Surgical resection for simultaneous intraductal papillary mucinous neoplasm of the bile duct and pancreatic duct: A case report

Abstract

BACKGROUND

Intraductal papillary mucinous neoplasm (IPMN) and intraductal papillary neoplasm of the bile duct (IPNB) are mucinous cystic tumors with intraductal papillary growth and malignant potential. Their concurrent occurrence is exceptionally rare.

CASE SUMMARY

A 58-year-old Chinese man presented with recurrent upper abdominal pain. Imaging and laboratory tests revealed lesions consistent with IPNB and IPMN. Postoperative pathological examination confirmed IPNB with high-grade dysplasia and main-duct type IPMN with low-grade dysplasia. The patient underwent extrahepatic bile duct resection with Roux-en-Y choledochoenterostomy and distal pancreatectomy. He had an excellent prognosis with no tumor recurrence during the 30-month follow-up.

CONCLUSION

This case emphasizes the importance of comprehensive preoperative assessment and individualized management for these complex tumors. Further research is needed to understand their pathogenesis and improve treatment strategies.

Key Words: Intraductal papillary neoplasm of the bile duct; Intraductal papillary mucinous neoplasm of the pancreas; Simultaneous; Surgery; Dysplasia; Case report

Core Tip: This case highlights the rare coexistence of intraductal papillary mucinous neoplasm (IPMN) and intraductal papillary neoplasm of the bile duct (IPNB) in a 58-year-old Chinese man presenting with abdominal pain. The patient underwent successful surgical resection and had an excellent prognosis with no recurrence during the 30-month follow-up. This case emphasizes the importance of comprehensive preoperative assessment using multiple imaging modalities and individualized management for complex tumors such as IPNB and IPMN.

INTRODUCTION

Intraductal papillary mucinous neoplasm (IPMN) is a mucinous cystic tumor that develops from pancreatic ductal cells. It is characterized by intraductal papillary growth and copious mucin secretion, which often results in pancreatic duct dilatation[1]. Intraductal papillary neoplasm of the bile duct (IPNB), which is regarded as the biliary counterpart of IPMN, shares similar pathological features. Both tumors exhibit varying degrees of dysplasia, ranging from low grade to high grade, and possess malignant transformation potential[2], which underscores the importance of early diagnosis and timely treatment. While advances in diagnostic techniques and early screening have steadily increased the detection rate of IPMN and IPNB[3], their concurrent occurrence is still extremely rare and it poses significant challenges in diagnosis and management. A comprehensive assessment using multiple imaging modalities can facilitate preoperative identification of these lesions and enable more precise treatment. Despite noted differences between IPNB and IPMN in some studies[4,5], their co-occurrence may hint at a shared tumorigenic mechanism, such as underlying genetic or epigenetic alterations. Further investigation is needed to improve our understanding of their pathogenesis and to refine management strategies.

Herein, we present a case of simultaneous IPNB and IPMN in a 58-year-old Chinese man. He underwent successful surgery and had a favorable prognosis.

CASE PRESENTATION

Chief complaints

A 58-year-old Chinese man was hospitalized due to recurrent upper abdominal pain, lasting more than a year.

History of present illness

The patient had been experiencing upper abdominal pain repeatedly over the past year, without fever, nausea, vomiting, diarrhea, or significant weight loss or gain.

History of past illness

His medical history was unremarkable.

Personal and family history

The patient had no family history of malignant tumors.

Physical examination

Upon admission, the patient was alert with stable vital signs and was cooperative during the physical examination. No obvious jaundice was observed in the skin or sclera, and no significantly enlarged superficial lymph nodes were palpable. The heart and lung examinations were unremarkable. The abdomen was flat and soft, with neither the liver nor the spleen palpable below the costal margin. No obvious masses were detected in the abdomen. There was tenderness in the upper abdomen, but no rebound tenderness. Bowel sounds were not hyperactive.

Laboratory examinations

The preoperative blood and urine routine tests showed no abnormalities. Biochemistry tests indicated elevated alanine aminotransferase (173 U/L), aspartate aminotransferase (76 U/L), alkaline phosphatase (395 U/L), and γ-glutamyl transpeptidase (1414 U/L), while bilirubin levels were normal. Serum carbohydrate antigen 19-9 (CA19-9) (120.00 U/mL) showed a significant elevation, while α-fetoprotein and carcinoembryonicantigen were within normal ranges.

Imaging examinations

Abdominal ultrasound showed upper common bile duct dilation (a maximal inner diameter of 1.5 cm) with a 4.2 cm × 1.6 cm hypoechoic mass inside, which had clear borders and non-uniform internal echoes, accompanied by intrahepatic bile duct dilation. Magnetic resonance imaging (MRI) revealed a soft tissue signal filling in the upper segment of the common bile duct (approximately 21 mm × 31 mm × 36 mm, Figure 1A and B), with restricted diffusion and mild enhancement, involving the cystic duct and accompanied by intrahepatic bile duct dilatation. An irregular cystic lesion (approximately 39 mm × 49 mm) was detected in the pancreatic tail. It was closely associated with the main pancreatic duct (MPD) and demonstrated edge and septum enhancement. Multiple enhanced mural nodules were observed in the cyst, with the largest nodule being approximately 15 mm in diameter (Figure 1C). Duodenoscopy revealed an enlarged, fish-mouth duodenal papilla with visible mucin drainage (Figure 1D and E).

Figure 1 Abdominal magnetic resonance imaging scan and duodenoscopy findings. A: On the coronal magnetic resonance imaging (MRI)/T2-weighted imaging (T2WI), a soft-tissue mass was seen in the middle and upper segments of the common bile duct, as indicated by the orange arrow; B: Magnetic resonance cholangiopancreatography shows a cystic lesion in the pancreatic tail continuous with the main pancreatic duct, as indicated by the orange arrow; C: The axial MRI/T2WI indicates a cystic lesion in the pancreatic tail with visible mural nodules, as indicated by the orange arrow; D and E: Duodenoscopy revealed an enlarged, fish-mouth papilla resulting from excessive mucinous secretion from the bile duct or pancreatic duct-a characteristic endoscopic sign of intraductal papillary mucinous neoplasm or intraductal papillary neoplasm of the bile duct.

FINAL DIAGNOSIS

The patient was diagnosed with IPNB with high-grade dysplasia as well as with main-duct (MD) type IPMN with low-grade dysplasia, based on postoperative pathological examination.

TREATMENT

Extrahepatic bile duct resection with Roux-en-Y choledochoenterostomy, distal pancreatectomy, and standard lymph node dissection were performed.

OUTCOME AND FOLLOW-UP

The patient underwent successful surgical treatment and had an excellent prognosis. The patient had no tumor recurrence during the 30-month follow-up. The timeline of the patient's illness, treatment, and follow-up is presented in Figure 2.

Figure 2 Timeline of the patient’s disease course, treatment, and follow-up. US: Ultrasonography; MRI: Magnetic resonance imaging.

