Neuroendocrine neoplasms

Glucagonoma (alpha cell tumors)

Editor-in-Chief: Debra L. Zynger, M.D.
Raul S. Gonzalez, M.D.

Topic Completed: 17 February 2021

Minor changes: 24 February 2021

Copyright: 2002-2022,, Inc.

PubMed Search: Glucagonoma alpha cell tumor AND pancreas AND free full text[sb]

Raul S. Gonzalez, M.D.
Page views in 2021: 1,294
Page views in 2022 to date: 41
Cite this page: Gonzalez RS. Glucagonoma (alpha cell tumors). website. Accessed January 19th, 2022.
Definition / general
  • Rare, poorly characterized pancreatic neuroendocrine tumor that produces glucagon
Essential features
  • WHO recognized diagnosis
  • Produces glucagon, akin to alpha cells of the pancreas
  • Clinical glucagonoma symptoms include necrolytic migratory erythema, diabetes, weight loss and anemia
  • Necrolytic migratory erythema: skin rash of legs, perineum, groin; rash becomes blisters with central clearing, heals with hyperpigmentation but without scarring in 7 - 14 days (Am J Surg Pathol 1986;10:445)
ICD coding
  • ICD-10: D37.8 - Neoplasm of uncertain behavior of pancreas
  • More common in tail of pancreas
Clinical features
  • Causes glucagonoma syndrome (necrolytic migratory erythema, diabetes mellitus, weight loss, anemia, angular stomatitis)
  • Necrolytic migratory erythema may become infected
  • Roughly half of cases metastasize, often to liver
  • Determined clinically, not by immunohistochemical positivity for glucagon
  • Elevated blood glucagon levels
Radiology description
  • MRI: low signal intensity on T1, slightly high signal intensity on T2
Radiology images

Images hosted on other servers:
Missing Image


Missing Image


Missing Image

Liver metastases

Case reports
Clinical images

AFIP images

Necrolytic migratory erythema

Images hosted on other servers:
Missing Image

Necrolytic migratory erythema

Gross description
  • Average gross tumor size is 5.0 cm
Microscopic (histologic) description
  • Nests of monotonous low grade neuroendocrine cells with salt and pepper nuclei and ample amphophilic cytoplasm
Microscopic (histologic) images

Images hosted on other servers:
Missing Image

H&E and immunostains

H&E and glucagon

Missing Image

Liver metastasis


Positive stains
Electron microscopy description
Sample pathology report
  • Pancreas and duodenum, Whipple procedure:
    • Pancreatic neuroendocrine tumor, WHO grade 1 (see synoptic report and comment)
    • Comment: The patient’s clinical history of necrolytic migratory erythema is noted. This may be due to glucagon secretion by this tumor, which would make it a glucagonoma. Immunohistochemical stains for synaptophysin and chromogranin are positive and the Ki67 index is approximately 1.2%.
Differential diagnosis
Board review style question #1
    Which of the following is a potential clinical symptom of pancreatic glucagonoma?

  1. Angular stomatitis
  2. Hypochlorhydria
  3. Hypoglycemia
  4. Water diarrhea
Board review style answer #1
A. Angular stomatitis (though the most common finding is necrolytic migratory erythema). Hypochlorhydria is sometimes seen in somatostatinoma. Hypoglycemia is typical of insulinoma. Watery diarrhea is typical of VIPoma.

Comment Here

Reference: Glucagonoma (alpha cell tumors)
Board review style question #2
    Which of the following is necessary to confirm a diagnosis of glucagonoma in a patient with a pancreatic mass?

  1. Classic radiologic findings
  2. Clinical glucagonoma type symptoms
  3. Immunohistochemical positivity for glucagon
  4. Specific histologic findings
Board review style answer #2
B. Clinical glucagonoma type symptoms. The diagnosis of glucagonoma is made on clinical grounds in the setting of a pancreatic mass lesion.

Comment Here

Reference: Glucagonoma (alpha cell tumors)
Back to top
Image 01 Image 02