The diagnosis of carcinoid is established by the histological examination of a tissue sample taken from either the original tumor or, if necessary, from a metastasis. Neuroendocrine tumors of the stomach or the duodenum are diagnosed by esophagogastroduodenoscopy; tumors of the rectum, the colon and the last segment of the small intestines, i.e. the terminal ileum are visualized by an ileo-colonoscopy. Tissue samples from the neuroendocrine tumor are taken during the endoscopic examination, which today is performed under short-term anesthesia. The tissue samples are sent to the pathologist for histological examination. Carcinoid tumors of the jejunum and the ileum can be detected using capsule endoscopy or balloon enteroscopy. Most often the diagnosis of metastatic carcinoid disease is made clinically, by laboratory tests, ultrasound or radiological examinations.
Very small tumors of the pancreas are most reliably detected using endoscopic ultrasound (endosonography). Tumors of the pancreas can also be detected by magnetic resonance tomography and computed tomography, bronchial and thymic carcinoids mainly by using computed tomography. A tissue biopsy is necessary for a histological diagnosis. For bronchial carcinoids the tissue samples are achieved by bronchoscopy and for pancreatic tumors by endosonography-guided biopsies or fine needle-aspiration. The patient receives short-term anesthesia for these endoscopic examinations.

If metastases are present in the liver at the time of diagnosis, a tissue sample is taken from one of the liver metastases. The patient may also receive a sedative during this procedure.

Figure 4:
Esophago-gastro-duodenoscopy (= endoscopy of the esophagus, stomach and duodenum). Multiple, 2-4 mm sized carcinoids of the stomach are shown on the left.

A 4 mm-sized carcinoid of the duodenum is shown on the right. The endosonographic gray image (directly below) shows that the carcinoid is limited to the superficial layers of the duodenal wall and thus can be removed endoscopically.

Figure 4Figure 4b

Figure 5:
Endoscopy of the colon and rectum (colonoscopy). Each endoscopic image shows a small (< 1cm), well-differentiated (G1) carcinoid of the rectum.

Figure 5Figure 5b

Figures 4 and 5 modified according to Scherübl & Stölzel, Glandula Net 2009; 31-32 and according to Scherübl & Klöppel, Zeitschrift Gastroenterologie 2009; 47: 365-371

Figure 6:
Capsule endoscopy (for example Olympus Europe). The capsule is swallowed by the patient and passes through the esophagus, stomach and gut before it is excreted. The capsule takes thousands of endoscopic images of the small intestines while traveling through the body.

Figure 6Figure 6b

Figure 7:
Diagram of a capsule endoscope (for example Given M2ATM, Given Imaging Ltd., Yoqneam, Israel).

Figure 8:
Diagram of a double balloon enteroscope. Using a double balloon endoscope it was possible to get to this 12 mm-sized carcinoid of the ileum (on the right) and to take tissue samples for histological examination.

Figure 7figure 8b

Figures 6, 7 and 8 are modified according to Scherübl & Faiss, Glandula Net 2007; 14-16 and according to Scherübl et al., Gastrointestinal Endoscopy 2005; 62: 994-5

Computed tomography, positron emission tomography, somatostatin receptor scintigraphy, 68-Gallium-DOTATOC-PET/CT

In order to detect unknown metastases, computed tomographic (CT) scans of the chest and the abdomen as well as somatostatin receptor scintigraphy are performed. Somatostatin receptor scintigraphy uses a radioactive-marked somatostatin analog that is injected into the blood stream to search for well-differentiated neuroendocrine metastases that have somatostatin receptors on the cell surface. Somatostatin receptors are special antenna or marker proteins on the surface (of the majority) of well-differentiated, neuroendocrine (tumor) cells. Various imaging procedures may be combined for optimal visualization, e.g. the 68-Gallium-DOTATOC-PET/CT (or 68-Gallium-DOTATATE-PET/CT or 68-Gallium-DOTANOC-PET/CT) combines PET and CT.

PET means positron emission tomography. PET is comparable with scintigraphy. In addition to localization it provides information on metabolic activity. It is for this reason that the combined imaging with 68-Gallium-DOTATOC-PET and computed tomography (CT) yields a better imaging of well-differentiated neuroendocrine tumors (G1, G2) than each procedure on its own.

In contrast, 18-FDG-PET/CT is preferred to 68-Gallium-DOTATOC-PET/CT for examining undifferentiated (G3) neuroendocrine carcinomas. 18-FDG-PET uses fluorinated deoxyglucose (18-F-Deoxyglucose) to reveal glucose metabolism that is increased in undifferentiated (fast proliferating) neuroendocrine tumor cells (G3). Well-differentiated neuroendocrine tumors (G1, G2), on the other hand, have a (very) low glucose metabolism. As a result 18-FDG-PET is not suitable for examining well-differentiated neuroendocrine tumors (G1, G2).

Explanation of frequent acronyms used in nuclear medicine:

DOTA          =  1,4,7,10-tetra-aza-cyclododecane-1,4,7,10-tetraacetic acid
DOTATOC    =  DOTA-phe1-tyr3-octreotide (DOTA-tyrosine conjugate with octreotide)
DOTANOC    =  DOTA-naphthyl3-octreotide (DOTA-naphthyl-alanine conjugate with octreotide)
DOTATATE   =  DOTA-tyr3-thre8-octreotide (DOTA-threonine conjugate with octreotide             
18-FDG        =  Fluorinated deoxyglucose (18-F-Deoxyglucose)                                              
SPECT         =   Single photon emission computed tomography                                                    
CT               =  Computed tomography                                                                                       
PET             =  Positron emission tomography                                                         
PET/CT        =  Combined examination using PET and CT

Figure 9:
Scintigraphic, computed tomographic and PET/CT images of neuroendocrine metastases

figure 9figure 9b

68-Gallium-DOTATATE-PET/CT-images by courtesy of the PET-Center of Vivantes GmbH, Berlin

figure 9cfigure 9d
figure 9e

Laboratory test

Functional neuroendocrine tumors can be diagnosed by taking typical clinical symptoms and specific hormone levels into consideration. Gastrin is determined in the case of a gastrinoma, insulin, C-peptide and proinsulin in the case of an insulinoma, serotonin or 5-hydroxyindoleacetic acid in the case of a carcinoid of the small bowels, aso). Furthermore chromogranin A is considered a general tumor marker of neuroendocrine tumors. Chromogranin A, gastrin, insulin, C-peptide, proinsulin and serotonin can be measured by blood tests. 5-hydroxyindoleacetic acid can be determined in urine collected for 24 hours.


Prof. Dr. med. Hans Scherübl


Center of Neuroendocrine Tumors
Prof. Dr. med. Hans Scherübl
Vivantes Klinikum Am Urban
Academic Teaching Hospital of Charité-University Medicine, Berlin
Dieffenbachstraße 1
10967 Berlin, Germany
Tel: + 49 30 130 225201
Fax: + 49 30 130 225205
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