C80-03 Mediastinal Mass: The Presenting Sign of a Rare, Multi-System Disease

Abstract Introduction The diagnosis of rare conditions is challenging, particularly with variable multi-system involvement. Often, symptoms are incorrectly attributed to multiple processes rather than a unifying diagnosis. This case describes the delayed diagnosis of a rare disease despite symptoms and prior testing consistent with the condition. Description of Case An 84-year-old man with longstanding idiopathic diabetes insipidus presented with subacute dyspnea and leg swelling. Family members also endorsed progressive cognitive decline and imbalance over the past two years. Vital signs were unremarkable. On exam, he was cooperative but unable to answer detailed questions. He had bilateral pitting edema, decreased right-sided breath sounds, and otherwise clear lungs. Initial labs were unremarkable except for an elevated B-type natriuretic peptide level. Imaging revealed a moderate right-sided pleural effusion and a middle mediastinal mass encasing the aorta and pulmonary artery (Figure 1). A PET/CT scan revealed the mediastinal mass to be mildly hypermetabolic, and intramedullary sclerosis was noted in the bilateral femurs; there were no hypermetabolic lymph nodes. Echocardiography revealed impaired biventricular systolic function. Right-sided thoracentesis yielded 1.2 liters of transudative fluid with negative cultures, flow cytometry, and cytology. Due to its proximity to vascular structures, the mediastinal mass was unsuitable for biopsy. Retrospective chart review identified a bone scan six years prior that revealed symmetric increased uptake in the bilateral femurs; a repeat bone scan redemonstrated this. Biopsy of the left femur showed clusters of histiocytes admixed with marrow fibrosis. Advanced studies on the pleural fluid revealed a histiocyte:mesothelial cell ratio of 20:1. A Guardant 360 test on peripheral blood showed a positive BRAF mutation in 0.3% of cells. The patient was diagnosed with Erdheim-Chester Disease. Discussion Erdheim-Chester Disease (ECD) is characterized by idiopathic somatic mutation in a myeloid progenitor cell, leading to clonal proliferation of non-Langerhans cell histiocytes. Affected patients are often older men, with variable manifestations including symmetric osteosclerosis of long bones (most common), peri-aortic fibrosis, right heart infiltration, pleural disease, diabetes insipidus, and central nervous system involvement. In hindsight, this patient had multiple classic manifestations of ECD, but he was undiagnosed for years likely due to clinician unfamiliarity with ECD and multi-organ symptoms attributed to independent diagnoses. Fewer than 1000 cases of ECD have ever been reported. This abstract adds to the growing literature on this likely under-diagnosed condition, and it demonstrates the importance of considering a unifying diagnosis to account for multiple pathologies that lack a clear explanation. This abstract is funded by: None