Primary non-functional pancreatic paraganglioma: A case report and review of the literature

Abstract

Primary pancreatic paragangliomas are rare. They are mainly non-functional tumours that lack typical clinical manifestations. Definite diagnosis relies on histopathology and immunohistochemistry, and the main treatment is surgery. We report here a case of primary, non-functional, pancreatic paraganglioma in a 49-year-old woman. The tumour was approximately 5.0 × 3.2 ×4.7 cm in size and located in the pancreatic neck and body. We undertook 3D laparoscopic complete resection of the tumour. The patient developed a pancreatic fistula (biochemical leak) post-surgery, but she recovered and was discharged from hospital 11 days after surgery. We describe this case study and briefly summarize previous related reports.

Keywords

Pancreatic paraganglioma pancreatic tumour paraganglioma pancreas

Introduction

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumours and are collectively called pheochromocytoma/paraganglioma (PPGL).¹ Pheochromocytomas are located in adrenal medulla, whereas paragangliomas are formed outside the adrenals, commonly near nerves.¹ All PPGL exhibit a malignant potential.¹ In a population-based setting, standardized incidence rates of PPGL were reported to have increased almost five-fold from 1977 to 2015.² The authors suggested that the increase was due to newly diagnosed patients (>50 years) and incidentally discovered PPGLs of small size (<4 cm). However, it could also be due to improved detection of PPGLs due to an increase in imaging.³ The tumours are slightly more common in women than men with a prevalence of 51–57%, and median age of diagnosis has been estimated to be between 48–55 years.³ Most PPGLs are discovered following signs and symptoms suspected to be related to catecholamine excess (i.e., paroxysmal hypertension and the classic triad of headaches, sweating and palpitations).³ However, only one fifth of patients show the classic triad, and some patients are completely asymptomatic.³

The incidence of PGLs is low and estimated to occur in approximately 2–8 cases/million people, and the tumours can arise in sympathetic and parasympathetic nervous systems.⁴ The parasympathetic PGLs are often located in the head and neck, and are mostly non-functional.^3,4 The sympathetic PGLs are often located in the abdomen, followed by the chest and pelvis.⁵ Abdominal PGLs can produce, store, and secrete catecholamines; and they can produce typical signs and symptoms such as hypertension, palpitations, dizziness, anxiety, blushing, headaches, and sweating.⁶

Pancreatic PGLs are extremely rare and to the best of our knowledge, only 53 cases have been reported worldwide over the past 50 years. We present here a case of primary, non-functional, pancreatic PGL and briefly summarize and discuss related reports.

Case Report

A 49-year-old woman presented with a complaint of intermittent epigastric pain which had lasted for one month. The patient had undergone cholecystectomy for gallstones five years previously and had no history of chronic diseases (e.g., hypertension or diabetes). Her personal and family histories were unremarkable. On abdominal examination the patient had abdominal tenderness in the epigastrium.

Routine blood examination, liver, renal, and coagulation function tests, and tumour marker levels (i.e., alpha-fetoprotein, carbohydrate antigen 15-3, carbohydrate antigen 19-9, carbohydrate antigen 72-4, carbohydrate antigen 125, and carcinoembryonic antigen) were within the normal range. Other parameters (i.e., cortisol; angiotensin II; renal activin A; aldosterone; dopamine; adrenaline; noradrenaline) were judged by an endocrinologist, to be within the normal range.

Abdominal computed tomography (CT) showed a pancreatic body tumour approximately 4.6 × 2.9 cm in size and oval in shape with a slightly low-density shadow and clear boundary. Edge enhancement was obvious in the arterial phase and inward-filling enhancement in the portal vein phase. An ectopic pheochromocytoma and splenic arteriovenous compression were considered (Figure 1).

Figure 1.

Computed tomography (CT) and magnetic resonance image (MRI) of the tumour: (a) From the CT image, the mass (blue arrow) showed obvious inhomogeneous enhancement in the enhanced arterial phase, (b) From the CT image the mass (blue arrow) showed continuous enhancement in the portal vein stage, (c) An oval, cystic, solid mass (blue arrow) with equal T2 signal in wall and septum, with multiple long T2 hyperintense cystic changes was shown on MRI and (d) The diffusion weighted imaging (Dw1) sequence of the mass (blue arrow) showed a strong signal.

