Solid pseudopapillary neoplasms of the pancreas do not express major pancreatic markers in pediatric patients

Summary Solid pseudopapillary neoplasms (SPNs) of the pancreas are classified as “exocrine” pancreatic tumors by the World Health Organization. However, despite numerous studies using immunohistochemistry, electron microscopy, animal models, and molecular biology, the histogenesis of SPN remains unclear. At the same time, our knowledge of human pancreas development has significantly increased. It is now well known that the undifferentiated PDX1+ pancreatic progenitors proliferate and differentiate into endocrine, ductal, and acinar cells, thanks to the expression of numerous transcription factors, which can be used to better characterize pancreatic tumors. In a series of 14 pediatric SPN, we investigated the expression of 4 transcription factors associated with pancreatic development (PDX1, SOX9, PTF1A, and NKX2.2) to obtain new insights into the pathogenesis of SPN. In addition, we tested the expression of different markers of epithelial, endocrine, exocrine, and neural differentiation using both immunohistochemical and immunofluorescence analyses. All tumors displayed the typical histologic features of SPN, with both pseudopapillary and solid patterns. The immunoprofile was characterized by immunoreactivity for β-catenin (100%), progesterone receptor (100%), cyclin D1 (100%), synaptophysin (65%), and S100 (15%). In all cases, tumor cells were negative for the following markers: PDX1, SOX9, PTF1A, NKX2.2, chromogranin A, glucagon, insulin, somatostatin, ghrelin, pancreatic polypeptide, amylase, GFAP, calretinin, EPCAM, and estrogen receptor α. To conclude, SPNs do not express major transcription factors involved in pancreatic development and differentiation, which does not allow for precise pancreatic lineage of tumor cells. Thus, additional studies are still required to determine the origin of SPN.