Clinical and Histopathologic Features of Interstitial Lung Disease in Erdheim⁻Chester Disease.

Sara Haroutunian,S Mirmomen,Ashkan Malayeri,Juvianee Estrada-Veras,Jianhua Yao,Louisa Boyd,William Gahl,Bernadette Gochuico,Kavya Mathur,David Kleiner,Elaine Jaffe,Kevin O’Brien

doi:10.3390/jcm7090243

Abstract

Limited information is available regarding interstitial lung disease (ILD) in Erdheim–Chester disease (ECD), a rare multisystemic non-Langerhans cell histiocytosis. Sixty-two biopsy-confirmed ECD patients were divided into those with no ILD (19.5%), minimal ILD (32%), mild ILD (29%), and moderate/severe ILD (19.5%), based on computed tomography (CT) findings. Dyspnea affected at least half of the patients with mild or moderate/severe ILD. Diffusion capacity was significantly reduced in ECD patients with minimal ILD. Disease severity was inversely correlated with pulmonary function measurements; no correlation with BRAF V600E mutation status was seen. Reticulations and ground-glass opacities were the predominant findings on CT images. Automated CT scores were significantly higher in patients with moderate/severe ILD, compared to those in other groups. Immunostaining of lung biopsies was consistent with ECD. Histopathology findings included subpleural and septal fibrosis, with areas of interspersed normal lung, diffuse interstitial fibrosis, histiocytes with foamy cytoplasm embedded in fibrosis, lymphoid aggregates, and focal type II alveolar cell hyperplasia. In conclusion, ILD of varying severity may affect a high proportion of ECD patients. Histopathology features of ILD in ECD can mimic interstitial fibrosis patterns observed in idiopathic ILD.

Highlights

Erdheim–Chester disease (ECD) is a rare, multisystemic, non-Langerhans cell histiocytic neoplasm of unknown etiology [1,2,3,4]
Sixty-twwoo patiennttss (455 males, 17 females) with ECD were evaluated for interstitial lung disease (ILD)
Our results show that DLCO is more sensitive than FVC or TLC in detecting ILD, which agrees with previous findings in early familial pulmonary fibrosis [17]

Summary

Introduction

Erdheim–Chester disease (ECD) is a rare, multisystemic, non-Langerhans cell histiocytic neoplasm of unknown etiology [1,2,3,4]. Histopathologic features of ECD include foamy or granular histiocytes with well-defined borders, Touton-type giant cells, lymphocytes, and scattered plasma cells with surrounding fibrosis [5]. Lesional cells are generally positive for cluster of differentiation (CD) markers. CD68, CD163, and factor XIIIa, and negative for CD1a and Langerin. S-100 is variably positive, and ultrastructural studies show absent Birbeck granules. Accumulation of ECD histiocytes results in chronic inflammation, fibrosis, and organ dysfunction [5]. A BRAF V600E mutation has been found in ECD and Langerhans cell histiocytosis, and the presence of this mutation helps differentiate the histiocytosis [6,7]

Results

Discussion

Conclusion