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.

Current considerations on intraductal papillary neoplasms of the bile duct and pancreatic duct

“…We read the paper by Mocchegiani et al [ 1 ] with great interest, and we would like to congratulate the authors for their very nice work on intraductal papillary neoplasm of the bile duct (IPNB), which is an updated impressive approach. This neoplasm resembles the pancreatic intraductal papillary mucinous neoplasm (IPMN).…”

“…IBNB, first described by Chen et al [ 6 ] in 2001, is a slow-growing precancerous lesion that evolves into carcinoma[ 1 , 7 , 8 ]. The other precursor lesion of invasive cholangiocarcinoma, an aggressive disease with poor outcomes, is biliary intraepithelial neoplasia[ 7 , 9 ].…”

“…The involved mutations included mutations in the Tp16, TP53, KRAS, GNAS , BRAF, SMAD4, STK11 CTNNB1, PIK3CA, RNF43 , APC , CTNNB1 , ZNRF3 , CDKNZA, BRCA 1 and BRCA 2 genes[ 1 , 13 , 14 ]. There is an association between KRAS and GNAS gene mutations in IPNNs and between the PRKACA and PRKACB genes in IOPNs, which influences oncocytic tumorigenesis and morphology and may lead to therapeutic targets[ 13 ].…”

“…Magnetic resonance imaging (MRI)-magnetic resonance cholangiopancreatography (MRCP) features may be valuable in distinguishing between the two types of lesions and evaluating the risk of malignancy[ 15 ]. These tumors may be adenomas, borderline neoplasias, in situ carcinomas with regular overgrowth, or tubular mucinous adenocarcinomas with irregular overgrowth[ 1 ]. High peritumoral and intratumoral budding may be prognostic factors for worse outcomes in patients with extrahepatic distal cholangiocarcinoma[ 16 ].…”

“…A recent European multicenter study showed a median postoperative survival of 5.7 years and a 5-year overall survival of 63%[ 17 ]. In unfit patients, novel endoscopic resection[ 1 ], endoscopic radiofrequency ablation or photodynamic therapy can be performed[ 8 ]. High-risk imaging findings and strong indications for surgery included a mural nodule more than 12 mm in length and mural nodule enhancement[ 1 ].…”