Poorly Differentiated Neuroendocrine Carcinoma of the Pancreas

Abstract

Poorly differentiated neuroendocrine carcinomas (PD-NECs) of the pancreas are highly aggressive and rapidly fatal tumors constituting less than 1 % of all pancreatic carcinomas. Although these are classified as grade 3 NECs by the 2010 WHO classification system, suggesting they are part of a continuum with the well-differentiated neuroendocrine tumors of the pancreas, there is now evidence that PD-NECs actually constitute a genetically and biologically distinct tumor entity. Morphologically, some are akin to small cell carcinomas as defined in the lung, but more commonly they resemble large cell neuroendocrine carcinomas such as those described in the lung or elsewhere in the gastrointestinal tract. Parallel to the high degree of mitotic activity, their Ki-67 labeling index also tends to be very high (about 70 %), and necrosis is frequently extensive. Immunohistochemical labeling commonly reveals positivity for chromogranin or synaptophysin, although it may be very focal (especially for chromogranin). It has been shown recently that PD-NECs of the pancreas exhibit genetic changes frequently seen in these carcinomas in other organs, such as inactivation of the TP53 and the Rb/p16 pathways, which are rarely observed in well-differentiated neuroendocrine tumors. Conversely, mutations in DAXX, ATRX, and MEN1 are exclusively found in the well-differentiated neuroendocrine tumors.