Net of the pancreas D44.9

Neuroendocrine tumors of the pancreas (PETs) account for about 5% of all diagnosed pancreatic tumors. Macroscopically, they are well-defined, mostly solitary round tumours with a diameter of between 1 and 4 cm, which occur in all sections of the pancreas.

In contrast to the much more common pancreatic cancer (tumours of the so-called exocrine part of the gland), the long-term life expectancy of patients with these tumours (PETs) is significantly better.

NETs of the pancreas are 65-70% functional (hormonally active). Depending on the predominant hormone secretion they are called insulinomas, gastrinomas, VIPomas, glucagonomas (see also there). Insulinomas are mostly benign, the remaining NETs of the pancreas are often malignant.

Functional neuroendocrine tumors leading to hypersecretion syndromes (e.g. insulinomas, gastrinomas, VIPomas, etc.) account for 65-70% of pancreatic NETs.

Non-functional neuroendocrine tumors (30-35%).

Rare overall. Neuroendocrine tumors of the pancreas account for about 5% of all diagnosed pancreatic tumors.

Among functional tumors, insulinomas are the most common. They are 95% between 1.0 and 2.0 cm in size. Multiple insulinomas and insulinomas within the scope of a MEN-1 are observed in about 10% of cases. They do not show an increased malignancy rate compared to solitary or sporadic insulinomas.

The pancreatic gastrinomas are usually > 2.0 cm in size. They have metastasized in up to 60% of cases at diagnosis. In contrast to duodenal gastrinomas, pancreatic gastrinomas rarely occur in the context of MEN-1.

VIPomas, glucagonomas are very rare. Size at the time of diagnosis: > 2 cm. In most cases they have already metastasized. This also applies to the non-functional NETs of the pancreas.

Sporadic functional NETs of the pancreas become manifest between the 5th and 6th decade of life. Non-functional tumors may be present in multiple forms, especially in MEN-I syndrome, and may then occur simultaneously with functional pancreatic tumors. In the case of non-functional pancreatic tumours, the diagnosis is made relatively late.

DETs of the pancreas in childhood are extremely rare. They occur in adulthood in all age groups and with equal frequency in men and women.

Functional tumors of the pancreas. They are clinically conspicuous by a hypersecretion syndrome, whereby the clinical symptoms depend on the hormone secreted (see below insulinoma, gastrinoma, glucagonoma, VIPom). By far the most frequent functional NET of the pancreas is the insulinoma. The insulinoma is clinically characterized by the Whipple triad (spontaneous hypoglycaemia, autonomic symptoms such as sweating, sensation of heat, tachycardia, etc., etc., prompt improvement after oral glucose administration). The gastrinoma (syn: Zollinger -Ellison syndrome - D37.78) is mostly malignant and in 50% of cases metastasized at diagnosis. The hypersecretion of gastrin leads to excessive acid secretion of the stomach and to multiple ulcerations in the upper gastrointestinal tract.

Other functional NETs of the pancreas are very rare. A VIPom forms vasoactive intestinal polypeptide and releases this hormone in an unregulated manner. As a result, severe diarrhoea occurs. Glucagonoma is the release of glucagon. The main symptom is erythema necrolyticum migrans combined with diabetes mellitus.

Non-functional nets of the pancreas: They are not hormonally active. First symptoms - abdominal pain (35-55%), a palpable tumour (10-40%), weight loss (30-45%) - are caused by the space-consuming tumour growth and are therefore late symptoms. Up to 25 % of tumours are diagnosed by chance as "incidental tumours of the pancreas" (tumours discovered by chance).

Functional NETs of the pancreas: insulinoma: Wipple-Trias; in all other NETs of the pancreas biochemical backup of the predominant hormone secretions: gastrin in the gastrinoma of the pancreas, glucagon in the glucagonomer of the pancreas, vasoactive polypeptide in the VIPom.

Functional and non-functional pancreatic NETs: use of imaging techniques such as sonography and endosonography; one-stop-shop MRI. Exclusion of diffuse distant metastasis. In the case of non-functional NETs of the pancreas, findings are often random.

Pancreatic carcinoma. Somatostatin receptor scintigraphy is used for this purpose. Elevated serum concentrations of the tumour marker chromogranin A or pancreatic polypeptide (PP) can support the diagnosis of "neuroendocrine tumour".

Symptomatic therapy for pancreatic gastrinoma is carried out with proton pump inhibitors (PPI, e.g. "Pantozol"). PPIs successfully inhibit acid secretion and thus the clinical symptoms of gastrinoma in almost all patients.

In insulinoma, hypoglycaemia must be counteracted by suitable dietary measures.

If a neuroendocrine tumour of the pancreas is inoperable, palliative chemotherapy with streptozotocin + 5-FU or doxorubicin is considered to be the standard drug therapy. The indication for this must be determined individually, depending on the growth dynamics (see insulinoma, gastrinoma, glucagonoma, etc.)

Functional NETs of the pancreas: resection of sporadic pancreatic NETs by enucleation or distal pancreatic resection the gastrinoma persists or recurs in 40-60% of cases, but the long-term prognosis is good. Even in the case of gastrinoma in the context of a MEN-1 syndrome, biochemical evidence provides an indication for surgery if there is no diffuse liver metastasis.

Non-functional tumours of the pancreas: The primary therapy is surgery. The experienced surgeon will be able to localize and enucleate a large part of the primary tumors by palpation of the pancreas and the small intestine wall or with intraoperative ultrasound.

Surgical indication for liver metastases (see below neuroendocrine tumors of the gastroentero-pancreatic system).

NETs of the pancreas, they often behave malignant with the exception of the insulinoma. This concerns especially gastrinomas, VIPomas, glucagonomas and non-functional NETs.

The most important criteria for malignancy, apart from metastasis in the regional lymph nodes and the liver or infiltration of neighbouring organs, are a tumour size > 2 cm, angioinvasion and a proliferative activity > 2 percent. Apparently, the factor "angioinvasion" is particularly important. It is therefore recommended to assume malignancy if angioinvasion has been reliably proven, even if there are no other criteria for malignancy.

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