Figure 5.

a) Alveolar proteinosis pattern. A 2-week-old female, born at term, with respiratory distress from birth. Radiology reported a persistent hazy shadowing in the lung fields with no focal lesions. A lung biopsy was obtained. Subsequent genetic analysis showed mutation of the SFP-B gene. There is mild thickening of the interstitium of the alveolar septa by type 2 pneumocyte hyperplasia and a cellular infiltrate. The alveoli and alveolar ducts are distended by granular eosinophilic material, and some foamy macrophages are present within this material. There is no significant inflammatory cell infiltration. Staining for surfactant protein-B was completely negative. Haematoxylin and eosin, original magnification 10×. b) Chronic pneumonitis of infancy pattern. A 2-month-old infant born at term who developed severe respiratory distress at 1 week of age requiring ventilation. Chest CT findings were in keeping with severe interstitial lung disease. The infant was CPAP dependent by 5 weeks of age. Genetic analysis showed mutation of SFP-B gene. The infant died aged 3 years awaiting transplant. The lung shows florid proliferation of type 2 pneumocytes many of which have abundant pink cytoplasm. Airspaces are scarcely discernible and some contain inflammatory cells. Haematoxylin and eosin, original magnification 10×. c) Desquamative interstitial pneumonitis pattern. A 2-year-old female with chronic lung disease with compound heterozygous mutation in the ABCA3 gene. There is thickening of the interstitium with smooth muscle proliferation. There is type 2 pneumocyte hyperplasia and the airspaces contain large numbers of macrophages that demonstrate fine granular PAS positivity. PAS, original magnification 20×. d) Ultrastructure. A 30-day old, ventilator-dependent male who underwent lung biopsy. The biopsy showed a chronic pneumonitis of infancy pattern. Ultrastructural examination of the abundant type 2 pneumocytes shows them to contain abnormal lamellar bodies; three are shown in the figure. They are rounded and contain tightly packed phospholipid lamellae with a barely perceptible lamellar arrangement. All three show dense rounded inclusions characteristic of the lamellar bodies in ABCA3 disease. Subsequent genetic analysis showed a homozygous pathogenic missense mutation in ABCA3. Uranyl acetate and lead citrate, magnification 15 000×. Image courtesy of G. Anderson (Great Ormond St Hospital, London, UK).