Bledsoe JR, Ferry JA, Neyaz A, et al. - Researchers assessed the histopathologic features of lymph nodes from 41 patients with established immunoglobulin G4-related disease (IgG4-RD), with comparison to 60 lymph nodes from patients without known or subsequent development of IgG4-RD in an attempt to identify features specific for nodal IgG4-RD. They distinguished an increase in immunoglobulin (Ig) G4-positive plasma cells > 100/HPF and IgG4/IgG ratio > 40% in 51% of IgG4-RD cases and 20% of control cases. This research validates that elevated IgG4-positive plasma cells and IgG4/IgG ratio are neither sensitive nor specific for the diagnosis of IgG4-related lymphadenopathy, and most described morphologic patterns are nonspecific. It was shown that nodal involvement by IgG4-rich fibrosis akin to extranodal IgG4-RD or diffuse interfollicular expansion by IgG4-positive plasma cells are highly specific features of true IgG4-related lymphadenopathy. The outcomes provide for a clinically meaningful approach to the assessment of lymph nodes that will guide pathologists in identifying IgG4-related lymphadenopathy from its mimics.