DISCUSSION

IPMN was first reported by Morohoshi et al[6] in 1989 as "intraductal papillary neoplasms of the pancreas" and later was officially named IPMN in the 2000 WHO histological classification[7]. IPNB was first reported by Zen et al[8] in 2006, and in 2010, the WHO officially adopted IPNB for "non-invasive papillary or villous biliary neoplasm covering delicate fibrovascular stalks with dilated bile ducts"[9]. Given the anatomic proximity of the biliary tree and pancreas, and the intraductal papillary growth pattern, IPNB was once regarded as the biliary counterpart to IPMN. Molecular studies have identified overlapping genetic alterations in IPNB and IPMN. KRAS mutations were found in 32%-49% of IPNB cases and 60%-70% of IPMN cases, while GNAS mutations were detected in 30%-32% of IPNB cases and 50%-70% of IPMN cases[10-12]. A 2015 study by Date et al[13] highlighted the role of KRAS and GNAS mutations in the pathogenesis of synchronous IPNB and IPMN. These mutations are crucial in tumor development. However, IPNB and IPMN also exhibit distinct molecular profiles. Based on genetic and pathological features, IPNB can be classified into Type 1 and Type 2. Type 1 IPNB shares many molecular characteristics with IPMN, such as frequent KRAS and GNAS mutations. In contrast, Type 2 IPNB is associated with mutations in TP53, SMAD4, and KMT2C, and rarely harbors GNAS mutations[14]. This suggests that while Type 1 IPNB and IPMN may follow similar molecular pathways, Type 2 IPNB follows a distinct pathogenic route. The Wnt/β-catenin pathway is another area of divergence. In IPNB, particularly Type 1, mutations in APC and CTNNB1 are relatively common[14]. These mutations lead to β-catenin stabilization and nuclear translocation, contributing to tumor progression. In contrast, IPMN is more frequently associated with RNF43 mutations, which modulate the Wnt pathway in a unique manner[15]. This difference highlights the tissue-specific factors influencing tumor biology. Nonetheless, there are numerous important distinctions between the two conditions. Although almost all IPMN secrete mucus, only some IPNB do so. About half of IPNBs show pathological features similar to IPMNs[4,5]. However, compared to IPMNs, IPNBs often present at a more advanced stage, are more frequently associated with invasive cancer, and have a worse prognosis[14]. Based on our experience, the clinical detection rate of IPNB is significantly lower than that of IPMN. And the coexistence of IPNB and IPMN in the same patient is extremely rare. To our knowledge, only about 12 cases of coexisting IPNB and IPMN have been reported in the literature up to date[13,16-26]. The summary is presented in Table 1. Among the 13 reported cases (including ours), patients aged from 53 to 76 with a median age 67, 8 were males; 7 cases showed elevated CA19-9, 4 cases showed obstructive jaundice. Postoperative pathological examination revealed that invasive carcinoma was found in the IPNB of six cases but only in the IPMN of two cases. Except for one patient who received only chemotherapy, other patients underwent individualized surgery. All patients were followed up for 6 to 52 months. During this period, two patients died and four experienced tumor recurrence.

Table 1 A summary of 13 cases of coexisting intraductal papillary neoplasm of the bile duct and intraductal papillary mucinous neoplasm.

No.	Ref.	Age (years)	Sex	IPMN			IPNB		CA19-9	Jaundice	Treatment	Follow-up (months)	Status	Recurrence
				Location	Type	Grade	Location	Grade
1	Joo et al[16]	60	Male	Tail	BD	LGD	Left intrahepatic bile ducts	LGD	Elevated	Yes	Distal pancreatectomy and left hepatic lobectomy	10	Alive	No
2	Ishida et al[17]	67	Male	Uncinate process	BD	LGD	Caudate lobe	LGD	Normal	No	Left hepatectomy + Caudate lobectomy +segmental resection of uncinate process	14	Alive	No
3	Yamaguchi et al[18]	69	Male	Head	BD	CA	Left intrahepatic bile ducts	CA	Elevated	No	Left lateral hepatolobectomy and pylorus-preserving pancreaticoduodenectomy	8	Alive	Yes
4	Zalinski et al[19]	65	Female	Head	MD	HGD	Left and right posterior intrahepatic ducts	CA	/	/	/	/	/	/
5	Park et al[20]	67	Male	Tail	MT	HGD	Left intrahepatic bile ducts	LGD	Normal	No	Distal pancreatectomy with splenectomy and a lateral segmentectomy of the liver	10	Alive	No
6	Valente et al[21]	76	Female	Uncinate process, Tail	BD	/	Right intrahepatic bile ducts	CA	Normal	Yes	Chemoradiotherapy	36	Alive	Yes
7	Xu et al[22]	68	Female	Tail	BD	LGD	Left intrahepatic bile ducts	LGD	Normal	No	Left lateral hepatolobectomy and spleen-preserving distal pancreatectomy	6	Alive	No
8	Moon et al[23]	66	Female	Head	MD	HGD	Right intrahepatic bile ducts	HGD	Elevated	No	Pylorus-preserving total pancreatectomy and right hepatectomy	41	Alive	No
9	Date et al[13]	69	Female	Body and tail		CA	Right intrahepatic bile ducts	CA	Elevated	No	Right hepatectomy combined with bile duct resection, and distal pancreatectomy	12	Die	Yes
10	Luvira et al[24]	53	Male	Diffuse	MT	LGD	Diffuse	CA	Elevated	Yes	Left trisectionectomy, pyloric-preserving pancreaticoduodenectomy, and total pancreatectomy	8	Die	No
11	Ren et al[25]	52	Male	Head	MD	LGD	Common bile duct	CA	Normal	Yes	Pylorus-preserving pancreaticoduodenectomy	52	Alive	No
12	Kitahama et al[26]	73	Male	Body	MT	HGD	Left intrahepatic bile ducts	LGD	Elevated	No	Hepatic left lobectomy and distal pancreatectomy	45	Alive	Yes
13	Our case	58	Male	Tail	MD	LGD	Common bile duct	HGD	Elevated	No	Extrahepatic bile duct resection and distal pancreatectomy	30	Alive	No

