Consensus statement on the pathology of IgG4-related disease

Abstract

IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; andoften but not always-elevated serum IgG4 concentrations. An international symposium on IgG4-related The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4 þ plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum.

Idiopathic sclerosing orbital inflammation mimicking a malignant spindle cell tumor in a dog

“…Recently characterized, human IgG4‐related disease comprises a group of fibro‐inflammatory conditions of unknown origin featuring tumor‐like expansions in one or multiple organs, with sclerosing fibrosis and a dense lymphoplasmacytic infiltrate rich in IgG4‐positive plasma cells 6, 7. A significant proportion of human ISOI cases are now known to be IgG4‐related, and importantly, this trait imparts favorable susceptibility to steroid and radiation therapy 31.…”

“…A significant proportion of human ISOI cases are now known to be IgG4‐related, and importantly, this trait imparts favorable susceptibility to steroid and radiation therapy 31. Although the canine lesion exhibited many characteristics of IgG4‐related ISOI, the relative density of IgG4‐positive plasma cells was insufficient to make this diagnosis based on the proposed human criteria 6, 7. This is consistent with the steroid resistance observed initially, however, we cannot exclude the possibility that early treatment with antiinflammatory doses of prednisolone may have altered the IgG4‐positive component of our immunohistochemical readout in favor of an ISOI diagnosis 31.…”

“…5). However, the lesion did not fulfill suggested histological criteria for IgG4‐related disease (including an IgG4+/IgG+ plasma cell ratio of >40%) and the final diagnosis was most consistent with ISOI 6, 7.…”

IgG4-related disease: A relatively new concept for clinicians

“…Sometimes formation of germinal centers and infiltration of eosinophils in affected tissues are observed (34).…”

“…per HPF is considered highly specific, but different cut-offs are proposed for different tissues and surgical specimens (34). Inflammation can become "burned-out" in advanced IgG4-related lesions.…”