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Questions and Answers
What is the leading cause of cancer death in Australia?
Which risk factor is NOT associated with an increased likelihood of developing lung cancer?
What is the 5-year relative survival rate for lung cancer in Australia?
Which of the following is a method used for the diagnosis of lung cancer?
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Which trend in lung cancer incidence has been observed among males and females in Australia?
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Which type of lung cancer is usually treated with chemoradiotherapy and is associated with widespread metastases?
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What is the most common type of lung cancer in non-smokers?
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What percentage of patients with non-small cell lung carcinoma (NSCLC) present with unresectable disease?
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Which immunohistochemical markers are typically positive in small cell carcinoma?
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Which immunohistochemistry marker is associated with primary lung adenocarcinoma?
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What characterizes adenocarcinoma in-situ?
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What is a common mutation found in exon 19 of EGFR-mutated lung adenocarcinoma?
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Which of the following methods is NOT typically used for analyzing EGFR mutations?
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What is a common characteristic of squamous cell carcinoma?
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In subtyping NSCLC, what does the combination of morphology and ancillary studies aim to achieve?
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In which type of lung cancer is 'druggable' target identification emphasized for treatment?
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What type of growth pattern is associated with adenocarcinomas that often carry EGFR mutations?
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What type of lung cancer is characterized by a peripheral location and extrathoracic metastases?
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Which oncogenic driver is commonly associated with lung adenocarcinoma?
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Which demographic shows the highest frequency of EGFR mutations among lung adenocarcinoma patients?
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What is the priority in managing small biopsy samples for NSCLC diagnosis?
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What is the gold standard method for detecting ALK rearrangements in lung adenocarcinoma?
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Which patient demographic is most commonly associated with ALK-rearranged lung adenocarcinoma?
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What type of cancer is most often preceded by squamous dysplasia or carcinoma in situ?
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Which of the following immunohistochemistry markers indicates eligibility for pembrolizumab therapy?
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What is a common characteristic of squamous cell carcinoma of the lung?
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Which histological pattern is associated with ALK-rearranged lung adenocarcinoma?
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After two cycles of crizotinib therapy, which type of lung cancer is specifically targeted?
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How common is ALK-rearranged lung adenocarcinoma among all non-small cell lung cancers (NSCLC)?
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Study Notes
Lung Cancer Statistics in Australia
- Lung cancer is the leading cause of cancer death in Australia.
- It's the fifth most commonly diagnosed cancer in both males and females.
- Incidence rates have fallen in males but risen in females, resulting in a slight decrease overall.
- Prognosis is poor, with a five-year relative survival rate of 17%.
Lung Cancer Risk Factors
- Tobacco smoking is the primary risk factor.
- Occupational and environmental carcinogens, such as asbestos, silica, radon, heavy metals, polycyclic aromatic hydrocarbons, and diesel exhaust, are significant contributors.
- Radiation exposure can increase risk.
- Chronic inflammation, like tuberculosis and pulmonary fibrosis, are also linked to lung cancer.
- Family history, particularly with relatives diagnosed at a young age or multiple family members affected, can increase susceptibility.
- Specific inherited conditions, such as Li Fraumeni syndrome and alpha-1 antitrypsin deficiency, are associated with higher risk.
Lung Cancer Sampling Techniques
- Transbronchial FNA (with or without EBUS): A biopsy technique that uses a bronchoscope to collect cells from the lung. EBUS (Endobronchial Ultrasound) can guide the procedure for more precise sampling.
- Percutaneous Transthoracic FNA/core biopsy (CT guided): This technique involves using a needle to collect tissue from the lung through the chest wall, guided by a CT scan.
- Bronchial washings and brushings: A bronchoscope collects fluid and cells from the airways.
- Pleural fluid aspiration: Fluid is collected from the space between the lungs and the chest wall.
- Endobronchial biopsy: Tissue samples are taken from the lining of the airways using a bronchoscope.
- Sputum collection: Patients cough up sputum (mucus) for analysis.
