Diagnosis, risk stratification, and management of ampullary dysplasia by DNA flow cytometric analysis of paraffin-embedded tissue
The limited accuracy of endoscopic biopsy in detecting high-grade dysplasia or adenocarcinoma within ampullary adenoma or dysplasia has been reported. The natural history of ampullary dysplasia is also unclear, and there are no established guidelines to determine which patients with ampullary dyspla...
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| Veröffentlicht in: | Modern pathology 2019-09, Vol.32 (9), p.1291-1302 |
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| description | The limited accuracy of endoscopic biopsy in detecting high-grade dysplasia or adenocarcinoma within ampullary adenoma or dysplasia has been reported. The natural history of ampullary dysplasia is also unclear, and there are no established guidelines to determine which patients with ampullary dysplasia require resection versus surveillance endoscopy. DNA flow cytometry was performed on 47 ampullary biopsies with low-grade dysplasia, 18 high-grade dysplasia, and 23 negative for dysplasia, as well as 11 cases of ampullary adenocarcinoma. Abnormal DNA content (aneuploidy or elevated 4N fraction > 6%) was identified in 9 (82%) of adenocarcinoma, 13 (72%) of high-grade dysplasia, 7 (15%) of low-grade dysplasia, and none (0%) of non-dysplastic mucosa. One-, 2-, and 7-year detection rates of high-grade dysplasia or adenocarcinoma in low-grade dysplasia patients with abnormal DNA content were 57%, 86%, and 88%, respectively, whereas low-grade dysplasia patients in the setting of normal DNA content had 1-, 2-, and 7-year detection rates of 10%, 10%, and 10%, respectively. The univariate and multivariate hazard ratios (HRs) for subsequent detection of high-grade dysplasia or adenocarcinoma in low-grade dysplasia patients with DNA content abnormality were 16.8 (
p
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| doi_str_mv | 10.1038/s41379-019-0272-2 |
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p
= <0.01) and 9.8 (
p
= <0.01), respectively. Among the 13 high-grade dysplasia patients with DNA content abnormality, 5 patients (38%) were subsequently found to have adenocarcinoma within a mean follow-up time of 3 months, whereas only 1 (20%) of the remaining 5 patients in the setting of normal DNA content developed adenocarcinoma in a month (HR = 2.6,
p
= 0.39). The overall 1- and 2-year detection rates of adenocarcinoma in all high-grade dysplasia patients (regardless of flow cytometric results) were 34% (95% confidence interval = 16–63%) and 47% (95% confidence interval = 23–79%), respectively. In conclusion, the majority of low-grade dysplasia patients (86%) in the setting of abnormal DNA content developed high-grade dysplasia or adenocarcinoma within 2 years and thus may benefit from resection, whereas those with normal DNA content may be followed with surveillance endoscopy. The presence of DNA content abnormality can also confirm a morphologic suspicion of high-grade dysplasia, which should be managed with resection, as nearly 50% of the high-grade dysplasia patients were found to have adenocarcinoma within 2 years.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/s41379-019-0272-2</identifier><identifier>PMID: 30976103</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>13/31 ; 692/53/2423 ; 692/699/1503/1504 ; Adenocarcinoma ; Adenocarcinoma - pathology ; Adenoma ; Adenoma - pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aneuploidy ; Biopsy ; Child ; Confidence intervals ; Deoxyribonucleic acid ; DNA ; DNA - analysis ; Duodenal Neoplasms - pathology ; Dysplasia ; Endoscopy ; Female ; Flow cytometry ; Flow Cytometry - methods ; Humans ; Laboratory Medicine ; Male ; Medical diagnosis ; Medicine ; Medicine & Public Health ; Middle Aged ; Mucosa ; Paraffin ; Paraffin Embedding ; Pathology ; Precancerous Conditions - pathology ; Risk Assessment ; Surveillance ; Young Adult</subject><ispartof>Modern pathology, 2019-09, Vol.32 (9), p.1291-1302</ispartof><rights>United States & Canadian Academy of Pathology 2019</rights><rights>United States & Canadian Academy of Pathology 2019.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-ae68086e60fd01d395c6cd00e6e5ccc35c942c91f0a45694539119c316407dfe3</citedby><cites>FETCH-LOGICAL-c470t-ae68086e60fd01d395c6cd00e6e5ccc35c942c91f0a45694539119c316407dfe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2285071532?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,780,784,885,27922,27923,64383,64385,64387,72239</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30976103$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wen, Kwun Wah</creatorcontrib><creatorcontrib>Kim, Grace E.</creatorcontrib><creatorcontrib>Rabinovitch, Peter S.</creatorcontrib><creatorcontrib>Wang, Dongliang</creatorcontrib><creatorcontrib>Mattis, Aras N.</creatorcontrib><creatorcontrib>Choi, Won-Tak</creatorcontrib><title>Diagnosis, risk stratification, and management of ampullary dysplasia by DNA flow cytometric analysis of paraffin-embedded tissue</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>The limited accuracy of endoscopic biopsy in detecting high-grade dysplasia or adenocarcinoma within ampullary adenoma or dysplasia has been reported. The natural history of ampullary dysplasia is also unclear, and there are no established guidelines to determine which patients with ampullary dysplasia require resection versus surveillance endoscopy. DNA flow cytometry was performed on 47 ampullary biopsies with low-grade dysplasia, 18 high-grade dysplasia, and 23 negative for dysplasia, as well as 11 cases of ampullary adenocarcinoma. Abnormal DNA content (aneuploidy or elevated 4N fraction > 6%) was identified in 9 (82%) of adenocarcinoma, 13 (72%) of high-grade dysplasia, 7 (15%) of low-grade dysplasia, and none (0%) of non-dysplastic mucosa. One-, 2-, and 7-year detection rates of high-grade dysplasia or adenocarcinoma in low-grade dysplasia patients with abnormal DNA content were 57%, 86%, and 88%, respectively, whereas low-grade dysplasia patients in the setting of normal DNA content had 1-, 2-, and 7-year detection rates of 10%, 10%, and 10%, respectively. The univariate and multivariate hazard ratios (HRs) for subsequent detection of high-grade dysplasia or adenocarcinoma in low-grade dysplasia patients with DNA content abnormality were 16.8 (
p
= <0.01) and 9.8 (
p
= <0.01), respectively. Among the 13 high-grade dysplasia patients with DNA content abnormality, 5 patients (38%) were subsequently found to have adenocarcinoma within a mean follow-up time of 3 months, whereas only 1 (20%) of the remaining 5 patients in the setting of normal DNA content developed adenocarcinoma in a month (HR = 2.6,
p
= 0.39). The overall 1- and 2-year detection rates of adenocarcinoma in all high-grade dysplasia patients (regardless of flow cytometric results) were 34% (95% confidence interval = 16–63%) and 47% (95% confidence interval = 23–79%), respectively. In conclusion, the majority of low-grade dysplasia patients (86%) in the setting of abnormal DNA content developed high-grade dysplasia or adenocarcinoma within 2 years and thus may benefit from resection, whereas those with normal DNA content may be followed with surveillance endoscopy. The presence of DNA content abnormality can also confirm a morphologic suspicion of high-grade dysplasia, which should be managed with resection, as nearly 50% of the high-grade dysplasia patients were found to have adenocarcinoma within 2 years.</description><subject>13/31</subject><subject>692/53/2423</subject><subject>692/699/1503/1504</subject><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenoma</subject><subject>Adenoma - pathology</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aneuploidy</subject><subject>Biopsy</subject><subject>Child</subject><subject>Confidence intervals</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - analysis</subject><subject>Duodenal Neoplasms - pathology</subject><subject>Dysplasia</subject><subject>Endoscopy</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Flow Cytometry - methods</subject><subject>Humans</subject><subject>Laboratory Medicine</subject><subject>Male</subject><subject>Medical diagnosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Mucosa</subject><subject>Paraffin</subject><subject>Paraffin Embedding</subject><subject>Pathology</subject><subject>Precancerous Conditions - pathology</subject><subject>Risk Assessment</subject><subject>Surveillance</subject><subject>Young Adult</subject><issn>0893-3952</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kUtv1TAQhS0EopfCD2CDLLFh0cD4ldgbpKrlJVWwgbXl68fFJYmDnYCy5J_j6JbykFjYljXfHPvMQegxgecEmHxROGGdaoDURTva0DtoRwSDepPiLtqBVKxhStAT9KCUawDChaT30QkD1bVVYod-XEZzGFOJ5QznWL7gMmczxxBt3dN4hs3o8GBGc_CDH2ecAjbDtPS9ySt2a5l6U6LB-xVfvj_HoU_fsV3nNPg5R1ubTb9W7a1tMtmEEMfGD3vvnHd4jqUs_iG6F0xf_KOb8xR9ev3q48Xb5urDm3cX51eN5R3MjfGtBNn6FoID4qor21oH4FsvrLVMWMWpVSSA4aJVXDBFiLKMtBw6Fzw7RS-PutOyH7yz1U02vZ5yHKoXnUzUf1fG-Fkf0jctBVe8U1Xg2Y1ATl8XX2Y9xGJ9HcXo01I0paCEkq3kFX36D3qdllyHsVFSQFdTopUiR8rmVEr24fYzBPQWsD4GrGvAegtYbz1P_nRx2_Er0QrQI1BqaTz4_Pvp_6v-BLXnszQ</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Wen, Kwun Wah</creator><creator>Kim, Grace E.</creator><creator>Rabinovitch, Peter S.</creator><creator>Wang, Dongliang</creator><creator>Mattis, Aras N.</creator><creator>Choi, Won-Tak</creator><general>Nature Publishing Group US</general><general>Elsevier Limited</general><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>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190901</creationdate><title>Diagnosis, risk stratification, and management of ampullary dysplasia by DNA flow cytometric analysis of paraffin-embedded tissue</title><author>Wen, Kwun Wah ; Kim, Grace E. ; Rabinovitch, Peter S. ; Wang, Dongliang ; Mattis, Aras N. ; Choi, Won-Tak</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-ae68086e60fd01d395c6cd00e6e5ccc35c942c91f0a45694539119c316407dfe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13/31</topic><topic>692/53/2423</topic><topic>692/699/1503/1504</topic><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenoma</topic><topic>Adenoma - pathology</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aneuploidy</topic><topic>Biopsy</topic><topic>Child</topic><topic>Confidence intervals</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - analysis</topic><topic>Duodenal Neoplasms - pathology</topic><topic>Dysplasia</topic><topic>Endoscopy</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Flow Cytometry - methods</topic><topic>Humans</topic><topic>Laboratory Medicine</topic><topic>Male</topic><topic>Medical diagnosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Mucosa</topic><topic>Paraffin</topic><topic>Paraffin Embedding</topic><topic>Pathology</topic><topic>Precancerous Conditions - pathology</topic><topic>Risk Assessment</topic><topic>Surveillance</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wen, Kwun Wah</creatorcontrib><creatorcontrib>Kim, Grace E.</creatorcontrib><creatorcontrib>Rabinovitch, Peter S.</creatorcontrib><creatorcontrib>Wang, Dongliang</creatorcontrib><creatorcontrib>Mattis, Aras N.</creatorcontrib><creatorcontrib>Choi, Won-Tak</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Neurosciences Abstracts</collection><collection>PHMC-Proquest健康医学期刊库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wen, Kwun Wah</au><au>Kim, Grace E.</au><au>Rabinovitch, Peter S.</au><au>Wang, Dongliang</au><au>Mattis, Aras N.</au><au>Choi, Won-Tak</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diagnosis, risk stratification, and management of ampullary dysplasia by DNA flow cytometric analysis of paraffin-embedded tissue</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>32</volume><issue>9</issue><spage>1291</spage><epage>1302</epage><pages>1291-1302</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><abstract>The limited accuracy of endoscopic biopsy in detecting high-grade dysplasia or adenocarcinoma within ampullary adenoma or dysplasia has been reported. The natural history of ampullary dysplasia is also unclear, and there are no established guidelines to determine which patients with ampullary dysplasia require resection versus surveillance endoscopy. DNA flow cytometry was performed on 47 ampullary biopsies with low-grade dysplasia, 18 high-grade dysplasia, and 23 negative for dysplasia, as well as 11 cases of ampullary adenocarcinoma. Abnormal DNA content (aneuploidy or elevated 4N fraction > 6%) was identified in 9 (82%) of adenocarcinoma, 13 (72%) of high-grade dysplasia, 7 (15%) of low-grade dysplasia, and none (0%) of non-dysplastic mucosa. One-, 2-, and 7-year detection rates of high-grade dysplasia or adenocarcinoma in low-grade dysplasia patients with abnormal DNA content were 57%, 86%, and 88%, respectively, whereas low-grade dysplasia patients in the setting of normal DNA content had 1-, 2-, and 7-year detection rates of 10%, 10%, and 10%, respectively. The univariate and multivariate hazard ratios (HRs) for subsequent detection of high-grade dysplasia or adenocarcinoma in low-grade dysplasia patients with DNA content abnormality were 16.8 (
p
= <0.01) and 9.8 (
p
= <0.01), respectively. Among the 13 high-grade dysplasia patients with DNA content abnormality, 5 patients (38%) were subsequently found to have adenocarcinoma within a mean follow-up time of 3 months, whereas only 1 (20%) of the remaining 5 patients in the setting of normal DNA content developed adenocarcinoma in a month (HR = 2.6,
p
= 0.39). The overall 1- and 2-year detection rates of adenocarcinoma in all high-grade dysplasia patients (regardless of flow cytometric results) were 34% (95% confidence interval = 16–63%) and 47% (95% confidence interval = 23–79%), respectively. In conclusion, the majority of low-grade dysplasia patients (86%) in the setting of abnormal DNA content developed high-grade dysplasia or adenocarcinoma within 2 years and thus may benefit from resection, whereas those with normal DNA content may be followed with surveillance endoscopy. The presence of DNA content abnormality can also confirm a morphologic suspicion of high-grade dysplasia, which should be managed with resection, as nearly 50% of the high-grade dysplasia patients were found to have adenocarcinoma within 2 years.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>30976103</pmid><doi>10.1038/s41379-019-0272-2</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Free E-Journal (出版社公開部分のみ）; Alma/SFX Local Collection; ProQuest Central |
| subjects | 13/31 692/53/2423 692/699/1503/1504 Adenocarcinoma Adenocarcinoma - pathology Adenoma Adenoma - pathology Adolescent Adult Aged Aged, 80 and over Aneuploidy Biopsy Child Confidence intervals Deoxyribonucleic acid DNA DNA - analysis Duodenal Neoplasms - pathology Dysplasia Endoscopy Female Flow cytometry Flow Cytometry - methods Humans Laboratory Medicine Male Medical diagnosis Medicine Medicine & Public Health Middle Aged Mucosa Paraffin Paraffin Embedding Pathology Precancerous Conditions - pathology Risk Assessment Surveillance Young Adult |
| title | Diagnosis, risk stratification, and management of ampullary dysplasia by DNA flow cytometric analysis of paraffin-embedded tissue |
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