A 56-year-old man comes to the office after 2 episodes of low-volume hemoptysis. He describes the episodes as "streaks of blood" in his sputum. The patient has had a chronic cough over the last several years, most prominently in the morning. He has also had several recent respiratory infections. The patient has smoked a pack of cigarettes daily for the last 40 years. Chest x-ray shows hyperinflated lungs but no infiltrates or masses. Bronchoscopy is performed and several suspicious foci of bronchial mucosa are biopsied. Microscopic examination of the bronchial mucosa reveals patches of stratified squamous epithelium. The development of this patient's mucosal lesions most closely resembles which of the following disease processes?
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Normal bronchi are lined mainly by pseudostratified ciliated columnar cells that propel inhaled particles toward the oropharynx for removal by swallowing or expectoration. Interspersed goblet cells produce mucus that traps inhaled debris. The ciliated and goblet cells of respiratory epithelium are together responsible for mucociliary clearance.
In response to chronic irritation, such as smoking, the respiratory epithelium may be replaced with squamous epithelium. This change of cell types is called squamous metaplasia and is seen histologically as a transition to stratified polygonal epithelial cells. This transition is initially adaptive because squamous cells are more resistant to irritation than columnar cells. However, the lack of cilia and goblet cells prevents effective mucociliary clearance and increases the risk of respiratory infections. Squamous bronchial metaplasia is reversible and may resolve on discontinuation of smoking, but persistent irritant exposure can cause progression to dysplasia or squamous cell carcinoma.
Other examples of metaplasia include Barrett esophagus, in which esophageal squamous epithelium is replaced by intestinal columnar epithelium with goblet cells in response to chronic acid exposure, and squamous metaplasia of the cervix.
(Choice B) Cervical squamous cell carcinoma (CSCC) is almost always caused by oncogenic strains of human papillomavirus (HPV) that integrate into the host cell genome. Although HPV infects the metaplastic epithelium at the cervical transformation zone, development of CSCC is primarily driven by the expression of viral genes that inactivate host tumor-suppressor proteins.
(Choice C) Hypertrophic cardiomyopathy is an autosomal dominant disease caused by defects in the contractile proteins of the cardiac sarcomere. These abnormalities lead to disordered myocardial fibers, left ventricular outflow obstruction, arrhythmia, and increased risk of sudden death.
(Choice D) Interstitial cystitis is characterized by urinary frequency and urgency, and pelvic pain. Gross findings include erythema and ulceration of the bladder mucosa. Histopathology shows inflammatory infiltrates and fibrosis.
(Choice E) Minimal change disease is associated with effacement of the processes of glomerular podocytes and is visible only on electron microscopy. The underlying cell type is not altered.
Educational objective:
Squamous bronchial metaplasia is a reversible, adaptive response to chronic irritation, such as smoking. The normal columnar epithelium is replaced by squamous epithelium, which is more resistant to irritation but has reduced mucociliary clearance. Metaplasia also occurs with Barrett esophagus, in which esophageal squamous epithelium is replaced by intestinal columnar epithelium with goblet cells in response to chronic acid exposure.