Pathophysiology of lung cancer Flashcards
Discuss the epidemiology of lung cancer
Epidemiology of Lung Cancer
- In 2007, lung cancer was the 4th most commonly diagnosed cancer in both males and females.
- 80% were over 60 years old.
- Deaths decreased by 32% in men and increased by 72% in females, leading to similar death rates.
- 5-year survival rates were 11% for males and 15% for females (2000–2007).
- Approximately 1 in 6 Australian adults smoke.
Epidemiology of Lung Cancer Statistics
Global Incidence
- 1.3 million deaths/year worldwide.
- Lung cancer causes more deaths than any other cancer.
- Leading cause of death in men and second in women.
- 5-year survival rate remains at 14%.
- Risk factors: radon, asbestos, air pollution.
- Tobacco smoke responsible for 87% of lung cancer cases.
President Clinton August 23, 1996: “Cigarette smoking is the most significant public health problem facing our people. More Americans die every year from smoking-related diseases than from AIDS, car accidents, murders, suicides, and fires — combined.”
Discuss the various consequences of smoking
- Cancers
- Atherosclerosis, cardiovascular disease
- Respiratory diseases: Asthma, Chronic Bronchitis, Emphysema, Respiratory Bronchiolitis (RB)
List smoking related cancers
- Mouth, nose, and throat
- Larynx
- Trachea
- Esophagus
- Lungs
- Stomach
- Pancreas
- Liver
- Kidneys and ureters
- Bladder
- Colon and rectum
- Cervix
- Bone marrow and blood (leukemia)
Discuss the relatiosnhip between smoking and lung cancer
- Relationship between smoking and lung cancer depends on:
- Amount of daily smoking?
- Tendency to inhale?
- Duration of smoking?
- Age of initiation of smoking.
- The Cancer Prevention Study found that:
- 1 pack per day = 22 times the risk of dying from lung cancer.
- 2 packs per day = 45 times the risk of dying from lung cancer.
Discuss the risks of smoking and lung cancer
Smoking and Lung Cancer Risks
- Risk significantly decreases when smoker stops; takes 15 years to approach non-smoker risk.
- Passive smoking (second-hand smoke): Risk is 1.25 times higher for individuals in a non-smoking environment.
Second-Hand Smoke and Children
- Second-hand smoke causes various health issues in children, including sudden infant death syndrome, ear infections, colds, pneumonia, bronchitis, and more severe asthma.
- increases a non-smoker’s chances of developing lung cancer by 20
- to 3 for other cancers
- causes 3000 lung cancer deaths per year
Smoking during Pregnancy
- Smoking during pregnancy leads to complications, premature birth, low-birth-weight infants, stillbirth, abruption, ectopic pregnancy, preterm delivery, and more.
- before pregnancy: causes infertility, and worse response to IVF
Discuss the common presentations of lung cancer
Common Presentations
- Asymptomatic (by chance, usually on CXR done for other reasons) - 15%
- Cough - 45-74%
- Weight loss - 46-68%
- Dyspnoea - 37-58%
- Chest pain - 27-49%
- Haemoptysis - 30%
- Bone pain - 20%
- Hoarseness - 8-18%
List some paraneoplastic syndromes associated with lung cancer
Paraneoplastic syndromes are a group of clinical disorders that are associated with malignant diseases and are not directly related to the physical effects of the primary or metastatic tumours
Neuromuscular
- Polymyositis
- Myasthenic Syndrome
- Sensorimotor Neuropathy
- Encephalopathy
- Myelopathy
- Cerebellar Degeneration
Endocrine
- Superficial Thrombophlebitis
- Thrombosis
- Marantic Endocarditis
- Cushing’s Syndrome
- SIADH (Syndrome of Inappropriate Antidiuretic Hormone)
- Hypercalcaemia
- Carcinoid Syndrome
- Gynaecomastia
- Hyperglycaemia
- Galactorrhoea
- GH (Growth Hormone) Excess
- TSH (Thyroid Stimulating Hormone) Excess
- Calcitonin Secretion
Musculoskeletal/Cutaneous
- Clubbing
- Dermatomyositis
- Acanthosis Nigricans
- Pruritis
- Urticaria
- Erythema Multiforme
- Hyperpigmentation
Hematological
- Haemolytic Anaemia
- Red Cell Aplasia
- Polycythaemia
- Thrombocytopenic Purpura
- Thrombocytosis
- Dysproteinaemia
- Eosinophilia
- Leuco-erythroblastic Reaction
- Nephrotic Syndrome
- Hyperuricaemia
- Amyloidosis
- Secretion of Alkaline Phosphatase
- Secretion of IgA
Disucss the risk factors for lung cancer
- Smoking:
- Primary risk factor accounting for 90% of lung cancers.
- Squamous and small cell lung carcinoma have the strongest correlation with tobacco exposure
- Adenocarcinoma has the weakest association with smoking.
Other Risk Factors
- Asbestos exposure
- Radon exposure
- Halogen ether exposure
- Chronic interstitial pneumonitis
- Smoking + Beta-carotene (Vitamin A) supplements (with alcohol)
- Inorganic arsenic exposure
- Radioisotope exposure, ionizing radiation
- Atmospheric pollution
- Chromium, nickel exposure
- Vinyl chloride exposure
- Possible HIV association
- Genetic polymorphisms (CYP1A1 system)
Lung Cancer in Non-Smokers
- 10-25% of lung cancer cases.
- Women are more affected (possible hormonal element).
- Passive smoking and workplace carcinogens are contributing factors.
- Adenocarcinomas are more common.
- Genetic factors, such as EGFR mutations and EML4-ALK fusions, play a role in young Asian non-smokers.
- Decreased incidence of p53 mutations and KRAS mutations.
Distinguish between the normal lung and the smoker’s lung*
Recall: normal bronchial mucosa have 4 cell types: ciliated, mucous, neuro-endocrine and basal
Describe the pathophysiology of smoking
Squamous Metaplasia –> Dysplasia –> Carcinoma in Situ
Atypical Adenomatous Hyperplasia (AAH) and Bronchioloalveolar Carcinoma (BAC)
Discuss the classification of lung carcinoma
Classification of Lung Carcinoma
- Small Cell Lung Carcinoma (SCLC)
VERSUS - Non-Small Cell Carcinoma (NSCLC)
Lung Cancers
- Small Cell Lung Cancer (15%)
- Non-Small Cell Lung Cancer (85%)
- Adenocarcinoma: 35-40%
- Squamous Cell Carcinoma (SCC): 25-30%
- Large Cell (Neuroendocrine) Carcinoma: 10-15%
List reasons for the importance of tumour classification
- Prognosis
- Treatment
- Pathogenesis/Biology
- Epidemiology
Describe adenocarcinoma
- Peripherally located and slower growing
- Disseminate widely early in disease progression
- Most common primary tumor in:
- Women
- Lifetime non-smokers
- Patients <45 years old
- Histology: Acinar, papillary & solid types, mucin production
Describe squamous carcinoma
- Commonest tumor type
- More common in males
- Centrally hilar located in major bronchi
- Spread to local hilar lymph nodes
- Extra-thoracic dissemination occurs later
- Histology: Keratin pearl formation, intercellular bridges
Describe small cell carcinoma
- Centrally located
- Rapid growth and early dissemination to hilar/mediastinal LNs
- Primary tumor may be difficult to find
- Derived from neuroendocrine cells of lung
- Surgery not the mainstay of treatment
- Microscopically: cells have very little cytoplasm, cells show molding, hyperchromatic cells with salt-pepper chromatin
