Sporadic versus hereditary gastrinomas of the duodenum and pancreas: Distinct clinico-pathological and epidemiological features

Table 1 Classification of neuroendocrine tumors of the pancreas (WHO classification 2004)[41]

1	Well-differentiated neuroendocrine tumor
	• Benign: confined to pancreas, < 2 cm in size, nonangioinvasive, ≤ 2 mitoses/HPF and ≤ 2% Ki-67-positive cells
	- Functioning: insulinoma
	- Nonfunctioning
	• Benign or low grade malignant (uncertain malignant potential): confined to pancreas, ≥ 2 cm in size, > 2 mitoses/HPF, > 2% Ki-67-positive cells,  or angioinvasive
	- Functioning: gastrinoma, insulinoma, VIPoma, glucagonoma, somatostatinoma, or ectopic hormonal syndrome
	- Nonfunctioning
2	Well-differentiated neuroendocrine carcinoma
	• Low grade malignant: invasion of adjacent organs and/or metastases
	- Functioning: gastrinoma, insulinoma, glucagonoma, VIPoma, somatostatinoma or ectopic hormonal syndrome
	- Nonfunctioning
3	Poorly-differentiated neuroendocrine carcinoma
	• High grade malignant

Table 2 Classification of neuroendocrine tumors of the duodenum and upper jejunum

1	Well-differentiated neuroendocrine tumor
	• Benign: nonfunctioning, confined to mucosa-submucosa, nonangioinvasive, ≤ 1 cm in size
	- Gastrin-producing tumor (upper part of the duodenum)
	- Serotonin-producing tumor
	- Gangliocytic paraganglioma (any size and extension, periampullary)
	• Benign or low grade malignant (uncertain malignant potential): confined to mucosa-submucosa, with or without angioinvasion, or > 1 cm in size
	- Functioning gastrin-producing tumor (gastrinoma), sporadic or MEN-1 associated
	- Nonfunctioning somatostatin-producing tumor (ampullary region) with or without neurofibromatosis type 1
	- Nonfunctioning serotonin-producing tumor
2	Well-differentiated neuroendocrine carcinoma
	• Low grade malignant: invasion of the muscularis propria and beyond or metastases
	- Functioning gastrin-producing carcinoma (gastrinoma), sporadic or MEN-1 associated
	- Nonfunctioning somatostatin-producing carcinoma (ampullary region) with or without neurofibromatosis type 1
	- Nonfunctioning or functioning carcinoma (with carcinoid syndrome)
	- Malignant gangliocytic paraganglioma
3	Poorly-differentiated neuroendocrine carcinoma
	• High grade malignant