Clinical outcomes of small cell neuroendocrine carcinoma and adenocarcinoma of the gallbladder

Table 1 Grading of gastroenteropancreatic neuroendocrine tumors

Grade	GET-NETs
Low (ENETS G1)	< 2 mitoses/10 HPF and < 3% Ki-67 index
Intermediate (ENETS G2)	2-20 mitoses/10 HPF or 3%-20% Ki-67 index
High (ENETS G3)	> 20 mitoses/10 HPF or > 20% Ki-67 index

ENETS: European Neuroendocrine Tumor Society; HPF: High-power fields.

Table 2 Clinicopathologic features

Characteristic	GB-adenocarcinoma(n = 38)	GB-NEC-SCC(n = 4)	P value
Sex			1.000
Male	15	1
female	23	3
Age, yr	67.89 ± 11.15	55.75 ± 10.31	0.029
Age groups, n			0.080
< 65 yr	10	3
≥ 65 yr	28	1
Operation type, n			1.000
Simple cholecystectomy	10	1
Extended cholecystectomy	28	3
Tumor size, cm	2.56 ± 1.75	3.98 ± 3.74	0.788
Tumor size groups, n			0.609
< 2 cm	11	2
≥ 2 cm	21	2
Tumor stage, n			0.410
T2	34	3
T3	4	1
Lymphovascular invasion, n			0.245
-	29	2
+	8	2
Perineural invasion, n			0.107
-	26	1
+	11	3
Lymph node metastasis, n			0.537
-	18	1
+	9	2
Lymph node ratio	0.15 ± 0.29	0.18 ± 0.28	0.485
Recurrence, n			1.000
-	28	3
+	10	1

GB: Gallbladder; GB-NEC-SCC: Small cell neuroendocrine carcinoma of the gallbladder.

Table 3 Clinicopathologic features of patients with small cell neuroendocrine carcinoma of the gallbladder

Characteristic	Patient 1	Patient 2	Patient 3	Patient 4
Sex	Female	Male	Female	Female
Age, yr	49	66	63	45
Tumor size, cm	1.9	1.5	3	9.5
Operation	RC	RC	C	RC1
Combined adenocarcinoma	-	+	-	+
Gross finding	Polypoid	Fungating	Fungating	Mutilobulated
Lymphovascular invasion	+	-	-	+
Perineural invasion	+	+	+	-
Tumor stage	T2	T2	T2	T3
Lymph node metastasis	0/15	1/2	0/0	1/39
Mitosis (/10 HPF)	2	8	20	22
Synaptophysin	+	+	-	-
Chromogranin A	+	+	-	-
CD56	+	+	+	+
P53	+	+	NA	NA
Ki-67	30%	25%	40%	50%

¹This patient underwent hepatopancreaticoduodenectomy and right hemicolectomy. C: Cholecystectomy; HPF: High-power fields; NA: Not available; RC: Radical cholecystectomy.

Table 4 Small cell neuroendocrine carcinoma of the gallbladder of the literature

Ref.	Age(yr)	Sex	Size (cm)	Meta or local inv	Mixed tumor	Survival (mo)	Tumor stage	Chromogranin A	Recurrence (site)	Operation type
Moskal et al[22], 1999	69	F	NA	Regional LN meta, pancreas inv	+	44	T3	NA	+ (abdomen)	Radical
	57	F	NA	Regional LN meta, liver inv	-	31	T3	NA	+ (abdomen, bone)	Radical
	69	M	NA	Regional LN meta	-	21	T2	NA	+ (retroperitoneum)	C
	71	F	NA	Regional LN meta peritoneum meta	+	13	T2	NA	+ (retroperitoneum)	C
	40	M	NA	Regional LN meta	+	189, alive	T2	NA	+ (lung, abdomen)	C
Maitra et al[21], 2001	85	F	4.0	Liver meta	+	13	≥ T2	+	NA	Surg
	77	F	2.8	Pancreas inv, LN meta	+	25	≥ T2	NA	NA	Surg
	43	F	2.0	Liver meta	+	9	≥ T2	+	NA	Surg
	73	F	2.5	LN meta	+	7	≥ T2	+	NA	Surg
	82	M	1.0	Liver meta	+	8	≥ T2	NA	NA	Surg
	77	F	3.0	-	+	10	≥ T2	+	NA	Surg
	73	M	6.3	Liver meta	-	6	≥ T2	NA	NA	Surg
	71	M	NA	-	-	3	T1	NA	NA	Surg
	37	F	8.0	LN meta	-	7	≥ T2	NA	NA	Surg
	68	M	2.0	LN meta	-	14	≥ T2	+	NA	Surg
	67	F	2.8	-	-	NA	≥ T2	+	NA	Surg
	78	M	1.8	LN meta	-	16	≥ T2	NA	NA	Surg
Lane et al[11], 2002	67	M	NA	-	-	11	T1b	+	+ (liver, LN)	C
Iype et al[16], 2008	32	F	2.0	Regional LN meta, liver meta	-	14, alive	T2	+	+ (liver, LN)	Radical
Current study, 2014	49	F	1.9	-	-	37, alive	T2	+	-	Radical
	66	M	1.5	Regional LN meta	+	13, alive	T2	+	-	Radical
	63	F	3.0	-	-	67, died	T2	-	+ (liver)	C
	45	F	9.5	LN inv, colon inv, liver inv	+	50, alive	T3	-	-	Radical

C: Cholecystectomy; F: Female; inv: Invasion; LN: Lymph node; M: Male; meta: Metastasis; NA: Not available; Surg: Extent of surgery not reported.