Glucagonoma

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Pancreatic tumor with neuroendocrine symptoms; unexplained hyperglycemia with rash

Laboratory Testing

  • Serum glucose – elevated
  • Glucagon – level >500 pg/mL is highly suggestive of glucagonoma

Histology

  • Tumor size >5 cm associated with malignancy in 60-80% of cases
  • Nested or trabecular arrangement of small- to medium-sized cells
    • Finely granular eosinophilic cytoplasm
    • Central round to oval nuclei
    • Stippled chromatin (“salt and pepper”)
  • Immunohistochemistry
    • Basic testing for pancreatic neuroendocrine tumors (PNETs) – chromogranin A, synaptophysin, cytokeratin, Ki-67 (Mib-1), neuron specific enolase polyclonal, pan cytokeratin (AE1,3), protein gene product 9.5
    • Tumor-specific confirmation – glucagon

Imaging Studies

  • Multiphasic contrast enhanced CT or MRI – diagnostic for tumor
    • If negative, proceed to scintography for tumor identification
  • Somatostatin-receptor scintigraphy (Indium-111 OctreoScan) may help localize small lesions

Differential Diagnosis

Glucagonomas are pancreaticneuroendocrine tumors (PNETs) that produce excessive amounts of glucagon and are associated with a distinctive clinical syndrome. These tumors have a very high malignant potential, and are the third most common functional PNET.

Epidemiology

  • Incidence – <1/1,000,000
  • Age – 50s-60s (median)
  • Sex – M:F, equal

Risk Factors

  • Genetic – rarely associated with genetic variations; however, patients diagnosed with MEN1 or von Hippel-Lindau syndrome are at higher risk for glucagonomas

Pathophysiology

  • Usually sporadic
  • Tumor of the alpha cells of the pancreatic islets – small number in proximal duodenum
    • Most frequently malignant, calcified, and located in the body and tail of the pancreas with regional node involvement
    • Secretes excessive amounts of glucagon – stimulates glycogenolysis, gluconeogenesis, ketogenesis, lipolysis, and insulin secretion
  • Tumor is usually large (5-10 cm) when discovered
    • Typically, a single tumor is found
  • ~15% of functional PNETs

Clinical Presentation

  • Laboratory – hyperglycemia, panhypoaminoaciduria
  • Glossitis, stomatitis, angular cheilitis
  • Skin rash
    • Migratory necrolytic erythema
    • Starts as annular erythema at intertriginous sites
    • Progresses to papulobullous stage that waxes and wanes
  • Increased risk of deep-vein thrombosis
  • Diarrhea
  • Weight loss
  • Frequently metastatic at presentation
    • Liver is the most common site of metastasis, followed by lymph nodes or bone

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Glucagon 0099165
Method: Quantitative Radioimmunoassay

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Chromogranin A by Immunohistochemistry 2003830
Method: Immunohistochemistry

Ki-67 with Interpretation by Immunohistochemistry 2007182
Method: Immunohistochemistry

Synaptophysin by Immunohistochemistry 2004139
Method: Immunohistochemistry

Neuron Specific Enolase, Polyclonal (NSE P) by Immunohistochemistry 2004052
Method: Immunohistochemistry

Pan Cytokeratin (AE1,3) by Immunohistochemistry 2003433
Method: Immunohistochemistry

Protein Gene Product (PGP) 9.5 by Immunohistochemistry 2004091
Method: Immunohistochemistry

Guidelines

NCCN Clinical Practice Guidelines in Oncology, Neuroendocrine Tumors. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Sep 2015]

Protocol for the Examination of Specimens from Patients with Carcinoma of the Endocrine Pancreas. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: June 2012. College of American Pathologists (CAP). Northfield, IL [Accessed: Nov 2015]

Vinik AI, Woltering EA, Warner RR P, Caplin M, O'Dorisio TM, Wiseman GA, Coppola D, Go VLiang W, North American Neuroendocrine Tumor Society (NANETS). NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas. 2010; 39(6): 713-34. PubMed

General References

Cruz-Bautista I, Lerman I, Perez-Enriquez B, Padilla LS, Torres CL, Lopez A, Cabrera T, Mehta RP, Gómez-Pérez FJ, Rull JA, Orozco-Topete R. Diagnostic challenge of glucagonoma: case report and literature review. Endocr Pract. 2006; 12(4): 422-6. PubMed

Jabbour SA, Davidovici BB, Wolf R. Rare syndromes. Clin Dermatol. 2006; 24(4): 299-316. PubMed

Klöppel G, Couvelard A, Perren A, Komminoth P, McNicol A, Nilsson O, Scarpa A, Scoazec J, Wiedenmann B, Papotti M, Rindi G, Plöckinger U, Mallorca Consensus Conference participants, European Neuroendocrine Tumor Society. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification. Neuroendocrinology. 2009; 90(2): 162-6. PubMed

Morgan KA, Adams DB. Solid tumors of the body and tail of the pancreas. Surg Clin North Am. 2010; 90(2): 287-307. PubMed

Oberg K. Pancreatic endocrine tumors. Semin Oncol. 2010; 37(6): 594-618. PubMed

Öberg K, Knigge U, Kwekkeboom D, Perren A, ESMO Guidelines Working Group. Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012; 23 Suppl 7: vii124-30. PubMed

Medical Reviewers

Last Update: December 2015