Histological Classification of Tumours of the Gallbladder and Extrahepatic Bile Ducts

Albores‐Saavedra, Jorge; Henson, Donald E.; Sobin, Leslie H.

doi:10.1007/978-3-642-84241-2_2

Cited by 95 publications

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“…7 While biliary intraepithelial neoplasia are the microscopic/incidental form of low-(biliary intraepithelial neoplasia-1) to high-grade dysplasia (biliary intraepithelial neoplasia-3/'carcinoma in-situ'), intraductal papillary neoplasm of the bile duct is the term used for the tumoral intraepithelial neoplasms that are grossly visible, prominent intraductal tumors with predominantly papillary growth. 2,4 Based on the cell type and mucin expression profile, four intraductal papillary neoplasms of the bile duct subtypes, similar to the subtypes of pancreatic intraductal papillary mucinous neoplasms, can be distinguished: pancreatobiliary, gastric, intestinal, and oncocytic. 8,9 We have recently shown that the progression of non-invasive intraductal papillary neoplasms of the bile duct to invasive carcinoma involves common molecular pathways.…”

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confidence: 99%

Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases

et al. 2015

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Intraductal tubulopapillary neoplasm is a well-established entity in the pancreas. A similar, if not identical, tumor occurs also in the biliary tract. We conducted a multicenter study of 20 such lesions, focusing on their clinicopathologic characteristics and molecular profile. Biliary intraductal tubulopapillary neoplasms were seen in patients in their 60s (mean 62 years). The tumors were intrahepatic 70%, extrahepatic 10%, and perihilar 20%; mean tumor size was 6.9 cm. Histologically, all intraductal tubulopapillary neoplasms showed, in addition to their typical tubular pattern, solid areas (70%) or abortive papillae (50%). Necrosis was common (85%), predominantly focal (40%), and with 'comedocarcinoma-like pattern' in 40%. Immunohistochemically, these neoplasms were characterized by the expression of MUC1 (80%) and MUC6 (30%) and by the absence of MUC2 and MUC5AC. Associated invasive carcinomas were present in 16 (80%), mainly conventional tubular adenocarcinoma (50%). The molecular alterations observed included CDKN2A/p16 (intraductal components 44%, invasive 33%) and TP53 (intraductal components 17%, invasive 9%). Mutations in KRAS (intraductal 6%, invasive 0%), PIK3CA (intraductal 6%, invasive 0%), and loss of SMAD4/DPC4 (intraductal 7%, invasive 0%) were rare. No alterations/mutations were identified in IDH1/2, BRAF, GNAS, EGFR, HER2, and β-catenin. Follow-up information was available for 17 patients (85%) with mean follow-up 44 months. Overall combined survival rates showed favorable prognosis: 1 year 100%, 3 years 90%, and 5 years 90%. In conclusion, despite the relatively high incidence of invasive carcinoma (80%), available follow-up suggests that biliary intraductal tubulopapillary neoplasms have an indolent behavior. Molecular analyses highlight the low prevalence of alterations of common oncogenic signaling pathways in intraductal tubulopapillary neoplasm. Further studies using whole-exome sequencing are required to discover yet unknown molecular changes and to understand the carcinogenesis of intraductal tubulopapillary neoplasms.

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confidence: 99%

Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases

et al. 2015

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“…The histopathological diagnosis and grading, as well as staging, followed the recommendations of the World Health Organisation. 3,4 The study was approved by the ethics committee of the Technische Universität Mü nchen, Mü nchen, Germany. Patients were followed after resection or biopsy until death or last follow-up in March 2012.…”

Section: Patient Selection and Follow Upmentioning

confidence: 99%

“…Invasive carcinomas were subdivided in tubular, colloidmucinous and oncocytic, 3,4 where applicable. Tumor tissue obtained from biopsy was considered as noninvasive if no clear stromal infiltration was present.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

“…Two entities are considered to be precursor lesions of cholangiocarcinoma: biliary intraepithelial neoplasia 1 and intraductal papillary neoplasms. 2 Intraductal papillary neoplasms of the bile duct have been recently included in the World Health Organisation classification of bile duct tumors 3,4 and comprise the previous categories of biliary papilloma and papillomatosis. Intraductal papillary neoplasms of the bile duct are considered to be the biliary counterpart of pancreatic intraductal papillary mucinous neoplasms.…”

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confidence: 99%

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Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways

Schlitter

Born

Bettstetter³

et al. 2014

Modern Pathology

130

120

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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 highgrade 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, b-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 ¼ 0.552). The development of biliary intraductal papillary neoplasms of the bile duct follows an adenomacarcinoma 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.

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“…The slides were reviewed to confirm the diagnosis according to the WHO classification (2001) and to study the extension of the neoplastic disease [17]. In each tumor, we considered both the main histological pattern (intestinal or BP) and a second or a third pattern when present in more than 10% of neoplastic tissue according to the criteria reported by Albores-Saavedra et al [2].…”

Section: Histological and Immunohistochemical Studymentioning

confidence: 99%

Prognostic factors for ampullary adenocarcinomas: tumor stage, tumor histology, tumor location, immunohistochemistry and microsatellite instability

et al. 2007

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Prognostic factors for ampullary carcinomas (ACs) are poorly defined. Fifty three resected ACs were analyzed for CDX2, MUC1, MUC5AC, MUC6, MUC2, and for mismatch repair proteins (hMLH1, hMSH2, PMS2, hMSH6) using immunohistochemistry. Microsatellite instability (MSI) status was evaluated by fluorescently labeled PCR using an automated sequencer. Univariate and multivariate analysis was performed for clinicopathological, immunohistochemical and molecular parameters. CDX2 was found in 32 out of 53 (60%) ACs with a significantly higher frequency among intestinal ACs compared with biliopancreatic (BP) ACs. The MUC1, MUC5AC, MUC6, MUC2 apomucins were expressed in 75, 43, 39, and 28% of ACs, respectively, with a significantly higher coexpression of MUC1/MUC5AC in BP ACs. MSI and loss of expression of hMLH1/PMS2 or hMSH2/hMSH6 proteins were observed only in intestinal ACs. Factors significantly correlated with improved survival in the univariate analysis were: low stage, absence of lymph nodes metastases, negative surgical margins (R0 status), and presence of MSI. In the multivariate analysis, stage was the only independent prognostic factor of survival. We conclude that stage is the only independent prognostic factor of survival in the multivariate analysis, whereas histological criteria and the immunohistochemical expression of apomucins and CDX2 are helpful in the classification and understanding of the histogenesis of ACs.

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Histological Classification of Tumours of the Gallbladder and Extrahepatic Bile Ducts

Cited by 95 publications

References 0 publications

Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases

Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases

Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways

Prognostic factors for ampullary adenocarcinomas: tumor stage, tumor histology, tumor location, immunohistochemistry and microsatellite instability

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