Invasive Pancreatic Adenocarcinoma with Squamous Differentiation Arising in an IOPN with Novel MDM2 Amplification

Abstract

Abstract Introduction/Objective Intraductal oncocytic papillary neoplasms (IOPNs) are rare pancreatic tumors that are genetically distinct from intraductal papillary mucinous neoplasms (IPMNs). Morphologic and molecular characterization of invasive adenocarcinomas associated with IOPNs remains limited due to the rarity of this entity. Methods/Case Report We present a 68-year-old female who initially presented with abdominal pain and jaundice. MRI revealed a 2.6 cm mass in the pancreatic head with abutment of the superior mesenteric vein and dilation of the biliary and pancreatic duct. Biopsy revealed adenocarcinoma with mucinous features. The patient was started on gemcitabine and abraxane. Her treatment course was complicated by biliary and duodenal obstruction requiring common bile duct and duodenal stenting. Surgical management with pancreaticoduodenectomy was performed six months following initial diagnosis. Gross examination revealed a 2.5 cm ill-defined tumor surrounding the main pancreatic duct adjacent to the common bile duct. Microscopy revealed an IOPN arising within the pancreatic duct exhibiting a complex papillary growth pattern. There was an associated moderately to poorly differentiated invasive carcinoma with mucinous and squamous differentiation with lymph node metastasis. Molecular testing (FoundationOne®CDx) revealed ARID1A mutation and amplification of MDM2, CDK4, and ERBB3. Patient is alive and without radiologic evidence of disease recurrence at 6 months follow-up. Results (if a Case Study enter NA) NA Conclusion To our knowledge, our case is the first report of an invasive pancreatic adenocarcinoma with squamous differentiation arising in association with an IOPN. In addition, our case showed MDM2 amplification which has not been previously identified in pancreatic adenocarcinoma arising in IOPNs. Although recent literature demonstrated that less than 30% of IOPN showed invasive disease and even fewer cases with lymph node metastasis, our case showed extensive invasion with metastases to 2 lymph nodes. This may suggest that MDM2 amplification may play a role in more aggressive disease since it is implicated with poorer outcome in conventional pancreatic adenocarcinoma. Further molecular studies of IOPN may help to identify prognostic features of this entity.