Question: A 51-year-old man presented with severe epigastric abdominal pain, an amylase of 171 U/L (normal, 25–115) and lipase of 3365 U/L (normal, 114–286). Computed tomography (CT) of the abdomen and pelvis demonstrated localized heterogenous hypoattenuation in the tail of the pancreas (TOP) with adjacent inflammatory changes consistent with acute pancreatitis with no evidence of gallbladder disease. He denied alcohol use, had a normal serum triglyceride level, and was treated conservatively for acute pancreatitis of unclear etiology. Follow-up magnetic resonance imaging demonstrated a subtle, 1.1 × 1.4-cm TOP mass with an appearance suggestive of a neuroendocrine tumor (Figure A). Positron emission tomography/CT failed to show any evidence of F-18 fluorodeoxyglucose avid malignant disease. On endoscopic ultrasound (EUS) examination performed 4 months later, a slightly hypoechoic TOP mass was demonstrated (Figure B; upper panel, arrow denoting pancreatic duct (PD) with an adjacent upstream area of hypoechoic, lobulated and atrophic pancreas). There was a sharp demarcation between the abnormal parenchyma upstream of the mass and the normal parenchyma downstream of the mass (Figure B, lower panel). The splenic vein seemed to be encased by the TOP mass. The remainder of the EUS examination was unremarkable. The mass was sampled with a 25-gauge fine needle aspiration (FNA) revealing a highly cellular smear of epithelial cells with acinar features, including granular eosinophilic cytoplasm, round to oval nuclei and mild anisonucleosis (Figure C, left inset). The patient underwent a distal pancreatectomy with splenectomy (Figure C, right inset). What is the etiology of the pancreatitis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Histologic examination of the surgical specimen demonstrated a 1.1-cm nodule of granular eosinophilic cytoplasm with centrally placed nuclei consistent with oncocytic metaplasia surrounded by nodules of acinar cells and focal pancreatitis (Figures C). There was no evidence of acinar cell or ductal carcinoma. The decision to operate was based upon the false-positive high suspicion of acinar cell carcinoma from the initial EUS-FNA. Oncocytic metaplasia is characterized by the conversion of epithelial cells into relatively larger cells with abundant eosinophilic granular cytoplasm due to an abundance of mitochondria.1Hamperl H. Benign and malignant oncocytoma.Cancer. 1962; 15: 1019-1027Crossref PubMed Scopus (286) Google Scholar The cause and significance of oncocytic differentiation are subjects of debate. Oncocytes may represent mild cellular degeneration with loss of specialized function as a result of age and cellular “burnout.”1Hamperl H. Benign and malignant oncocytoma.Cancer. 1962; 15: 1019-1027Crossref PubMed Scopus (286) Google Scholar Oncocytes have been described in the normal state of health in most organs, including the stomach, hepatobiliary tract, pancreas, and colon.2Chang A. Haragwi S. Oncocytes, oncocytosis and oncocytic tumors.Pathol Ann. 1992; 27: 263-304Google Scholar Tumors composed of oncocytes occur most commonly in salivary, thyroid, and parathyroid glands, and in the kidneys. There are <30 reports of oncocytic lesions of the pancreas, of which 6 describe nonendocrine lesions, as in our case.3Volante M. La Rosa S. Castellano I. et al.Clinico-pathological features of a series of 11 oncocytic endocrine tumours of the pancreas.Virchows Arch. 2006; 448: 545-551Crossref PubMed Scopus (30) Google Scholar To our knowledge, this is the first reported case of a patient with pancreatitis caused by an oncocytoma of the pancreas. Pancreatic oncocytomas with endocrine features follow a more malignant course, whereas nonendocrine types tend to be more benign.3Volante M. La Rosa S. Castellano I. et al.Clinico-pathological features of a series of 11 oncocytic endocrine tumours of the pancreas.Virchows Arch. 2006; 448: 545-551Crossref PubMed Scopus (30) Google Scholar Several EUS findings suggested that this oncocytoma was the likely cause of the localized pancreatitis. The main PD was of equal diameter downstream and upstream of the mass (rather than the typical gradual tapering to a smaller caliber as it is followed to the distal TOP; Figure B). This suggested a relative dilation of the PD in the TOP, likely owing to compression of the PD by the downstream mass with resultant parenchymal changes abruptly beginning just upstream of the mass. Surgical pathology demonstrated a focus of pancreatitis adjacent to the oncocytoma. Postoperatively, the patient had no further episodes of pancreatitis and no evidence of disease recurrence at 2-year follow-up. This case highlights a previously undescribed cause of pancreatitis.