Comparison of the Malignant Predictors in Intrahepatic and Extrahepatic Intraductal Papillary Neoplasm of the Bile Duct

Abstract

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a precancerous lesion of cholangiocarcinoma, for which surgical resection is the most effective treatment. We evaluated the predictors of malignancy in IPNB according to anatomical location and the prognosis without surgery. Methods: A total of 196 IPNB patients who underwent pathologic confirmation by surgical resection or endoscopic retrograde cholangiography or percutaneous transhepatic cholangioscopic biopsy were included. Clinicopathological findings of IPNB with invasive carcinoma or mucosal dysplasia were analyzed according to anatomical location. Results: Of the 116 patients with intrahepatic IPNB (I-IPNB) and 80 patients with extrahepatic IPNB (E-IPNB), 62 (53.4%) and 61 (76.3%) were diagnosed with invasive carcinoma, respectively. Multivariate analysis revealed that mural nodule > 12 mm (p = 0.043) in I-IPNB and enhancement of mural nodule (p = 0.044) in E-IPNB were predictive factors for malignancy. For pathologic discrepancy before and after surgery, IPNB has a 71.2% sensitivity and 82.3% specificity. In the non-surgical IPNB group, composed of nine I-IPNB and seven E-IPNB patients, 43.7% progressed to IPNB with invasive carcinoma within 876 days. Conclusions: E-IPNB has a higher rate of malignancy than I-IPNB. The predictive factor for malignancy is mural nodule > 12 mm in I-IPNB and mural nodule enhancement in E-IPNB.

Pathologies of Precursor Lesions of Biliary Tract Carcinoma

“…Approximately half of type 2 IPNBs are associated with invasive carcinoma at the time of surgical resection, whereas a limited amount of type 1 IPNB show invasion [ 7 , 38 ]. Extrahepatic IPNB more frequently shows invasive carcinoma than intrahepatic IPNB [ 137 ].…”

“…Multiple IPNB occurrences are occasionally multiple synchronously and non-synchronously observed along the bile duct [ 137 , 138 , 139 , 140 ]. Multiple IPNB tumors usually have similar histopathological and phenotypic characteristics, although their grades may differ.…”

“…Multiple IPNB tumors usually have similar histopathological and phenotypic characteristics, although their grades may differ. The intraluminal dissemination of tumor cells in the bile duct appears to be more likely because the majority of recurrent tumors develop in more distal parts of the bile duct compared with the primary tumor and show higher grade than those near the liver [ 137 , 138 , 139 ]. However, a widespread neoplastic field defect [ 88 , 89 ] may also occur in the bile duct resulting in multiple carcinomas.…”

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

“…Anatomical location and geographical distribution of IPNBs have been correlated with the risk of stromal invasion. Stromal invasion is higher in tumors originating in the extrahepatic bile ducts, and in those affecting Caucasian patients, suggesting a more indolent course of intrahepatic IPNBs (I-IPNBs) and in those occurring in Asian countries[ 2 , 3 , 28 , 38 , 40 ]. Nakanuma et al [ 41 ] recently reviewed the pathological features of invasive carcinoma associated with IPNB, identifying three different patterns of increasing invasiveness, A, B and C. The first showed a favorable postoperative overall survival (OS) similar to that of noninvasive types, in contrast to the latter two that might be considered clinically advanced entities.…”

“…Nevertheless, the discrepancy between the preoperative biopsy and the definitive histology after surgical resection might be notable, particularly in E-IPNB, with a reported negative predictive value of ~40%. This means that ~60% of patients with a preoperative diagnosis of nonmalignancy actually have an invasive carcinoma by definitive pathology[ 40 ]. Since these two methods have been widely applied in the evaluation of IPNBs, the current applications of endoscopic retrograde cholangiography are limited, apart from determining the presence of mucobilia or direct communication between a cystic lesion and the bile duct[ 4 ] (Figure 5 ).…”