Pancreatic Pathology Online

Pathology of Beta cell Tumours (Insulinomas)

 Dr Sampurna Roy MD         July 2016


Beta cell tumours are the most common of the islet cell neoplasms.

The functional variant releases sufficient insulin to induce severe hypoglycemia ( serum glucose less than 50 mg/dl ) and a syndrome of sweating, nervousness, and hunger, which may progress to confusion, lethargy, and coma.

Attacks are promptly relieved by glucose feeding or infusion.

Since the symptoms are often relieved by eating, it is common for patients to be overweight.

Frequently, the diagnosis is delayed by the prominence of symptoms of abnormal behavior that cause some patients to be under psychiatric care.

Most cases are characterized by only a mild hypoglycemia, and in some the tumour is not functional, which may delay the diagnosis.

Neoplastic beta cells, unlike their normal counterparts, are not regulated by the blood glucose level and continue to secrete insulin autonomously even when the level of glucose is very low.

Most beta cell tumours are benign solitary adenomas (70%) in the body or tail of the pancreas, 10% are multiple adenomas, 10% are metastasizing carcinomas, and the remainder are diffuse islet  hyperplasia and adenomas in ectopic pancreatic tissue.

They may be minute, as small as 1 mm in diameter to greater than 2 cm diameter lesions, usually encapsulated, firm, yellow-brown nodules composed of cords and nests of well-defined beta cells, with typical beta cell granules by electron microscopy.

Diffuse hyperplasia is characteristic of infants born to diabetic mothers, subjected to sustained hyperglycemia in utero.

In the majority surgical enucleation is accompanied by a rapid disappearance of symptoms.

Histologically, the insulinoma cells usually resemble normal beta cells.

The tumour has the typical histological features of an islet cell tumour cuboidal cells with compact nuclei and eosinophilic granular cytoplasm arranged in ribbons.

The only absolute criteria for malignancy in islet cell tumours are invasion and metastasis at presentation.

Stromal amyloid and psammoma bodies may be present.

These are rarely seen (although they are said to be more frequently associated with somatostatinomas).

The diagnosis is established by the demonstration of high levels of insulin in the blood and in the tumour cells.

Clinical and biochemical information will usually reveal what product(s) the tumour is secreting, prior to pathological examination.

This is important information because it affects malignant potential.

For example, only 10% of insulinomas are malignant where as 4 - 60% is usually quoted as the malignancy rate for gastrinomas in or around the pancreatic region.

The pro-insulin in insulinomas stains with aldehyde fuschin and other dyes which bind to -SH groups.

Immunohistochemistry is the method of choice for demonstrating secretory products.

Electron microscopy of the tumor is also valuable which usually shows the pleomorphic, paracrystalline cores surrounded by a clear halo that are typical of insulin stored in normal beta cells.

Rarely, the insulin granules are atypical.  

With the exception of insulin (which forms rectangular crystals as the dense core of neurosecretory granules) the other secretions form round granules which are only partially distinguished by size.


Further reading:

A rare case of insulinoma presenting with postprandial hypoglycemia.

Clinical Implications of Various Criteria for the Biochemical Diagnosis of Insulinoma.

Malignant insulinoma presenting as metastatic liver tumor. Case report and review of the literature.


Recurrent hyperinsulinemic hypoglycemia caused by an insulin-secreting insulinoma.

Missed hyperinsulinaemia in a patient with an insulinoma.

Insulinoma presenting with hyperandrogenism: a case report and a literature review.

Diagnosis and management of insulinoma.

The surgical management of insulinoma.

Review of eight cases of insulinoma

Insulinoma in pregnancy: a case report and review of the literature.

Surgical treatment and outcome in insulinoma].

Rational preoperative diagnosis of insulinoma.


Insulinoma--experience from 1950 to 1995.

[Special diagnostic and therapeutic aspects of insulinoma].

[Insulinoma. Clinical and surgical considerations concerning a case].

Gastrointestinal endocrine tumours. Insulinoma.

Insulinoma: 31 years of tumor localization and excision.

[Recently experienced ten cases of insulinoma--preoperative diagnosis of localization and intraoperative simultaneous monitoring of glucose and insulin].

Insulinoma. The value of intraoperative ultrasonography.

Occult sporadic insulinoma: localization and surgical strategy

Insulinoma: critical study of methods of localization and strategy.

Insulinoma: clinical and diagnostic features of 60 consecutive cases.




Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)






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