When Morphology Falls Short: ATP1B1::PRKACB Fusion in a Morphologically Atypical Pancreatic Intraductal Oncocytic Neoplasm

Intraductal oncocytic papillary neoplasm (IOPN) is a rare pancreatic intraductal neoplasm characterized by distinctive oncocytic morphology and recurrent gene fusions involving PRKACA or PRKACB.While conventional IOPN exhibits complex arborizing papillae lined by oncocytic epithelium, morphologically atypical lesions may lack these hallmark features and demonstrate overlap with intraductal papillary mucinous neoplasm (IPMN).A 76-year-old man presented with a pancreatic cystic lesion that remained radiographically stable over five years of surveillance and was initially considered indeterminate, though it was favored to represent a sidebranch IPMN.Persistent main pancreatic duct dilation to 10 mm and a cyst measuring approximately 4.5 cm prompted multidisciplinary evaluation and subsequent pancreaticoduodenectomy. Histologic examination revealed a 3.4-cm intraductal neoplasm predominantly composed of foveolar-type and pancreatobiliarytype epithelium, with focal oncocytic differentiation and extensive high-grade dysplasia.The classic complex arborizing architecture characteristic of conventional IOPN was absent, and no invasive carcinoma was identified.RNA-based next-generation sequencing identified an ATP1B1::PRKACB fusion, while KRAS and GNAS alterations were not detected, strongly supporting its classification as a morphologically atypical intraductal oncocytic neoplasm within the IOPN spectrum.This case underscores the diagnostic value of integrating morphologic and molecular assessment when oncocytic differentiation is present, but conventional IOPN morphology is incompletely developed.Additionally, it provides uncommon longitudinal documentation of an IOPN-spectrum lesion that remained radiographically stable for five years.