No communication between the bile duct and intraductal papillary neoplasm of the bile duct on imaging

1 Introduction

A 46-year-old male patient presented to our hospital due to a left lobe cystic solid lesion. Hematological examination showed that his total bilirubin level had risen to 20.7μmolL (normal range is 3.4–20.4μmolL) on that day. MRI was performed using GE Discovery 750 w (GE, USA), and 0.2 ml/kg body weight of gadoteric acid (Dotaream, China) was administered intravenously at a rate of 2 ml/s. MRI suggested the foci of cystic solid lobular abnormal signal was seen in the left lateral lobe of the liver. T1WI showed the cystic component of the lesion was low signal and the solid component was slightly low signal (Fig. 1a); T2WI showed that the cystic component of the lesion was significantly hyperintense, and the solid component was mildly hyperintense (Fig. 1b). The maximum cross-section of the mass was about 65 × 97 mm, with a clear boundary. Contrast-enhanced MRI revealed the lesion was not connected to the bile duct, and small cystic non-enhanced lesions were seen in the liver, with no enhancement of cystic components and continued enhancement of solid components and walls (Fig. 1c, d). The lesion was considered as a biliary malignancy in the left lateral lobe of the liver by MRI.

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Fig. 1

T1-weighted and T2-weighted MRI scan (a, b) demonstrated a cystic and solid mass, and contrast-enhanced MRI scan showed wall nodules are significantly enhanced in arterial phase (c), relatively iso-low signal in portal phase (d).

Conventional ultrasound and contrast-enhanced ultrasound (CEUS) were both conducted using SIEMENS Sequoia I ultrasound system. Conventional ultrasound showed a 72 mm × 65 mm hypoechoic parenchymal mass, with parenchymal echogenicity visible on the lateral wall of the mass, measuring approximately 34 mm × 23 mm with clear margins (Fig. 2a, b). Color Doppler flow imaging (CDFI) indicated no colored blood flow seen within the parenchyma (Fig. 2c). The contrast medium used was SonoVue (Bracco, Italy), a 2.4 ml bolus through the antecubital vein, followed by flushing with 5 ml saline. A total of the first 3 min dynamic images were observed. CEUS manifested a markedly homogeneous overall enhancement of the lesion starting at 16 s and peaking at 40 s, with no enhancement in the cystic areas. The enhancement of the lesion lasted longer than 2 minutes (Fig. 2d, e, f). In CEUS, parenchymal part of the lesion always enhanced and decreased synchronously with the surrounding hepatic parenchyma. On this basis, it was diagnosed as a benign condition of cystadenoma.

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Fig. 2

(a, b) Two-dimensional ultrasound showed a hypoechoic mass with well-defined boundaries. (c) No significant blood flow signal in the parenchyma was observed on CDFI. (d) CEUS showed synchronous enhancement of arterial stage lesions and bile duct wall. (e) The peak enhancement of contrast-enhanced ultrasound was homogeneous. (f) Hypoenhancement relative to the liver parenchyma in portal and delayed phases.

The patient finally underwent a hepatic lobectomy. Gross examination showed that the remaining liver measured 19 × 10 × 7 cm, with multifocal cystic dilatation of the bile ducts ranging from 9.5 × 8 cm, of which papillary masses were visible in a few bile ducts, the largest of which was 3 × 2.5 × 2 cm.

The results of immunohistochemistry revealed strong positivity (+++) for CK7, CK19, and MUC5AC, suggesting high malignancy and poor prognosis (Fig. 3a, b, c). Combined with immunohistochemistry, the final diagnosis was Intraductal papillary neoplasm of the bile duct (IPNB) with oncocytic subtype (Fig. 3d).

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Fig. 3

(a, b, c) Immunostaining for CK7 (× 100), CK19 (× 100) and MUC5AC (× 100) was strongly positive (+++). (d) The papillary surface is lined with a large number of eosinophilic granular cytoplasm cells.

