What are the risk factors for lung carcinoma? Describe the morphological features of three major histological types of lung carcinoma.

Risk Factors for Lung Carcinoma

Lung carcinoma arises from genetic damage to the DNA of lung cells, leading to uncontrolled cell proliferation and tumor formation. While multifactorial, several prominent risk factors have been identified:

• Tobacco Smoking: This is the single most significant risk factor, accounting for approximately 80% of lung cancer deaths. The risk escalates with the duration and intensity of smoking (number of packs per day). This includes cigarettes, cigars, pipe tobacco, snuff, and chewing tobacco. Even low-tar or "light" cigarettes carry a substantial risk.
• Secondhand Smoke (Passive Smoking): Exposure to the smoke of others significantly increases the risk of developing lung cancer in non-smokers. It is considered the third most common cause of lung cancer in some regions.
• Exposure to Radon: Radon is a naturally occurring radioactive gas emanating from the decay of uranium in soil and rocks. When inhaled, it can damage lung tissue, particularly in smokers, increasing lung cancer risk.
• Occupational Exposures: Certain workplaces expose individuals to carcinogens that elevate lung cancer risk. These include:
  • Asbestos (mines, mills, shipyards, insulation work)
  • Radioactive ores (e.g., uranium)
  • Inhaled chemicals such as arsenic, beryllium, cadmium, silica, vinyl chloride, nickel compounds, chromium compounds, coal products, mustard gas, and chloromethyl ethers.
  • Diesel exhaust.
• Air Pollution: Both outdoor and household air pollution are significant contributors. Outdoor pollution from vehicular emissions, industrial pollutants, and construction dust is a serious risk factor. Household air pollution, especially from burning solid fuels (wood, coal) for cooking, particularly impacts women in rural areas.
• Prior Radiation Therapy to the Chest: Individuals who have received radiation therapy to the chest for other cancers have an increased risk of developing lung cancer.
• Personal History of Cancer: A history of other cancers, including head and neck cancer, or previous lung cancer, can increase the risk of recurrence or new primary lung cancer.
• Family History of Lung Cancer: Genetic predisposition can play a role, with a family history of lung cancer increasing an individual's risk.
• Chronic Lung Diseases: Conditions such as Chronic Obstructive Pulmonary Disease (COPD) and pulmonary fibrosis are associated with an elevated risk.
• Age: The risk of lung cancer generally increases with age, with an average onset around 70 years.
• HIV Infection: Infection with Human Immunodeficiency Virus (HIV) is also a recognized risk factor.

Morphological Features of Three Major Histological Types of Lung Carcinoma

Lung carcinomas are broadly classified into Small Cell Lung Carcinoma (SCLC) and Non-Small Cell Lung Carcinoma (NSCLC). NSCLC comprises the majority of cases and includes three major histological types: Adenocarcinoma, Squamous Cell Carcinoma, and Large Cell Carcinoma. Accurate histological classification is vital for prognosis and guiding treatment.

1. Adenocarcinoma (Approx. 40% of Lung Cancers)

Adenocarcinomas are the most common type of lung cancer, particularly in non-smokers and women. They typically arise in the peripheral regions of the lungs.

• Cellular Features:
  • Cells often grow in three-dimensional clumps and resemble glandular cells.
  • May produce mucin (mucus).
  • Nuclei can be pleomorphic (varied in size and shape) and hyperchromatic.
  • Often express pneumocytic markers like Thyroid Transcription Factor (TTF-1) and Napsin-A, which are useful for immunohistochemical diagnosis.
• Growth Patterns: Adenocarcinomas exhibit diverse growth patterns, including:
  • Lepidic: Cells grow along the surface of intact alveolar walls, often associated with less aggressive behavior.
  • Acinar: Formation of glandular structures.
  • Papillary: Finger-like projections.
  • Micropapillary and Solid: Often associated with more aggressive behavior and poorer prognosis.
• Location: More commonly found in the periphery of the lung.

2. Squamous Cell Carcinoma (Approx. 30% of Lung Cancers)

Squamous cell carcinomas (SCCs) are strongly linked to smoking and typically originate in the central regions of the lungs, near larger airways.

• Cellular Features:
  • Defined by the presence of keratinization or intercellular bridges.
  • Cells are often polygonal with distinct cell borders.
  • Nuclei are typically hyperchromatic and irregular.
  • Cytoplasm is abundant and eosinophilic (pink-staining).
  • May form "keratin pearls" (concentric layers of keratinized cells) centrally within solid tumor nests.
  • Lacks glandular structures or mucin production.
  • Immunohistochemically, SCCs often express p63, p40, CK5, and CK5/6, while typically being negative for TTF-1 and Napsin-A.
• Growth Patterns: Tend to form sheets of cells with varying degrees of keratinization. A hollow cavity and associated cell death are commonly found at the center of the tumor.
• Location: Commonly found in the central airways (bronchi).

3. Small Cell Lung Carcinoma (SCLC) (Approx. 15% of Lung Cancers)

SCLC is a highly aggressive form of lung cancer, almost exclusively found in heavy smokers, and is characterized by rapid growth and early metastasis. It is distinct from NSCLC due to its unique biological behavior and treatment response.

• Cellular Features:
  • Composed of small, round to oval cells with scant cytoplasm.
  • Nuclei are hyperchromatic (darkly stained), finely granular chromatin ("salt and pepper" appearance), and inconspicuous nucleoli.
  • Nuclear molding (nuclei conforming to each other's shapes) is a characteristic feature.
  • Frequent mitoses and extensive necrosis are common.
  • Cells show neuroendocrine differentiation and typically express neuroendocrine markers such as chromogranin, synaptophysin, and CD56.
• Growth Patterns: Typically grows in solid sheets or clusters with little stromal support.
• Location: Often arises in the central part of the lungs, near the major airways.
• Clinical Relevance: Highly sensitive to chemotherapy and radiation therapy but has a very poor prognosis due to its aggressive nature and early metastasis.

Feature	Adenocarcinoma	Squamous Cell Carcinoma	Small Cell Lung Carcinoma
Prevalence	Most common (approx. 40%)	Second most common (approx. 30%)	Less common but aggressive (approx. 15%)
Association with Smoking	Less strong (can occur in non-smokers)	Strongest association	Almost exclusively in heavy smokers
Typical Location	Peripheral lung	Central airways	Central airways
Key Morphological Features	Glandular differentiation, mucin production, lepidic/acinar/papillary patterns	Keratinization, intercellular bridges, keratin pearls	Small cells, scant cytoplasm, nuclear molding, "salt and pepper" chromatin, neuroendocrine features
Immunohistochemistry Markers	TTF-1, Napsin-A positive	p40, p63, CK5/6 positive; TTF-1 negative	Chromogranin, Synaptophysin, CD56 positive