The following summary is from Orphanet
, a European reference portal for information on rare diseases and orphan drugs.
Orpha Number: 97253
Pancreatic endocrine tumor, also known as pancreatic neuroendocrine tumor (PNET), describes a group of endocrine tumors originating in the pancreas that are usually indolent and benign, but may have the potential to be malignant. They can be functional, exhibiting a hormonal hypersecretion syndrome, but can be non-functional presenting with non-specific symptoms and include insulinoma, glucagonoma, VIPoma, somatostatinoma (SSoma), PPoma and Zollinger-Ellison syndrome (ZES, or gastrinoma) and other ectopic hormone producing tumors (such as GRFoma) (see these terms).
Prevalence in the U.S. is estimated at 1/4,000-1/3,300 and 1/37,000 in Japan, but this is likely an underestimate due to a low detection rate.
PNETs, when functional, usually present in the 5th decade of life as various hypersecretion syndromes. These include insulinoma presenting with hyperinsulinemic hypoglycemia; glucagonoma with necrolytic migratory erythema, diabetes mellitus, and thomboembolisms; VIPoma with watery diarrhea, hypokalemia and or hypo/achlorhydia; SSoma with diabetes mellitus, cholelithiasis, steatorrhea and hypochlorhydria; and ZES with severe peptic ulcer disease. Rarely PNETs secrete ectopic hormones (i.e. growth regulatory hormone). Non-functioning PNETs are not associated with distinct hormonal features but may still secrete hormones (i.e. PPoma). They are usually discovered incidentally in the 4-5th decade of life, due to non-specific symptoms, and in many cases have already metastasized to the liver. Malignant behavior is seen in >50% of PNETs (except insulinoma, ~10%). PNETs can also be associated with familial endocrine tumor syndromes (10% of cases) such as multiple endocrine neoplasia type 1, neurofibromatosis type 1, and Von Hippel-Lindau disease (see these terms).
Etiology is unknown. They are thought to be derived from pluripotential epithelial cells in pancreatic ductules or Langerhans islet cells and are most commonly located in the pancreas. SSoma and gastrinoma can also be found in the upper small intestine. Inactivation of tumor suppressor genes or activation of oncogenes may be causative as seen in familial endocrine tumor syndromes.
Diagnosis requires clinical examination, endocrine testing, imaging studies and histopathology examination (HPE) of the tumor. Computed tomography, MRI, endoscopic ultrasound and somatostatin receptor scintigraphy allows for the visualization of a PNET (>0.5) as well as liver, lymph node and peritoneal metastases. HPE and immunohistochemistry help to identify and grade the tumor. Chromogranin A, neuron-specific enolase and pancreastatin are often elevated. Elevated hormone levels may help to identify functional PNETs.
Differential diagnosis is tumor specific and includes endocrine tumor and carcinoid syndrome (see this term).
Most PNETs are sporadic but about 10% are associated with autosomal dominantly inherited endocrine tumor syndromes.
Management and treatment
Management involves resolving the hormone-excess state and treating the tumor itself. Removal of as much of the primary and (if present) metastatic tumors is the current approach. Systemic therapy, with somatostatin analogues (octreotide and lanreotide), effectively treats most functional tumors. If ineffective, systemic interferon-alpha can be given. Complications caused by specific functional tumors should equally be addressed. Surgical procedures involve enucleation and pancreatectomies (with regional lymphadenectomy in most cases). In those with liver metastases, locoregional therapy (i.e. chemoembolization as well as radiofrequency, alcohol and microwave ablation) is recommended to treat liver metastases. Chemotherapy is considered only in those with an intermediate-high grade PNET.
Prognosis is variable. A less favorable prognosis is associated with higher tumor grade and liver and lymph node metastasis. The 5-year survival rate is 30% for nonfunctional PNETs and up to 97% for functional resectable PNETs. Hormonal complications can be life threatening.
Last updated: 11/30/2014