Targeted Therapy in Erdheim-Chester Disease: A Case Report and Review of the Literature

Erdheim-Chester disease is a rare, aggressive non-Langerhans cell histiocytosis characterized by multisystem infiltration of histiocytes. It commonly affects middle-aged men and is driven by acquired mutations in the MAPK signaling pathway. This essential cellular pathway relays extracellular signals to the nucleus and regulates cell proliferation and survival. We report the case of a 39-year-old male who presented with progressive, severe left-sided frontal and temporal headaches. Imaging revealed a symptomatic craniocervical mass, a nonsecreting pituitary lesion, and bilateral perinephric soft tissue infiltration extending throughout the retroperitoneum. Histopathologic evaluation demonstrated foamy histiocytes consistent with Erdheim-Chester disease, and molecular testing identified a BRAF mutation. Notably, no FDG-avid skeletal involvement was identified on available whole-body FDG PET/CT imaging, an uncommon feature in Erdheim-Chester disease. The patient was treated with the BRAF inhibitor vemurafenib, with dose reduction due to dermatologic toxicity, and subsequently tolerated therapy well. He has maintained a stable disease course at one-year follow-up. This report demonstrates the variable clinical manifestations of Erdheim-Chester disease and emphasizes the importance of molecular profiling in directing targeted therapeutic strategies.