IgG4-related disease of the tubular gastrointestinal tract: A rare cause of lymphoplasmacytosis, eosinophilia, and mass-forming lesions

IgG4-related disease (IgG4RD) is a systemic fibroinflammatory condition that can affect multiple organs, but rarely involves the tubular gastrointestinal (GI) tract. We identified patients with definitive or possible IgG4RD of the GI tract diagnosed at our institution. Our cohort included 8 patients with a median age of 37 years (range 15–73) and a slight male predominance (63 %). Sites of disease included the esophagus (5 biopsies), terminal ileum (2 biopsies), and colon (1 biopsy with subsequent resection). Two patients presented with masses (1 colon, 1 terminal ileum) and 1 with an esophageal stricture. All cases featured a prominent plasma cell-rich infiltrate with scattered eosinophils and neutrophils; a subset had variably prominent histiocytes (3 cases) and lymphoid aggregates (4 cases). The colonic resection specimen demonstrated subserosal storiform fibrosis and obliterative phlebitis, features not detectable in the biopsies. All cases had >50 IgG4-positive cells per high-power field and an IgG4:IgG ratio >40 % when evaluable (5 cases). One of two patients with terminal ileal involvement had serum IgG4 >135 mg/dL, and both patients responded to steroid treatment. Three patients with esophageal involvement had serum IgG4 <135 mg/dL. We conclude that IgG4RD is a rare cause of mass-forming lesions in the terminal ileum and colon, and a possible cause of esophageal inflammation and strictures. Diagnosing IgG4RD on biopsies is challenging, as the full histologic spectrum of features is not detectable in mucosa. Lymphoplasmacytic and eosinophilic infiltration, elevated IgG4-positive cell counts by immunohistochemistry, and correlation with serum IgG4 levels and response to steroids may aid in diagnosis.