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Explain the progression of cancer to strong carcinogen clones?

Genetic progression: cumulative damage to DNA (mutation) over many years > carcinogenesis

Genomic selection&raquo_space; evolution of strong carcinogenic clones

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What are the 5 stages in squamous cell carcinoma model?

normal

metaplasia / hyperplasia

mild-moderate dysplasia

severe dysplasia/ carcinoma-in-situ (premalignant)

SCC

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What are the 3 stages in the adenocarcinoma model?

dysplasia

carcinoma-in-situ (still premalignant)

adenocarcinoma (invades into stroma)

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What are the 4 major histological types of primary lung carcinoma?

Adenocarcinoma (AD)

Squamous cell carcinoma (SCC)

Small cell carcinoma (SCLC)

Large cell carcinoma (LC)

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Rank the 4 types of primary lung carcinoma in terms of prevalence?

from most to least prevalent:

AD > SCC > SCLC > LC

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Which primary lung carcinomas are associated with smoker/ non-smokers?

AD = smokers and non-smokers

SCC = smoker

SCLC = smoker

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What are the 4 different patterns of AD?

 Acinar-predominant

 Papillary-predominant

 Lepidic-predominant

 Solid adenocarcinoma

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What is the morphorlogy in papillary predominant AD?

finger-like projections

 Stromal core contains fibroblasts, capillaries
 Cancer cells proliferate on surface

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What is the morphology of solid AD?

poorly differentiated

but still recognizable as glandular cells due to mucin production that stains red

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How does Mucinous AD progress?

Tumor cells spread along alveolar wall, produce

large amounts of mucin

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What are the symptoms of Mucinous AD?

Severe cough with sputum

Pneumonia-like symptoms

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Which type of pneumonia appears very similar to Mucinous AD?

lobar pneumonia

On CXR, both appear diffuse and consolidated

Difference:
- airspace in mucionous AD is filled with tumour masses;

lobar pneu. airspace = filled with exudates and fluid

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What are the 2 distinctive histopathological features of SCC?

Keratin formation&raquo_space; intracellular / extracellular “pearls” (rounded structure stains pink / orange-red)
Intercellular bridges (fine hair-like lines/ slit in between cell junctions)

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What is the morphology of SCLC?

 Diffuse sheets of small tumor cells
 Uniformly hyperchromatic nuclei (very dark blue), indistinct nucleoli, scanty cytoplasm
 No pattern

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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

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What is the morphology of LC?

 Poor / little / no recognizable differentiation features  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?

Irregular edges 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 2) Esophagus 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 >> | heart failure

Apart from direct spread, what are 2 other routes for lung cancer spread? Which one is common for lung carcinoma?

Lymphatic (common for carcinoma) Haematogenous

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 lymph trunk 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?

Hilar Mediastinal Supraclavicular

Result of lung cancer spread via pleural lymphatics?

Pleural effusion

Name some organs that lung cancers can haematogenously spread to?

Liver Adrenals Bone Brain

Which lung cancers spread via blood commonly?

SCLC | AD

What does the T in TNM assess?

``` Size:  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?

Node:  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?

General Ectopic hormone effect Autoimmune effects

Which lung carcinoma shows ectopic hormone effects most? Why? Name some ectopic hormones?

SCLC 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?

Metastatic

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?

 Carcinomas  Sarcomas  Lymphomas

Same a pleura primary cancer?

Mesothelioma

Compare the spread an aggression between SCLC and Non-SCLC (SCC, AD, LC)

SCLC:  Aggressive  Early blood spread NSCLC:  Less aggressive  Initially local spread

What determines the outcome between SCLC and NSCLC?

SCLC: 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?

Poor outcome 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?

Crizotinib

Name some SCC mutations?

PTEN loss PTEN mutation PIK3CA mutation FGFR1 amplification

`When is targeted molecular therapy used in lung cancer?

1) Late stage Adenocarcinoma 2) Determine whether EGFR or ALK are wild type or mutant 3) Wild type = chemo, Mutant = targeted therapy

L74 – Lung Carcinoma Flashcards

(76 cards)