Diagnosis, treatment, and current concepts in the endoscopic management of gastroenteropancreatic neuroendocrine neoplasms

Table 1 2019 World Health Organization classification of neuroendocrine neoplasms of the gastrointestinal tract and hepatopancreatobiliary organs

NENs	Differentiation	Grade	Mitotic rate	Ki-67 index %
NET, G1	Well differentiated	Low	< 2	< 3
NET, G2	Well differentiated	Intermediate	2-20	3-20
NET, G3	Well differentiated	High	> 20	> 20
NEC, small cell type	Poorly differentiated	High	> 20	> 20
NEC, large cell type	Poorly differentiated	High	> 20	> 20
MiNEN	Well or poorly differentiated	Variable	Variable	Variable

NEN: Neuroendocrine neoplasm; NET: Neuroendocrine tumor; NEC: Neuroendocrine carcinoma; MiNEN: Mixed neuroendocrine-non-neuroendocrine neoplasm.

Table 2 The hormones produced by the primary gastroenteropancreatic neuroendocrine neoplasms

Tissue	Hormones	Symptoms/Syndrome
Gastric	Histamine, CGA	Atypical flush, wheeze, angioedema
Duodenal	CGA, somatostatin, gastrin	Cholelithiasis, steatorrhea, diabetes, ZE syndrome (gastrinoma)
Jejuno-ileal, appendiceal, cecal	Serotonin, CGA, pancreastatin	Carcinoid syndrome
Colorectal	Pancreatic polypeptide	No hormonal symptoms
Pancreatic	Insulin	Recurrent hypoglycemia
	Glucagon	Diarrhea, glossitis, necrolytic migratory erythema, weight loss, hyperglycemia, blood clots
	VIP	Diarrhea, hypokalemia, achlorhydria
	ACTH	Cushingoid facies, weight gain, diabetes, hypertension
	GHRH	Acromegalic features, diabetes
	PTHRP	Hypercalcemia
	Gastrin	Pain, diarrhea (ZE syndrome)
	Somatostatin	Diabetes, cholelithiasis, steatorrhea, weight loss
	Serotonin	Flushing, diarrhea (carcinoid syndrome)

5HIAA: 5-hydroxyindoleacetic acid; ACTH: Adrenocorticotrophic hormone; CGA: Chromogranin A; F-PNET: Functional pancreatic neuroendocrine tumor; GHRH: Growth hormone releasing hormone; MEN1: Multiple endocrine neoplasia type 1; NF1: Neurofibromatosis type 1; PTHRP: Parathyroid hormone-related peptide; VIP: Vasoactive intestinal polypeptide; ZE: Zollinger Ellison.

Table 3 Characteristics of the subtypes of neuroendocrine neoplasms of the stomach

Characteristics	Type I	Type II	Type III
Prevalence	70%-80%	5%-10%	10%-20%
Background	Autoimmune chronic atrophic gastritis	Gastrinomas (Zollinger-Ellison syndrome)	Normal mucosa
Number of lesions	Multiple	Multiple	Single
Size of tumors	1-2 cm	1 cm	> 2 cm
Site of tumor	Corpus and/or fundus	Corpus and/or fundus	Anywhere
Serum gastrin levels	Elevated	Elevated	Normal
Gastric pH	High	Low	Normal
Invasion	Rare	More common	Common
Prognosis (5-yr survival)	Excellent (90%-95%)	Good (70%-90%)	Worse (less than 35%)