CNS Erdheim-Chester Disease: A Challenge to Diagnose

Erdheim-Chester disease (ECD) is a rare nonLangerhans cell histiocytosis. Although approximately 50% of cases eventually involve the central nervous system (CNS), the CNS has seldom been reported as the initial biopsy site. The diagnosis of CNS ECD can be challenging due to morphologic overlap with reactive histiocytic proliferation, Langerhans cell histiocytosis (LCH), and extranodal Rosai-Dorfman disease (RDD). We present 3 cases from our files that illustrate the protean manifestations of ECD. Case 1 was a 47-year-old man with ataxia, dysarthria, and intermittent ophthalmoplegia whose cerebellar biopsy had shown only profuse, nonspecific Rosenthal fiber-rich piloid gliosis; ECD was diagnosed only at autopsy. The gliosis and marked variations in histiocyte morphology in different anatomical sites added to the diagnostic challenge. Case 2 was a 67-year-old female with chronic progressive symptoms and a pontine lesion that had been considered to be CLIPPERS by neuroimaging. Identification of a BRAFV600E mutation allowed an ECD diagnosis and treatment with the specific BRAFV600E inhibitor vemurafenib, which resulted in a marked sustained clinical response. Case 3 was diagnosed as ECD after positive bone biopsy with typical foamy histiocytes. Six years later, there was massive dural involvement that showed RDD-like, BRAF-mutation-negative histiocytosis. These cases highlight the clinical and histologic overlap that can occur among these disorders.