Intraductal papillary neoplasm of the left intrahepatic bile duct found during early gastric cancer treatment: A case report

Abstract

BACKGROUND

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease of the bile duct. It is characterized by a papillary growth within the bile duct lumen. IPNB was formally recognized as a distinct disease entity in 2010, and its etiology remains unknown. IPNB is a complex disease and generally requires multidisciplinary investigation.

CASE SUMMARY

We report the case of a 67-year-old patient who was asymptomatic but diagnosed with IPNB during treatment of early gastric cancer due to an obvious elevation of γ-glutamyl transpeptidase. Computed tomography, magnetic resonance cholangiopancreatography, endoscopic ultrasonography, and endoscopic retrograde cholangiopancreatography with EyeMaxÔ direct visualization system were crucial for the diagnosis of IPNB. Hepatic surgery was performed, and the patient was discharged without complications.

CONCLUSION

IPNB is a complicated disease and difficult to diagnose, especially when the patient is asymptomatic. Aggressive surgical resection can achieve adequate clinical outcomes, particularly when IPNB is diagnosed in early stages.

Key Words: Intraductal papillary neoplasm of the bile duct; Premalignant neoplasm; Intrahepatic; Extrahepatic; Jaundice; Case report

Core Tip: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease of the bile duct. We report the management of a 67-year-old patient who was asymptomatic but diagnosed with IPNB during treatment of early gastric cancer. Multiple imaging modalities were required to successfully diagnose the patient with IPNB. After successful hepatic surgery the patient was discharged without complications. Asymptomatic presentation of IPNB is particularly complicated to diagnose, but aggressive surgical resection can result in satisfactory patient outcomes.

INTRODUCTION

Intraductal papillary neoplasm of the bile duct (IPNB) was officially recognized as a distinct disease entity in the revised World Health Organization Classification of Tumours of the Digestive System in 2010[1]. Before this nomenclature change, IPNB was given multiple terms including palilloma adenoma, leading to confusion in the characterization and management of the disease. It is a relatively rare disease involving both the extrahepatic and intrahepatic bile ducts[2,3]. Based on the World Health Organization Classification, IPNB is classified as a visible premalignant neoplasm which grows in intraductal bile duct with papillary appearance[1]. The lesion has features of intraductal papillary growth. An overproduction of mucin can cause symptoms by blocking the bile duct lumen[2]. However, some patients remain asymptomatic. Recent studies revealed pathological similarities between IPNB and intraductal papillary mucinous neoplasms of the pancreas[4]. Due to the low incidence of IPNB and the confusion before it was classified, the diagnosis of IPNB remains challenging[1]. Here, we present a patient diagnosed with and incidental IPNB of the left hepatic duct during the treatment of early gastric cancer.

CASE PRESENTATION

Chief complaints

In April 2024 a 67-year-old male patient presented to the Department of Gastroenterology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The patient presented with upper gastric pain lasting 10 years that had worsened in the month prior to presentation.

History of present illness

The patient presented with upper gastric pain lasting 10 years that had worsened in the month prior to presentation.

History of past illness

The patient had a history of hypertension and diabetes.

Personal and family history

The patient had no history of smoking or drinking. He denied a history of allergies, and his family history was unremarkable.

Physical examination

At admission the patient’s temperature was 36.5 °C, heart rate was 80 beats per min, respiratory rate was 20 breaths per minute, and blood pressure was 125/75 mmHg. Abdominal, lung, and heart examinations were normal.

Laboratory examinations

Routine blood tests before endoscopic submucosal dissection showed elevated alanine aminotransferase (ALT; 105 U/L, normal range: 9-50 U/L), aspartate aminotransferase (AST; 46 U/L, normal range: 15-40 U/L), alkaline phosphatase (ALP; 300 U/L, normal range: 45-125 U/L), and γ-glutamyl transpeptidase (GGT; 1585 U/L, normal range: 10-71 U/L). Serum carcinoembryonic antigen and carbohydrate antigen (CA19-9) were at normal levels.

