Neuroendocrine GEP-Tumors (GEP-NET)

PPoma / pancreatic Polypeptidoma
pancreatic NET originating from PP-cells with elevated secretion of pancreatic polypeptide (PP) - PP discovered in 1975
incidence of "true" PPoma difficult to delineate, PPoma incidence estimated as 1 - 2 % of all pancreatic NET
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Pathology - Pathophysiology


solitary, frequently large tumors ( <1 cm to > 10 cm) mostly in the pancreatic head, rarely extrapancreatic ( < 10% )

neoplastic PP-cells or PP-secretion frequently found in other NETs (Glucagonoma - 70 %, Vipoma - 42 %, Somatostatinom, Insulinoma - 37 %, Gastrinoma - 34 %, non-functioning NETs - 43 %, Carcinoid): PP may serve as a marker for the diagnosis of NETs

Many assumed non-functioning GEP-NETs of the pancreas may represent clinically silent PPomas

PP inhibits pancreatic and biliary secretion, CCK-antagonism, stimulation of PP via oral nutrient intake (proteins)
no typical clinical syndrome
mostly clinically silent PPomas
abdominal pain, icterus due to tumor mass and hepatic rmetastases
skin rash, watery diarrhea mediated through elevated PP-secretion ?
oberserved: ulcer-diathesis, weight loss, diabetes mellitus
preprandial PP-concentration > 300 pmol/l typical and diagnostic
failure to inhibit PP by
atropin, overstimulation with secretin iv.
imaging techniques
surgical resection (partial pancreatectomy, duodeno-pancreatectomy) - liver surgery (metastases) - chemoperfusion and -embolisation
Somatostatin-Analogs, streptozotocin

Neurotensinoma / Ntoma
ectopic pancreatic NET with elevated secretion of neurotensin -
first reported in 1981
"pure" Ntomas very rare and often associated with gastrinomas, vipomas;
> 50 Ntomas being described as GEP-NET

Pathology - Pathophysiology



Neurotensin: peptide of jejunal and ileal N-cells; stimulated by food intake;
intestinal secretion, ileal contractions, duodenal relaxation & gastrooesophageal sphincter relaxation; inhibits interdigestive myoelectrical complex of the intestine, stimulates insulin
mostly solitary, large tumors ( > 4 - 10 cm ) located in entire pancreas, extrapancreatic location extremely rare
postulated symptoms: exaggerated intestinal secretion (diarrhea), reduced intestinal motility (obstipation), retarded stomach emptying; symptoms associated with ZES (gastrinoma) and VMS (vipoma); rarely hypoglycemia-syndrome (insulin)
cosecreted peptides of Ntomas: gastrin, VIP, PP, calcitonin, bombesin, motilin
clinical syndrome - variations
1. Zollinger-Ellison-Syndrome, Verner-Morrison-Syndrome
2. diarrhea with loss of electrolytes; obstipation

possible symptoms (due to pharmacologic neurotensin actions): vasodilation, hypotension, edemas, cyanosis, tachycardia, hypoglycemia

abdominal pain, icterus due to tumor mass and liver metastases



many neurotensinomas remain undetected due to lacking assay analysis, which may be difficult (rapid degradation of a rather small peptide containing only 13 amino acids, AA)

no established diagnostic tests available addressing stimulation or inhibition of NT - elevation of general markers of GEP-NET

correct postsurgical diagnosis often only by means of specific immunohistochemical staining in neuroendocrine tumor cells

imaging techniques
surgical resection (partial pancreatectomy, e.g. duodeno-pancreatectomy) - liver surgery (metastases) - chemoperfusion and -embolisation
Somatostatin analogs (?), streptozotocin (?)