To further define the lesion, magnetic resonance cholangiopancreatography (MRCP) was performed. This showed irregularly long T1 and T2 signal shadows behind the pancreatic body. The diffusion weighted imaging (Dw1) sequence showed a strong signal. Enhancement scanning was uneven, the size was estimated to be 4.3 × 2.7 × 3.9 cm and it was considered a benign neoplastic lesion; the main pancreatic duct was not dilated, and the splenic artery and vein were compressed (Figure 1). Following consultation with endocrinologists and imaging physicians, the final diagnosis was non-functional PGL of the pancreas

The patient was prescribed oral phenbenzylamine 10 mg bd for a month to keep her hormones stable and prevent her blood pressure from increasing during intraoperative tumour removal. On re-examination four weeks later, her levels of methoxy epinephrine, methoxy norepinephrine and 3-methoxytyramine were within normal ranges. The patient then underwent 3D laparoscopic complete resection of the pancreatic mass. During the operation, the soft resected mass was located behind the junction of the pancreatic body and neck and was closely related to the pancreas; the size was approximately 5.0 × 3.2 × 4.7 cm and it was adjacent to the left side of the abdominal aorta, in front of the left renal vein, between the splenic artery and vein (with obvious compression), and close to the confluence of the splenic and portal veins (Figure 2). On the third day post-surgery, a pancreatic fistula (biochemical leak) was detected which was treated conservatively. The patient fully recovered and was discharged from hospital 11 days post-surgery.

Figure 2.

Gross examination of the surgical specimen showed the tumour was approximately 5.0 × 3.2 × 4.7 cm in size with a rough texture.

Histological examination post-surgery showed that the tumour cells were separated by capillary nests, forming the classic Zellballen pattern (Figure 3). Immunohistochemistry reports showed SYN (+), CGA (+), CD56 (+), Ki-67 (≤2%), S-100 (−), Sox-10 (+), p53 (−), ERG (−), CD31 (+), CD34 (+), NSE (+), GFAP (+), AE1/3 (−), Cam5.2 (−), GATA3(+). These findings were consistent with the characteristics of PGL Although the patient had no symptoms of hypertension or palpitations, and her blood catecholamine hormones were within normal levels, the postoperative pathological results were consistent with a PGL. Following consultation with endocrinologists and pathologists, the patient was diagnosed as having a non-functional pancreatic PGL. According to the grading system for adrenal PCC and PGL, the total score for this patient was 1, indicating a low-risk grade.⁷ Six months following hospital discharge there was no recurrence or evidence of metastasis.

Figure 3.

Postoperative histological and immunohistochemical examinations of the resected tumour. Typical “Zellballen” cell nests and lymphocytes were observed.

The case study was approved by Ethics Committee of Qinghai Provincial People's Hospital (2021-wjzdx-18) and signed informed consent was obtained from the patient for publishing her anonymised data. The reporting of this study conforms to CARE guidelines.⁸

Discussion

Primary pancreatic PGL is rare and according to our literature review, only 53 cases have been reported worldwide from 1974 to 2021 (Table. 1).^4,9–48 Across the 16 men and 37 women the average age was 52 years (range 19–85 years). Of the 53 cases, 28 cases presented with abdominal pain, low back pain, constipation or dyspepsia, 20 were found on physical examination, and only five cases presented with hypertension, palpitation, headache, or fatigue. Twenty-five cases were located in the pancreatic head (including the uncinate process), one in the pancreatic head, neck and body, one in the pancreatic head and neck, two in the pancreatic neck, twelve in the pancreatic body, two in the pancreatic body and tail, eight in the pancreatic tail, and two in the peripancreatic area. Tumour markers did not show any significant abnormalities (data not shown). Six cases were diagnosed as PGL following examination of fine-needle aspiration (FNA) or frozen section (FS)^20,27,48 Of the 53 cases, eight had been diagnosed as pancreatic PGL before surgery,^{13,20,24,27,47,48} twenty-five had been diagnosed as pancreatic neuroendocrine neoplasm (pNEN),^{4,10–12,15,20,23,29–38,40,41,44–46} and five had been diagnosed as other diseases (i.e., pancreatic cystadenoma,⁹ insulinoma,¹⁴ pancreatic cancer,¹⁶ pancreatic pseudocyst,²⁰ and gastrointestinal stromal tumour (GIST).⁴² Forty-seven cases underwent surgery (15 tumour local resection (TLR),^{9,11,13,15,20,21,25,27,28,38–40,42,47} one case of TLR + splenectomy,³⁰ 10 cases of pancreaticoduodenectomy (PD),^{10,19,20,22,23,29,31,45,46} one case of PD and hepatectomy,²⁴ three cases of pylorus preserving pancreaticoduodenectomy (PPPD),^14,26,34 one case of PPPD + distal pancreatectomy (DP) + left adrenalectomy (L-ADX),³⁷ seven cases of DP,^4,20,41,43 one case of DP + L-ADX,¹⁶ one case of DP + splenectomy,³³ three cases of resection of the pancreas head (RPH),^12,18,44 three cases of central pancreatectomy (CP)^32,35,36 and one case of surgery radiotherapy.¹⁷ Six cases did not specify the surgical procedure. Of the 24 studies that specified follow-up times, the range was 1–60 months; only six tumours were reported as functional,^{13,24,27,43,46} and seven had definite metastases (data not shown).^17,20,24,27

