Pancreato-hepatobiliary neuroendocrine tumors diagnosed through endoscopic ultrasound: Clinical characteristics and factors associated with high-grade lesions

Table 1 Extra-pancreatic lesions included in the detection of neuroendocrine neoplasms with upper gastrointestinal echoendoscope

	Region	Structures biopsied
1	Porta hepatis	Lymph nodal masses along inferior surface of liver
		Solid masses, distinct from liver along inferior surface of liver
2	Peri-gastric	Lymph nodal masses in areas anterior and lateral to stomach
		Solid peri-pancreatic or peri-splenic masses
3	Retroperitoneal	Lymph nodal masses posterior to stomach (excluding the pancreas), behind upper peritoneal cavity
		Para-aortic or para-caval masses
4	Hepatic	Lesions in left lobe of liver
5	Periampullary	Deep periampullary masses (not visible on luminal examination)
6	Mediastinal	Subcarinal, right or left hilar LNs (metastatic from subsequently biopsy proven malignant neuroendocrine PHB primary)

PHB: Pancreato-hepatobiliary; LN: Lymph node.

Table 2 The WHO neuroendocrine neoplasms classification for pancreato-biliary and gastrointestinal tract

Neuroendocrine neoplasm	Classification	Diagnostic criteria
Well-differentiated neuroendocrine tumors (NET)	NET, grade 1	< 2 mitoses/2 mm2 and/or Ki67 < 3%
	NET, grade 2	2-20 mitoses/2 mm2 and/or Ki67 3-20%
	NET, grade 3	> 20 mitoses/2 mm2 and/or Ki67 > 20%
Poorly differentiated neuroendocrine carcinoma (NEC)	Small cell NEC	> 20 mitoses/2 mm2 and/or Ki67 > 20% (often > 70%), and small cell cytomorphology
	Large cell NEC	> 20 mitoses/2 mm2 and/or Ki67 > 20% (often > 70%), and large cell cytomorphology

Table 3 Clinical features of patients with pancreato-hepatobiliary neuroendocrine tumors (n = 36)

		No. of patients	Percentage (%)
Age	< 40 years	9	25.0
	> 40 years	27	75.0
Gender	Males	18	50.0
	Females	18	50.0
PHB regions affected	Pancreas	20	55.6
	Others	16	44.4
Grade of NETs	WHO grade I (Ki 67: < 2%)	19	52.8
	WHO grade II (Ki 67: 2-20%)	5	13.9
	WHO grade III (Ki 67: > 20%)	12	33.3
Histologic type	Large cell	17	47.2
	Small cell	8	22.2
	Mixed	1	2.8
	Undetermined	10	27.8
Functionality	Non-functioning	32	88.9
	Functioning	4	11.1

PHB: Pancreato-hepatobiliary; LN: Lymph node; NET: Neuroendocrine tumor.

Table 4 Frequency of different pancreato-hepatobiliary regions affected by benign and malignant neuroendocrine tumors (n = 36)

PHB region affected		n (%)	Benign NET (n)	NEC (n)	Benign NET (%) (no/total)	NEC (%) (no/total)
Pancreas (n = 20)	Body	9 (45)	7	2	85%; (17/20)	15%; (3/20)
	Tail	5 (25)	5	0
	Head	5 (25)	4	1
	Neck	1 (5)	1	0
Extra-pancreatic PHB-NETs (n = 16)	Porta hepatis mass	8 (50)	2	6	43.7%; (7/16)	56.3%; (9/16)
	Peri-gastric mass	3 (18.7)	3	0
	Liver	1 (6.2)	0	1
	Ampulla	1 (6.2)	1	0
	Retroperitoneal mass	1 (6.2)	1	0
	Mediastinal LN1	2 (12.5)	0	2

¹Mediastinal lymphadenopathy (associated with malignant pancreato-hepatobiliary neuroendocrine cancer, not biopsiable through endoscopic ultrasound for technical reasons and proven later with percutaneous image guided biopsy).

PHB: Pancreato-hepatobiliary; LN: Lymph node; NEC: Neuroendocrine cancer; NET: Neuroendocrine tumor.

Table 5 Clinical factors associated with high grade neuroendocrine cancers

Clinical characteristics		NEC	NET	Odds ratio	Confidence interval	P value
Age	> 40	12	15	1.80	1.285-2.522	0.016
	< 40	0	09
Gender	Male	5	13	1.655	0.408-6.714	0.725
	Female	7	11
Origin of NET	Extra pancreatic	9	7	0.137	0.028-0.663	0.014
	Pancreatic	3	17
Largest lesion diameter	> 20 mm	11	15	0.152	0.017-1.378	0.115
	< 20 mm	1	9
Functionality	Functional	0	4	0.625	0.478-0.817	0.278
	Non-functional	12	20
Histology	Small cell	8	0	7.000	2.825-17.343	< 0.0001
	Non-small cell	4	24

NEC: Neuroendocrine cancer; NET: Neuroendocrine tumor.