[Presence of IgG4-positive cells in Erdheim-Chester disease. Epiphenomenon or overlap?]

Erdheim-Chester disease (ECD) and IgG4-related disease (IgG4-RD) are rare conditions with overlapping clinical and imaging manifestations that complicate their diagnosis. The finding of an infiltrate rich in IgG4- positive plasma cells in ECD lesions adds complexity, raising the question of whether this is an epiphenomenon or a true pathogenic overlap. We present the case of a 61-year-old man with systemic symptoms and a retroperitoneal mass causing the "hairy kidney" sign on imaging. Histopathology was ambiguous: a perirenal biopsy met the criteria for IgG4-RD, showing storiform fibrosis, phlebitis, and an infiltrate of >50 IgG4+ cells/HPF; however, a sample from the omentum contained foamy histiocytes (CD68+) characteristic of ECD. Molecular analysis was decisive: the BRAF V600E mutation was negative, but an activating mutation in the MAP2K1 gene was identified, confirming the diagnosis of ECD. The patient had an excellent clinical and radiological response to targeted therapy with the MEK inhibitor, trametinib. This case underscores the critical importance of molecular biology, beyond the BRAF mutation, in the differential diagnosis of complex fibro-inflammatory lesions. The coexistence of diagnostic criteria for both entities in the same patient suggests that the presence of IgG4 cellularity in ECD should be represent a true pathogenic overlap, where the neoplastic clone triggers a secondary immune response, rather than a mere reactive epiphenomenon.