Pancreatic primitive neuroectodermal tumors: Clinical features, treatment, and influencing factors

Table 1 Overview of reported cases of pancreatic primitive neuroectodermal tumor

Ref.	Age in years	Sex	Site	Size in cm	Symptoms at diagnosis	Treatment	Chemotherapy regimens	Surgical margin	Local metastasis	Regional lymph node metastasis	Distant metastasis	Follow up in months	Cytogenetics and molecular diagnostics			Pathologic features	Necrosis	Recurrence	Site of recurrence	Outcomes
													Chromosomal translocation	Karyotype analysis method	Gene fusion transcript
Mao et al[6], 2013	13	F	Pancreatic head	3.5 × 2.5 × 1	Abdominal pain, T2DM	Resection of the uncinate process of pancreas, radiotherapy, chemotherapy	VAC	(-)	(+)	(-)	(-)	41	t (11; 22) (q24; q12)	NR	NR	CD99, NSE, small round cells	Yes	(+)	Liver, kidney, colon	Died of disease after 41 months
Jayant et al[11], 2013	20	F	Pancreatic body and tail	11 × 9	Abdominal pain	Distal pancreatectomy, splenectomy, radiotherapy, chemotherapy	VAC	(-)	(-)	(-)	(-)	24	NR	NR	NR	CD99, NSE, small round cells	Yes	(+)	Bone, liver, lungs	Died of disease after 24 months
Shi et al[12], 2013	19	M	Pancreas	3.0 × 4.0	Abdominal pain	Whipple resection	No chemotherapy	(-)	(-)	(-)	(-)	48	NR	NR	NR	CD99, NSE, vimentin, small round cells	Nr	(+)	Pancreas	No evidence of disease after 48 months
Changal et al[13], 2014	60	NA	Pancreatic head	4 × 3.7 × 2.5	Abdominal pain	No surgical resection	VIDE	(+)	(+)	(+)	(-)	3	t (11; 22) (q24; q12)	FISH	EWS-FLI1	CD99, NSE, small round cells	Yes	NR	NR	Alive with disease
Nishizawa et al[14], 2015	22	M	Pancreatic head	8.5 × 5.2 × 6.2	Abdominal pain	Whipple resection	No chemotherapy	NA	(+)	(+)	(-)	2	t (11; 22) (q24; q12)	FISH	NR	CD99, vimentin, small round cells	Nr	NR	NR	Alive with disease
Amaro et al[15], 2015	8	F	Pancreatic head	4.5 × 4.0	Abdominal pain, jaundice	Cholecystojejunal anastomosis	NA	NA	NA	NA	NA	NA	NA	NA	NA	CD99, vimentin, small round cells	Yes	NR	NR	NA
Teixeira et al[16], 2015	28	F	Pancreatic head and body	12.8 × 12.1 × 10.9	Abdominal pain, jaundice	Gastroduodenopancreatectomy	No chemotherapy	(-)	(-)	(-)	(-)	36	NR	NR	NR	CD99, vimentin, small round cells	Yes	(-)	(-)	No evidence of disease after 36 months
Liu et al[17], 2018	36	M	Pancreatic head	6.3 × 3.6 × 4.8	Abdominal pain, jaundice	RouxenY choledochojejunostomy	No chemotherapy	(+)	(+)	(+)	NA	2	NR	NR	NR	CD99, vimentin, Ki-67, S-100, small round cells	Nr	(+)	Liver	Died of disease after 2 months
Achufusi et al[18], 2020	61	M	Pancreatic head	NA	Abdominal pain, weight loss	cholecystectomy, gastrectomy, Roux-en-Y gastrojejunostomy	No chemotherapy	(+)	(+)	(+)	(+)	0.33	NR	NR	NR	NA	Nr	(+)	Liver	Died 10 days after discharge
Bülchmann et al[19], 2000	6	F	Pancreatic head	6 × 5 × 5	Paleness, dizziness, tiredness	Modified Whipple-Operation	No chemotherapy	(-)	(+)	(+)	(-)	6	t (11; 22) (q24; q12)	FISH	EWSR1	CD99, small round cells	Nr	(+)	NA	Died of disease after 6 months
Saif et al[20], 2017	38	F	Pancreatic body and tail	8 × 10	Abdominal pain	Distal pancreatectomy, splenectomy, chemotherapy	IE, VAC	NA	NA	(-)	(-)	6	t (11; 22) (q24; q12)	FISH	NR	CD99, small round cells	Yes	(-)	(-)	No evidence of disease after 6 months
Patil et al[21], 2021	51	F	Pancreatic tail	6.2 × 5.5 × 4	Asymptomatic	Distal pancreatectomy, splenectomy, chemotherapy	IE, VAC	(+)	(-)	(-)	(-)	2	NR	NR	NR	CD99, small round cells, FLI-1	Nr	(-)	(-)	No evidence of disease after 2 months
Schutte and Knight[22], 2006	2	F	Pancreatic body	6 × 4	Precocious puberty	Distal pancreatectomy, splenectomy, chemotherapy	VAC, cisplatinum and VP-16	NA	(-)	(-)	(-)	12	NR	NR	NR	CD99, vimentin, S-100	Nr	(-)	(-)	No evidence of disease after 12 months
