Pleuropulmonary Involvement in Erdheim-Chester Disease: Analysis of 24 Biopsy-Proven Cases

To determine the clinicoradiologic features and clinical outcomes associated with intrathoracic Erdheim-Chester disease (ECD).

Electronic medical records of all consecutive patients with ECD encountered at Mayo Clinic from January 2005 to August 2024 were reviewed. Twenty-four patients were included. Treatment response was defined by the Response Evaluation Criteria in Solid Tumors and metabolic response on follow-up positron emission tomography scans. Survival analyses were performed from time of intrathoracic ECD diagnosis.

Median age at diagnostic biopsy was 65 years (range, 43-79 years) and pleuropulmonary/mediastinal biopsy provided the first diagnosis of ECD in 77.8% of patients. Most patients (95.8%) were symptomatic. The BRAF^V600E pathogenic variant or BRAF gene fusions were identified in 58.3% of patients. Common radiographic findings included ground-glass opacities (91.7%), interlobular septal thickening (79.2%), pulmonary nodules (70.8%), and pleural abnormalities (66.7% to 70.8%). Pulmonary function testing revealed predominantly restrictive patterns (40.0%). Diffusion capacity of the lungs for carbon monoxide was almost always reduced (median: 56.5% of predicted; range, 25.0% to 106.0%). Complete response was 10.5%, partial response was 10.5%, and objective response rate was 21.0%. Stable disease and progressive disease were noted in 57.9% and 21.1%, respectively. Median overall survival was 10.9 years (95% CI, 5.5-undefined) and estimated 5-year survival was 85.0%.

Erdheim-Chester disease causes symptomatic pleuropulmonary disease, which may be the initial presenting feature. Erdheim-Chester disease characteristically manifests interlobular septal thickening with ground-glass and/or small nodular opacities, often combined with pleural thickening and/or pleural effusions. Targeted therapy may provide durable therapeutic responses.