Long-term clinical outcome of the surgically resected intraductal papillary neoplasm of the bile duct
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. Journal of Hepatology
(Impact Factor: 11.34).
05/2012; 57(4):787-93. DOI: 10.1016/j.jhep.2012.05.008
Intraductal papillary neoplasm of the bile duct (IPNB) is a biliary neoplasm with predominant intraductal papillary growth and various degrees of malignant transformation. Although IPNB has been recently added to the WHO classification, the classification system needs refinements.
We retrospectively reviewed 93 non-invasive and invasive IPNB cases, surgically resected from 1996 to 2006. To further characterize their biologic behavior, we modified the WHO classification into a 4-tier category system in which non-invasive IPNB cases with complex fused or cribriform papillae were separately designated. Epithelial types such as intestinal, gastric, pancreatobiliary, and oncocytic type were determined by morphology and mucin core protein immunohistochemistry. Resection margins were classified based on their microscopic appearances. The prognostic values of mucinous histology and MUC1 protein expression were also determined.
IPNB with complex fused or cribriform papillae showed a worse prognosis than IPNB with simple papillae and one such case showed a metachronous metastasis. In addition, a positive surgical margin including dysplasia was associated with worse outcomes. Among the invasive IPNB cases, MUC1-positive tumors were more aggressive than MUC1-negative tumors.
We propose that non-invasive IPNB with complex fused or cribriform papillae might be better classified as mucosa-confined cholangiocarcinoma rather than IPNB with high grade dysplasia. In addition, aggressive further resection is recommended when a positive surgical margin including dysplasia is reported during intraoperative histopathological evaluation.
Available from: Toshio Tsuyuguchi
- "Tumor location varies by a report. Some reports showed that the majority of IPNB was located at the intrahepatic bile duct [16, 17], whereas the other showed that the most common location of IPNB was the hepatic hilum . Despite these variable locations, IPNB tends to be found in the left-sided biliary ductal system, when IPNB exists in the intrahepatic bile duct, due to unknown reasons [13, 20, 21]. "
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ABSTRACT: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors characterized by papillary growth within the bile duct lumen and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas. IPNBs display a spectrum of premalignant lesion towards invasive cholangiocarcinoma. The most common radiologic findings for IPNB are bile duct dilatation and intraductal masses. The major treatment of IPNB is surgical resection. Ultrasonography, computed tomography, magnetic resonance image, and cholangiography are usually performed to assess tumor location and extension. Cholangioscopy can confirm the histology and assess the extent of the tumor including superficial spreading along the biliary epithelium. However, pathologic diagnosis by preoperative biopsy cannot always reflect the maximum degree of atypia, because IPNBs are often composed of varying degrees of cytoarchitectural atypia. IPNBs are microscopically classified into four epithelial subtypes, such as pancreatobiliary, intestinal, gastric, and oncocytic types. Most cases of IPNB are IPN with high-grade intraepithelial neoplasia or with an associated invasive carcinoma. The histologic types of invasive lesions are either tubular adenocarcinoma or mucinous carcinoma. Although several authors have investigated molecular genetic changes during the development and progression of IPNB, these are still poorly characterized and controversial.
05/2014; 2014(2):459091. DOI:10.1155/2014/459091
Available from: Kenji Wakayama
- "Kim et al. reported that surgically treated patients with pancreatobiliary-type IPNB demonstrated poorer survival than those with the gastric and intestinal types because pancreatobiliary-type IPNB was associated with a higher frequency of invasive carcinoma
. A positive surgical margin of the bile duct was associated with poor prognosis
, but long-term survival may be achieved with complete resection
. We performed complete resection of the cyst in this patient, and no recurrence was observed during the follow-up period. "
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ABSTRACT: An intraductal papillary neoplasm of the bile duct is a biliary, epithelium-lined, cystic lesion that exhibits papillary proliferation and rarely causes large hemorrhagic cystic lesions. Here, we report a case of an intraductal papillary neoplasm of the bile duct mimicking a hemorrhagic hepatic cyst in a middle-aged man with large hemorrhagic hepatic cysts who experienced abdominal pain and repeated episodes of intracystic bleeding. Following portal vein embolization, extended right hepatic lobectomy was performed, and intraoperative cholangiography revealed communication between the intracystic space and the hepatic duct. Although histological studies revealed that the large hemorrhagic lesion was not lined with epithelium, the surrounding multilocular lesions contained biliary-derived epithelial cells that presented as papillary growths without ovarian-like stroma. A diagnosis of oncocytic-type intraductal papillary neoplasm of the bile duct was made, and we hypothesized that intracystic bleeding with denudation of the lining epithelial cells might occur as the cystically dilated bile duct increased in size. Differential diagnosis between a hemorrhagic cyst and a cyst-forming intraductal papillary neoplasm of the bile duct with bleeding is difficult. However, an intraductal papillary neoplasm of the bile duct could manifest as multilocular hemorrhagic lesions; therefore, complete resection should be performed for a better prognosis.
World Journal of Surgical Oncology 05/2013; 11(1):111. DOI:10.1186/1477-7819-11-111 · 1.41 Impact Factor
Available from: nature.com
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ABSTRACT: Intraductal papillary neoplasms of the bile duct are still poorly characterized regarding (1) their molecular alterations during the development to invasive carcinomas, (2) their subtype stratification and (3) their biological behavior. We performed a multicenter study that analyzed these issues in a large European cohort. Intraductal papillary neoplasms of the bile duct from 45 patients were graded and subtyped using mucin markers and CDX2. In addition, tumors were analyzed for common oncogenic pathways, and the findings were correlated with subtype and grade. Data were compared with those from 22 extra- and intrahepatic cholangiocarcinomas. Intraductal papillary neoplasms showed a development from preinvasive low- to high-grade intraepithelial neoplasia to invasive carcinoma. Molecular and immunohistochemical analysis revealed mutated KRAS, overexpression of TP53 and loss of p16 in low-grade intraepithelial neoplasia, whereas loss of SMAD4 was found in late phases of tumor development. Alterations of HER2, EGFR, β-catenin and GNAS were rare events. Among the subtypes, pancreato-biliary (36%) and intestinal (29%) were the most common, followed by gastric (18%) and oncocytic (13%) subtypes. Patients with intraductal papillary neoplasm of the bile duct showed a slightly better overall survival than patients with cholangiocarcinoma (hazard ratio (cholangiocarcinoma versus intraductal papillary neoplasm of the bile duct): 1.40; 95% confidence interval: 0.46-4.30; P=0.552). The development of biliary intraductal papillary neoplasms of the bile duct follows an adenoma-carcinoma sequence that correlates with the stepwise activation of common oncogenic pathways. Further large trials are needed to investigate and verify the finding of a better prognosis of intraductal papillary neoplasms compared with conventional cholangiocarcinoma.Modern Pathology advance online publication, 5 July 2013; doi:10.1038/modpathol.2013.112.
Modern Pathology 07/2013; 27(1). DOI:10.1038/modpathol.2013.112 · 6.19 Impact Factor
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