Can a High-grade Neuroendocrine Carcinoma be Functional?

We present a rare high-grade, functional, neuroendocrine carcinoma of the pancreas secreting vasoactive intestinal peptide. This case is unique, given the tumor's aggressive features and high Ki-67 index while also secreting functional hormones, which is unusual in high-grade neuroendocrine tumors (NETs). Our patient initially presented with diarrhea and was found to have a 4.7 × 3.1 × 3.3 cm pancreatic mass with diffuse hepatic metastasis staining positive for vasoactive intestinal peptide, chromogranin A and synaptophysin. She was initially underscored as grade 2 NET due to low mitosis, but subsequently restaged based on Ki-67 index as a grade 3 neuroendocrine carcinoma. She unfortunately was not a candidate for chemotherapy at that time. We conclude that high-grade NETs have the potential to secrete active peptide hormones. We therefore recommend that NETs with aggressive features be biopsied and assessed for Ki-67 activity and mitosis regardless if they are functional tumors, with goal for early initiation of chemotherapy.