Decoding Erdheim–Chester Disease: a Pictorial Essay of the Radiologic and Pathologic Findings, and its Main Differential Diagnoses

Abstract

Erdheim–Chester disease (ECD) is a rare non–Langerhans cell histiocytic neoplasm that primarily affects adults in their fifth to seventh decades of life. It is characterized by multisystem infiltration of CD68-positive, CD1a-negative foamy histiocytes and is driven by mutations in the MAPK and PI3K-AKT pathways, classifying it as a clonal myeloid neoplasm. ECD manifests with a wide spectrum of clinical features, including skeletal, cardiovascular, central nervous system, retroperitoneal, pulmonary, and endocrine involvement, frequently causing delays in diagnosis due to its nonspecific presentation. Targeted therapies, particularly BRAF and MEK inhibitors, have transformed the management of ECD, leading to significant improvements in patient outcomes.

Imaging plays a pivotal role in raising diagnostic suspicion, evaluating disease extent, and monitoring treatment response. Early recognition and accurate diagnosis rely on a multidisciplinary approach, integrating clinical evaluation, histopathology, molecular mutation analysis, and radiological findings. This pictorial essay aims to enhance radiologists’ familiarity with the key imaging findings of ECD across affected organ systems, highlighting characteristic patterns, potential diagnostic pitfalls, and important differentiating features from other mimicking conditions. We also provide an overview of the disease’s pathogenesis and modern treatment strategies. By increasing awareness of this challenging and often under-recognised condition, we aim to facilitate earlier diagnosis, more accurate imaging interpretation, and improved patient care.