Table 1.

Summary of reported cases of pancreatic paraganglioma from the literature (1974 to 2021).

No.	Reference	Sex	Age y	Signs/symptoms	Imaging features	Location*/size, cm	FNA/FS	Preoperative diagnosis	Treatment	Functional	Follow-up
1	Cope et al. 1974 ⁹	F	72	Physical findings	US: low echo	Head, neck and body; 13 × 11 × 7	FS: benign	PCN	TLR	no	48m
2	Fujino et al. 1998¹⁰	M	61	Abdominal pain	CT: solid mass; MRI: T1 and T2 equal signals	Uncinate process; 2.5 × 4.2 × 1.8	–	pNEN	PD	no	60m
3	Parithivel et al. 2000¹¹	M	85	Physical findings	CT: abundant blood supply; cystic solid	Head; 6.0	FS: NET	pNEN	TLR	no	40m
4	Ohkawara et al. 2005¹²	F	72	Abdominal pain	CT: abundant blood supply; cystic solid	Head; 4.0	–	pNEN	RPH	no	–
5	Perrot et al. 2007¹³	F	41	Weakness; hyperglycaemia	EUS: low echo; CT: abundant blood supply, inhomogeneous density and necrosis; MRI: T1 low signal and T2 high signal	Tail; 4.3 × 3.2 × 2.5	–	p-PGL	TLR	yes	18m
6	Kim et al. 2008¹⁴	F	57	Lumbar discomfort	US: blood flow signal; EUS: low echo; CT: clear boundary, arteriovenous phase enhancement (low attenuation)	Head; 6.5 × 6.0 × 6.0	–	non-functional insulinoma	PPPD	no	–
7	Tsukada et al, 2008¹⁵	F	57	Physical findings	US: low echo; CT: obvious enhancement; MRI：T1 and T2 low signal, obvious enhancement	Uncinate process; 2.5 × 2.0	–	pNEN	TLR	no	–
8	Paik. 2009¹⁶	F	70	Physical findings	CT: inhomogeneous enhancement	Tail; 5.5 × 4.4	–	–	DP + L-ADX	no	12m
9	Sangster et al. 2010¹⁷	M	50	Abdominal pain	CT: abundant blood supply; PET: strong uptake	Uncinate process	FNA: poorly differentiated carcinoma	Pancreatic cancer	Surgery; radiotherapy	no	36m
10	He et al. 2011¹⁸	F	40	Physical findings	CT: clear boundary; solid; obvious enhancement in arteriovenous phase	Head; 4.5 × 4.2	–	–	RPH	no	–
11	Lightfoot et al. 2011¹⁹	M	66	Abdominal pain	CT: cystic solid; PET: mild metabolic elevation	Head and uncinate process; 6.0	–	–	PD	no	–
12	Singhi et al. 2011²⁰	F	52	Abdominal pain	unknown	Body; 14.0	FNA: PGL	p-PGL	–	–	–
13	Singhi et al. 2011²⁰	F	61	Abdominal pain	unknown	Tail; 14.0	FNA: PPC	PPC	DP: 4 cases; PD: 2 cases; TLR: 2 cases	–	–
14	Singhi et al. 2011²⁰	F	54	Abdominal pain	unknown	Head; 6.5	FNA: PGL	p-PGL		–	–
15	Singhi et al. 2011²⁰	M	40	Physical findings	unknown	Body; 5.1	FNA: NET	pNEN		–	–
16	Singhi et al. 2011²⁰	F	78	Abdominal pain	unknown	Body; 17.0	FNA: spindle cell tumour	unknown		–	–
17	Singhi et al. 2011²⁰	M	44	Physical findings	unknown	Head; 5.5	FNA: PGL	p-PGL		–	–
18	Singhi et al. 2011²⁰	M	38	Abdominal pain	unknown	Body; 15.0	FS: PGL	unknown		–	–
