Lung carcinomas arise from normal bronchial cells that have acquired multiple genetic lesions and are capable of expressing a variety of phenotypes. There are four major subtypes of lung cancer: small cell, squamous cell, adenocarcinoma, and large cell. Squamous cell, adenocarcinoma, and large cell are collectively referred to as non–small-cell lung cancer (NSCLC). NSCLC represents 85% of the lung cancer diagnoses while the aggressive histology small-cell lung cancer (SCLC) represents 15% of lung cancer diagnoses. Adenocarcinoma is the most common histology of NSCLC (50% of all lung cancer) and is associated with a high incidence of distant metastasis at diagnosis. Squamous cell is the second most common histology of NSCLC (30% of all lung cancer) followed by large cell. Adenocarcinoma and large-cell lung cancer generally present as peripheral lesions in the lung, whereas squamous cell and small-cell histologies commonly present as central lesions, often causing hemoptysis or postobstructive pneumonia.
Smoking is the primary risk factor for development of lung cancer. The risk of lung cancer increases with the amount and duration of smoking. Smoking history is defined by packs per day (amount) and duration (eg, 2 packs per day × 20 years = 40 pack years). The risk of lung cancer decreases after smoke cessation but remains above the risk of a nonsmoker. Additionally, asbestos exposure increases the risk of lung cancer by fivefold and is synergistic with smoking for causing lung cancer. Although the most common lung cancer associated with asbestos exposure is NSCLC; patients with mesothelioma almost always have a history of asbestos exposure. Other risk factors associated with lung cancer include radon exposure, ionizing radiation, a diet low in fruit, vegetables, β-carotene, and vitamin E, a family history of lung cancer, and occupational exposures (eg, coal, arsenic, nickel, and other mining jobs).
Signs and symptoms of lung cancer include cough, increased sputum production, pleuritic chest pain, dyspnea, wheezing, and stridor. However, these symptoms are also common in smokers in general. A suspicion of lung cancer should increase if the patient experiences hemoptysis. Extrapulmonary symptoms associated with lung cancer include bone pain and/or fracture from bone metastasis, neurologic deficits secondary to brain metastasis, and spinal cord compression secondary to bone metastasis in the spinal vertebrae. Multiple paraneoplastic syndromes can occur in lung cancer. Paraneoplastic syndromes are caused by proteins secreted by the malignancy (Table 13-1).
TABLE 13-1Paraneoplastic Syndromes Associated With Lung Cancer ||Download (.pdf) TABLE 13-1Paraneoplastic Syndromes Associated With Lung Cancer
|Paraneoplastic Syndrome ||Comments |
|Cachexia ||Extreme muscle wasting and malnutrition |
|SIADH ||Hyponatremia due to ADH secretion |
|Hypercalcemia ||Caused by PTH-rp secretion; associated with squamous cell histology |
|Cushing syndrome ||Caused by the tumor secreting ACTH |
|Pulmonary hypertrophic osteoarthropathy ||Associated with clubbing of the fingers and toes, and painful swollen joints |
|Hypercoagulable state ||Increased risk of DVTs and PE |
|Eaton-Lambert syndrome ||Upper extremity weakness and diminished reflexes |