Epidemiology and presentation
The majority NETs are sporadic,
with a median age at diagnosis of 63 years ,
but they could,
occur in patients with complex tumor susceptibility genetic syndromes.
The tumor distribution varies in different parts of the world [3,4] (Fig.1,
These tumors occur most frequently in the gastrointestinal tract (67% of cases),
followed by the tracheobronchial system (24%).
In the gastrointestinal tract 30% of neuroendocrine tumors (NETs) occur in the ileum (5),
followed by the rectum (21%–27%) and the appendix (17%–20%).
Stomach (6%–9%) and duodenum and jejunum (2%–3%) are other less common sites of disease (6),
and the colon is an uncommon location  (Fig.2,
Pancreatic NETs account for 7% of all gastroenteropancreatic (GEP)-NETs and for up to 10% of all pancreatic neoplasms
Up to 25% of gastroenteropancreatic (GEP) NETs are associated with complex genetic syndromes such as MEN-1,
or Wermer syndrome,
neurofibromatosis type 1 (NF-1 or von Recklinghausen disease),
Von Hippel–Lindau disease,
and tuberous sclerosis complex) .
In these patients,
NETs manifest about 15 years earlier than the age typical for sporadic tumors .
Diagnosis and classification of NETs
NETs lesions are frequently being detected incidentally on high-resolution imaging studies.
The classification of these tumors is based on their proliferation and differentiation.
The World Health Organization classification is the one that is most widely accepted and used,
based on mitotic index and Ki-67 index.
The staging system of European Neuroendocrine Tumor Society is based on 2 issues: the cell characteristics/proliferation capacity of the tumor,
and an adapted tumor node metastasis (TNM) staging system . (Table 1)
NETs are divided also into functioning and non-functioning.
When NETs produces metabolically active hormones and amines the clinical manifestation of the lesions can be due to their hypersecretion .
Serotonin can give rise to the carcinoid syndrome,
flushing and chronic diarrhea.
The more common nonfunctioning tumors frequently manifest as locally advanced disease (e.g.
or with metastases (mainly to the liver) [11,12,13].
The diagnosis of neuroendocrine tumor is made with clinical manifestation,
PETs and GEP-NETs
It is usually accepted to divide pancreatic and extra-pancreatic NETs.
Pancreatic endocrine tumors (PETs)
Pancreatic endocrine tumors arise from the islet cells of Langerhans and include:
· Insulinoma (arising from b cells,
producing insulin )
associated with Zollinger–Ellison syndrome (arising from G cells,
producing gastrina) Gastrinomas are often located in the ‘gastrinoma triangle’ formed by the junction between the neck and body of the pancreas medially,
the 2nd and 3rd parts of the duodenum inferiorly and the junction of the cystic and common ducts superiorly
associated with Verner–Morrison syndrome,
arising dorm D2 cells
arising from A cells
arising from D cells,
may be associated with NF 1
·Pancreatic polypeptidoma (PPoma) (involvement of D1 cells)
are usually benign and by far the most common pancreatic endocrine tumor,
accounting for up to 50% of all cases; the remainder of pancreatic endocrine tumors are more likely to be malignant,
with gastrinoma the next most common .
Carcinoids are divided in three different categories:
- Foregut carcinoids,
include gastric carcinoids,
thymic carcinoids and bronchial carcinoids
- Midgut carcinoids,
are defined as neuroendocrine tumors arising beyond the ligament of Treitz to the level of the mid-transverse colon.
They are the commonest primary malignant tumor of the small intestine.
- Hindgut carcinoids,
distal to the mid-transverse colon.
CT FINDINGS OF NEUROENDOCRINE TUMORS
A contrast-enhanced CT CECT is currently the first-instance method and indispensable for the research of NET.
A recommended protocol for imaging of pancreatic NETs would require the patient to be adequately fasted.
Ingestion of water just before the CT scan would act as a negative contrast for visualization of periampullary tumors.
A multiphasic study is helpful for detection of both primary and metastatic disease (Table 2):
• Unenhanced acquisition
• Arterial phase
• Portal venous phase
An unenhanced CT can initially be performed to look for calcifications,
which occur in about 20% of cases,
and differentiate this from pancreatic adenocarcinomas,
which calcify in only approximately 2% of cases.
In the arterial phase,
that are hypervascular tumors with avid early enhancement (Figure 3),
may present as a limited and circumscribed thickening of the visceral wall or as a polypoid lesion or as a mesenteric mass.
The typical NET lesion is isodense on unenhanced CT and shows homogeneous avid arterial enhancement.
Vascular encasement and biliary obstruction are considered rare.
Atypical lesions include those that are hypovascular (or hypoenhancing),
hyperdense on unenhanced CT,
cystic ( Figure 9 and 10) or calcified .
Non-functioning lesions tend to be larger,
and present with mass effect such as biliary dilatation.
They could appear as heterogeneous lesions,
with central areas of necrosis or cystic degeneration.
Functioning tumors are usually small lesions with no mass effects.
Lymph node metastasis
retroperitoneal or mesenteric lymph node metastases are very frequent.
Liver metastases are seen in the majority of patients with a midgut carcinoid at presentation,
depending on the site of the primary tumor,
being important prognostic factors (Fig.8).
Mesenteric and peritoneal disease
NET spreads by contiguity to the mesentery,
through the lymphatic way,
through the infiltration of the spleno-portal venous axis.
Mesenteric masses greater than 1.5 cm are seen in approximately 50%–75% of cases of midgut carcinoid,
with a median size of 3 cm .
Masses are of soft-tissue density,
and a ‘spoke-wheel’ appearance with radiating strands of soft tissue (64%–100%).
Calcification is commonly seen within mesenteric masses (40%–70%) ( Fig.5).
Other sites of metastases are lung and bone.
The main differential for pancreatic NETs would be metastases from clear cell type renal cell carcinoma,
both of which may be present in patients with von Hippel Lindau's disease.
Treatment and follow-up
Surgical resection is the only curative treatment technique for pancreatic and carcinoid neuroendocrine tumors.
For metastatic NETs,
palliation of symptoms may play a role.