CPA1 and REG1a as New Markers for Pancreatic Acinar Cell Carcinoma
2020
Acinar cell carcinoma (ACC) is a rare tumor that differentiates towards pancreatic acinar cells and shows evidence of pancreatic enzyme production. Mixed acinar-neuroendocrine carcinoma (MANC) is defined as having more than 30% of both acinar and neuroendocrine cell types by immunohistochemistry. Trypsin is currently the most commonly used stain for acinar differentiation. In this study, we investigate the utility of two novel markers, carboxypeptidase A1 (CPA1) and regenerating islet-derived 1α (REG1a), in diagnosing ACC/MANC. Immunohistochemical staining for CPA1 and REG1a was performed on 14 ACC and 5 MANC, as well as on 80 other pancreatic tumors including 20 cases each of: ductal adenocarcinoma, well differentiated neuroendocrine tumor, mucinous cystic neoplasm and solid pseudopapillary tumor. All ACC and MANC were positive for CPA1 (all diffuse) and REG1a (12 diffuse, 4 patchy, 3 focal). A diffuse or patchy staining pattern was significantly more common in ACC/MANC cases (100% diffuse/patchy for CPA1 and 84% for REG1a) compared to other pancreatic tumors (5% diffuse/patchy for CPA1 and 7.5% for REG1a) with a P value of <0.0001 for both CPA1 and REG1a. The sensitivity and specificity of diffuse/patchy staining for CPA1 and REG1a in diagnosing pancreatic ACC/MANC were 100% and 95% for CPA1 and 84% and 93% for REG1a. In conclusion, CPA1 and REG1a are sensitive markers for ACC that can be used as additional acinar cell differentiation markers to help in the diagnosis of pancreatic ACC and MANC. A negative result for CPA1 virtually excludes ACC/MANC.
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