Three cases of BRAF mutation negative Erdheim-Chester disease with a challenging distinction from IgG4-related disease

BACKGROUND: Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis with slow progression over the years that is particularly difficult to diagnose. CASES: Here we report three cases of ECD without BRAF mutation presenting with a renal mass, hairy kidney appearance, and a rather benign course, for which the diagnosis of ECD was delayed, characterized by multiple investigations and unsuccessful treatments attempts. In two cases the distinction from IgG4-related disease required multiple investigations and reevaluation of the clinical, radiological, histological, and immunological characteristics. CONCLUSION: A correct diagnosis of ECD may take several years and often requires revisiting previous hypotheses. Reassessment of histological slides and more modern complementary exams such as PET-CT or BRAF and MAPK-ERK mutation analysis can help to confirm the diagnosis of ECD and to select effective therapy.