Tissue Is the Issue - A Case of Malignant Insulinoma

Abstract

Introduction: Insulinomas are rare, functioning pancreatic neuroendocrine tumors, predominantly benign (90%). Most are sporadic, but they can occur as part of inherited disorders. Large size insulinomas are more likely to be malignant. 68Gallium (Ga)-DOTATATE scan is an essential tool in diagnosis and treatment of pancreatic neuroendocrine tumors. However, tissue diagnosis is the ultimate prognosis predictor and treatment guide.Clinical Case: An 80-year-old man presented with left ankle fracture after a syncopal episode. In the past several months he reported multiple episodes of lightheadedness. He denied history of diabetes. Past medical and surgical history included prostate cancer, gastroesophageal reflux disease and bilateral orchiectomy for undescended testes. His left ankle appeared swollen, otherwise the exam was unremarkable: he was well-nourished, the abdomen was soft and nontender, there were no palpable masses. He was noted to have several episodes of hypoglycemia. Hypoglycemia work up included negative sulfonylurea screen, plasma glucose 51 mg/dl (60-99 mg/dl), insulin of 31 uIU/ml (3-25 uIU/ml), proinsulin 85.4 pmol/L (<8 pmol/L), C peptide 3.4 ng/ml (1.1-4.4 ng/ml). Abdominal Computed Tomography with contrast showed a 4.7 x 3.1 cm exophytic mass in the body of pancreas, a 5.3 x 5 cm mass in the head of pancreas and multiple ill-defined hepatic lesions concerning for metastatic disease. 68Ga-DOTATATE scan revealed an avid pancreatic mass and multiple avid foci throughout the liver suspicious for metastatic disease. Octreotide and intravenous dextrose were started for the treatment of persistent hypoglycemia. He underwent Whipple procedure and resection of the metastatic liver lesions. Postoperatively hypoglycemia resolved. The pathology revealed large cell pancreatic neuroendocrine carcinoma with areas of well differentiated tumor and multiple liver metastatic neuroendocrine carcinoma, Ki-67 of 50-80% was reported in the primary tumor and metastatic lesions.Discussion: Metastatic insulinomas carry a significant morbidity and mortality risk. Surgical resection to decrease tumor burden can reduce the risk of hypoglycemia. Histopathology is essential in treatment decision making. Surprisingly our patient’s pathology revealed poorly differentiated neuroendocrine carcinoma, changing the prognosis and treatment. Treatment with platinum-based chemotherapy and etoposide is the standard of care for aggressive neuroendocrine neoplasms. Despite hypoglycemia resolution following surgery and good DOTATATE uptake by the well differentiated neuroendocrine tumor portion, our patient’s prognosis remained poor in view of the high-grade carcinoma. Due to complicated hospital course, and decreased functional status patient was not a candidate for chemotherapy immediately post hospital discharge.