Erdheim–Chester disease with repeatedly nondiagnostic biopsies: the diagnostic value of molecular analysis — a case report

Erdheim–Chester disease (ECD) is a rare clonal histiocytic neoplasm characterized by recurrent activation of the mitogen-activated protein kinase (MAPK) signaling pathway and multisystem infiltration by lipid-laden (foamy) histiocytes. Histopathological confirmation is generally considered the cornerstone of diagnosis; however, obtaining representative biopsy specimens may be challenging because histiocytic infiltration is often sparse and lesions are frequently fibrotic. We report the case of a 38-year-old Caucasian man presenting with central diabetes insipidus, progressive exertional dyspnea, dry cough, bilateral hydronephrosis, and chronic kidney disease. High-resolution computed tomography demonstrated a diffuse reticulonodular interstitial pattern, while abdominal imaging revealed bilateral perinephric soft-tissue infiltration (“hairy kidneys”) and circumferential periaortic sheathing (“coated aorta”). Central diabetes insipidus preceded the onset of systemic manifestations by eight years. Whole-body ^18F-FDG PET/CT demonstrated metabolically active perirenal, pulmonary, mediastinal, and skeletal involvement, including symmetric uptake in the metaepiphyseal regions of the distal femora and proximal tibiae. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and repeated CT-guided core needle biopsies demonstrated only limited foamy histiocytic infiltration and chronic inflammatory changes, without providing definitive histopathological confirmation of ECD. Molecular analysis of the perinephric core biopsy specimen subsequently identified the BRAF V600E mutation. As surgical biopsy was not feasible because the patient declined the procedure, the diagnosis of ECD was established by integrating the clinical, radiological, histopathological, and molecular findings. Because targeted therapy was not reimbursed as first-line treatment and self-funded treatment was financially inaccessible, interferon-α therapy was initiated, resulting in clinical, functional, and radiological stability during 12- month of follow-up. This case highlights the diagnostic value of molecular analysis in patients with suspected ECD when conventional histopathological evaluation remains inconclusive despite repeated tissue sampling. Detection of the BRAF V600E mutation in minimally invasive biopsy specimens, interpreted together with characteristic clinical and radiological findings, may substantially increase diagnostic confidence and guide subsequent therapeutic decision-making.