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

• Skin rash
  • Psoriasis
  • Paraneoplastic syndromes
  • Vitamin deficiency syndromes (pellagra)
  • Toxic epidermal necrolysis
  • Pemphigus
  • Pemphigoid
  • Herpes
  • Seborrheic/contact dermatitis
• Hyperglycemia
  • Diabetes mellitus (type 1 or type 2)
  • Metabolic syndrome
• Deep vein thrombosis
  • Thrombophilia
• Other malignancy
  • Pancreatic adenocarcinoma

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