Lung, Primary Malignancies



  • Primary lung cancers are the leading cause of cancer-related deaths in the United States (estimated 130,180 deaths in 2021 which accounts for 25% of all cancer-related deaths). Lung cancer is mainly diagnosed in older people at average age of diagnosis at 70 years. Lung cancer has the lowest 5-year survival rate at only 18% compared to breast cancer at 90%, prostate cancer at 99%, and colorectal cancer at 65%. Vast majority (85%) of lung cancer is due to smoking, whereas the other 15% is caused by genetics, second hand smoking, asbestos, radon, and other air pollution.
  • Divided into two broad categories
    • Non–small cell lung cancer (NSCLC) (85% of all lung cancers)
      • Adenocarcinoma (~40% of NSCLC): most common type in the United States and occurs in both smokers and nonsmokers; metastasizes earlier than squamous cell; usually starts from peripheral lung tissue
      • Squamous cell carcinoma (SCC) (30% of NSCLC) usually occurs close to large airways.
      • Large cell (~10% of NSCLC): named because of the cells’ large nuclei
    • Small cell lung cancer (SCLC) (15% of all lung cancers): centrally located, aggressive, and metastasizes very easily through the blood seeding lymph nodes, bones, brain, adrenals, and liver
  • 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)
      • Most commonly metastasize to lymph nodes (pulmonary, mediastinal) and then liver, adrenal glands, bones, brain



  • There are 236,000 new cases of lung cancer and 130,000 deaths annually in the United States in 2021.
  • Overall, lung cancer causes more deaths than breast, prostate, colorectal, and brain cancers combined.
  • Average age of diagnosis: 70 years old
  • Due to decreases in smoking, lung cancer deaths are declining in the United States.

Etiology and Pathophysiology


  • Oncogenes: Ras family (H-ras, K-ras, N-ras), EGFR, NTRK, ALK, etc.
  • Tumor suppressor genes: retinoblastoma, p53
  • Genetics accounts for 8% of lung cancers.

Risk Factors

  • Smoking
  • Secondhand smoke exposure
  • Radon
  • Environmental and occupational exposures
    • Air pollution
    • Asbestos exposure (synergistic increase in risk for smokers)
    • 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
  • As of March 9, 2021, the USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (1).
  • 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.

Commonly Associated Conditions

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

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