19	Singhi et al. 2011²⁰	M	47	Abdominal pain	unknown	Body; 7.5	FS: NET	pNEN		–	–
20	Singhi et al. 2011²⁰	F	37	Abdominal pain	unknown	Tail; 5.7	FS: NET	pNEN		–	–
21	Liu et al. 2011²¹	F	50	Physical findings	US: mixed echo; CT: hybrid density; arteriovenous phase enhancement	Tail; 10.0	–	–	TLR	no	–
22	Higa and Kapur. 2012²²	F	65	Physical findings	CT: hybrid density; arterial phase enhancement gradually attenuated	Uncinate process; 2.0	–	–	PD	no	–
23	Ganc et al. 2012²³	F	37	Physical findings	EUS: low echo	Head; 4.8 × 3.2 × 4.3	FNA: NET	pNEN	PD	no	–
24	Al-Jiffry et al. 2013²⁴	F	19	Abdominal pain	CT: solid; hepatic parenchymal infiltration	Head and neck; 9 × 5 × 9.5	FNA: NET	p-PGL	PD + hepatic segmentectomy	yes	36m
25	Borgohain et al. 2013²⁵	F	55	Abdominal pain	CT: cystic; pancreatic cancer tendency	Tail; 17 × 19	–	–	TLR	no	10m
26	Straka et al. 2014²⁶	F	53	Abdominal discomfort	CT: abundant blood supply	Head; 8.1 × 8.5	–	–	PPPD	no	49m
27	Zhang et al. 2014²⁷	F	50	Hypertension; headache; palpitations; sweating	CT: solid; abundant blood supply; liver metastasis	Head; 6.0	FNA: PGL	p-PGL	–	yes	death 4 years later
28	Zhang et al. 2014²⁷	M	63	Hypertension	CT: solid; abundant blood supply; 123I-MIBG: abnormal uptake	Head; 4.0	–	–	TLR	yes	3m
29	Meng et al. 2015²⁸	F	54	Abdominal pain	US: low echo; abundant blood flow signals; CT: unclear boundary; equal density; inhomogeneous enhancement in arterial phase; homogeneous enhancement in venous phase	Head; 3 × 2.5	–	–	TLR	no	–
30	Meng et al. 2015²⁸	F	41	Physical findings	US: clear boundary; low echo; partial blood flow signal; CT: inhomogeneous density; arterial phase enhancement	Head; 6 × 5	–	–	–	no	–
31	Misumi et al. 2015²⁹	F	47	Physical findings	US and EUS: low-density inhomogeneous echo; blood flow signal; CT: arteriovenous phase enhancement (low attenuation); MRI: T1 low signal and T2 high signal	Head; 1.5 × 1.2	–	pNEN	PD	no	12m
32	Ünver et al. 2015³⁰	F	41	Loss of appetite; tired; weakness	USG: pancreatic tail and splenic hilum mass; MRI: mass invading splenic hilum	Tail; 8 × 7 × 8	–	–	TLR + splenectomy	no	6m
33	Liang and Xu. 2016³¹	M	41	Physical findings	CT: arteriovenous phase enhancement (low attenuation); MRI: T1 low signal; T2 slightly high signal; inhomogeneous enhancement	Uncinate process; 4 × 6	FNA: unidentified	pNEN	PD	no	1m
34	Lin et al. 2016³²	F	42	Abdominal pain	CT: solid low density; arterial phase enhancement	Body; 5.2 × 6.3	–	pNEN	CP	no	12m
35	Tumuluru et al. 2016³³	F	62	Physical findings	EUS: solid hypoechoic	Body; 2.8 × 2.8 × 2.7	FNA: chronic pancreatitis	pNEN	DP + splenectomy	no	18m
