title: A Clinicopathological Study of Malignant Insulinoma in a Contemporary Series.
abstract: The aim of the study was to address the origin and natural history of malignant insulinoma.
  
  
  
  Retrospective review of medical records of patients diagnosed with insulinoma at Cedars-Sinai Medical Center between 2000 and 2015 was conducted. Hormonal expression in tumor specimens was examined by immunostaining.
  
  
  
  All the 9 patients with malignant insulinoma (35% of 26 patients with insulinoma) already had liver metastasis at hypoglycemia presentation with bulky cumulative tumor burden. Six patients had de novo diagnosis, 2 had known metastatic nonfunctioning pancreatic neuroendocrine tumor, and 1 had a known pancreatic mass. Tumor grade at presentation was G1 in 4 patients, G2 in 4, and unknown in 1. Four patients died 2 to 32 months after presentation, all with extensive liver tumor involvement. Tumor expression of proinsulin and insulin was heterogeneous and overall infrequent. The proinsulin levels and proinsulin/insulin molar ratio in patients with malignant versus benign insulinoma were 334 versus 44 pmol/L and 2.1 versus 0.9, respectively.
  
  
  
  Malignant insulinoma seems to arise from and behave like nonfunctioning pancreatic neuroendocrine tumor oncologically but with metachronous hyperinsulinemic hypoglycemia. High proinsulin levels and proinsulin/insulin molar ratio may suggest malignant insulinoma.
authors.affiliation: From the *Division of Endocrinology, Cedars-Sinai Medical Center; †Division of Endocrinology, UCLA David Geffen School of Medicine, ‡Department of Surgery, §Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA; ∥Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY; ¶Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China; and #Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Run
authors.initials: R
authors.lastname: Yu
authors.forename: Nicholas N
authors.initials: NN
authors.lastname: Nissen
authors.forename: Andrew
authors.initials: A
authors.lastname: Hendifar
authors.forename: Laura
authors.initials: L
authors.lastname: Tang
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Song
authors.forename: Yuan-Jia
authors.initials: YJ
authors.lastname: Chen
authors.forename: Xuemo
authors.initials: X
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D002096:C-Peptide / Q000378:metabolism; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications; D007003:Hypoglycemia / Q000150:complications; D007328:Insulin / Q000378:metabolism; D007340:Insulinoma / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D011384:Proinsulin / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin