Precancerous Bile Duct Pathology in End-stage Primary Sclerosing Cholangitis, With and Without Cholangiocarcinoma
Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). However, the morphology of precursor lesions and the prevalence of biliary dysplasia among patients undergoing liver transplantation for PSC are incompletely defined, and the earlier stu...
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| Veröffentlicht in: | The American journal of surgical pathology 2010, Vol.34 (1), p.27-34 |
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| description | Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). However, the morphology of precursor lesions and the prevalence of biliary dysplasia among patients undergoing liver transplantation for PSC are incompletely defined, and the earlier studies using relatively small number of cases have yielded conflicting results. We retrospectively evaluated 100 consecutive formalin-fixed PSC liver explants (including 30 with CCA) by randomly sampling the hilar and large intrahepatic bile ducts (10 additional tissue cassettes submitted per case). The following histologic features were evaluated and quantitated according to the number of ducts involved: mucinous metaplasia, pyloric metaplasia, intestinal metaplasia, pancreatic acinar metaplasia, and biliary dysplasia [low-grade vs. high-grade (biliary intraepithelial neoplasia-2 or neoplasia-3), papillary vs. flat]. Using Fisher exact test and t test, these features were correlated with the presence or absence of CCA and with the following clinical parameters: sex, age, PSC duration, cirrhotic-stage liver disease, and inflammatory bowel disease at the time of transplant. We found high frequencies of mucinous metaplasia (77%), pyloric metaplasia (73%), and pancreatic acinar metaplasia (10%), which did not differ between CCA and non-CCA livers. However, livers with CCA were more likely to harbor intestinal metaplasia (43% vs. 19%, P=0.013), dysplasia (of any grade) (83% vs. 36%, P |
| doi_str_mv | 10.1097/PAS.0b013e3181bc96f9 |
| format | Article |
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However, the morphology of precursor lesions and the prevalence of biliary dysplasia among patients undergoing liver transplantation for PSC are incompletely defined, and the earlier studies using relatively small number of cases have yielded conflicting results. We retrospectively evaluated 100 consecutive formalin-fixed PSC liver explants (including 30 with CCA) by randomly sampling the hilar and large intrahepatic bile ducts (10 additional tissue cassettes submitted per case). The following histologic features were evaluated and quantitated according to the number of ducts involved: mucinous metaplasia, pyloric metaplasia, intestinal metaplasia, pancreatic acinar metaplasia, and biliary dysplasia [low-grade vs. high-grade (biliary intraepithelial neoplasia-2 or neoplasia-3), papillary vs. flat]. Using Fisher exact test and t test, these features were correlated with the presence or absence of CCA and with the following clinical parameters: sex, age, PSC duration, cirrhotic-stage liver disease, and inflammatory bowel disease at the time of transplant. We found high frequencies of mucinous metaplasia (77%), pyloric metaplasia (73%), and pancreatic acinar metaplasia (10%), which did not differ between CCA and non-CCA livers. However, livers with CCA were more likely to harbor intestinal metaplasia (43% vs. 19%, P=0.013), dysplasia (of any grade) (83% vs. 36%, P<0.0001), and high-grade dysplasia (60% vs. 11%, P<0.0001), and also contained greater numbers of dysplastic ducts than non-CCA cases (P<0.0001). The relative frequency of papillary (44%) versus flat (56%) dysplasia did not differ between CCA and non-CCA cases. Overall, intestinal metaplasia was a significant predictor of bile duct dysplasia (P=0.0005) and CCA (P=0.013), low-grade dysplasia predicted high-grade dysplasia (P<0.0001) and CCA (P=0.0004), and high-grade dysplasia predicted CCA (P<0.0001). Among the clinical parameters, there were no significant differences in