Review
Copyright ©The Author(s) 2020.
World J Gastroenterol. May 21, 2020; 26(19): 2305-2322
Published online May 21, 2020. doi: 10.3748/wjg.v26.i19.2305
Table 1 Pancreatic neuroendocrine tumors-associated hormonal syndromes and biomarkers
Tumor/syndromeLocationIncidence (million per year)BiomarkerMain symptoms
InsulinomaPancreas1-32InsulinHypoglycaemia
GastrinomaPancreas, duodenum0.5-21.5GastrinZollinger-Ellison syndrome: Gastroesophageal reflux and complicated peptic ulcer disease
VIPomaPancreas0.05-0.2Vasoactive intestinal peptideVerner-Morrison syndrome: Watery diarrhea, hypokalemia, and achlorhydria
GlucagonomaPancreas0.01-0.1GlucagonNecrotic migratory erythema, weight loss, hypoalbuminemia, and diabetes mellitus or impaired glucose tolerance
SSomaPancreas, duodenum, jejunumRareSomatostatinHyperglycemia, cholelithiasis, and maldigestion of food
ACTHomaPancreasRareACTHCushing syndrome
GRHomaPancreas, lung, jejunumRareGRHAcromegaly
Carcinoid syndrome caused by pNETPancreasRareSerotonin, 5-hydroxyindoleacitic acidSkin flushing, diarrhoea, bronchospasm, and cardiac valve fibrosis
Hypercalcemia caused by pNETPancreasRareParathyroid hormone-related peptideHypercalcaemia and abdominal pain
Table 2 Definitions of American Joint Committee on Cancer and European Neuroendocrine Tumor Society staging for pancreatic neuroendocrine tumors
AJCC 7th staging classificationAJCC 8th and ENETS staging classification
T1Limited to the pancreas, ≤ 2 cm in greatest dimensionT1Tumor limited to the pancreas, ≤ 2 cm
T2Limited to the pancreas, > 2 cm in greatest dimensionT2Tumor limited to the pancreas, 2-4 cm
T3Beyond the pancreas but without involvement of the superior mesenteric arteryT3Tumor limited to the pancreas, > 4 cm, or invading the duodenum or common bile duct
T4Involvement of the celiac axis or superior mesenteric artery (unresectable tumor)T4Tumor invades adjacent structures
N0No regional lymph node metastasisN0No regional lymph node metastasis
N1Regional lymph node metastasisN1Regional lymph node metastasis
M0No distant metastasisM0No distant metastasis
M1Distant metastasisM1Distant metastasis
M1aMetastasis confined to liver
M1bMetastasis in at least one extrahepatic site
M1cBoth hepatic and extrahepatic metastases
Table 3 Definitions of American Joint Committee on Cancer, European Neuroendocrine Tumor Society, and modified European Neuroendocrine Tumor Society staging for pancreatic neuroendocrine tumors
AJCC 7th staging classificationAJCC 8th and ENETS staging classificationmENETS
StageTNMTNMTNM
IAT1N0M0T1N0M0T1N0M0
IBT2N0M0T2N0M0T2N0M0
IIAT3N0M0T3N0M0T3N0M0
IIBT1-3N1M0T4N0M0T1-3N1M0
IIIT4Any NM0Any TN1M0T4Any NM0
IVAny TAny NM1Any TAny NM1Any TAny NM1
Table 4 Several editions of World Health Organization (pathological classification)
EditionGrading standards
2000/2004G1: Well-differentiated NET; ≤ 2 cm in size, Ki-67 ≤ 2%G2: Well-differentiated NEC; > 2 cm in size, Ki-67 3%-20% or angioinvasiveG3: Poorly differentiated NEC; Ki-67 > 20%
2010NET-G1: Well-differentiated, mitotic count < 2/2 mm2, Ki-67 ≤ 2%NET-G2: Well-differentiated, mitotic count 2-20/2 mm2, Ki-67 3%-20%NEC-G3: Poorly differentiated, mitotic count > 20/2 mm2, Ki-67 > 20%
2017/2019NET-G1: Well-differentiated, mitotic count < 2/2 mm2, Ki-67 ≤ 2%NET-G2: Well-differentiated, mitotic count 2-20/2 mm2, Ki-67 3%-20%NET-G3: Well-differentiated, mitotic count > 20/2 mm2, Ki-67 > 20%NEC-G3: Poorly differentiated, mitotic count > 20/2 mm2, Ki-67 > 20%