Insulinoma-associated protein 1 (INSM1) is a robust marker for identifying and grading pancreatic neuroendocrine tumors

Background: Pancreatic neuroendocrine tumor (PNET) is a diagnostic challenge with limited samples in not only identification but grading. Prior studies have shown insulinoma-associated protein 1 (INSM1) to be a robust marker in identifying PNETs from other solid pancreatic tumors on resection specimens. In this study, we investigated the utility of INSM1 not only for identifying PNETs but also for grading in cell blocks (CBs) and surgical resections (SRs). Methods: A search for PNET cases between 2000 and 2019 identified 55 samples (26 CBs and 29 SRs) that were further separated into high (2 CBs, 3 SRs), intermediate (4 CBs, 7 SRs), and low (20 CBs, 19 SRs) grades based on their final pathology report and Ki-67 level. Immunohistochemical (IHC) staining for INSM1 (C-8, Santa Cruz Biotechnology [1:100]) was performed and quantified using an H score of 0 to 300. Non-PNET solid pancreatic tumors were compared and included acinar cell carcinoma, solid pseudopapillary neoplasm, and ductal adenocarcinoma. Results: All 55 cases of PNET demonstrated nuclear INSM1 staining. The average H scores for INSM1 staining of PNET were 254 and 252 in CB and SR, respectively. The H scores decreased with increasing tumor grade, with low-grade (G1), intermediate-grade (G2), and high-grade (G3) tumors showing average INSM1 H scores of 229 and 253, 266 and 253, and 30 and 33 in both CB and SR, respectively. Conclusion: IHC with INSM1 plays a role in identifying and potentially grading PNETs.