Surfactant Deficiency Disorders: Review of Histopathologic and Ultrastructural Features.
John Hicks, Claire Langston, Eric Wartchow, Gary Mierau. Texas Children's Hospital & Baylor College of Medicine, Houston; The Children's Hospital, Denver, CO
Background: Surfactant is comprised of phospholipids and proteins packaged in lamellar bodies and secreted by alveolar type II pneumocytes. There are 4 surfactant-associated proteins (SP-A, SP-B, SP-C, SP-D) and a phospholipid transporter (ABCA3). SP-B, SP-C and ABCA3 gene mutations are associated with respiratory disease in children.
Design: 2 pediatric hospital archives identified 29 patients with surfactant deficiencies (2 SP-B, 11 SP-C, 16 ABCA3). Clinical features for SP-B deficiency were respiratory distress (RDS) shortly after birth requiring mechanical ventilation, and chest radiograph with diffuse haziness and air bronchograms. Clinical features of SP-C deficiency were variable. Some presented in the newborn period with RDS, indistinguishable from SP-B. Others presented in infancy and early childhood with gradual onset of respiratory insufficiency, hypoxemia, failure to thrive and interstitial lung disease. ABCA3 deficiency typically presented in the newborn period with RDS. Lung biopsies were performed and evaluated by routine histologic and electron microscopic (EM) techniques.
Results: SP-B deficiency showed alveolar wall widening without inflammation, mild to moderate alveolar epithelial hyperplasia, mild PAS positive intra-alveolar material, increased airspace macrophages, mild to minimal alveolar proteinosis, and no remodeling. EM showed lack of tubular myelin, disorganized lamellar bodies and irregular multivesicular bodies. SP-C deficiency shared features with chronic pneumonitis of infancy, lipoid pneumonia and cholesterol pneumonia, with alveolar wall widening with prominent alveolar epithelial hyperplasia, increased structural cells, mild chronic inflammation, and PAS positive globules, macrophages, eosinophils and cholesterol clefts in alveolar spaces. EM showed normal lamellar bodies and infrequent disorganized lamellar bodies. ABCA3 deficiency showed features overlapping with desquamative interstitial pneumonitis, pulmonary alveolar proteinosis, and nonspecific interstitial pneumonitis, with lobular remodeling, increased alveolar macrophages, pneumocyte hyperplasia, alveolar proteinosis (neonates and infants) and cholesterol clefts. EM showed small lamellar-like bodies with concentric phospholipid membranes and eccentric dense cores.
Conclusions: Ultrastructural findings associated with lamellar body formation in SP-B and ABCA3 are distinctive and distinguish these conditions from SP-C. These findings may guide genetic testing for the specific mutation responsible for the child's underlying respiratory disease.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 282, Wednesday Morning