Role of INSM1 expression in the diagnostic work-up of pancreatic acinar cell carcinoma with special reference to the differential diagnosis with neuroendocrine tumor.

Acinar cell carcinomas (ACCs) of the pancreas are rare neoplasms composed of cells showing acinar cell differentiation demonstrated by the immunoreactivity for acinar cells markers including trypsin, chymotrypsin, and BCL10. The differential diagnosis with more common pancreatic neuroendocrine tumors (PanNETs) may be difficult due to some overlapping morphological features and the expression of general neuroendocrine markers (synaptophysin and chromogranin A) by acinar cells, a phenomenon observed in about 35% of cases. These tumors showing a dual acinar and neuroendocrine differentiation need to be separated from PanNETs since their clinical management and prognosis are different. Little is known about the possible diagnostic role of INSM1, a highly specific and sensitive "second generation" neuroendocrine marker recently identified. With this aim we investigated INSM1 expression in 58 ACCs that, based on the expression of synaptophysin and chromogranin A, were separated into 36 pure ACCs lacking any neuroendocrine marker expression, 21 ACCs with divergent acinar and neuroendocrine differentiation, and one mixed neuroendocrine/non-neuroendocrine neoplasm (MiNEN) consisting of two separate acinar and neuroendocrine components. INSM1 expression overlapped that of synaptophysin and chromogranin A, although in several cases the number of INSM1 positive cells was less than that of chromogranin A. In conclusion, our results show that INSM1 expression in a pancreatic neoplasm should be carefully considered and interpreted in conjunction with morphology and a comprehensive immunohistochemical panel and does not give any diagnostic advantage respect to "traditional" neuroendocrine markers.