Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis
Abstract The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review....
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| Veröffentlicht in: | Journal of neuropathology and experimental neurology 2018-06, Vol.77 (6), p.422-425 |
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| container_title | Journal of neuropathology and experimental neurology |
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| creator | Hasselblatt, Martin Jaber, Mohammed Reuss, David Grauer, Oliver Bibo, Annkatrin Terwey, Stephanie Schick, Uta Ebel, Heinrich Niederstadt, Thomas Stummer, Walter von Deimling, Andreas Paulus, Werner |
| description | Abstract
The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review. DNA methylation status and copy number profiles were assessed by Infinium HumanMethylation450k BeadChip. Only 25/212 patients harbored tumors without IDH1/IDH2 hotspot mutations and without contrast enhancement. By DNA methylation profiling, 10/25 tumors were classified as glioblastoma, IDH-wildtype, and an additional 7 cases could not be classified using methylome analysis, but showed genetic characteristics of glioblastoma. Histologically, all of these 17 tumors were low-grade diffuse astrocytomas. Nevertheless, 10/17 patients experienced early malignant progression. Other methylation classes included diffuse midline glioma, H3 K27M-mutant, diffuse astrocytoma, IDH-mutant, pilocytic astrocytoma, and normal or reactive brain tissue (total n = 8). In conclusion, no convincing diffuse astrocytoma, IDH-wildtype, was identified. Most IDH-wildtype tumors showing histopathological and radiological features of low-grade diffuse astrocytoma exhibit molecular and clinical features of high-grade glioma and may represent an early stage of primary glioblastoma. Our findings have implications for the biology, classification and neuropathological diagnosis of diffuse astrocytoma, IDH-wildtype in adults. |
| doi_str_mv | 10.1093/jnen/nly012 |
| format | Article |
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The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review. DNA methylation status and copy number profiles were assessed by Infinium HumanMethylation450k BeadChip. Only 25/212 patients harbored tumors without IDH1/IDH2 hotspot mutations and without contrast enhancement. By DNA methylation profiling, 10/25 tumors were classified as glioblastoma, IDH-wildtype, and an additional 7 cases could not be classified using methylome analysis, but showed genetic characteristics of glioblastoma. Histologically, all of these 17 tumors were low-grade diffuse astrocytomas. Nevertheless, 10/17 patients experienced early malignant progression. Other methylation classes included diffuse midline glioma, H3 K27M-mutant, diffuse astrocytoma, IDH-mutant, pilocytic astrocytoma, and normal or reactive brain tissue (total n = 8). In conclusion, no convincing diffuse astrocytoma, IDH-wildtype, was identified. Most IDH-wildtype tumors showing histopathological and radiological features of low-grade diffuse astrocytoma exhibit molecular and clinical features of high-grade glioma and may represent an early stage of primary glioblastoma. Our findings have implications for the biology, classification and neuropathological diagnosis of diffuse astrocytoma, IDH-wildtype in adults.</description><identifier>ISSN: 0022-3069</identifier><identifier>EISSN: 1554-6578</identifier><identifier>DOI: 10.1093/jnen/nly012</identifier><identifier>PMID: 29444314</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Astrocytoma ; Astrocytoma - classification ; Astrocytoma - diagnosis ; Astrocytoma - genetics ; Brain Neoplasms - classification ; Brain Neoplasms - diagnosis ; Brain Neoplasms - genetics ; Diagnosis ; Disease Progression ; DNA Methylation ; Female ; Genetic aspects ; Glioblastoma - classification ; Glioblastoma - diagnosis ; Glioblastoma - genetics ; Health aspects ; Humans ; Immunohistochemistry ; Isocitrate dehydrogenase ; Isocitrate Dehydrogenase - biosynthesis ; Isocitrate Dehydrogenase - genetics ; Male ; Middle Aged ; Molecular Diagnostic Techniques ; Mutation - genetics ; Young Adult</subject><ispartof>Journal of neuropathology and experimental neurology, 2018-06, Vol.77 (6), p.422-425</ispartof><rights>2018 American Association of Neuropathologists, Inc. All rights reserved. 2018</rights><rights>2018 by American Association of Neuropathologists, Inc.</rights><rights>COPYRIGHT 2018 Oxford University Press</rights><rights>Copyright © 2018 American Association of Neuropathologists</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5192-227385abad0d48136de1b4940824a3bf79191fc190db42c75c05e3f79ae9645d3</citedby><cites>FETCH-LOGICAL-c5192-227385abad0d48136de1b4940824a3bf79191fc190db42c75c05e3f79ae9645d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29444314$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hasselblatt, Martin</creatorcontrib><creatorcontrib>Jaber, Mohammed</creatorcontrib><creatorcontrib>Reuss, David</creatorcontrib><creatorcontrib>Grauer, Oliver</creatorcontrib><creatorcontrib>Bibo, Annkatrin</creatorcontrib><creatorcontrib>Terwey, Stephanie</creatorcontrib><creatorcontrib>Schick, Uta</creatorcontrib><creatorcontrib>Ebel, Heinrich</creatorcontrib><creatorcontrib>Niederstadt, Thomas</creatorcontrib><creatorcontrib>Stummer, Walter</creatorcontrib><creatorcontrib>von Deimling, Andreas</creatorcontrib><creatorcontrib>Paulus, Werner</creatorcontrib><title>Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis</title><title>Journal of neuropathology and experimental neurology</title><addtitle>J Neuropathol Exp Neurol</addtitle><description>Abstract
The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review. DNA methylation status and copy number profiles were assessed by Infinium HumanMethylation450k BeadChip. Only 25/212 patients harbored tumors without IDH1/IDH2 hotspot mutations and without contrast enhancement. By DNA methylation profiling, 10/25 tumors were classified as glioblastoma, IDH-wildtype, and an additional 7 cases could not be classified using methylome analysis, but showed genetic characteristics of glioblastoma. