Neuroendocrine tumors of the gastroentero-pancreatic system D44.9

The gastroenteropancreatic neuroendocrine tumors (acronym "GEP-NET") which are also known under various terms such as carcinoid, islet cell tumor or gastrinoma, among others. GEP-NETs originate from the neuroendocrine cells of the gastroenteropancreatic (GEP) system. This endocrine cell system and its tumors are characterized by the expression of cell type-specific peptide hormones and different types of tumors. neurotransmitters such as synaptophysin and chromogranin-A. The increased secretion of these hormones often leads to path-breaking hypersecretion syndromes (e.g. flush symptoms) with corresponding clinical symptoms. Such functionally active GEP-nets are called gastrinoma, insulinoma or glucagonoma depending on the secretion product.

WHO classification of NETs/proliferation-based grading:

• Highly/well differentiated neuroendocrine tumor (G1) -Ki-67 index: =/<2%
• Highly/well differentiated neuroendocrine tumor (G2) -Ki-67-Index: 3-20%
• Low/well differentiated neuroendocrine tumor (G3) =NEC -Ki-67 index > 20% (large-cell and small-cell variant)

Classification of NETs according to localization:

• NET of the stomach
• NET of the duodenum and proximal jejunum
• NET of the ileum and the appendix
• NET of the colon and rectum
• NET of the pancreas

The incidence of gastroenteropancreatic neuroendocrine tumors is estimated at 1-2/100,000 per year.

The clinical picture of neuroendocrine tumors is directly dependent on their respective secretion product:

• Insulinoma (secretion of insulin)
• Glucagonoma (secretion of glucagon)
• Somatostatinoma (secretion of somatostatin)
• VIPom (secretion of vasoactive intestinal polypeptide)
• Gastrinom (secretion of gastrin)
• NET of jejunum, ileum, ascending colon (secretion of serotinin, neurotensin; in metastasis flush syndrome)
• NET of colon transversum, colon descendens, sigmoid colon, rectum (non-functional secretion of chromium granin A)

The clinical symptoms of patients with GEP-NET depend on the hormonal activity of the tumours and on the localisation and extent of the tumour:

• Insulinoma: recurrent hypoglycaemia, which manifests itself in adrenergic symptoms such as tachycardia, anxiety, sweating and palpitations. In the absence of carbohydrate intake, a neuroglycopenic symptom with loss of consciousness may occur.
• Gastrinomas: recurrent duodenal ulcerations and gastroesophagial reflux are the leading symptoms of duodenal or pancreatic gastrinomas. Rarely only diarrhea occurs.
• Glucagonoma: the combination of necrolytic-migratory erythema, pronounced weight loss and glucose intolerance characterize the glucagonoma.
• VIPom (VIP = acronym for vasocative intestinal polypeptide): abdominal cramps, aqueous diarrhoea with consecutive dehydration, weight loss.
• NET of the ileum and appendix: diarrhea, abdominal cramps and typical flush, especially in the face, neck and thorax region, are symptoms of metastasized ileal NET. The solitary appendical carcinoid is a mostly benign incidental finding.

1. Perren A et al (2010): Classification and pathology of gastroenteropancreatic neuroendocrine tumors. Visceralmed 26: 234-240