Answer: Pancreatic neuroendocrine tumor (insulinoma)

Histology: The specimen consists of a small excisional biopsy (the surgeons shelled out the lesion) with extensive cautery at the periphery. However, despite the cautery, there is appreciable benign pancreatic parenchyma with pancreatic acini at the periphery, suggesting that this is primary pancreatic lesion. The lesion consists of nests and cords of bland cells with granular, pink cytoplasm and oval nuclei. The chromatin is finely dispersed with delicate nucleoli. No mitoses are evident. There are focal fibrous bands and no stromal calcifications.

Discussion: This is an insulinoma, in this case a well differentiated (grade 1) pancreatic neuroendocrine tumor (PanNET) that is functional and secretes insulin, and not surprisingly these lesions are usually detected clinically due to severe hypoglycemia secondary to the hyper-insulinemia. In general, this also means that even small lesions are detected, since they are functional, and can be removed hopefully before they have spread. Pancreatic neuroendocrine neoplasms may occur sporadically or can be syndromic such as in MEN type 1 (MEN1 gene) and von Hippel-Lindau (VHL gene).

Neuroendocrine tumors in the pancreas are graded on the basis of the mitotic count in 50 high power fields) or the Ki67, and whichever is higher is the count to use for grading. Well-differentiated neuroendocrine neoplasms are grade 1 (mitoses <2/10 HPF or Ki67 <2%) or grade 2 (mitoses 2-20/10 HPF or Ki67 3-20%), and neuroendocrine carcinomas are grade 3 (mitoses >20/10 HPF or Ki67 >20%). The differential diagnosis on the basis of the finding of a solid mass with this nested histology in the pancreas is acinar cell carcinoma, solid pseudopapillary neoplasms, metastases to the pancreas, etc., and immunohistochemistry can aid in the differential. Not all PanNETs tumors are hormonally functional, but all should display some degree of neuroendocrine positivity (synaptophysin, chromogranin, CD56). The functionality can be confirmed with immunohistochemistry, and in this case, the lesion was confirmed to be positive for insulin. Serotonin secreting PanNETs are another subset of neuroendocrine tumors of the pancreas which often display dense fibrous bands admixed with the neuroendocrine cells.

Reference(s):
– McCall CM, Shi C, Cornish TC, Klimstra DS, Tang LH, Basturk O, Mun LJ, Ellison TA, Wolfgang CL, Choti MA, Schulick RD, Edil BH, Hruban RH. Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate. Am J Surg Pathol. 2013 Nov;37(11):1671-7.