Mixed serous-neuroendocrine neoplasm of the pancreas: A case report and review of the literature

Table 1 Time line

Time line
2019.03-2019.04	Collecting the data and follow-up
2019.04-2019.05	Reading the literature
2019.05-2019.06	Writing
2019.06-2019.07	Revising and plotting
2019.08-	Submitting

Table 2 Clinicopathological characteristics of mixed serous-neuroendocrine neoplasms

Ref.	Sex/age	Symptoms	Other conditions	PSCN		PanNET					Distribution pattern of PSCN and PanNET	Family history	VHL	Follow-up (mo)
				Location/ size(cm)	Pathologic diagnosis	Location/ size (cm)	Pathologic diagnosis	Invasion/metastasis	IHC hormone expression	Clinical function
Diffuse PSCN
Kim et al[3]	F/67	Melena	Diabetes mellitus	EP/16	SMA	Head/2.8	NET/NA	DWI and LYI	No	No	DT/NET separated from SMA	NA	NA	NA
Baek et al[4]	F/29	Abdominal distension and vomiting	NA	EP/30	SCN	Head/NA	NET/NA	PNI and LYI	Insulin	NA	DT/NET within SCN	No	Yes	NA
Jung et al[5]	F/29	Nausea, vomiting, and weight loss	No	EP/NA	SMA and SOA	Head/2	NET/NA	PNI and LYI	Insulin	NA	DT/NET within SCN	No	No	NA
Blandamura et al[6]	F/31	Jaundice	Renal clear cell carcinoma, cerebellar hemangioblastoma, and multiple liver angiomas	EP/NA	SMA	Head/4	NET/G2	DWI and VI	Glucagon and VIP	NA	DT/NET collision with SMA	NA	Yes	NA
Agarwal et al[7]	F/35	Abdominal pain, anorexia, and postprandial fullness	Small cysts in both kidneys and syringohydromyelia in the lower thoracic cord	EP/16	SMA and SOA	Head/<0.5	NET/NA	LNM	NA	NA	DT/NET collision with SCN	No	Suspected	3
Hsieh et al[8]	F/28	No	Cerebellar hemangioblastoma	EP/NA	SOA	Uncinate process/2.8	NET/NA	LYI, PSI, and PNI	NA	NA	DT/NET collision with SOA	No	Yes	8
Tewari et al[9]	F/25	Abdominal pain	No	EP/NA	SOA	NA/NA	NET/NA	PNI	NA	NA	DT/NA	NA	No	24
Maeda et al[10]	F/39	No	Cerebellar and retinal hemangioblastomas	EP/NA	SMA and SOA	Tail/3	NET/G1	N	NA	NA	DT/NET within SCN	No	Yes	8
Our case	F/45	No	Multiple renal cysts in both kidneys	EP/16	SMA	Head/3.5	NET/G	PSI and PNI	No	NA	DT/NET separated from SMA	No	Suspected	30
Multiple PSCN
Kamei et al[13]	F/72	Jaundice and abdominal distension	No	Six tumors involving head and body/0.5-10	SMA	Tail/1.5	NET/NA	No	NA	NA	ST/NET separated from SMA	No	No	NA
Kakkar et al[14]	M/38	Abdominal pain and jaundice.	Bilateral adrenal pheochromocytomas, paravertebral paraganglioma, and lymph node tuberculosis	Multiple tumors involving head and body/NA	SMA	Head/5	NET/G2	DWI	No	NA	CT/NET collision with SMA	No	Yes	10/dead of acute adrenal crisis
Isolated PSCN
Keel et al[15]	F/47	Abdominal pain and jaundice	Lupus	Head/7.5	SMA	Head/1.5	NET/NA	NA	No	No	MT/NET within SMA	NA	NA	NA
Ustün et al[16]	F/49	Abdominal pain, nausea, and vomiting	Diabetes mellitus	Head and body/13	SMA	Head/NA	NET/NA	No	Glucagon and insulin	NA	MT/NET within SMA	NA	No	12
Slukvin et al[17]	M/53	No	No	Head/4	SMA	Head/1.2	NET/NA	No	Somatostatin	NA	MT/NET within SMA	No	No	NA
Alasio et al[18]	F/78	Abdominal pain and peptic ulcer	Hypertension, stable exertional angina, and chronic obstructive pulmonary disease	Body and tail/14	SMA	Body/5	NET/NA	No	NA	NA	MT/NET within SMA	NA	No	NA
Goh et al[19]	M/52	No	Hepatitis B carrier	Head/1.5	SMA	Tail/0.3	NET/NA	No	Glucagon	No	ST/NET separated from SMA	No	No	24
Mohan et al[20]	F/52	Abdominal pain, nausea, and vomiting	Diabetes mellitus.	Body/10	SMA	Body/NA	NET/NA	NA	NA	NA	MT/NET within SMA	NA	No	2
Blandamura et al[6]	F/71	No	Uterine leiomyomastosis and renal oncocytoma	Body/2.5	SOA	Body/1.1	NET/ G1	No	Glucagon	NA	ST/NET separated from SOA	NA	No	NA
Blandamura et al[6]	F/57	No	Left adnexal adenoma, gallbladder microlithiasis, and diabetes mellitus	Body/2.3	SOA	Body/0.5	NET/G1	No	Insulin	NA	ST/NET separated from SOA	NA	No	NA
Hsieh et al[8]	F/64	Abdominal pain	Diabetes mellitus and asthma	Body/1.3	SMA	Body/0.6	NET/NA	No	NA	NA	ST/NET separated from SMA	NA	No	14
Borka et al[21]	F/69	WDHA syndrome	Parathyroid adenoma	Tail/NA	SCN	Tail/NA	NET/G1	NA	VIP	VIPoma	MT/NET within SCN	NA	No	36
Li et al[22]	F/73	No	Hypertension	Tail/2.5	SOA	Tail/1.2	NET/G1	PNI and PSI	NA	NA	CT/NET collision with SOA	NA	No	54
NA
Reid et al[12]	12 cases	NA	NA	NA	NA	NA	NET/NA	NA	NA	NA	NA	No	No	NA

