Neuroendocrine GEP-Tumors (GEP-NET)

CARCINOID - (Syndrome)

NET of enterochromaffin (EC-cells) of GI-tract, often secreting serotonin :
forgut NET: pancreas - stomach - duodenum - jejunum - respiratory tract - thymus;
midgut NET:
ileum - appendix; hindgut NET: colorectal, urogenital tract
© /
up to 15 per 1 Mill per year / ~ 50 % of all GEP-NET

Pathology - Pathophysiology


- most frequent NET of the GEP-system; up to 75% of all carcinoids are present as ileal carcinoids; pancreatic carcinoids are rare tumors

- often all neuroendocrine GEP-tumors and islet-cell tumors are being referred to as "carcinoids" due to histological similarities and according to older classifications (see WHO-Classification)

- pancreatic carcinoids expressing / secreting serotonin, often associated with an atypical Carcinoid-Syndrome are classified as true "SEROTONINOMA" .

possible tumorigenesis: mutations of tumor-suppressor-gene (MEN-1-gene, menin-gene) discussed in MEN-1 patients, p53-tumo-rsuppressor-gene
Carcinoids of the stomach frequent in genetic disposition (pernicious anemia, chron. atrophic gastritis, hypergastrinemia, hyperplasia of gastrin-producing cells (ECL-system) and in Zollinger-Ellison-Syndrome (Gastrinoma)
symptoms due to serotonin and other vasoactive peptides; serotonin stimulates gastrointestinal motility and secretion; proliferation of fibroblasts


typical clinical syndrome

in up to 50 % of all carcinoids

1. flush (kinins: kallikrein, bradykinin)
2. secretory diarrhea (serotonin)
3. abdominal pain
4. endocardial fibrosis (lesions, valvular stenosis, arrhythmia)
other symptoms: bronchial constriction, asthmatic attacks



Laboratory: plasma serotonin concentration highly variable: (normal ~ 100 - 300 ng/ml ) / 24 hr excretion of 5-HIAA (metabolite) in acidified urin (normal < 10 mg/ day) variable; dependent upon nutrition (5-hydroxy-tryptamine: walnut, avocado, banana, pineapple), dep. upon medical drugs (phenothiazine, serotonin antagonists)
Differential diagnosis: flushing without HIAA caused by menopause, alcohol, medical drugs, systemic mastocytosis, vipoma
HIAA-excretion elevated in malabsorption syndromes (M.Whipple - sprue - celiac diseaes)
Imaging of pimary tumor / metastases by means of octreotid scan OCTREOSCAN (somatostatin-receptor-szintigraphy), CAT scan, NMR, endoscopic sonography)



surgical resection - liver surgery (metastasectomy), lymph node surgery
embolisation of liver metastases (transarterial), combination with chemotherapy -
somatostatin analogs (Octreotide)
interferon: alpha-interferon (IFN)
system. chemotherapy

radionuclid therapy, radiopeptide therapy (DOTATOC): Indium111 or Yttrium90 coupling (DOTA, DTPA) to synthetic somatostatin analog