When Morphology Falls Short: ATP1B1::PRKACB Fusion in a Morphologically Atypical Pancreatic Intraductal Oncocytic Neoplasm.
Publication/Presentation Date
9-1-2026
Abstract
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 side-branch 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 pancreatobiliary-type 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.
Volume
18
Issue
9
First Page
117098
Last Page
117098
ISSN
2168-8184
Published In/Presented At
Han, S., Chu, Y. H., Schat, R., Elbaz Younes, I., Brauer, D., Cartwright, D., Khalid, A., Turner, K., & Park, B. U. (2026). When Morphology Falls Short: ATP1B1::PRKACB Fusion in a Morphologically Atypical Pancreatic Intraductal Oncocytic Neoplasm. Cureus, 18(9), e117098. https://doi.org/10.7759/cureus.117098
Disciplines
Medicine and Health Sciences
PubMedID
42953497
Department(s)
Department of Pathology and Laboratory Medicine
Document Type
Article