Lung cancer was diagnosed in about 115,610 men and 105,590 women in the United States in 2015, and 86% of pts die within 5 years. Lung cancer, the leading cause of cancer death, accounts for 28% of all cancer deaths in men and 26% in women. Peak incidence occurs between ages 55 and 65 years. Incidence is decreasing in men and increasing in women.
Four major types account for 88% of primary lung cancers: epidermoid (squamous), 29%; adenocarcinoma (including bronchioloalveolar), 35%; large cell, 9%; and small cell (or oat cell), 18%. Histology (small-cell versus non-small-cell types) is a major determinant of treatment approach. Small cell is usually widely disseminated at presentation, whereas non-small cell may be localized. Epidermoid and small cell typically present as central masses, whereas adenocarcinomas and large cell usually present as peripheral nodules or masses. Epidermoid and large cell cavitate in 20–30% of pts.
The major cause of lung cancer is tobacco use, particularly cigarette smoking. Lung cancer cells may have ≥10 acquired genetic lesions, most commonly point mutations in ras oncogenes; amplification, rearrangement, or transcriptional activation of myc family oncogenes; overexpression of bcl-2, Her2/neu, and telomerase; and deletions involving chromosomes 1p, 1q, 3p12-13, 3p14 (FHIT gene region), 3p21, 3p24-25, 3q, 5q, 9p (p16 and p15 cyclin-dependent kinase inhibitors), 11p13, 11p15, 13q14 (rb gene), 16q, and 17p13 (p53 gene). Loss of 3p and 9p is the earliest event, detectable even in hyperplastic bronchial epithelium; p53 abnormalities and ras point mutations are usually found only in invasive cancers. A small but significant subset of pts with adenocarcinoma have activating mutations in the gene for the epidermal growth factor (EGF) receptor, or activating fusion events involving the alk or ros gene. Driver mutations in lung cancer are depicted in Fig. 69-1.
Driver mutations in adenocarcinomas.
Only 5–15% are detected while asymptomatic. Central endobronchial tumors cause cough, hemoptysis, wheeze, stridor, dyspnea, pneumonitis. Peripheral lesions cause pain, cough, dyspnea, symptoms of lung abscess resulting from cavitation. Metastatic spread of primary lung cancer may cause tracheal obstruction, dysphagia, hoarseness, Horner’s syndrome. Other problems of regional spread include superior vena cava syndrome, pleural effusion, respiratory failure. Extrathoracic metastatic disease affects 50% of pts with epidermoid cancer, 80% with adenocarcinoma and large cell, and >95% with small cell. Clinical problems result from brain metastases, pathologic fractures, liver invasion, and spinal cord compression. Paraneoplastic syndromes may be a presenting finding of lung cancer or first sign of recurrence (Chap. 76). Systemic symptoms occur in 30% and include weight loss, anorexia, fever. Endocrine syndromes occur in 12% and include hypercalcemia (epidermoid), syndrome of inappropriate antidiuretic hormone secretion (small cell), gynecomastia (large cell). Skeletal connective tissue syndromes ...