Glucagonoma

Diagnosis

Indications for Testing

  • Neuroendocrine symptoms compatible with tumor site; pancreatic tumor with neuroendocrine symptoms

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

Clinical Background

Glucagonomas are pancreatic neuroendocrine 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 neuroendocrine tumor.

Epidemiology

  • Incidence – <1/1,000,000 (~15% of functioning PNET tumors)
  • 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

  • Tumor of the alpha cells of the pancreatic islets (97%); 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 are glucagonomas

Clinical Presentation

  • Usually sporadic
  • Diabetes mellitus
  • Glossitis, stomatitis, angular cheilitis
  • Panhypoaminoaciduria
  • 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 bones

Treatment

  • Symptomatic relief
  • Somatostatin analogues
  • Resection – patients typically present at advanced stage; however, tumor usually has indolent behavior
  • Total parenteral nutrition may be considered in patients experiencing severe weight loss

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
Glucagon 0099165
Method: Quantitative Radioimmunoassay

Aids in diagnosis of glucagonoma

   
Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Aids in diagnosis of glucagonoma

   
Chromogranin A by Immunohistochemistry 2003830
Method: Immunohistochemistry

Aid in histologic diagnosis of PNETs

Stained and returned to client pathologist; consultation available if needed

   
Ki-67 with Interpretation by Immunohistochemistry 2007182
Method: Immunohistochemistry

Aid in histologic diagnosis of PNETs

Stained and resulted by ARUP

   
Synaptophysin by Immunohistochemistry 2004139
Method: Immunohistochemistry

Aid in histologic diagnosis of PNETs

Stained and returned to client pathologist; consultation available if needed

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

Aid in histologic diagnosis of PNETs

Stained and returned to client pathologist; consultation available if needed

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

Aid in histologic diagnosis of PNETs

Stained and returned to client pathologist; consultation available if needed

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

Aid in histologic diagnosis of PNETs

Stained and returned to client pathologist; consultation available if needed

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential