Non-functional neuroendocrine tumors of the pancreas: Advances in diagnosis and management

Table 1 Current pancreatic neuroendocrine tumor classification and staging systems

WHO 2010/ENETS grading
Grade	Differentiation	Ki-67 index (%)	Mitotic count/10 HPF
G1 (low)	Well	≤ 2	< 2
G2 (intermediate)	Well	3-20	2-20
G3 (high)	Poorly	> 20	> 20
ENETS T staging1
T stage	Description
TX	Cannot be assessed
T0	No evidence of tumor
T1	< 2 cm, limited to pancreas
T2	2-4 cm, limited to pancreas
T3	> 4 cm, limited to pancreas
T4	Involving adjacent organs or large blood vessels
AJCC T staging1
T stage	Description
TX	Cannot be assessed
T0	No evidence of tumor
T1	≤ 2 cm, limited to pancreas
T2	> 2 cm, limited to pancreas
T3	Involves adjacent organs
T4	Involving celiac axis or superior mesenteric artery
Stage	ENETS staging	AJCC staging
IA	T1 N0 M0	T1 N0 M0
IB		T2 N0 M0
IIA	T2 N0 M0	T3 N0 M0
IIB	T3 N0 M0	T1-3 N1 M0
IIIA	T4 N0 M0	T4 N1 M0
IIIB	T1-4 N1 M0
IV	T1-4 N0-1 M1	T1-4 N0-1 M0

¹Both AJCC and ENETS share common N and M staging: N0, no regional lymph node metastatic; N1, regional lymph node metastasis; M0, no distant metastasis; M1, distant metastasis. WHO: World Health Organization; ENETS: European neuroendocrine tumor society; AJCC: 7^th edition American joint committee on cancer.

Table 2 Clinical features of functional pancreatic neuroendocrine tumors

Tumor	Percentage	Secreted hormone	Malignant	Clinical features	Biochemical evaluation
Insulinoma	40%-60%	Insulin	< 10%	Hypoglycemia	Insulin, pro-insulin, C-peptide, 72 h fasting insulin/glucose ratio
Gastrinoma	20%-50%	Gastrin	60%-90%	PUD, GERD, diarrhea	Fasting gastrin (off PPI), secretin stimulation test
Glucagonoma	Rare	Glucagon	50%-80%	Necrolytic migratory erythema, diabetes, venous thrombosis, depression	Glucagon
Somatostatinoma	Rare	Somatostatin	> 70%	Diabetes, hypochlorhydria, cholelithiasis, diarrhea	Somatostatin (not widely available)
VIPoma	Rare	Vasoactive Intestinal Peptide	40%-70%	Watery diarrhea, hypokalemia, achlorhydria	VIP

PUD: Peptic ulcer disease; GERD: Gastroesophageal reflux disease; PPI: Proton pump inhibitor.