title: Giant insulinoma: report of a case and review of published reports.
abstract: BACKGROUND
  Larger insulinomas are reportedly more likely to be malignant; however, their biological behavior has not been clearly elucidated. We here report the characteristics and treatment of a giant insulinoma with local invasion and lymph node metastasis. We also review published reports concerning the clinical features of giant insulinomas and comparing their grading with that of pancreatic neuroendocrine tumors.
  
  
  METHODS
  A 71-year-old man was referred to our hospital for investigation of persistent hypoglycemia. On the current presentation, laboratory tests showed serum glucose, immunoreactive insulin, and C peptide concentrations of 45 mg/dL, 17.2 μIU/mL and 4.1 ng/mL, respectively. Dynamic magnetic resonance imaging showed a hypervascular tumor measuring 13.5 cm in the head of the pancreas. Computed tomography scanning demonstrated local invasion and lymph node involvement. He thus had Whipple's triad, which is associated with malignant insulinoma. No distant metastases having been identified, pancreaticoduodenectomy was performed. Intraoperatively, three separate tumors were identified in the pancreatic head. Pathological examination showed all three tumors were pancreatic neuroendocrine tumors; the tumor cells in the largest mass were strongly immunoreactive for insulin. The Ki-67 index was 2-5% in most parts of the largest tumor and over 20% in the poorly differentiated areas. This tumor was classified as neuroendocrine carcinoma in accordance with the 2010 World Health Organization classification of pancreatic endocrine neoplasms. He remains free of evidence of recurrence 2 years postsurgery. A review of published reports indicated that giant insulinomas are more malignant than smaller ones, and metastatic disease is found on presentation in 56% of patients with giant insulinomas; however, we were unable to identify any correlation between grade of pancreatic neuroendocrine tumor and biological behavior of giant insulinomas.
  
  
  CONCLUSIONS
  Giant insulinomas more frequently exhibit malignant behavior, such as local invasion, lymph node involvement, and liver metastasis, than smaller ones. However, there was no relationship between grade and rate of metastases or survival in this small case series. Identification of useful biological markers is necessary.
authors.affiliation: Department of Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan. kafureyuharyo@gmail.com.
authors.forename: Kazumitsu
authors.identifier: http://orcid.org/0000-0003-0310-7308
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Taira
authors.affiliation: Department of Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hakoda
authors.affiliation: Department of Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Nakata
authors.affiliation: Department of Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Okata
authors.affiliation: Department of Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Aoki
authors.affiliation: Department of Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
authors.affiliation: Department of Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sako
authors.affiliation: Department of Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan.
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Department of Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Okumura
keywords: Giant insulinoma; Grade; Ki-67 index; Malignant insulinoma; Pancreatic neuroendocrine tumor