Ancillary Studies in Lung Cancer Diagnosis
- Histochemical stains: These help identify specific features of cells, such as mucin (a type of protein).
- Immunohistochemistry (IHC): Uses antibodies to identify specific proteins within cells, aiding in classification and understanding the biology of the cancer.
- Sanger and Next-Generation Sequencing (NGS): These methods analyze DNA or RNA to identify mutations or changes in genes associated with lung cancer.
- Polymerase Chain Reaction (PCR) based techniques: These techniques can amplify specific DNA sequences for diagnosis and monitoring of lung cancer.
- Fluorescence In-Situ Hybridization (FISH): This technique uses fluorescent probes to detect specific DNA sequences or chromosomal changes associated with lung cancer.
- Electron microscopy: Provides detailed images of cells, helping to characterize lung cancer subtypes.
- Flow cytometry: This technique measures the properties of individual cells, such as their size, shape, and protein expression, to identify different cell populations.
Major Categories of Lung Cancer
-
Small Cell Carcinoma (SCC):
- Highly aggressive, representing 14% of lung cancers.
- Typically non-resectable (not surgically removable).
- Treated with chemoradiotherapy (a combination of chemotherapy and radiation therapy).
-
Non-Small Cell Lung Carcinoma (NSCLC):
- Comprises the remaining 86% of lung cancers.
- Includes several subtypes:
- Adenocarcinoma (38%)
- Squamous Cell Carcinoma (20%)
- Large Cell Carcinoma
- Adenosquamous Carcinoma
- Sarcomatoid Carcinoma
- Surgical resection is an option for some NSCLC subtypes.
- Treatment often involves targeted therapies based on specific molecular features of the cancer.
Characteristics of Small Cell Carcinoma
- Highly aggressive epithelial tumor: Features neuroendocrine differentiation (resembling cells in the nervous system).
- Strongly associated with smoking: Predominant in smokers.
- Males > Females: More common in males.
- Central >> peripheral: Frequently originates in the central airways of the lungs.
- Ectopic hormone production: Cancer cells may produce hormones not normally found in that location.
- Widespread metastases: Frequently spreads to distant sites.
- Virtually always fatal: Has a poor prognosis.
Microscopic Features of Small Cell Carcinoma
- Small cells with scant cytoplasm: Cells are small and have little cellular material surrounding the nucleus.
- Finely granular chromatin: The genetic material within the nucleus appears finely speckled.
- Absent/inconspicuous nucleoli: The nucleolus, a structure within the nucleus, is small or absent.
- Nuclear molding: Cell nuclei are often irregularly shaped and press against each other.
- Necrosis: Dead cells are often present.
- Mitoses++: Frequent cell division.
- Immunohistochemistry: Cancer cells demonstrate positive staining for specific proteins, including CD56, synaptophysin, chromogranin (sometimes), and TTF-1.
- Electron microscopy: Neuroendocrine granules are often present within the cells.
Characteristics of Adenocarcinoma
- Invasive malignant epithelial tumor: Has a glandular structure (resembles normal lung tissue).
- Glandular differentiation or mucin production: Shows features of glandular cells or produces mucus.
- Males = Females: Equally prevalent in both genders.
- Most cases in smokers, but commonest type in non-smokers: More common in smokers, but also found in non-smokers.
- Increasing incidence relative to squamous cell carcinoma: Becoming more frequent than squamous cell carcinoma.
- Peripheral > Central: More often found in the outer parts of the lungs.
- Extrathoracic metastases common: Frequently spreads to distant sites beyond the chest, such as the adrenal glands, bone, and brain.
Types of Adenocarcinoma
-
Adenocarcinoma in-situ:
- Non-invasive, confined to the lining of the alveoli (air sacs).
- ≤3 cm in size with a lepidic growth pattern (following the alveolar walls).
- No invasion into surrounding tissues.
- Most are non-mucinous, but some produce mucin.
- Often appears as a ground glass nodule on CT scans.
- 100% five-year disease-free survival if completely resected.
-
Invasive adenocarcinoma:
- Infiltrates the stroma (supporting tissue) and may spread to distant sites.
