Metastatic pancreatic acinar cell carcinoma to the liver mimicking neuroendocrine tumor (NET) and pancreatic ductal adenocarcinoma (PDAC): A series of seven cases

Acinar cell carcinomas (ACCs) of the pancreas typically demonstrate distinct morphologic features including minimal fibrous stroma, acinar architecture, relative nuclear uniformity, single prominent nucleoli and eosinophilic cytoplasmic granules. We report seven cases of metastatic carcinomas to the liver with acinar cell differentiation (two acinar cell carcinomas, four carcinomas with mixed acinar and neuroendocrine differentiation, one mixed acinar ductal carcinoma) that lacked many of these features, and, as a result, were misclassified. The cases were prospectively identified in our routine confirming consultation service. Clinical data and histology were retrospectively reviewed. The seven patients ranged in age from 48 to 72 years with a male predominance (5 males, 2 females). Five patients had a known pancreatic mass, and all patients had multiple liver lesions on initial imaging, prompting liver biopsies. Three of seven liver tumors were diagnosed at the submitting institution as high-grade neuroendocrine tumors (NETs) as they all expressed synaptophysin and/or chromogranin, had a high Ki67 proliferation index, and lacked cytoplasmic granules or acinar architecture. The remaining four liver tumors were diagnosed as adenocarcinoma as they lacked prominent nucleoli, had prominent fibrotic stroma (3 cases), lacked eosinophilic cytoplasmic granules (3 cases), lacked acinar architecture (2 cases) and/or had significant nuclear pleomorphism (1 case). In all cases, reevaluation at the time of consultation with an extended immunohistochemical panel revealed the expression of pancreatic exocrine enzymes (trypsin, chymotrypsin, and/or BCL10), confirming acinar differentiation. All six patients with follow-up died within 1 to 24 months of initial diagnosis. In conclusion, metastatic ACC should be considered in differential diagnosis of the more common liver metastasis of pancreatic origin, NET and PDAC. ACC metastatic to the liver may lack hallmark morphologic features such as acinar architecture, prominent nucleoli and eosinophilic cytoplasmic granules and may express neuroendocrine markers (mimicking NET) or exhibit prominent fibrotic stroma and pleomorphism (mimicking PDAC). Immunolabeling for acinar cell markers is warranted for cases of purported PDAC/NET with atypical features, such as purported NET with high Ki67 index and/or only patchy neuroendocrine marker labeling, or purported PDAC with luminal proteinaceous secretions rather than mucin and/or minimal pleomorphism.