Interstitial pneumonia in Hermansky-Pudlak syndrome: significance of florid foamy swelling/degeneration (giant lamellar body degeneration) of type-2 pneumocytes

Although usual interstitial pneumonia (UIP)-like IP has been known as the m ost serious complication of Hermansky-Pudlak syndrome (HPS), its pathologic features and pathogenesis are poorly understood. We investigated biopsied and autopsied lung tissues from five patients who died of UIP-like IP assoc iated with HPS (HPSIP). The salient histopathologic features of HPSIP obser ved were: (1) alveolar septa displaying florid proliferation of type-2 pneu mocytes (2PCs) with characteristic foamy swelling/degeneration; (2) patchy fibrosis with lymphocytic and histiocytic infiltration centered around resp iratory bronchioles, occasionally showing constrictive bronchiolitis; and ( 3) honeycomb change without predilection for the lower lobes or subpleural area. Those peculiar 2PCs were histochemically characterized by the over ac cumulation of phospholipid, immunohistochemically by a weak positivity for surfactant protein, and ultrastructurally by the presence of numerous giant lamellar bodies that compressed the nucleus with occasional cytoplasmic di sruption, together suggesting a form of cellular degeneration with an over accumulation of surfactant (giant lamellar body degeneration). The present study strongly indicates that there is a basic defect in the formation/secr etion process of surfactant by the 2PCs in HPS, which may well be the trigg ering factor for the HPSIP development. Other factors, such as macrophage d ysfunction, may be working synergistically for further acceleration of the inflammatory process.