Definition
• Autosomal recessive disease with mutation of cystic fibrosis transmembrane conductance regulator (CFTR) gene and multisystem involvement. Patients have abnormal transport of chloride and sodium across the respiratory epithelium, resulting in thickened airway secretions and susceptibility to recurrent infections
Clinical features
Epidemiology
• Common hereditary disease in whites, affecting approximately 1/3000 live births
• Less common in blacks, occurring in approximately 1/17,000 live births
• Rare among Asians, seen in approximately 1/90,000 live births
Presentation
• Clinical presentation and severity vary considerably
• Pulmonary manifestations: wheezing, chronic cough, atelectasis, recurrent pneumonia, and bronchiolitis
• Extrapulmonary manifestations: meconium ileus, steatorrhea, malabsorption, recurrent pancreatitis, nasal polyps, absence of sperm in semen
Prognosis and treatment
• Dramatically improved survival with advanced multidisciplinary management
• Management of pulmonary disease includes controlling infection and maintaining airway clearance
Pathology
Histology
• Gross pathologic findings for endstage disease: widespread bronchiectasis (more severe in upper lobe) with thick mucus plugs, pleural fibrosis/adhesions, pneumonic consolidation, and lobar atelectasis
• Microscopic findings: acute and chronic inflammation involving the large and small airways associated with bronchial gland and goblet cell hyperplasia, squamous metaplasia, and mucostasis
Immunopathology/special stains
• Not contributory
Main differential diagnoses
• Recurrent pneumonia and bronchitis, bronchiectasia in non–cystic fibrosis patients: may share similar clinical, radiographic and histological features but no CFTR gene mutation
Fig 1 Cystic fibrosis. Cut surface of the explanted lung specimen shows severely dilated airways with thick fibrotic walls and purulent mucous plugs; the lung parenchyma is solidified with significant fibrosis.
Fig 2 Cystic fibrosis. A, The bronchiolar wall is fibrotic and infiltrated with mixed inflammatory cells; the bronchial epithelium is hyperplastic with goblet cell hyperplasia. Intraluminal mucostasis and numerous neutrophils are also present. Note secondary pulmonary arterial hypertensive changes in upper left. B, Florid acute inflammation of a bronchiole and intraluminal neutrophilic abscess. Adjacent alveoli are relatively spared.
Fig 3 Cystic fibrosis. At the late stage of the disease, concentric fibrosis of bronchiolar wall (A) and complete obliteration of the bronchiolar lumen (B) are seen (shown in this explanted lung).