Intraductal Tubulopapillary Epithelial Proliferation Associated with Type 1 Autoimmune Pancreatitis

A 70-year-old man was referred to our hospital with exacerbation of diabetes. His blood tests showed elevated levels of serum IgG4 and HbA1c. Computed tomography of the pancreatic body demonstrated a weakly enhanced mass, 2 cm in size, with indistinct borders. Magnetic resonance cholangiopancreatography revealed a narrowing of the main pancreatic duct (MPD) at the pancreatic body, a markedly dilated upstream duct, and a slightly dilated downstream duct. Endoscopic ultrasonography demonstrated an iso-hypoechoic heterogeneous mass, protruding and spreading in the pancreatic duct. The histology of a fine needle aspiration sample demonstrated fibrous tissue containing abundant IgG4-positive plasma cells and atypical epithelial cells. The imaging findings and histology were not typical for either pancreatic ductal adenocarcinoma or type 1 autoimmune pancreatitis (AIP), but these were not completely excluded, and a distal pancreatectomy was performed. Histological examination showed an intraductal tubulopapillary epithelial proliferation, which contained cytoplasmic mucin (MUC5AC and MUC6), and severe IgG4-positive lymphoplasmacytic infiltration in the interstitium around the MPD. Next-generation sequencing using DNA extracted from the tumor revealed no mutation of K-ras, GNAS, or TP53. The entire lesion was ultimately diagnosed as AIP with an intraductal tubular and papillary epithelial hyperplasia producing gastric-type mucin. Some recent reports have described AIP development in the background of intraductal papillary mucinous neoplasms, and some have hypothesized a paraneoplastic occurrence of IgG4-related disease. The current case indicates issues in the clinical diagnosis of rare variants of AIP, and raises questions about the relationship between AIP and pancreatic epithelial lesions.