Somatostatinoma

Pancreatic Neuroendocrine Tumors (PNETs)

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

Indications for Testing

  • Undiagnosed pancreatic tumor
  • Symptoms of somatostatin excess including mild diabetes, diarrhea, and/or steatorrhea, sometimes in combination with gallstones

Laboratory Testing

  • Somatostatin level
    • Usually elevated manyfold above normal
    • Intestinal somatostatinomas may have normal or only slightly increased levels
  • Provocative tests are available with infusion tolbutamide and arginine

Histology

  • Nested or trabecular arrangement of small- to medium-sized cells
    • Unique occurrence of psammoma bodies
    • Finely granular eosinophilic cytoplasm
    • Central round to oval nuclei
    • Stippled chromatin (“salt and pepper”)
    • Typically >5cm
  • Immunohistochemistry
    • Synaptophysin, chromogranin A, pan cytokeratin, Ki-67, neuron specific enolase (NSE), protein gene product (PGP) 9.5
    • Tumor-specific confirmation – somatostatin with diffuse immunoreactivity

Imaging Studies

  • Computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound
    •  Generally can detect most tumors (National Cancer Institute [NCI], 2015)
  • Somatostatin-receptor scintigraphy

Differential Diagnosis

Somatostatinomas are rare, functional neuroendocrine tumors (NETs) that produce excessive amounts of somatostatin. Somatostatin inhibits cholecystokinin, insulin, and pancreatic exocrine function. Tumors are usually malignant with metastases at diagnosis.

Epidemiology

  • Incidence – 1/40 million
  • Age – median is early 50s
  • Sex – M<F, 1:2 (Vinik, 2010)
  • Occurrence – usually sporadic

Risk Factors

  • Genetic
    • May also be associated with von Hippel-Lindau syndrome, tuberous sclerosis, and neurofibromatosis type 1 (von Recklinghausen disease)

Pathophysiology

  • Locations for tumor – duodenum (~40%) or pancreas (~60%) (Jensen, 2016)
  • Hormone secreted is somatostatin
    • Inhibits release of many hormones (gut hormones, including insulin, pancreatic polypeptide, glucagon, gastrin, secretin, glucose-dependent insulinotropic peptide, and motilin; and growth hormone)
    • Has limited neurotransmitter function, primarily in the pituitary gland

Clinical Presentation

  • Somatostatinoma syndrome
  • Abdominal pain, weight loss, icterus, nausea/vomiting, anemia, abdominal tumor, hepatomegaly may also be presenting symptoms
  • Tumor may be found incidentally, especially if not associated with the syndrome, as patient may be asymptomatic until tumor is large and causing compressive symptoms or symptoms due to metastases
  • Metastatic disease is frequently present at time of diagnosis
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.

Somatostatin Quantitative, Plasma 2010001
Method: Quantitative Extraction/Immunoassay

Synaptophysin by Immunohistochemistry 2004139
Method: Immunohistochemistry

Chromogranin A by Immunohistochemistry 2003830
Method: Immunohistochemistry

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

Ki-67 with Interpretation by Immunohistochemistry 2007182
Method: Immunohistochemistry

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

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]

O'Toole D, Grossman A, Gross D, Fave GD, Barkmanova J, O'Connor J, Pape U, Plöckinger U, Mallorca Consensus Conference participants, European Neuroendocrine Tumor Society. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: biochemical markers. Neuroendocrinology. 2009; 90(2): 194-202. PubMed

Oberg K, Couvelard A, Fave GD, Gross D, Grossman A, Jensen RT, Pape U, Perren A, Rindi G, Ruszniewski P, Scoazec J, Welin S, Wiedenmann B, Ferone D, all other Antibes Consensus Conference participants. ENETS Consensus Guidelines for Standard of Care in Neuroendocrine Tumours: Biochemical Markers. Neuroendocrinology. 2017; PubMed

Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ) – Health Professional Version. National Cancer Institute. [Updated Apr 2015; Accessed: Aug 2017]

Protocol for the Examination of Specimens from Patients with Neuroendocrine Tumors (Carcinoid Tumors) of the Small Intestine and Ampulla. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Revised Oct 2013; Accessed: Jun 2017]

Protocol for the Examination of Specimens from Patients with Neuroendocrine Tumors (Carcinoid Tumors) of the Stomach. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Revised Jun 2014; Accessed: Jun 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

Batcher E, Madaj P, Gianoukakis AG. Pancreatic neuroendocrine tumors. Endocr Res. 2011; 36(1): 35-43. PubMed

Garbrecht N, Anlauf M, Schmitt A, Henopp T, Sipos B, Raffel A, Eisenberger CF, Knoefel WT, Pavel M, Fottner C, Musholt TJ, Rinke A, Arnold R, Berndt U, Plöckinger U, Wiedenmann B, Moch H, Heitz PU, Komminoth P, Perren A, Klöppel G. Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity. Endocr Relat Cancer. 2008; 15(1): 229-41. 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

Content Reviewed: 
August 2017

Last Update: September 2017