age, sex, history of inflammatory bowel disease, or PSC duration, but patients transplanted for CCA were less likely to have cirrhosis (60% vs. 86%, P=0.008). These data strongly support a metaplasia-low-grade dysplasia-high-grade dysplasia-carcinoma sequence in PSC-associated CCA, and underscore the known lack of relationship between patient age and PSC duration in the development of CCA. Even in the absence of CCA, bile duct dysplasia is still a relatively frequent finding, seen at least focally in 36% of benign end-stage PSC explants. Dysplasia, however, is generally confined to large and septal-size bile ducts and its presence may not be recognized unless multiple sections specifically targeted to the biliary tree are examined.</description><identifier>ISSN: 0147-5185</identifier><identifier>EISSN: 1532-0979</identifier><identifier>DOI: 10.1097/PAS.0b013e3181bc96f9</identifier><identifier>PMID: 19898228</identifier><identifier>CODEN: AJSPDX</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adolescent ; Adult ; Aged ; Bile Duct Neoplasms - pathology ; Bile Ducts, Intrahepatic - pathology ; Biological and medical sciences ; Cholangiocarcinoma - pathology ; Cholangitis, Sclerosing - pathology ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Metaplasia ; Middle Aged ; Other diseases. Semiology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Precancerous Conditions - pathology ; Retrospective Studies ; Tumors ; Young Adult</subject><ispartof>The American journal of surgical pathology, 2010, Vol.34 (1), p.27-34</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c336t-22afbc87a53761cc8925fcde6061da17b552d099105f9df33f9b15bc22a8ac693</citedby><cites>FETCH-LOGICAL-c336t-22afbc87a53761cc8925fcde6061da17b552d099105f9df33f9b15bc22a8ac693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22340937$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19898228$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LEWIS, Jason T</creatorcontrib><creatorcontrib>TALWALKAR, Jayant A</creatorcontrib><creatorcontrib>ROSEN, Charles B</creatorcontrib><creatorcontrib>SMYRK, Thomas C</creatorcontrib><creatorcontrib>ABRAHAM, Susan C</creatorcontrib><title>Precancerous Bile Duct Pathology in End-stage Primary Sclerosing Cholangitis, With and Without Cholangiocarcinoma</title><title>The American journal of surgical pathology</title><addtitle>Am J Surg Pathol</addtitle><description>Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). However, the morphology of precursor lesions and the prevalence of biliary dysplasia among patients undergoing liver transplantation for PSC are incompletely defined, and the earlier studies using relatively small number of cases have yielded conflicting results. We retrospectively evaluated 100 consecutive formalin-fixed PSC liver explants (including 30 with CCA) by randomly sampling the hilar and large intrahepatic bile ducts (10 additional tissue cassettes submitted per case). The following histologic features were evaluated and quantitated according to the number of ducts involved: mucinous metaplasia, pyloric metaplasia, intestinal metaplasia, pancreatic acinar metaplasia, and biliary dysplasia [low-grade vs. high-grade (biliary intraepithelial neoplasia-2 or neoplasia-3), papillary vs. flat]. Using Fisher exact test and t test, these features were correlated with the presence or absence of CCA and with the following clinical parameters: sex, age, PSC duration, cirrhotic-stage liver disease, and inflammatory bowel disease at the time of transplant. We found high frequencies of mucinous metaplasia (77%), pyloric metaplasia (73%), and pancreatic acinar metaplasia (10%), which did not differ between CCA and non-CCA livers. However, livers with CCA were more likely to harbor intestinal metaplasia (43% vs. 19%, P=0.013), dysplasia (of any grade) (83% vs. 36%, P<0.0001), and high-grade dysplasia (60% vs. 11%, P<0.0001), and also contained greater numbers of dysplastic ducts than non-CCA cases (P<0.0001). The relative frequency of papillary (44%) versus flat (56%) dysplasia did not differ between CCA and non-CCA cases. Overall, intestinal metaplasia was a significant predictor of bile duct dysplasia (P=0.0005) and CCA (P=0.013), low-grade dysplasia predicted high-grade dysplasia (P<0.0001) and CCA (P=0.0004), and high-grade dysplasia predicted CCA (P<0.0001). Among the clinical parameters, there were no significant differences in age, sex, history of inflammatory bowel disease, or PSC duration, but patients transplanted for CCA were less likely to have cirrhosis (60% vs. 86%, P=0.008). These data strongly support a metaplasia-low-grade dysplasia-high-grade dysplasia-carcinoma sequence in PSC-associated CCA, and underscore the known lack of relationship between patient age and PSC duration in the development of CCA. Even in the absence of CCA, bile duct dysplasia is still a relatively frequent finding, seen at least focally in 36% of benign end-stage PSC explants. Dysplasia, however, is generally confined to large and septal-size bile ducts and its presence may not be recognized unless multiple sections specifically targeted to the biliary tree are examined.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Bile Duct Neoplasms - pathology</subject><subject>Bile Ducts, Intrahepatic - pathology</subject><subject>Biological and medical sciences</subject><subject>Cholangiocarcinoma - pathology</subject><subject>Cholangitis, Sclerosing - pathology</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Humans</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metaplasia</subject><subject>Middle Aged</subject><subject>Other diseases. Semiology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Precancerous Conditions - pathology</subject><subject>Retrospective Studies</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>0147-5185</issn><issn>1532-0979</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkF1LwzAUhoMobn78A5HciDd25iRNm1zq_ATBgYqXJT1NZqRrZ9Ne7N8b3ZjgVQLneZPzPoScAJsA0_nl7OplwkoGwgpQUKLOnN4hY5CCJ3Gud8mYQZonEpQckYMQPhkDroDvkxFopRXnaky-Zp1F06Dt2iHQa19bejNgT2em_2jrdr6ivqG3TZWE3swtnXV-YboVfcE6JoJv5nQaOdPMfe_DBX33_Qc1TfV7aYd-O23RdOibdmGOyJ4zdbDHm_OQvN3dvk4fkqfn-8fp1VOCQmR9wrlxJarcSJFngKg0lw4rm7EMKgN5KSWvmNbApNOVE8LpEmSJMacMZlockvP1u8uu_Rps6IuFD2jruI6NXYtcpBzSqCiS6ZrEWCl01hXLdc0CWPHjuoiui_-uY-x088FQLmz1F9rIjcDZBjABTe266NmHLce5SJkWufgGIWmKFA</recordid><startdate>2010</startdate><enddate>2010</enddate><creator>LEWIS, Jason T</creator><creator>TALWALKAR, Jayant A</creator><creator>ROSEN, Charles B</creator><creator>SMYRK, Thomas C</creator><creator>ABRAHAM, Susan C</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>2010</creationdate><title>Precancerous Bile Duct Pathology in End-stage Primary Sclerosing Cholangitis, With and Without Cholangiocarcinoma</title><author>LEWIS, Jason T ; TALWALKAR, Jayant A ; ROSEN, Charles B ; SMYRK, Thomas C ; ABRAHAM, Susan C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c336t-22afbc87a53761cc8925fcde6061da17b552d099105f9df33f9b15bc22a8ac693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Bile Duct Neoplasms - pathology</topic><topic>Bile Ducts, Intrahepatic - pathology</topic><topic>Biological and medical sciences</topic><topic>Cholangiocarcinoma - pathology</topic><topic>Cholangitis, Sclerosing - pathology</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Humans</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metaplasia</topic><topic>Middle Aged</topic><topic>Other diseases. Semiology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Precancerous Conditions - pathology</topic><topic>Retrospective Studies</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LEWIS, Jason T</creatorcontrib><creatorcontrib>TALWALKAR, Jayant A</creatorcontrib><creatorcontrib>ROSEN, Charles B</creatorcontrib><creatorcontrib>SMYRK, Thomas C</creatorcontrib><creatorcontrib>ABRAHAM, Susan C</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The American journal of surgical pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LEWIS, Jason T</au><au>TALWALKAR, Jayant A</au><au>ROSEN, Charles B</au><au>SMYRK, Thomas C</au><au>ABRAHAM, Susan C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Precancerous Bile Duct Pathology in End-stage Primary Sclerosing Cholangitis, With and Without Cholangiocarcinoma</atitle><jtitle>The American journal of surgical pathology</jtitle><addtitle>Am J Surg Pathol</addtitle><date>2010</date><risdate>2010</risdate><volume>34</volume><issue>1</issue><spage>27</spage><epage>34</epage><pages>27-34</pages><issn>0147-5185</issn><eissn>1532-0979</eissn><coden>AJSPDX</coden><abstract>Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). However, the morphology of precursor lesions and the prevalence of biliary dysplasia among patients undergoing liver transplantation for PSC are incompletely defined, and the earlier studies using relatively small number of cases have yielded conflicting results. We retrospectively evaluated 100 consecutive formalin-fixed PSC liver explants (including 30 with CCA) by randomly sampling the hilar and large intrahepatic bile ducts (10 additional tissue cassettes submitted per case). The following histologic features were evaluated and quantitated according to the number of ducts involved: mucinous metaplasia, pyloric metaplasia, intestinal metaplasia, pancreatic acinar metaplasia, and biliary dysplasia [low-grade vs. high-grade (biliary intraepithelial neoplasia-2 or neoplasia-3), papillary vs. flat]. Using Fisher exact test and t test, these features were correlated with the presence or absence of CCA and with the following clinical parameters: sex, age, PSC duration, cirrhotic-stage liver disease, and inflammatory bowel disease at the time of transplant. We found high frequencies of mucinous metaplasia (77%), pyloric metaplasia (73%), and pancreatic acinar metaplasia (10%), which did not differ between CCA and non-CCA livers. However, livers with CCA were more likely to harbor intestinal metaplasia (43% vs. 19%, P=0.013), dysplasia (of any grade) (83% vs. 36%, P<0.0001), and high-grade dysplasia (60% vs. 11%, P<0.0001), and also contained greater numbers of dysplastic ducts than non-CCA cases (P<0.0001). The relative frequency of papillary (44%) versus flat (56%) dysplasia did not differ between CCA and non-CCA cases. Overall, intestinal metaplasia was a significant predictor of bile duct dysplasia (P=0.0005) and CCA (P=0.013), low-grade dysplasia predicted high-grade dysplasia (P<0.0001) and CCA (P=0.0004), and high-grade dysplasia predicted CCA (P<0.0001). Among the clinical parameters, there were no significant differences in age, sex, history of inflammatory bowel disease, or PSC duration, but patients transplanted for CCA were less likely to have cirrhosis (60% vs. 86%, P=0.008). These data strongly support a metaplasia-low-grade dysplasia-high-grade dysplasia-carcinoma sequence in PSC-associated CCA, and underscore the known lack of relationship between patient age and PSC duration in the development of CCA. Even in the absence of CCA, bile duct dysplasia is still a relatively frequent finding, seen at least focally in 36% of benign end-stage PSC explants. Dysplasia, however, is generally confined to large and septal-size bile ducts and its presence may not be recognized unless multiple sections specifically targeted to the biliary tree are examined.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>19898228</pmid><doi>10.1097/PAS.0b013e3181bc96f9</doi><tpages>8</tpages></addata></record> |
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| subjects | Adolescent Adult Aged Bile Duct Neoplasms - pathology Bile Ducts, Intrahepatic - pathology Biological and medical sciences Cholangiocarcinoma - pathology Cholangitis, Sclerosing - pathology Female Gastroenterology. Liver. Pancreas. Abdomen Humans Investigative techniques, diagnostic techniques (general aspects) Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Metaplasia Middle Aged Other diseases. Semiology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Precancerous Conditions - pathology Retrospective Studies Tumors Young Adult |
| title | Precancerous Bile Duct Pathology in End-stage Primary Sclerosing Cholangitis, With and Without Cholangiocarcinoma |
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