Shaheed Merani, MD, PhD

Abstract: Pancreatic neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms. They can be functioning tumors with secretion of a variety of peptide hormones, or nonfunctioning tumors with metastases to the liver at the time of diagnosis. Well-differentiated tumors tend to be slow-growing and characterized by low tumor mutational burden (TMB) and lower propensity to express PD-L1. Hypercalcemia due to malignancy can occur in about 20% to 30% of patients with cancer. The secretion of parathyroid hormone–related protein (PTH-rP) is among the causes of malignant hypercalcemia and has seldom been associated with hypercalcemia of NETs. Although the therapeutic landscape for neuroendocrine neoplasms has evolved substantially over the past decade, the role of immunotherapy has not yet been completely explored in this group of patients. We present a rare case of a metastatic pancreatic NET with high TMB, high PD-L1 tumor proportion score, and high PTH-rP–related hypercalcemia.

Pancreatic ductal adenocarcinoma is a disease marked by high rates of mortality, with only about 7% of patients surviving 5 years after diagnosis. Here, the authors present a demonstrative case and review the available data on hereditary and familial PDAC.