Imaging examinations

Upper gastrointestinal endoscopy revealed a 0-IIc lesion in the anterior fundus of the stomach. Biopsy confirmed chronic inflammation with local high grade intraepithelial neoplasia. Endoscopic submucosal dissection was performed, and the final pathology indicated high grade intraepithelial neoplasia. The patient underwent abdominal contrast computed tomography (CT), revealing dilated common bile duct and left hepatic bile duct and atrophy of the left lobe of the liver (Figure 1A-C). Magnetic resonance cholangiopancreatography also showed dilation of the intrahepatic bile duct of the left lobe of the liver and the common bile duct (Figure 1D-F).

Figure 1 Abdominal computed tomography and magnetic resonance cholangiopancreatography. A-C: Computed tomography revealed a dilation of the common bile duct and left hepatic bile duct and atrophy of the left lobe of liver (orange arrows); D-F: Magnetic resonance cholangiopancreatography showed dilation of the common bile duct and left hepatic bile duct.

Endoscopic ultrasonography displayed obvious common bile duct dilation and intrahepatic bile duct dilation of the left lobe of liver. The widest common bile duct was 19.6 mm with no abnormal echo in the common bile duct wall (Figure 2A). High echo flocculent was observed in the left bile duct lumen (Figure 2B). Endoscopic ultrasonography led to a diagnosis of probable congenital cystic dilation of the bile duct. Endoscopic retrograde cholangiopancreatography (ERCP) was also performed, showing common bile duct dilation and multiple filling defects in the mid to proximal segment of the common bile duct (Figure 2C).

Figure 2 Endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography images. A: Endoscopic ultrasonography showed obvious common bile duct dilation; B: Endoscopic ultrasonography showed high echo flocculent in the left bile duct lumen; C: Endoscopic retrograde cholangiopancreatography showed common bile duct dilation and multiple filling defects in the mid-proximal segment of the common bile duct; D: Intrabile duct ultrasound mixed high echo flocculent was observed in the mid-proximal segment of the common bile duct.

Intrabile duct ultrasound of the common bile duct showed obvious dilation, and mixed high echo flocculent was observed in the mid-proximal segment of the common bile duct with the widest measuring 11.2 mm (Figure 2D). The EyeMaxÔ direct visualization system (Micro-Tech Endoscopy, Ann Arbor, MI, United States) was used to observe the bile duct, revealing abundant gelatinous mucus. No lesions were observed in the primary bile ducts. The EyeMaxÔ direct visualization system was inserted into the secondary branching bile duct in which papillary eminence was found (Figure 3A-C).

Figure 3 EyeMaxÔ direct visualization system. A-C: Papillary eminence was found in the secondary branching bile duct of left outer lobe; D: Papillary neoplasm was located in the secondary bile duct of left outer lobe of liver (the gross specimen), and abundant gelatinous mucus was observed in the excised specimen.

FINAL DIAGNOSIS

IPNB of the left intrahepatic bile duct, early gastric cancer, hypertension, and diabetes.

TREATMENT

The Hepatic Surgery Department was consulted. They recommended surgical treatment of the IPNB. Left hepatic lobectomy, cholecystectomy, and biliary-enteric anastomosis was performed. During the surgery the papillary neoplasm was located in the secondary bile duct of the left outer lobe of the liver. A significant volume of gelatinous mucus was observed in the excised specimen (Figure 3D).

OUTCOME AND FOLLOW-UP

After the surgery the patient recovered uneventfully. The final pathological diagnosis was IPNB. Immunohistochemical results showed CK7 (+), MUC2 (+), MUC5AC (+), CK20 (-), and MUC6 (-). Fifteen days after the surgery, ALT, AST and ALP levels were at normal levels. GGT levels were not within the normal range but had decreased to 155 U/L. The patient was discharged 20 days after the surgery.

At the 1-month and 1.5-year follow-ups, the patient showed no signs of recurrence with ALP and GGT within normal range.

DISCUSSION

Approximately 50% of patients with IPNB exhibit symptoms such as pain and jaundice. However, 10%-15% of patients are asymptomatic[5-7]. Mucin production is observed in almost all patients with IPNB, resulting in obstructive jaundice and cholangitis caused anatomically by the narrow diameter and thick wall of the bile duct. It can also lead to papillary biliary hyperplasia with mucus[8,9]. Another study showed that 79.1% of patients presented with symptoms of which jaundice being the most common symptom. The remaining 20.9% of patients were asymptomatic and diagnosed during routine medical examination[2]. In our patient CT and magnetic resonance cholangiopancreatography were performed due to the obviously elevated levels of ALP and GGT. A tumor in the left hepatic duct was revealed. No jaundice was observed in our patient.