36	Ginesu et al. 2016³⁴	M	55	Lumbago	US: solid; CT: arterial phase enhancement (low attenuation)	Uncinate process; 1.3	–	pNEN	PPPD	no	24m
37	Lin et al. 2016³⁵	F	42	Abdominal pain	CT: solid; clear boundary; arterial phase obvious enhancement; delay phase equal density	Body; 5.2 × 6.3	–	pNEN	CP	no	15m
38	Furcea et al. 2017³⁶	F	53	Dyspepsia	US: inhomogeneous low echo; CEUS: arterial phase enhancement	Neck; 3.5 × 2.5 × 2.5	–	pNEN	CP	no	–
39	Nonaka et al. 2018³⁷	F	68	Physical findings	EUS: low echo; CT: arterial phase enhancement; venous inhomogeneous enhancement; PET: high intake; malignant possibility	Body; 2.2× 2.2 × 1.0	FNA: insufficient material	pNEN	PPPD + DP + L-ADX	no	12m
40	Zeng et al. 2017³⁸	F	58	Abdominal pain	EUS: low echo; clear boundary; MRI: inhomogeneous signal	Body; 6.5 × 6.1 × 4.4	FNA: NET	pNEN	TLR	no	–
41	Zeng et al. 2017³⁸	F	53	Abdominal pain	CT: soft tissue mass	Head; 2.5 × 1.7 × 1.8	FNA: NET	pNEN	TLR	no	–
42	Nguyen et al. 2018³⁹	F	70	Constipation; early satiety	EUS: low echo; CT: cystic solid	Tail; 3.6 × 5 × 4.5	FNA: NET？	–	TLR	no	–
43	Fite & Maleki. 2018⁴⁰	M	40	Lumbago; haematuria	Image: abundant blood supply with necrosis	Peripancreatic; 5.1	FNA: NET	pNEN	–	no	–
44	Fite & Maleki. 2018⁴⁰	F	23	Palpitations	Image: heterogeneous mass	Peripancreatic; 7.0	FNA: NET	pNEN	–	no	–
45	Liu et al. 2018⁴¹	F	73	Physical findings	Isodensity, central with calcification; arterial phase enhancement; portal vein phase isodensity	Body; 1.2 × 1.4	–	pNEN	DP	no	6m
46	Chattoraj et al. 2019⁴²	F	36	Abdominal pain	CT: no enhancement	Body and tail; 7 × 4	–	GIST	TLR	no	–
47	Zongo et al. 2019⁴³	M	52	Abdominal pain	CT: inhomogeneous density	Body and tail; 8.6 × 8.3	–	–	DP	yes	17m
48	Wang et al. 2019⁴⁴	M	59	Physical findings	MRI: long T1 long T2 signal; DWI high signal; inhomogeneous enhancement	Head; 2.7 × 2.5 × 2.4	–	pNEN	RPH	no	–
49	Xu et al. 2019⁴⁵	M	50	Abdominal pain	CT: abundant blood supply	Head; 17.0	–	pNEN	PD	no	3m
50	Abbasi et al. 2020⁴⁶	F	61	Physical findings	MRI: T2 hyperintense; arterial phase enhancement	Head and uncinate process; 7.2 × 6.5	FNA: NET	pNEN	PD	yes	12m
51	Jiang et al. 2021⁴	M	41	Physical findings	EUS: low echo; CT: solid; inhomogeneous	Body; 4.1 × 4.2	FNA: malignant possibility; FS: pNEN	pNEN	DP	no	12m
52	Wang et al. 2021⁴⁷	F	75	Abdominal pain	CT: abundant blood supply; arterial phase enhancement; MRI: T1WI low or equal signal; T2WI high signal; obvious enhancement	Neck; 3.1 × 3.8	–	p-PGL; Castleman; pNEN	TLR	no	–
53	Lanke et al. 2021⁴⁸	F	73	Physical findings	EUS: low echo	Head; 2.0 × 1.1	FNA: PGL	p-PGL	–	no	12m

