Neuroendocrine neoplasms
Insulinoma (beta cell tumor)
Topic Completed: 1 August 2012

Revised: 30 January 2019

Copyright: (c) 2002-2019,, Inc.

PubMed Search: Insulinoma[TI] pancreas[TI] beta cell tumor
Page views in 2018: 3,242
Page views in 2019 to date: 744
Cite this page: Jain D. Insulinoma (beta cell tumor). website. Accessed March 18th, 2019.
Definition / general
  • Functionally active and commonly benign endocrine tumor of the pancreas with evidence of beta cell differentiation and clinical hypoglycemia due to inappropriate secretion of insulin (IARC: 8151 / 3 Insulinoma, Malignant [Accessed 22 December 2017])
  • Only 7 - 10% have malignant behavior (perhaps because hyperinsulinemia leads to early detection)
Clinical features
  • Usually adults
  • Whipple triad: symptoms of hypoglycemia (stupor, confusion, loss of consciousness), glucose < 50 mg/dl, symptoms relieved by glucose or symptoms caused by fasting or exercise
  • 10 - 15% associated with MEN1 syndrome; age < 20 years is suggestive of MEN1 (Endocr J 2012;59:859)
  • Functional status is NOT an independent prognostic factor
  • Insulinomatosis: synchronous and metachronous occurrence of insulinomas, multiple insulinoma precursor lesions and rare development of metastases but common recurrent hypoglycemia (Am J Surg Pathol 2009;33:339)
  • High insulin levels, intravenous tolbutamide administration detects serum proinsulin
  • Use arteriography (60% successful) or ultrasound to locate small tumors
  • High insulin levels and high insulin / glucose ratio
  • Hypoglycemia is mild in 80%
Case reports
  • Surgical exploration or subtotal pancreatectomy

  • Benign (90%):
    • Solitary, encapsulated, 1.5 cm or less
    • Solid / gyriform, no glands

  • Malignant (10%):
    • Based on local invasion or metastases
    • Usually causes more pronounced hypoglycemia

  • Note: amyloid may be derived from somatostatin and not amylin (Am J Surg Pathol 1998;22:360)
Gross images

Images hosted on other servers:

Tail tumor

Microscopic (histologic) description
  • Solid or gyriform patterns, usually without glands
  • In children are associated with nesidioblastosis (direct transformation of ductal epithelium into neoplastic islet tissue)
  • Amyloid present (Arch Pathol Lab Med 1978;102:227)
Microscopic (histologic) images

AFIP images

Tumor cells stained
for insulin with the

insulin producing
in MEN1 patient

Benign insulinoma

Endocrine carcinoma with trabecular and lobular pattern

Well differentiated
carcinoma with
cellular atypia

Amyloid in an insulinoma

Images hosted on other servers:

Insulin immunostains

Insulinoma with concurrent pancreatic adenocarcinoma

Positive stains
Electron microscopy description
  • Round secretory granules with irregular crystals separated from enclosing membrane by a distinct halo
  • Granules do NOT imply functional activity
Electron microscopy images

AFIP images

Left: crystalline granules; right: round haloed granules

Differential diagnosis
  • Hyperinsulinism: diffuse hyperplasia of islets in infants of diabetic mothers
  • Hypoglycemia: insulin sensitivity, diffuse liver disease, glycogenoses, solitary fibrous tumor of pleura / peritoneum (tumor cells secrete insulin-like growth factor II), hepatocellular carcinomas
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