Erdheim–Chester Disease: A Diagnostic Challenge Masquerading as Lymphoma, A Case Report and Literature Review

Background: Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by clonal proliferation of foamy histiocytes driven by MAPK–ERK pathway mutations, most commonly BRAF^V600E. The disease exhibits wide clinical heterogeneity and frequently involves the skeletal, cardiovascular, and retroperitoneal systems, often posing diagnostic challenges. Case Presentation: A 79-year-old Caucasian woman came to see us for six months of exertional dyspnea, cough and neck tightness, with a decrease in appetite and fatigue. The mass in the anterior mediastinum was seen to encase the great vessels and the trachea on contrast enhanced chest CT; the left retroperineal region showed infiltration, and the classic “hairy kidney” sign, was seen on abdominal imaging, suggesting systemic ECD. ^18F-FDG PET/CT showed mild hypermetabolism in these regions. Initial FNA biopsy failed to yield a diagnosis, but a thoracoscopic biopsy of fibrotic tissue was positive for foamy histiocytic infiltration with CD68 expression and CD1a negativity and cyclin D1 positivity. There was no BRAF V600E test performed, and further molecular testing was pending. Multidisciplinary management entailed a pericardial window for effusion removal and for the planning of a mutation-specific systemic therapy. Discussion: This case highlights the protean presentations and diagnostic challenges of ECD and the necessity for multi-systemic clinical, radiologic and pathologic assessment. Mediastinal, pericardial, and retroperitoneal involvement is a sign of systemic involvement. Conclusion: A diagnosis of ECD should be suspected when there is unexplained fibrosis of the mediastinum or retroperitoneum. Imaging, histopathology and molecular testing are all crucial for proper diagnosis and treatment planning. Multidisciplinary early care provides better diagnosis and targeted therapy in this rare disorder.

Keywords: Erdheim–Chester disease; non-Langerhans cell histiocytosis; mediastinal mass; retroperitoneal fibrosis; hairy kidney sign; BRAF mutation.