*Location in the pancreas; – not available or unknown.

Abbreviations: 123I-MIBG: metaiodobenzylguanidine; CT: computed tomography; CEUS: contrast-enhanced ultrasound; CP: central pancreatectomy; DP: distal pancreatectomy; DWI, diffusion weighted imaging; EUS: endoscopic ultrasound; F: female; FNA: fine needle aspiration; FS: frozen section; GIST: gastrointestinal stromal tumour; L-ADX: left adrenalectomy; M: male; MRI: magnetic resonance image; NET: neuroendocrine tumour; PCN: pancreatic cystadenoma; PD: pancreaticoduodenectomy; PET: positron emission tomography; pNEN: pancreatic neuroendocrine neoplasm; PPC: pancreatic pseudocyst; p-PGL: paraganglioma of pancreas; PPPD: pylorus preserving pancreaticoduodenectomy; RPH: resection of the pancreas head; TLR: tumour local resection; US: ultrasound; USG: ultrasonogram diagnosis.

Our present case report of a typical, primary, non-functional PGL is consistent with previous findings in that the patient was female and over 40 years of age.²⁷ In addition, our patient sought medical treatment because of the common PGL symptom of abdominal pain. Although tumour markers were within the normal range and we did not perform an FNA, we made a correct diagnosis before the operation based on typical imaging features and the differential diagnosis for similar diseases. During surgery, we located the tumour behind the pancreatic neck, between the splenic artery and vein, and close to the pancreatic parenchyma. We carefully removed the tumour which was both cystic and solid and approximately 4.5 × 4.7 × 5.1 cm in size. The patient developed a pancreatic fistula (biochemical leak) post-surgery suggesting that the pancreas had been damaged during the procedure. However, she fully recovered following conservative treatment and was discharged from hospital 11 days post-surgery. Pathology and immunohistochemical analysis post-surgery confirmed the diagnosis.

Due to the rarity of the condition, and the fact that most pancreatic PGLs are non-functional and lack typical clinical manifestations, the misdiagnosis rate can be high. Therefore, to improve the understanding of PGL, we have summarized its clinical features and compared them to those of other rare pancreatic tumours (i.e., PPGL, pNEN, serous cystadenoma [SCN], mucinous cystadenomas [MCN], and intraductal papillary mucinous tumour [(IPMN]) (Table 2).^49–51 Currently, there is no clear consensus regarding treatment of PGL. However, surgery is the principal treatment modality, supplemented by chemotherapy and radiotherapy for patients with malignant tendencies, but, as demonstrated by our present case study, the choice of surgical procedure should be determined according to the close relationship between the tumour and the pancreatic parenchyma and vessels. Definitive diagnosis of this rare pancreatic tumour depends on postoperative histopathological and immunohistochemical examinations.

Table 2.

