Glucagonoma is a rare, usually malignant, neuroendocrine tumour arising from pancreatic alpha cells, commonly manifesting as necrolytic migratory erythema and presenting as a hypervascular mass in the pancreas on imaging.
Description
Glucagonoma is a rare pancreatic neuroendocrine tumour (pNET) originating from alpha cells of the pancreatic islets of Langerhans. These tumours produce excessive amounts of the hormone glucagon, resulting in a characteristic clinical syndrome. The majority of glucagonomas are malignant and frequently have already metastasised by the time of diagnosis.
Pathogenesis
Glucagonomas arise from alpha cells, which are responsible for the production and secretion of glucagon. Overproduction of glucagon leads to elevated blood glucose levels, which manifests as the symptoms of glucagonoma syndrome. The exact mechanism of tumour development remains uncertain, but it likely involves complex interactions between genetic, environmental, and possibly immunological factors.
Subtypes
No known specific subtypes of glucagonoma are recognised. The disease is, however, a part of the larger group of pancreatic neuroendocrine tumours.
Epidemiology, Risk Factors & Associations
- Glucagonomas are extremely rare, with an estimated incidence of one in 20 million people per year.
- They occur more commonly in adults in their fourth to sixth decades of life.
- No significant gender predilection has been reported.
Clinical Features
Glucagonoma syndrome is characterised by:
- Necrolytic migratory erythema (almost pathognomonic)
- Hyperglycaemia or overt diabetes mellitus
- Weight loss
- Glossitis
- Diarrhoea
- Venous thrombosis
Complications
Approximately 50-80% of glucagonomas are malignant, and by the time of diagnosis, many have already metastasised, most frequently to the liver and lymph nodes.
Pathological Features
Histopathology
- Macroscopic: Glucagonomas are typically large tumours, often greater than 5 cm at presentation.
- Microscopic: These tumours show a trabecular pattern with cells that are positive for chromogranin, synaptophysin and glucagon on immunohistochemistry.
Serology
- Increased serum glucagon levels are found in most cases.
Biochemistry
- Hyperglycaemia is a common finding due to glucagon’s glycogenolysis effect.
Radiological Features
General Features
- Glucagonomas typically appear as large, well-defined, hypervascular masses.
- Frequently, the tumour has metastasised by the time of presentation, most often to the liver.
CT
- Non-contrast: The tumour may be isodense or slightly hyperdense to normal pancreatic tissue.
- Contrast-enhanced: Glucagonomas typically enhance avidly during the arterial phase due to their hypervascular nature.
MRI
- T1WI: The tumour is typically isointense or slightly hyperintense to the pancreas.
- T2WI: Tumour may appear hyperintense.
- T1 C+: Shows strong enhancement in arterial phase.
US
- Glucagonomas may be visualised as hypoechoic masses relative to the surrounding pancreatic tissue.
NM
- Somatostatin receptor scintigraphy (Octreoscan): Can be helpful in identifying both primary and metastatic disease.
Grading and Staging
The WHO 2017 grading system for neuroendocrine neoplasms applies, categorising tumours based on mitotic count and Ki-67 index.
Diagnosis
Diagnosis is based on clinical symptoms, detection of elevated glucagon levels in the plasma, and radiological identification of a pancreatic mass. Definitive diagnosis requires histopathological confirmation following biopsy.
Differential Diagnosis
- Other causes of necrolytic migratory erythema, such as liver disease and nutritional deficiencies, need to be excluded.
- Other pancreatic neuroendocrine tumours can have similar imaging features but will not result in glucagonoma syndrome.
- Metastases from other primary neuroendocrine tumours, such as carcinoid tumours, should be considered.
Management
Treatment typically involves surgical resection of the tumour where possible. If the disease is unresectable or metastatic, somatostatin analogues, targeted therapies, chemotherapy, and peptide receptor radionuclide therapy can be used.