|
non-functioning
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
|
NET
of the pancreas (p-NET, foregut
tumors)
/ NET of digestive GI-tract (d-NET)
|
"non-functioning islet-cell tumors"
(majority of
islet cell carcinomas) |
non-functioning
GEP-NET in GI-tract:
carcinoids without clin. carcinoid-syndrome
|
frequently
high index of malignancy.
patho-anatomical:
well-differentiated p-NET
or undifferentiated
p-NET |
Patho-anatomical
criteria:
"limited risk tumors" (LRT) / "increased risk
turmors" (IRT)
nuclear Ki67-expression, vascular and/or perineural invasion |
| non-functioning
p-NET mostly are tumors
presenting with circulating tumor markers (chromogranin A,
NSE, HCG, PP, calcitonin). |
Eventually
apparent hormonal secretion is insufficient to produce
a clinical syndrome or symptoms |
| non-secreting
p-NET are tumors presenting histochemical
(immunofluorescence) peptide- or tumor marker expression. |
reasons
for classifying problems: see below
WHO-Classification
of GEP-NET
|
|
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Classification
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
available,
6. : secretion of small amounts of peptides or simultaneous
secretion of inhibitory peptides,
7. : regulated secretion of peptides, absence of autonomous
secretion,
8. : failure to coordinate physiological function of peptide
in question and clinical symptoms.
Non-functional
GEP-NET sometimes are
misclassified despite clear evidence for the presence of
endocrine machinery (e.g. positive
markers, positive immunohistochemistry).
Example:
frequent pancreatic polypeptidoma (PPoma)
or pancreatic calcitoninoma in the
abesence of hypocalcemia or steatorrhea.
Exception:
"Proinsulinoma"
: Proinsulin which in comparison to insulin is
a weak agonist may be the dominant
peptide in many insulinomas and is causing the classical hypglycemia
syndrome.
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