GEP - NET do not secrete / produce
a measurable hormone in contrast to insulinoma, gastrinoma, glucagonoma.
These tumors are not associated with a typical clinical syndrome.
Very often these tumors may represent
clinically silent PPoma's
of the pancreas (p-NET, foregut
/ NET of digestive GI-tract (d-NET)
"non-functioning islet-cell tumors"
islet cell carcinomas)
GEP-NET in GI-tract:
carcinoids without clin. carcinoid-syndrome
high index of malignancy.
"limited risk tumors" (LRT) / "increased risk
nuclear Ki67-expression, vascular and/or perineural invasion
p-NET mostly are tumors
presenting with circulating tumor markers (chromogranin A,
NSE, HCG, PP, calcitonin).
apparent hormonal secretion is insufficient to produce
a clinical syndrome or symptoms
p-NET are tumors presenting histochemical
(immunofluorescence) peptide- or tumor marker expression.
for classifying problems: see below
problems of non-functional GEP-NET may be due to,
1. : failure to test for "rare" peptides,
2. : failure to investigate the patient carefully and
in depth (symptoms and history),
3. : seceretion of inactive precursors of the hormones
without any known physiological function,
4. : secretion of peptides which do not have any clinically
relevant action even if secreted in high quantities,
5. : secretion of peptides for which assays are not yet
6. : secretion of small amounts of peptides or simultaneous
secretion of inhibitory peptides,
7. : regulated secretion of peptides, absence of autonomous
8. : failure to coordinate physiological function of peptide
in question and clinical symptoms.
GEP-NET sometimes are
misclassified despite clear evidence for the presence of
endocrine machinery (e.g. positive
markers, positive immunohistochemistry).
frequent pancreatic polypeptidoma (PPoma)
or pancreatic calcitoninoma in the
abesence of hypocalcemia or steatorrhea.
: Proinsulin which in comparison to insulin is
a weak agonist may be the dominant
peptide in many insulinomas and is causing the classical hypglycemia