Oncogenic Drivers of Lung Adenocarcinoma
-
KRAS G12C:
- One of the most common driver mutations in lung adenocarcinoma.
- A mutation in the KRAS gene, leading to abnormal cell growth.
The Importance of Small Samples
- Approximately 70% of patients with NSCLC have unresectable disease.
- A small biopsy or cytology sample may be the only available tissue for diagnosis.
- Accurate subtyping is critical for treatment decisions.
- Careful tissue management is essential for diagnosis, IHC, and molecular studies.
Subtyping of NSCLC
- Combining morphology and ancillary studies allows for accurate subtyping of NSCLC.
- Periodic acid-Schiff + diastase (PASD) stain: Helps identify mucin.
-
Immunohistochemistry:
- TTF-1: Primarily expressed in lung adenocarcinomas.
- p40 and CK5/6: Indicate squamous cell carcinoma.
EGFR-Mutated Lung Adenocarcinoma
- Approximately 10-20% of Western and 30-50% of East Asian patients have EGFR mutations, particularly women and never smokers.
- More frequently found in adenocarcinomas with a lepidic growth pattern.
- Exon 19 and 21: Commonly affected by EGFR mutations.
- Detected through real-time PCR, Sanger sequencing, and next-generation sequencing.
- Patients respond well to EGFR tyrosine kinase inhibitors.
Epidermal Growth Factor Receptor (EGFR) Signaling Pathway
- EGFR is a cell surface receptor involved in cell growth and survival.
- Mutations in the EGFR gene disrupt normal signaling, leading to uncontrolled growth.
ALK-Rearranged Lung Adenocarcinoma
- Relatively uncommon (about 4% of all NSCLC).
- Usually mutually exclusive with other driver mutations (meaning they rarely occur together).
- More prevalent in younger patients, light or never smokers.
- Adenocarcinomas often have a solid-signet ring or mucinous cribriform pattern.
- Detection methods include IHC, FISH (gold standard), and NGS.
ALK Fusion Oncogenes and Downstream Signaling Pathways
- ALK rearrangements lead to the formation of abnormal fusion proteins that activate downstream signaling pathways associated with cell growth and survival.
Crizotinib Therapy for ALK+ Lung Cancer
- Crizotinib is a targeted therapy that specifically inhibits the ALK protein.
- Demonstrates significant effectiveness in shrinking tumors in patients with ALK-positive lung cancer.
Characteristics of Squamous Cell Carcinoma
- Invasive malignant epithelial tumor characterized by keratinization (formation of keratin, a protein found in skin and hair) or intercellular bridges (connections between cells).
- Males > Females: More frequent in men.
-
90% occur in smokers: Strongly associated with smoking.
- Central > Peripheral: Often found in the central airways of the lung.
- Prone to necrosis and cavitation (tissue death and formation of cavities).
- Locally aggressive: Spreads within the lung but metastasizes to distant sites less frequently than other subtypes.
Programmed Cell Death Ligand-1 (PD-L1) Immunohistochemistry
- PD-L1 is a protein that inhibits the immune system.
- High levels of PD-L1 expression in tumor cells can make the cancer less likely to respond to immunotherapy.
- Immunohistochemistry using the Dako 22C3 clone is used to assess PD-L1 expression.
- ≥50% membrane staining of tumor cells with the Dako 22C3 clone indicates potential eligibility for pembrolizumab (Keytruda) therapy.
Pembrolizumab (Keytruda) in NSCLC
- Pembrolizumab is a checkpoint inhibitor that blocks the PD-1/PD-L1 signaling pathway, allowing the immune system to recognize and attack tumor cells.
- Patients with NSCLC who have at least 50% PD-L1 expression on tumor cells are more likely to respond to pembrolizumab therapy.
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Description
Explore critical statistics and risk factors associated with lung cancer in Australia. Understand the impact of smoking, environmental hazards, and family history on lung cancer rates. This quiz will enhance your knowledge of lung cancer epidemiology and its implications.