Maxwell et al[23], 2011	11	M	Pancreatic head	9.8 × 7.8 × 6.4	Abdominal pain, fatigue	Whipple resection, chemotherapy	IE, VAC	NA	(+)	(+)	(-)	7	t (21; 22) (q22; q12)	RT-PCR	EWS-ERG	CD99, vimentin	Nr	(-)	(-)	NA
O'Sullivan et al[24], 2001	20	M	Pancreatic head	3.5	NA	Whipple resection, chemotherapy	NA	(-)	(+)	(+)	(+)	30	t (11; 22) (q24; q12)	RT-PCR	EWS-FLI1	CD99, vimentin, small round cells	Nr	(+)	Lung	Alive with disease
Movahedi-Lankarani et al[25], 2002	17	M	Pancreas	9	Abdominal pain, jaundice	Whipple resection, chemotherapy	VAC	(-)	NA	NA	NA	33	t (11; 22) (q24; q12)	FISH	NR	CD99, NSE, small round cells	Yes	NR	NR	No evidence of disease after 33 months
	20	M	Pancreas	3.6	Abdominal pain, jaundice	Whipple resection	NA	(-)	NA	NA	NA	27	t (11; 22) (q24; q12)	FISH	NR	CD99, NSE, small round cells	Yes	NR	NR	Alive with disease
	25	F	Pancreas	NA	Abdominal pain	Biopsy	NA	NA	NA	NA	NA	NA	NA	NA	NR	CD99, small round cells	Nr	NR	NR	NA
	21	F	Pancreatic head	NA	Abdominal pain	Whipple resection	NA	(-)	(+)	NA	NA	NA	t (11; 22) (q24; q12)	RT-PCR	EWS-FLI1	CD99, NSE, small round cells	Nr	NR	NR	Died of disease
	25	F	Pancreas	8	Abdominal pain, jaundice	Biopsy	NA	NA	NA	NA	NA	NA	(-)	RT-PCR	NR	CD99, NSE, small round cells	Nr	NR	NR	NA
	13	M	Pancreas	6	Abdominal pain	Biopsy, chemotherapy	VAC	NA	NA	NA	NA	43	NA	NA	NR	CD99, NSE, small round cells	Nr	NR	NR	No evidence of disease after 43 months
	6	M	Pancreas	3.5	Abdominal pain, jaundice	Whipple resection, chemotherapy	VAC	(-)	(+)	NA	NA	48	t (11; 22) (q24; q12)	RT-PCR	EWS-FLI1	CD99, NSE, small round cells	Nr	NR	NR	Died of disease
Perek et al[26], 2003	31	M	Pancreatic head and body	10 × 12	Fever of unknown etiology	Whipple resection, chemotherapy	Doxorubicin and ifosfamide	(-)	(-)	(-)	(+)	50	NR	NR	NR	CD99, vimentin, small round cells	Yes	(+)	Pancreas, lung, bone	Died of disease after 50 months
Welsch et al[27], 2006	33	M	Pancreatic body and tail	18 × 18 × 16	Abdominal pain	Whipple resection, Billroth II, chemotherapy	VIDE, VAI	NA	NA	(+)	(+)	12	t (21; 22) (q22; q12)	FISH	EWS-ERG	CD99	Yes	(+)	Liver	No evidence of disease after 12 months
Sang et al[7], 2006	13	F	Pancreatic head	9 × 11 × 17	Abdominal pain, loss of appetite	Resection of pancreatic leptomeningeal tumor, radiotherapy, chemotherapy	VAC	(-)	(-)	(-)	(-)	6	t (11; 22) (q24; q12)	RT-PCR	EWS-FLI1	CD99, NSE, small round cells	Yes	(-)	(-)	No evidence of disease after 6 months
Wu et al[28], 2006	19	F	Pancreas	10 × 8 × 7	Abdominal pain	Pancreatic tumor resection, chemotherapy	NA	(-)	(-)	(-)	(-)	10	NR	NR	NR	CD99, NSE, small round cells	Yes	(+)	NA	Died of disease after 10 months
Menon et al[29], 2009	8	F	Pancreas	10 × 6 × 10	Abdominal pain, Precocious puberty	Biopsy, radiotherapy, chemotherapy	NA	NA	(-)	(-)	(-)	19	NA	NA	NA	CD99	Nr	(-)	(-)	Died of disease after 19 months
Pappo et al[30], 1989	13	M	Pancreatic body and tail	NA	Anemia, headache	Bone marrow aspiration, chemotherapy	Vincristine, cytoxan, and prednisone	(+)	(+)	(+)	(+)	3.5	t (2: 13) , iso-17	Genomic DNA analysis	NA	NSE, vimentin, S-100	Nr	(+)	Bones, liver, spleen, pancreas, lungs, heart	Died of disease after 3.5 months
Doi et al[31], 2009	37	M	Pancreas	4.2	Jaundice	Whipple resection, hepatic resection, radiotherapy, chemotherapy	VAC, IE	NA	(+)	(+)	(+)	12	t (21; 22) (q22; q12)	FISH	EWS-R1	CD99, NSE, vimentin, small round cells	Nr	(+)	Liver, lungs	No evidence of disease after 12 months
Jing et al[32], 2011	24	F	Pancreatic head	10 × 10 × 8	Asymptomatic	Resection of pancreatic leptomeningeal tumor, radiotherapy, chemotherapy	NA	NA	(+)	NA	(-)	18	NR	NR	NR	NR	Yes	(+)	Pancreas	No evidence of disease after 18 months

