Consensus Statement on the Pathology of IgG4-Related Disease

Vikram Deshpande; Yoh Zen; John KC Chan; Eunhee E Yi; Yasuharu Sato; Tadashi Yoshino; Günter Klöppel; J Godfrey Heathcote; Arezou Khosroshahi; Judith A Ferry; Rob C Aalberse; Donald B Bloch; William R Brugge; Adrian C Bateman; Mollie N Carruthers; Suresh T Chari; Wah Cheuk; Lynn D Cornell; Carlos Fernandez-Del Castillo; David G Forcione; Daniel L Hamilos; Terumi Kamisawa; Satomi Kasashima; Shigeyuki Kawa; Mitsuhiro Kawano; Gregory Y Lauwers; Yasufumi Masaki; Yasuni Nakanuma; Kenji Notohara; Kazuichi Okazaki; Ji Kon Ryu; Takako Saeki; Dushyant V Sahani; Thomas C Smyrk; James R Stone; Masayuki Takahira; George J Webster; Motohisa Yamamoto; Giuseppe Zamboni; Hisanori Umehara; John H Stone


Mod Pathol. 2012;25(9):1181-1192. 

In This Article


IgG4-related disease is a recently recognized multi-organ system condition with pathological features that are largely consistent across a wide range of organ systems. Although the precise role of IgG4 in this disease is unknown, its presence in tissue in association with plasma cells provides a robust biomarker for diagnosis when interpreted in the proper histopathological and clinical contexts.

The diagnosis of IgG4-related disease requires collaboration between the pathologist and the treating physician. This dialogue is critical in excluding the variety of other diseases that may show elevated serum and tissue levels of IgG4. The isolated presence of IgG4+ plasma cells or an elevated IgG4-to-IgG ratio constitutes relatively non-specific findings. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4+ plasma cells. 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 use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum.