Long-term clinical outcome of the surgically resected intraductal papillary neoplasm of the bile duct.
ABSTRACT 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.
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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. · 1.09 Impact Factor
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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; · 5.25 Impact Factor
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ABSTRACT: Intraductal papillary neoplasm of the bile duct (IPNB) is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma. IPNBs are mainly found in patients from Far Eastern areas, where hepatolithiasis and clonorchiasis are endemic. According to the immunohistochemical profiles of the mucin core proteins, IPNBs are classified into four types: pancreaticobiliary, intestinal, gastric, and oncocytic. Approximately 40%-80% of IPNBs contain a component of invasive carcinoma or tubular or mucinous adenocarcinoma, suggesting that IPNB is a disease with high potential for malignancy. It is difficult to make an accurate preoperative diagnosis because of IPNB's low incidence and the lack of specificity in its clinical manifestation. The most common abnormal preoperative imaging findings of IPNB are intraductal masses and the involvement of bile duct dilation. Simultaneous proximal and distal bile duct dilation can be detected in some cases, which has diagnostic significance. Cholangiography and cholangioscopy are needed to confirm the pathology and demonstrate the extent of the lesions. However, pathologic diagnosis by biopsy cannot reflect the actual stage in many cases because different foci may be of different stages and because mixed pathologic findings may exist in the same lesion. Surgical resection is the major treatment. Systematic cholangioscopy with staged biopsies and frozen sections is recommended during resection to ensure that no minor tumors are left and that curative resection is achieved. Staging, histologic subtype, curative resection and lymph node metastasis are factors affecting long-term survival.World Journal of Gastroenterology 12/2013; 19(46):8595-8604. · 2.55 Impact Factor