Intraductal papillary neoplasm of the bile duct (IPNB) is a highly malignant precancerous lesion originating from the biliary epithelium, which is unusual in clinical practice [1, 2]. As a unique entity, IPNB accounts for 9.9% of bile duct tumors in Asians [3]. Previous studies have shown that IPNB is more common in elderly male patients, with the clinical presentations of persistent right upper quadrant or upper abdominal distention and discomfort, and jaundice and fever in some patients [5].

Most studies believe that the pathogenesis of the disease is due to bile duct stones, inflammation and long-term repeated stimulation of pancreatic juice, resulting in columnar cell proliferation and tissue ectopic in the bile duct epithelium [6, 7]. The jelly-like mucus secreted by IPNB is easy to block the bile ducts, and if not drained in time, serious complications may occur in the late stage [8, 9]. As long as patients undergo complete resection, their prognosis is generally favorable, regardless of the histological degree of neoplasia [10].

IPNB can be divided into low grade and high grade according to the degree of cell atypia. According to the structure and cell characteristics of the papillary, it can be divided into four subtypes: pancreaticobiliary type, gastric type, intestinal type and oncocytic type. Among them, oncocytic IPNB is rare [11, 12].

In addition, immunohistochemistry is helpful for typing. MUC1 and MUC2 are often expressed in pancreatic biliary type and intestinal type respectively. As for the gastric type, it usually expresses MUC5AC and MUC6 [13, 14]. In this case, the type of IPNB is oncocytic, with high expression of MUC5AC, which was consistent with the literature.

According to the 2019 WHO classification of digestive system tumors, intraductal papillary mucinous neoplasm (IPMN) and IPNB are highly similar histopathologically due to the common embryonic origin of the biliary tract and pancreas, which develop from the foregut endoderm [15]. Endoskopic ultrasound with CEUS can provide more detailed information of pancreatic lesions than MRI, but MRI combined with MRCP has the highest sensitivity for the diagnosis of IPMN [16, 17].

CT and MRI are commonly used for the diagnosis of IPNB. The most common findings are bile duct dilatation and intraductal mass. Because it is attached to the intima of the bile duct, the lesion and the wall of the bile duct are simultaneously enhanced after CEUS. Compared with the liver parenchyma, the portal vein blood supply is lacking, resulting in low enhancement compared with the liver parenchyma during the portal stage and the delayed phase. CEUS can well show the structure and continuity of the bile duct wall, and can also tell the filling defect of the dilated bile duct. In addition, ultrasound-guided PTCD can help smooth bile drainage and protect liver function. Moreover, intraoperative CEUS can provide significant value for decision-making in hepatopancreatic and biliary surgery [18]. Considering the convenience and non-radiation damage of CEUS, we recommend it as a screening for IPNB to improve diagnostic accuracy [5]. The most important features of the imaging are that the mass is connected to a dilated bile duct and multiple nodules are seen within the lesion [4], but not in line with this case. Tumors with ductal connectivity are considered cystic variants of IPN-B [14].

The differential diagnosis includes intrahepatic biliary cystadenoma (IBC), mucinous cystic neoplasm of the liver (MCN), cholangiocarcinoma, and et al. IBC is mostly seen in middle-aged women, and lesions mostly not connected to bile ducts and imaging manifestations of wall nodules are rare [19]. Ovarian-like stroma (OLS) is the key to distinguish IPNB from MCN [10]. To distinguish IPNB from CCa, we can start with three characteristic imaging findings: local bile duct dilation, dilated bile duct nodules and growth along the inner wall of the bile duct [4].

Our study can help readers fully understand the different radiographic features of IPNB, although judgments can be made in the absence of the characteristic manifestations of the disease, which requires the combination of other tests and clinical data. In addition, we suggested CEUS as an important means of examination in the article, because it can make up for the shortcomings of conventional ultrasound in the diagnosis of such diseases, with convenience and non-radiation damage.

In conclusion, IPNB is a biliary malignancy with a good long-term outcome. Surgical resection is the main treatment for IPNB. The presence or absence of traffic between the tumor and the bile duct is an important imaging feature. Due to a variety of factors, each imaging method has limitations in the detection of IPNB. Therefore, multimodal approaches are needed to diagnose IPNB.