Intraductal papillary neoplasm of the bile duct
Biliary papillary adenoma and noninvasive papillary carcinoma of the biliary tract were terms used to refer to localized low-grade and high-grade IPNBs 1. Whereas biliary papillomatosis was used to describe what is now known as diffuse IPNBs 1.
IPNBs have been reported to be more frequent in Asia, in regions where hepatolithiasis and clonorchiasis are endemic 2,6. They account for 10 to 30% of all bile duct tumors in countries such as Japan, China, and Korea, compared to ~9% in Western countries 2.
The affect age group ranges from 40 to 80 years, and there is a clear male predominance 1,2.
Other risk factors for IPNBs 2:
- primary sclerosing cholangitis (PSC)
- biliary tree malformations
- choledochal cysts
- familial adenomatous polyposis (Gardner syndrome)
Reported symptoms include abdominal pain and jaundice. Cholangitis has also been described in some cases 1,2.
IPNB is a counterpart for the intraductal papillary mucinous neoplasm of the pancreas (IPMN), with both showing intraluminal growth, same histological subtypes, and the association with mucin hypersecretion 1-4.
Although they potentially affect any segment of the biliary tree, IPNBs are more frequently found involving the intrahepatic ducts or at the hepatic hilum in Asia and, in Western countries, within the extra-hepatic ducts, due to different risk factors in those populations. For unclear reasons, when intrahepatic involvement, it most commonly affects the left-sided ducts 1,2.
The spread of IPNBs occurs superficially along the walls of the biliary tract 1.
On gross specimens, they present as solitary or multiple papillary lesions within a dilated bile duct 2. Different from pancreatic IPMN, only in about one-third of IPNB cases show mucin at a macroscopic level 1.
Different from the pancreatic IPMN, which are commonly lined by mucinous epithelium, IPNBs are lined by biliary epithelium 4. There is a papillary proliferation of the atypical epithelial cells with central fibrovascular cores, as well as mucinous cells 1,2.
Different from biliary intraepithelial neoplasia, IPNB is divided into two groups based on the degree of dysplasia: low or intermediate-grade dysplasia and high-grade dysplasia 1.
Histological subtypes are 1-6:
- more frequent in Western countries 1
- frequently associated with 1
- high-grade dysplasia or invasive carcinoma
- expression of the mucin core protein MUC1
- more frequent in Asia countries 1
- frequently associated with a large amount of mucin production
IPNB typically manifests as biliary tree dilatation, focal or diffuse, depending whereas the tumor is located. The obstruction generally can be either in consequence of the viscous mucin or due to the cellular tumor mass effect, depending on which component is predominant: papillary proliferation or mucin production 1. Excessive mucin production may lead to a cystic or aneurysmal dilatation of a bile duct 1.
An intraductal cauliflower-like papillary tumor associated with up and downstream biliary dilatation is referred to as the classic appearance of an IPNB 1.
Ultrasound may show a non-shadowing solid mass of intermediate echogenicity within a dilated duct. Lesions can be well defined and demarcated from the bile duct wall. Proximal ductal dilatation is usually present and focal liver atrophy may be seen.
- CEUS 1
- mass will show enhancement
- does not distinguish benign from malignant tumors
- intra- and extrahepatic duct dilatation may be seen
- mucin is difficult to identify due to its similar attenuation to the bile
- intraductal soft-tissue mass
- iso- or hyperattenuating compared to the adjacent liver
- enhancement in the late arterial phase only 1
- upstream focal liver atrophy may be present
Reported signal characteristics of the solid lesions include:
- T1: low or iso signal
T2: slightly hyperintense
- MRCP: may allow direct visualization of the papillary lesions or an irregular lumen
- mucin is difficult to demonstrate due to the similar signal intensity with the bile but may be seen as stringlike filling defects (also referred to as the “thread sign”) 1
- DWI/ADC: diffusion restriction may be seen within the papillary components 1
T1 C+ (Gd)
- do not significantly enhance and remain hypointense relative to the adjacent liver parenchyma
- hyperintensity during the late arterial phase may be present, but does not sustain in the portal venous and delayed phases (c.f. cholangiocarcinoma) 1
FDG-PET/CT will show lesion uptake when there is malignant degeneration 1.
Treatment and prognosis
IPNB is managed with surgical resection aiming tumor-free resection margins.
Patients with IPNB, even with invasive components, have been reported with a better prognosis compared to cholangiocarcinoma. After curative resection, they show a 5-year survival rate of 47% - 84% 1.
The recurrence rate is estimated from 20% to 60%, depending on the presence of an invasive component 1. Imaging postoperative surveillance with MRCP is usually recommended.
History and etymology
Biliary papillomatosis was initially described in 1894 by Chappet. In 1959 anatomical description was given by Caroli.
When presented with its typical appearance, intraductal mass with up and downstream biliary dilatation, it is difficult to entertain a differential. But other presentations, depending on the location and mucin production of the IPNB, might have differentials to consider 2:
- mass with upstream biliary dilation
- biliary dilatation without masses
- focal cystic lesion