IPNB is a relatively rare disease of the bile duct which has a high incidence in Asian people[10]. The etiology of IPNB remains unclear. Several conditions such as choledocholithiasis, hepatolithiasis, and clonorchiasis were reported to be related with IPNB, and further studies are required to determine the etiology of IPNB[11]. Kubota et al[10] reported a median age of 67 years in patients with IPNB, with a male-to-female ratio of 1.74 to 1.

Abnormal laboratory findings including abnormally high levels of serum bilirubin, AST, ALT, GGT, and ALP are typical findings in IPNB due to direct obstruction and inflammation of the biliary duct[12]. The most utilized tumor markers in patients with IPNB are carcinoembryonic antigen and CA19-9, which are prognostic factors for cholangiocarcinoma. Patients with extrahepatic lesions often present with jaundice and CA19-9 elevation[13].

Our patient presented with an extremely high GGT level (1585 U/L) yet maintained normal serum bilirubin levels and was clinically asymptomatic. This dissociation is a hallmark of segmental biliary obstruction. Specifically, the left lobe was obstructed by mucin while the right lobe remained patent. Isolated GGT elevation can be a key early sign of segmental IPNB. In IPNB, lesion location and tumor nature are associated with different features. The obvious elevation of GGT with normal bilirubin in our case was related to left bile intrahepatic duct obstruction. The patient also had a gastric precancerous lesion of local high-grade intraepithelial neoplasia, related to Helicobacter pylori infection. We believed that the gastric precancerous lesion and IPNB were independent oncological events.

The diagnosis of IPNB relied upon the imaging examinations. The classical imaging results are biliary dilatation and an intraluminal mass. CT and magnetic resonance imaging are usually used to show intraductal masses combined with bile duct dilatation. Endoscopic ultrasonography can be used for further evaluation of the depth of an intraductal mass and communication with adjacent bile ducts. ERCP was utilized in this case for further diagnosis and tissue biopsy. In our patient we also used the EyeMaxÔ direct visualization system to directly observe the characteristics of IPNB. The advantages of EyeMaxÔ over ERCP or endoscopic ultrasound are the image clarity and visualization of mucin. EyeMaxÔ also facilitates direct observation of the branch bile duct. Indeed, in our case, ERCP showed common bile duct dilation and multiple filling defects in the mid to proximal segment of the common bile duct; unfortunately, the secondary bile duct was not clearly visible due to mucin obstruction.

IPNB can be pathologically divided into gastric, oncocytic, pancreatobiliary, and intestinal types. The immunohistochemistry results from our patient (CK7+, MUC2+, MUC5AC+) strongly suggest intestinal IPNB. To further reveal the characteristics of different IPNB types and distinguish differences in the disease prognosis, a new classification system with two subtypes was developed[14]. Type 1 often grows in the intrahepatic bile ducts which is similar to intraductal papillary mucinous neoplasm of the pancreas in histology. The lesion from our patient was classified as type 1 IPNB. Type 2 often involves the extrahepatic bile ducts which has a more complex histological architecture. It is believed that type 2 IPNB is more likely to be associated with invasive cancer[15], and type 1 IPNB has a better prognosis than type 2 IPNB. The 1-year, 3-year, 5-year, and 10-year cumulative overall survival rates for IPNB are 86.9%, 65.8%, 49.8%, and 32.0%, respectively[2].

Currently, surgery is the recommended treatment for IPNB. The type and extent of surgical resection depends on the location of the IPNB with bile duct resection or pancreaticoduodenectomy applied to type 2 IPNB lesions and hepatic resection to type 1 IPNB lesions. R0 resection has been achieved in 90% of patients[15]. Some palliative treatments, such as percutaneous transhepatic biliary drainage, biliary stenting and endoscopic approaches, have been reported[7].

CONCLUSION

IPNB is a newly recognized preinvasive neoplasm of the bile duct with a high malignant potential. IPNB typically occurs in patients of advanced age. Jaundice is the most common preoperative symptom. However, a subset of patients are asymptomatic. Surgical resection is the most common treatment strategy to achieve satisfactory patient outcomes.

ACKNOWLEDGEMENTS

The authors thank all the faculty and staff in the Department of Gastroenterology and Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology for their clinical and technical support.