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Neuroendocrine Neoplasms of the Pancreas: The Pathological Viewpoint

Noriyoshi Fukushima

Neuroendocrine neoplasms of the pancreas are relatively rare, accounting for approximately 1–2% of all pancreatic neoplasms, and are composed of epithelial neoplastic cells with neuroendocrine differentiation. Neuroendocrine neoplasms are potentially malignant neoplasms including well-differentiated types (neuroendocrine tumors, neuroendocrine tumors) and poorly differentiated types (neuroendocrine carcinomas). The WHO classification released in 2010 led to a significant change in the grading system of neuroendocrine neoplasms of the digestive system. “Endocrine neoplasm” was changed to “neuroendocrine neoplasm”. Neuroendocrine neoplasms are graded according to the number of mitoses and/or Ki-67 index. These changes simplified the classification scheme. However, there are a number of remaining issues. Neuroendocrine tumors meeting the WHO criteria for neuroendocrine carcinoma (>20 mitoses/10 high power fields and/or Ki67 index > 20%) with a well-differentiated morphology, known as an “organoid pattern” have been identified. In the revised version of the “WHO Classification of Tumours of Endocrine Organs” published in 2017, to solve the problems of high-grade (grade 3) neuroendocrine neoplasms, they are divided into pancreatic neuroendocrine tumors, grade 3 (PanNET G3) and neuroendocrine carcinomas, grade 3 (PanNEC G3) depending on their histo-morphologic characteristics. The neuroendocrine tumor G3 category is associated with a better prognosis and does not significantly responds to cisplatin-based chemotherapy. Defining that subgroup of patients using a combination of tumor morphology and cell proliferation is important. Better strategies to treat and improve the outcomes of patients with pancreatic neuroendocrine neoplasms are required.