Glucagonoma

Pancreatic Neuroendocrine Tumors

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

Indications for Testing

  • Pancreatic tumor
  • Clinical symptoms of glucose intolerance, hyperglycemia, weight loss and cachexia, and migratory necrotic erythema rash

Laboratory Testing

  • Serum glucose – elevated
  • Glucagon
    • Concentration >500 pg/mL is highly suggestive of glucagonoma
  • Chromogranin A (Kulke, North American Neuroendocrine Tumor Society [NANETS], 2010)
    • Role in diagnosis not well defined
    • Can be used as a marker of disease activity for posttreatment surveillance

Histology

  • Diagnosis made by morphology and immunochemical testing

Imaging Studies

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

Differential Diagnosis

Chromogranin A may be used to monitor patients after glucagonoma resection (Kulke, NANETS, 2010).

Glucagonomas are a type of pancreatic neuroendocrine tumor (PNET) that produce excessive amounts of glucagon, which causes glucose intolerance, weight loss, and a distinctive rash (migratory necrolytic erythema). These tumors have a very high malignant potential and are the third most common functional PNET. They are rarely associated with genetic syndromes, in contrast to some other PNETs.

Epidemiology

  • Incidence – <1/million (Falconi, European Neuroendocrine Tumor Society [ENETS] consensus, 2016)
  • Age – 50s-60s (median)
  • Sex – M:F, equal

Familial Genetics

Rarely associated with genetic variations; however, patients diagnosed with multiple endocrine neoplasia 1 (MEN1), von Hippel-Lindau, neurofibromatosis type 1 (NF1), or tuberous sclerosis are at higher risk for PNETs (Falconi, ENETS, 2016)

Pathophysiology

  • Usually sporadic
  • Tumor is usually large (5-10 cm) when discovered
  • Typically, a single tumor is found
  • Tumor size >5 cm associated with malignancy in 60-80% of cases
  • ~15% of functional PNETs
  • Tumor of alpha cells of pancreatic islets – small number in proximal duodenum
    • Most frequently malignant (50-80%) (ENETS, 2016), calcified, and located in body and tail of pancreas with regional node involvement
    • Secretes excessive amounts of glucagon – stimulates glycogenolysis, gluconeogenesis, ketogenesis, lipolysis, and insulin secretion

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 and cachexia
  • Frequently metastatic at presentation
    • Liver is 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.

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Glucagon 0099165
Method: Quantitative Radioimmunoassay

Chromogranin A 0080469
Method: Quantitative Enzyme Immunoassay

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

Falconi M, Eriksson B, Kaltsas G, Bartsch DK, Capdevila J, Caplin M, Kos-Kudla B, Kwekkeboom D, Rindi G, Klöppel G, Reed N, Kianmanesh R, Jensen RT, Vienna Consensus Conference participants. ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors. Neuroendocrinology. 2016; 103(2): 153-71. PubMed

Jensen RT, Cadiot G, Brandi ML, de Herder WW, Kaltsas G, Komminoth P, Scoazec J, Salazar R, Sauvanet A, Kianmanesh R, Barcelona Consensus Conference participants. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology. 2012; 95(2): 98-119. 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

Kulke MH, Anthony LB, Bushnell DL, de Herder WW, Goldsmith SJ, Klimstra DS, Marx SJ, Pasieka JL, Pommier RF, Yao JC, Jensen RT, North American Neuroendocrine Tumor Society (NANETS). NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas. 2010; 39(6): 735-52. PubMed

NCCN Clinical Practice Guidelines in Oncology, Neuroendocrine Tumors. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Aug 2017]

Protocol for the Examination of Specimens from Patients with Tumors of the Endocrine Pancreas. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Jan 2016. College of American Pathologists (CAP). Northfield, IL [Revised Aug 2016; Accessed: Jun 2017]

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

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

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

Medical Reviewers

Last Update: September 2017