IgG4-RD shows organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis in various organs simultaneously or metachronously[3,4
]. The first International Symposium on IgG4-RD held in 2011 suggested that the term “IgG4-related disease” aptly recognizes the ubiquity of IgG4 within involved organs, and proposes a style that employs “IgG4-related” as a prefix to the organ system affected and pathological guidelines for the diagnosis of IgG4-RD[3,45
]. The diagnosis of IgG4-RD rests on the combined presence of the characteristic histopathological appearances and increased number of IgG4-positive plasma cells. A histologically high suspicion of IgG4-RD requires the presence of at least two of three characteristic histological features including (1) dense lymphoplasmacytic infiltration; (2) fibrosis, usually storiform in character; and (3) obliterative phlebitis. The IgG4 counts required for the diagnosis differ among affected organs, ranging from 10 to 200 cells/hpf. The diagnosis of IgG4-RD requires considering both histopathological findings and clinical information such as elevated serum IgG4 levels, other organ involvement that is consistent with IgG4-RD, and effective response to steroid therapy[45
Comprehensive clinical diagnostic criteria for IgG4-RD[4
] were proposed in 2011. In the criteria, IgG4-RD is diagnosed when there is a characteristic diffuse/localized swelling or mass in a single or multiple organs with elevation of serum IgG4 levels or IgG4-related histological findings. However, the concept of IgG4-related gastrointestinal diseases was not included as objects of the criteria. It is unclear whether IgG4-related gastrointestinal diseases exist or what gastrointestinal lesions are regarded as IgG4-RD. To clarify these questions, this review of IgG4-related gastrointestinal diseases, the first of its kind, was conducted.
Infiltration of many IgG4-positive plasma cells is detected in the gastric and colonic mucosa and the major duodenal papillae of some AIP patients, but none of the following are observed in these lesions: a mass-like formation; dense fibrosis; or obliterative phlebitis[5-10
]. They cannot be diagnosed as gastrointestinal lesions involved in IgG4-RD, because, as in many other organ systems, increased IgG4-positive plasma cells do not mean the disease is one of the family members of IgG4-RD. At this point, both the clinical finding of mass forming and histological finding of abundant infiltration of IgG4-positive plasma cells with fibrosis would appear to be necessary to make the diagnosis of IgG4-related gastrointestinal diseases.
IgG4-related pseudotumors have been reported in several organs, such as the liver and lung[46-48
]. On review of these papers, there appear to be two types of IgG4-related gastrointestinal disease. One is a gastrointestinal lesion showing marked thickening of the wall of the esophagus[11,12
] and stomach[17,23,24
], consisting of dense fibrosis with abundant infiltration of IgG4-positive plasma cells, which usually show submucosal spreading. The other is an IgG4-related pseudotumor occurring in gastrointestinal regions such as the stomach[18-22
], and major duodenal papilla[32
], showing polypoid or mass-like lesions. We currently consider these lesions to be IgG4-related gastrointestinal diseases. However, this is the first review of a few cases of IgG4-related gastrointestinal diseases; further studies should be conducted to confirm this concept.
Most solitary IgG4-related gastrointestinal lesions that are not associated with other IgG4-RD appear to be difficult to diagnose. It is of utmost importance to rule out malignancy. However, these lesions may respond to steroid therapy. To avoid unnecessary resection, IgG4-related gastrointestinal diseases should be considered in the differential diagnosis.