Summary of the characteristics of several rare pancreatic tumours.^49–51

DiseaseFeature	PPGL	p-PGL	pNEN	SCN	MCN	IPMN
Sex ratio, (male: female)	1: 1	1: 2	1: 1	3: 7	1: 10	1: 1
Age, y	30–50	40–70	40–70	60–70	40–50	60–70
Predilection site	Adrenal gland and adrenal sympathetic crest	Pancreatic head	No preference	Head, body and tail of pancreas	Body and tail of pancreas	Head and uncinate process of pancreas
Clinical signs and symptoms	Hypertension; cephalalgia; palpitations; hyperhidrosis; postural hypotension	Abdominal pain/ asymptomatic (non-functional); hypertension, palpitations and fatigue (functional)	Mostly asymptomatic; 66% non-functional; 33% functional; mainly insulinoma	Mostly asymptomatic; nonspecific nausea due to mass occupying effect	Mostly asymptomatic; abdominal pain (large mass)	Mostly asymptomatic; acute pancreatitis; more prone to clinical symptoms (malignant transformation)
Tumour markers	CgA↑;NSE↑ (possible)	CgA↑ (possible）	CgA↑; NSE↑; FAP, CEA, CA125 and CA19-9↑	CA19-9↑; CEA↑; (malignant tumour)	CA19-9↑; CEA↑ (malignant tumour)	CA19-9↑; CEA↑ (malignant tumour)
US features	Clear boundary; round or quasi round; high, low, equal echo; blood flow signal (solid part)	Low or inhomogeneous echo, with blood flow signal	Smooth edges; heterogeneous, with cystic degeneration or necrosis (large mass)	High echo; lobulate; clear boundary	Clear boundary; multilocular cystic, surrounded by walls	Echo (mucin rich); low echo (BD-IPMN); difficult to distinguish from pancreatic tissue
CT features	Round or quasi round; inhomogeneous density; mostly necrosis, bleeding and calcification; enhanced by contrast agent	Clear boundary; Abundant blood supply; enhancement (arterial phase) and slightly reduced (venous phase)	Large and inhomogeneous density (non-functional); small and uniform density (functional); obvious enhancement	Clear boundary; marginal lobulated; central fibrous scar; stellate calcification; vesicles (number ≥6, size ≤2 cm); septum and capsule wall enhanced (portal vein stage); fibrous scar enhanced (delayed period)	Multilocular large vesicles (number < 6, size > 2 cm); single room (minority)	Diffuse or staged expansion of main pancreatic duct (MD-IPMN); cystic lesions communicating with pancreatic duct and “grape cluster” appearance (BD-IPMN)
MRI features	T1 low signal; T2 high signal	T1 low signal; T2 high signal	T1 low signal; T2 high signal	T1 low signal; T2 high signal; scattered high signal cysts	T1 slightly high or low signal; T2 high signal	T1 low or high signa; T2 high signal; mural nodule enhancement
Pathology	“Zellballen” solid small cell nest with beam cord structure; round, oval or spindle shaped tumour cell surrounded by supporting cells and vascular spaces; rich cytoplasm	“Zellballen” solid small cell nest with beam cord structure; round, oval or spindle shaped tumour cell surrounded by supporting cells and vascular spaces; rich cytoplasm	Nuclei of uniform size; transparent cytoplasm with granules; NSE (+); CGA (+)	Composed of monolayer cubic epithelial cells or flat epithelial cells; rich glycogen	Cyst wall containing ovarian like stroma	Viscous mucin and pancreatic duct dilation (MD-IPMA); single cyst or multiple grape clusters communicating cyst, containing liquid, albumin and tumour cells (BD-IPMN)
Malignant risk	Metastatic rate: 10–17%.	Metastatic rate: 13%	(Malignant rate); insulinoma 5–10%; gastrinoma 50–60%; glucagon tumour 50–80%; somatostatin tumour 50–60%; neuroendocrine tumours producing ACTH >90%; vasoactive intestinal peptidoma 40–80%; non-functional tumour 60–90%	Benign and grow slowly	Potential malignancy; 5-year survival rate: 38%	Malignant rate: 57–92%; 5-year survival rate: 80%; (MD-IPMA) malignant rate: 6–46% (BD-IPMN, <3 cm)

Abbreviations: BD-IPMN: Branch duct intraductal papillary mucinous tumour; CEA, carcinoembryonic antigen; CgA: Chromogranin A; CT: computed tomography; FAP, Fibroblast-activation protein; IPMN: intraductal papillary mucinous tumour; MCN: mucinous cystadenomas; MD-IPMN: Main duct intraductal papillary mucinous tumour; MRI: magnetic resonance image; NSE: neuron specific enolase; pNEN: pancreatic neuroendocrine neoplasm; p-PGL: paraganglioma of pancreas; PPGL: pheochromocytoma and paraganglioma; SCN: serous cystadenoma.

In summary, pancreatic PGL is a rare entity and so preoperative diagnosis is challenging. The tumour tends to be non-functional and found either incidentally on imaging, or in a patient with abdominal pain. The main treatment is surgical resection and postoperative histopathological and immunohistochemical diagnosis is essential. This present case highlights the importance of a multidisciplinary team approach in the diagnosis of PGL involving radiologists, endocrinologists, pathologists, oncologists, and surgeons.

Footnotes

Acknowledgements

The authors are grateful to the Health Commission of Qinghai Province for their assistance. We would also like to thank Editage () for help with English language editing.

Declaration of conflicting interests

The authors declare that there are no conflicts of interest.

Funding

The authors disclose receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Health Commission of Qinghai Province (2021-wjzdx-18).

ORCID iD

Zhanxue Zhao

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