S100 Protein Expression in Primary and Metastatic Neuroendocrine Neoplasms: A Specific Marker of Pancreatic Origin

Neuroendocrine neoplasms can arise in a wide variety of anatomic sites including the gastrointestinal tract, pancreas, and lung, among others. Here, we report on the expression of S100 protein in a tissue microarray composed of 919 distinct primary and metastatic neuroendocrine neoplasms from 548 patients. S100 protein is a commonly used marker in many laboratories for the identification of neural and melanocytic neoplasms and occasionally used in the workup for neuroendocrine neoplasms when the diagnosis of paraganglioma is being considered. We show that strong S100 protein expression is highly specific to well-differentiated neuroendocrine tumors of pancreatic origin. This finding suggests potential diagnostic utility of this marker in cases of tumors of unknown origin, and emphasizes that S100 protein expression should not be an unexpected finding in neuroendocrine tumors of pancreatic origin.