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Insulinoma (beta cell tumor)

Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 8 December 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.


● Functionally active and commonly benign endocrine tumour of the pancreas with evidence of beta cell differentiation and clinical hypoglycemia due to inappropriate secretion of insulin (WHO)
● Only 7-10% have malignant behavior (perhaps because hyperinsulinemia leads to early detection)

Clinical features

● Usually adults
● Whipple’s 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

● Widely metastatic tumor with focal rhabdomyosarcomatous areas (Am J Surg Pathol 1989;13:422)


● 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

Tail tumor

Micro 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)

Micro images

Insulin immunostains

Nonfunctioning insulin-producing microadenoma in MEN1 patient

Insulinoma with concurrent pancreatic adenocarcinoma

Benign insulinoma has tumor trabeculae and microlobuli separated by abundant hyalinized stroma

Well differentiated malignant insulinoma metastatic to liver has large trabeculae and lobules

Well differentiated malignant insulinoma metastatic to liver has several cells with enlarged, hyperchromatic nuclei and conspicuous nucleoli

Amyoid deposits confirmed by Congo Red stain and polarized light, with characteristic green birefringence

Positive stains

● Insulin (less than normal beta cells), proinsulin (50%), chromogranin, amylin, islet amyloid polypeptide (Islets 2011;3:344)

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

This tumor contains sufficient number of crystalline granules for diagnostic identification

Insulinoma with prevalence of round haloed granules of low density, plus occasional crystalloid granules (arrow)

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

End of Pancreas > Tumors > Insulinoma (beta cell tumor)

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