Intraductal papillary neoplasm of the bile duct: The new frontier of biliary pathology

Abstract

Intraductal papillary neoplasms of the bile duct (IPNBs) represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen. Since their first description in 2001, several classifications have been proposed, mainly based on histopathological, radiological and clinical features, although no specific guidelines addressing their management have been developed. Bile duct neoplasms generally develop through a multistep process, involving different precursor pathways, ranging from the initial lesion, detectable only microscopically, i.e. biliary intraepithelial neoplasia, to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma. Complex and advanced investigations, mainly relying on magnetic resonance imaging (MRI) and cholangioscopy, are required to reach a correct diagnosis and to define an adequate bile duct mapping, which supports proper treatment. The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB, as well as their natural evolution with a particular focus on prognosis and survival. Aggressive surgical resection, including hepatectomy, pancreaticoduodenectomy or both, represents the treatment of choice, yielding optimal results in terms of survival, although several endoscopic approaches have been described. IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential. The novel subclassification of types 1 and 2 defines the histological and clinical aspects, prognosis and survival. Diagnosis is mainly based on MRI and cholangioscopy. Surgical resection represents the mainstay of treatment, although endoscopic resection is currently applied to nonsurgically fit patients. New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB, to identify targeted therapies.

Keywords: Bile duct neoplasms; Cholangiocarcinoma; Classification; Intraductal neoplasm of the bile duct; Intraductal papilloma; Treatment.

Figure 1

Histological subtypes of intraductal papillary neoplasms of the bile duct. A: Pancreatobiliary; B: Intestinal; C: Gastric; D: Oncocytic. Hematoxylin and eosin staining.

Figure 2

Histological features of intraductal papillary neoplasms of the bile duct with irregular growth pattern and foci of invasive carcinoma (pancreatobiliary type). A: Immunostaining positive for cytokeratin (CK)19; B: Immunostaining negative for CDX2; C: Immunostaining negative for CK20.

Figure 3

Subclassification of intraductal papillary neoplasms of the bile duct according to the Japan Biliary Association and the Korean Association of Hepato-Biliary-Pancreatic Surgery. A: Type 1 consists of papillary, villous or tubular homogenous structures with thin papillary fibrovascular stalks; B: Type 2 consists of thick papillary glands with irregular branching, often intermingled with solid irregular components. Hematoxylin and eosin staining.

Figure 4

Magnetic resonance imaging of intraductal papillary neoplasms of the bile duct. A: Magnetic resonance cholangiopancreatography showed an intraductal lesion of the left hepatic duct with upstream bile duct dilatation; B: Diffuse dilatation of the intrahepatic left lobe bile ducts with low intensity tumors (T2 weighted image, coronal section); C: Magnetic resonance cholangiopancreatography showed a cystic type intraductal papillary neoplasm of the bile duct; D: Cystic type intraductal papillary neoplasm of the bile duct (T2 weighted image, coronal section).

Figure 5

Endoscopic retrograde cholangiopancreatography of an intrahepatic intraductal papillary neoplasm of the bile duct showed a direct communication between the cystic lesion and the bile duct.