Lung, Primary Malignancies

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  • Primary lung cancers are the leading cause of cancer-related deaths in the United States (estimated 154,050 deaths in 2018, 25.3% of all cancer-related deaths).
  • Divided into two broad categories
    • Non–small cell lung cancer (NSCLC) (>85% of all lung cancers); normally originate in periphery
      • Adenocarcinoma (~40% of NSCLC): most common type in the United States and also nonsmokers; metastasizes earlier than squamous cell; lepidic growth, a subtype of adenocarcinoma has better prognosis.
      • Squamous cell carcinoma (SCC) (also known as epidermoid carcinoma) (~25% of NSCLC): dose-related effect with smoking; slower growing than adenocarcinoma
      • Large cell (~10% of NSCLC): prognosis similar to adenocarcinoma
    • Small cell lung cancer (SCLC) (16% of all lung cancers): centrally located, early metastases, aggressive
  • Others: mesothelioma and carcinoid tumor
  • Staging
    • Both NSCLC and SCLC: staged from I to IV based on: primary tumor (T), lymph node status (N), and presence of metastasis (M)
    • SCLC further staged by:
      • Limited disease: confined to ipsilateral hemithorax
      • Extensive disease: beyond ipsilateral hemithorax (stages IIIB and IV), which may include malignant pleural or pericardial effusion or hematogenous metastases (stage IV)
      • Tumor locations: upper: 60%; lower: 30%; middle: 5%; overlapping and main stem: 5%
      • May spread by local extension to chest wall, diaphragm, pulmonary vessels, vena cava, phrenic nerve, esophagus, or pericardium
      • Most commonly metastasize to lymph nodes (pulmonary, mediastinal), then liver, adrenal glands, bones, brain


  • Estimated 234,030 new cases in the United States in 2018
  • Usual age of diagnosis: between 65 and 74 years; peak at 70 years
  • Predominant sex: male > female

  • Most common cancer worldwide
  • Lifetime probability: men: 1 in 15; women: 1 in 17

Etiology and Pathophysiology

Multifactorial; see “Risk Factors.”



  • Oncogenes: Ras family (H-ras, K-ras, N-ras)
  • Tumor suppressor genes: retinoblastoma, p53

Risk Factors

  • Smoking
  • Secondhand smoke exposure
  • Radon
  • Environmental and occupational exposures
    • Asbestos exposure (synergistic increase in risk for smokers)
    • Air pollution
    • Ionizing radiation
    • Mutagenic gases (halogen ethers, mustard gas, aromatic hydrocarbons)
    • Metals (inorganic arsenic, chromium, nickel)
  • Lung scarring from tuberculosis
  • Radiation therapy to the breast or chest

General Prevention

  • Smoking cessation and prevention programs
  • Screening recommended by NCCN and shown to reduce mortality in National Lung Screening Trial (NLST) (1)[A]
  • Annual screening recommended with low-dose computed tomography (CT) in adults aged 55 to 74 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years
  • Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery.
  • Prevention via aggressive smoking cessation counseling and therapy; a 20–30% risk reduction occurs within 5 years of cessation.
  • Avoid hormone replacement therapy in postmenopausal smokers or former smokers (increased risk of death from NSCLC).

Commonly Associated Conditions

  • Paraneoplastic syndromes: hypertrophic pulmonary osteoarthropathy, Lambert-Eaton syndrome, Cushing syndrome, hypercalcemia from ectopic parathyroid-releasing hormone, syndrome of inappropriate antidiuretic hormone (SIADH)
  • Hypercoagulable state
  • Pancoast syndrome
  • Superior vena cava syndrome
  • Pleural effusion
  • Chronic obstructive pulmonary disease (COPD), other sequelae of cigarette smoking

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