201 Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a type of cholangiocarcinoma characterized by intraductal growth, mucin production and a better outcome compared to the more common nodular-sclerosing type. IPNB may be analogous to IPMN of the pancreas and may be a precursor of invasive cholangiocarcinoma, but its pathogenesis and natural history are ill-defined. This study examines the incidence, clinicopathologic features and outcome of IPNB in a single center. Methods: A consecutive cohort of patients with bile duct cancer (hilar, intrahepatic or distal) was reviewed and those with papillary features identified. Histopathologic morphology and immunohistochemical staining for cytokeratin and mucin proteins were utilized to classify IPNB into subtypes. Survival data were analyzed and correlated with clinicopathological parameters. Results: Between 1993 and 2008, 40 IPNBs were identified in hilar (24/144), intrahepatic (4/86) and distal (12/113) bile duct cancer specimens (11.7%). Histopathologic examination revealed 27 pancreatobiliary, 4 gastric, 3 intestinal, and 6 oncocytic subtypes; cytokeratin and mucin staining was similar to that of IPMNs of the pancreas. Invasive carcinoma was seen in 29/40 (72%) IPNBs. Overall median survival was 59 months and was not different between IPNB locations or subtypes. Factors associated with a worse median survival included depth of invasion (39 months for > 5mm, 128 months for < 5mm, and 144 months for none, p <0.05), R1 vs R0 resection (36 months vs 82 months, p <0.05), MUC1 expression (53 months for positive vs 144 months for negative, p <0.006), and CEA expression (42 months for positive vs 128 for negative, p<0.02). Expression of MUC2, MUC5A, MUC6, CDX2, mesothelin, p53, Ki67, HepPar1, and B72.3 were not predictive of outcome. Conclusions: IPNBs are an uncommon variant of bile duct cancer, representing approximately 10% of all cases, occur throughout the biliary tract and share histologic and clinical features with IPMNs of the pancreas. These lesions may represent an alternative carcinogenesis pathway. Given their significant malignant potential, they should be treated aggressively with margin-negative resection. No significant financial relationships to disclose.
Biliary cell lineage. New development of intrahepatic bile duct cancer: Hepatic tumor and intraductal papillary neoplasm of the bile duct, which may be derived from the stem cell.