BD: Branch duct; CA: Carcinoma; CA19-9: Carbohydrate antigen 19-9; HGD: High-grade dysplasia; IPMN: Intraductal papillary mucinous neoplasm; IPNB: Intraductal papillary neoplasm of the bile duct; LGD: Low-grade dysplasia; MD: Main duct; MT: Mixed type.

IPNB is anatomically categorized into extrahepatic, intrahepatic, and diffuse types depending on the tumor's location. IPNB, especially the extrahepatic type, often causes biliary obstruction due to intraductal masses or mucus secretion, elevating liver enzymes and bilirubin levels, and may induce acute cholangitis. In addition, due to its malignant potential, all IPNB require active treatment. Depending on the involvement of the pancreatic duct, IPMN is sorted into MD, branch-duct, and mixed types[27]. Notably, MD type IPMN has a higher risk of invasive cancer. Unlike IPNB, not all IPMN cases need surgery. The 2017 Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas and the 2024 International evidence-based Kyoto guidelines for the management of IPMN of the pancreas recommend surgery for IPMN with “high risk stigmata” or “worrisome features”, while others can be closely monitored[11,27]. Preoperative MRI revealed cystic dilation of the MPD in the pancreatic tail with a maximum width exceeding 10 mm, containing mural nodule larger than 5 mm in diameter, but no significant dilation in the proximal MPD; additionally, an intraluminal mass was found in the upper segment of the common bile duct. According to the 2017 “Fukuoka Guidelines”, the preoperative diagnosis of focal MD-IPMN with two "high - risk stigmata" (MPD diameter of ≥ 10 mm, mural nodule ≥ 5 mm) which were equivalent to "Absolute indications" in the 2018 European evidence-based guidelines on pancreatic cystic neoplasms[28] was determined. The 2017 “Fukuoka Guidelines” recommend using frozen-section biopsy during surgery to ensure the tumor is completely resected with negative margins, and advise cautious total pancreatectomy for diffuse MD-IPMN[27]. The preoperative surgical plan thus involved extrahepatic bile duct resection, distal pancreatectomy, standard lymphadenectomy, and intraoperative frozen-section biopsy. Depending on the intraoperative pathological results, the range of resection might be extended, even up to total pancreatectomy. Fortunately, intraoperative frozen-section examination confirmed negative resection margins for both bile duct and pancreas, and postoperative pathological examination also found no invasive cancer in either tumor.

A distinctive characteristic of IPMN is the possibility of developing clinically significant lesions in the residual pancreas, despite the resection of non-invasive IPMN with negative margins[11]. Thus, postoperative surveillance should focus on the remnant pancreas. Both the 2017 “Fukuoka Guidelines” and the 2024 “Kyoto Guidelines” recommend surveillance with annual MRI, computed tomography, and/or endoscopic ultrasonography for non-invasive IPMN with negative surgical margins until the patient is no longer suitable for further surgery[11,27]. For our patient, we designed a personalized follow-up plan: An MRI scan, liver function tests, and CA19-9 assessment at 6 months post-surgery, then annually for at least 5 years. Subsequent follow-up arrangements will be determined based on the patient's condition.

CONCLUSION

We presented a rare case of concurrent IPNB and IPMN in a 58-year-old Chinese man. IPNB and IPMN, although share some pathological and clinical features, have clear differences. Their coexistence is exceptionally rare, with only around 12 reported cases worldwide. Our patient underwent successful surgery with a good prognosis and no recurrence during the 30-month follow-up period. This case underscores the need for a comprehensive preoperative assessment using multiple imaging modalities and highlights the importance of individualized management and postoperative surveillance for these complex tumors. Further research is crucial to understand their pathogenesis and improve treatment strategies.