Silicosarcoidosis: Histologic and Clinical Features of an Occupational Granulomatous Disease

Abstract

Sarcoidosis is a multisystem inflammatory disease of unknown etiology. Growing evidence indicates that occupational exposure to respirable crystalline silica (RCS) is associated with an increased incidence of sarcoidosis. Yet a diagnosis of sarcoidosis rarely prompts investigation to identify preventable exposures. We sought to elucidate features that identify this important clinical syndrome of silicosarcoidosis. We assembled a multinational case series of workers with sarcoidosis who also reported occupational RCS exposure. We characterized clinical and histopathologic findings using a standardized instrument. We also assessed lung specimens using a novel quantitative microscopy technique to measure birefringent dust density in silicosarcoidosis cases and compared them to control groups. We identified 35 silicosarcoidosis cases (97% male, mean age 48 years) from the United States, Israel, and Taiwan who reported 21 ± 9 years of RCS exposure. On histology scoring, 25/29 (86%) had granulomas and 17/18 (94%) with evaluable lung tissue had lymphocytic inflammation and/or lymphoid aggregates. Common lung interstitial findings included silicotic nodules (39%), mixed-dust macules/nodules (44%), and birefringent dust (50%). Quantitative birefringent dust density was significantly greater (p < 0.001) in silicosarcoidosis cases compared with healthy controls (147 ± 179 vs. 12 ± 9 particles/mm²) but lower than in coal miners with silica-related progressive massive fibrosis (623 ± 777). We found significant differences in the frequency of histologic abnormalities in large versus small biopsy specimens, with fewer findings of RCS exposure in smaller tissue samples. The use of the term silicosarcoidosis should enhance recognition of this significant exposure-related granulomatous lung disease and will help guide clinical management that addresses exposure prevention in combination with appropriate pharmacologic treatment.