Copyright ©The Author(s) 2022.
World J Gastrointest Endosc. May 16, 2022; 14(5): 267-290
Published online May 16, 2022. doi: 10.4253/wjge.v14.i5.267
Table 1 World Health Organization 2019 Classification
Terminology, grade
Mitotic count (HPF2)
Ki-67 index (%)
NET, G1Well-differentiated < 2/10< 3
NET, G2Well-differentiated2-20/103-20
NET, G3Well-differentiated> 20/10> 20
NEC, G3 (small or large cell type)Poorly differentiated> 20/10> 20
Table 2 Gastric neuroendocrine tumors[88,90,91]

Type 1
Type 2
Type 3
Type 4
Proportion of gastric neuroendocrine tumors70%-80%5%15%-25%Very rare
Associated conditionsAtrophic gastritis Zollinger-Ellison and MEN-1SporadicSporadic
LocationGastric fundus and bodyGastric fundus and bodyAntrumAnywhere
Endoscopic findingsMultiple, small polypsMultiple, small polypsSolitary, largerSolitary, larger
Gastrin levelIncreasedIncreasedNormalNormal
pHIncreased Decreased Normal Normal
PrognosisExcellent GoodPoorVery poor
EvaluationGastric pH, gastrin, EUS 1-2 cm lesionsGastric pH, gastrin, EUS 1-2 cm lesions, abdominal imagingGastric pH, gastrin, EUS, abdominal imagingGastric pH, gastrin, EUS, abdominal imaging
Treatment Endoscopic resection for larger lesions and surveillance for lesions < 2 cmSimilar to type 1Surgery, endoscopic resection for superficial, well-differentiated lesions < 1 cmSurgery for local disease, systemic chemotherapy for metastatic
SurveillanceEGD every yearEGD every 6-12 mo, abdominal imaging every yearEGD every 6-12 mo, abdominal imaging every 3 mo
Table 3 Small intestinal neuroendocrine tumors[96,97,101,102,104,108,109]

Epidemiology2%-3% GEP-NETs0.3%-1% GEP-NETs1.2 cases/100000 incidence quadrupled over past 30 yr
Evaluation> 2 cm: CT and EUSCT, EUSChromogranin A, urine 5-HIAA, CT/MRI, gallium-DOTATATE PET CT, colonoscopy into terminal ileum
5-yr survivalNo metastases: 80%-95%; Regional metastases: 65%-75%; Zollinger-Ellison or MEN-1: > 90%59%Local disease: 80%-100%; Regional disease: 70%-80%; Distant metastases: 35%-80%
Treatment < 1 cm: Endoscopic resection; 1-2 cm: Endoscopic or surgical resection; > 2 cm: EMR or ESD, surgical resection for regional disease< 2 cm superficial without metastases: Pancreaticoduodenectomy or consider endoscopic ampullectomy; > 2 cm: PancreaticoduodenectomySurgery; Carcinoid syndrome: Long-acting SSA (octreotide LAR 20-30 mg IM)
SurveillanceEGD at least every 2 yrEGD at 1-2 yr intervalNANETS: Curative surgery-CT every 3-6 mo then 6-12 mo for 7 yr; Advanced disease- CT every 6 mo; ENETS: Curative surgery: Chromogranin A, urine 5-HIAA, CT every 6-12 mo; Slow-growing treated without curative intent: every 3-6 mo
Table 4 Risk of metastases by tumor size in appendiceal neuroendocrine tumors[169]
Tumor size
Nodal metastases
Distant metastases
≤ 1 cm0%0%
1-2 cm7.5%4%
≥ 2 cm33%12%
Table 5 Colorectal neuroendocrine tumors[103,112,114,121,124,126,170-173]

Epidemiology1.45% of appendectomies< 10% NETs29% GEP-NETs
PresentationIncidental or acute appendicitis; Carcinoid syndrome rareIncidental (yellowish polypoid or donut-shaped); 46% advanced at diagnosisIncidental (small, yellowish polypoid)
Evaluation(1) Colonoscopy; (2) CT/MRI if > 2 cm, incomplete resection1, suspected metastases; (3) Gallium DOTATATE PET CT: Incomplete resection1, suspected metastases, carcinoid syndrome; and (4) Chromogranin A and urine 5-HIAA: liver metastases or carcinoid syndromeCT, EUS, Gallium DOTATATE PET CTColonoscopy; EUS; > 2 cm, invasion beyond submucosa, lymph node disease: Gallium DOTATATE PET CT
5-yr survival< 2 cm without regional or distant disease: 100%; 2-3 cm with regional nodes or ≥ 3 cm: 78%; Distant metastases: 32%Stage I: 90%; Stage II: 77%; Stage III: 53%; Stage IV: 14% Localized: 98%-100%; Regional metastases: 54%-74%; Distant metastases: 15%-37%
Treatment Right hemicolectomy with lymph node dissection: (1) > 2 cm; and (2) 1-2 cm with high-risk features2; Appendectomy: (1) < 1 cm, well-differentiated; and (2) 1-2 cm without high-risk features2Local disease: segmental colectomy and lymphadenectomy; Metastatic disease: chemotherapy< 1 cm without invasion beyond submucosa: Endoscopic resection; 1-2 cm: Endoscopic resection or transanal resection; > 2 cm without metastatic disease: Radical surgical resection
Surveillance(1) ≤ 2 cm without high-risk features2 and confined to appendix: No follow-up; and (2) Larger or node positive, and right hemicolectomy: CT/MRI 3-12 mo post-surgery; consider baseline gallium DOTATATE PET CTAfter first year, annual CT/MRI< 1 cm: None; 1-2 cm: EUS or MRI at 6 and 12 mo; > 2 cm: CT/MRI at 3 and 12 mo, then every 12-24 mo
Table 6 Diagnosing pancreatic neuroendocrine tumors[136,174]

Diagnostic evaluation
All pancreatic NETMultiphasic CT/MRI
If results impact management, gallium DOTATATE PET CTEUS with biopsy
Insulinoma72 h fast test: Hypoglycemia with elevated insulin
Oral glucose tolerance test: May be necessary in minority with only postprandial hypoglycemia
GastrinomaFasting gastrin 10 times upper limit of normal + gastric pH < 2
If gastrin less elevated + gastric pH < 2, measure BAO with secretin test
BAO > 15 mEq/h or serum gastrin increase > 120 pg/mL
GlucagonomaFasting serum glucagon > 500 pg/mL
SomatostatinomaFasting plasma somatostatin > 30 pg/mL
VIPomaLarge volume diarrhea + serum VIP > 75 pg/mL