CT: Collision type; DT: Diffuse type; DWI: Duodenal wall invasion; EP: Entire pancreas; F: Female; LNM: Lymph node metastasis; LYI: Lymphatic invasion; MSNN: Mixed serous-neuroendocrine neoplasm; M: Male; MT: Mixed type; NA: Not available; NET: Neuroendocrine tumor; PNI: Perineural invasion; PSI: Pancreatic surrounding soft tissue invasion; ST: Solitary type; SMA: Serous microcystic cystadenoma; SOA: Serous oligocystic cystadenoma; SCN: Serous cystic neoplasm; VIP: Vasoactive intestinal polypeptide; VI: Venous invasion; WDHA: Watery diarrhea-hypokalemia-achlorhydria syndrome.

Table 3 Clinicopathological characteristics between Von Hippel-Lindau-associated and non-Von-Hippel-Lindau-associated mixed serous-neuroendocrine neoplasms

Characteristic	VHL	Non-VHL	P
Case number	5	17
Sex (female:male)	4:1	15:2	0.637
Age	33 (28-39)	55 (25-78)	<0.001
DT PSCN	4/5 (80%)	5/17 (29%)	0.043
PanNET size (cm)	3.7 (2.8-5)	1.7 (0.3-5)	0.016
Invasion	4/5 (80%)	6/17 (35%)	0.078
IHC hormone expression	2/5 (40%)	7/17 (41%)	0.962
Other tumors	4/5 (80%)	3/17 (18%)	0.009

DT: Diffuse type; IHC: Immunohistochemical staining; MSNN: Mixed serous-neuroendocrine neoplasm; PSCN: Pancreatic serous cystic neoplasm; PanNET: Pancreatic neuroendocrine tumor; VHL: Von Hippel-Lindau syndrome.