Personalized Management of Erdheim–Chester Disease: The Pivotal Role of Molecular and Cross-Sectional Imaging from Staging to Targeted Therapy Monitoring

Erdheim–Chester disease (ECD) is a rare, clonal non-Langerhans cell histiocytic neoplasm driven by activating mutations in the mitogen-activated protein kinase (MAPK) pathway, most notably the BRAF-V600E mutation. The discovery of these molecular alterations has shifted the therapeutic paradigm from non-specific immunosuppression to personalized targeted therapies, such as BRAF and MEK inhibitors, dramatically improving patient outcomes. Given its protean and insidious systemic manifestations, imaging plays an indispensable role in the personalized diagnostic and therapeutic pathway of ECD. Metadiaphyseal symmetrical osteosclerosis represents the skeletal hallmark, while extraskeletal involvement typically affects the cardiovascular, retroperitoneal, pulmonary, and central nervous systems, yielding pathognomonic imaging signatures such as the “coated aorta” and “hairy kidney.” Advanced cross-sectional techniques—including CT, MRI, and organ-specific mapping protocols—are crucial for baseline phenotype characterization, risk stratification, and guiding biopsies toward hypermetabolic sites for biomarker detection. Furthermore, molecular imaging with 18F-FDG PET/CT has emerged as the cornerstone for baseline systemic staging and quantitative metabolic response monitoring via PERCIST criteria, enabling early assessment of targeted treatment efficacy long before morphological changes occur. This review illustrates the multimodality imaging spectrum of ECD based on our institutional experience, emphasizing how precision imaging integrates with molecular profiling to guide personalized patient management.