CD99: Cluster of differentiation 99; EWS-FLI1: Ewing’s sarcoma and friend leukemia integration 1 transcription factor gene fusion; EWSR1: Ewing’s sarcoma breakpoint region 1; F: Female; FISH: Fluorescence in situ hybridization; IE: Ifosfamide and etoposide; M: Male; NA: Not available; NR: Not reported; NSE: Neuron-specific enolase; RT-PCR: Reverse transcription-polymerase chain reaction; T2DM: Type 2 diabetes mellitus; VAC: Vincristine, adriamycin, and cyclophosphamide; VAI: Vincristin, actinomycin D, and ifosfamide; VIDE: Vincristine, ifosfamide, doxorubicin, and etoposide.

Table 2 Analyses of overall survival

Variable	3-year survival, n	Univariate P value	Cox P value	RR	95%CI
Sex		0.573
Men	2
Women	3
Age in years		0.723
< 24	3
≥ 24	3
Size		0.795
< 8	4
≥ 8	3
Surgical resection		0.100
Yes	4
No	3
Chemotherapy		0.036
Yes	4
No	1
Local metastasis		0.041
Yes	1
No	2
Lymph node metastasis		0.003	0.012	3.74	2.536-17.198
Yes	0
No	3
Distant metastasis		0.049
Yes	0
No	1
Microscopic margin		0.048
Positive	0
Negative	1
Recurrence		0.088
Yes	2
No	3

CI: Confidence interval; RR: Relative risk.