Glucagonoma

Diagnosis

Indications for Testing

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

Laboratory Testing

  • Nonspecific testing
    • CBC – 90% have normocytic anemia
  • 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
  • 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

   
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential
Nonspecific testing in glucagonoma evaluation    
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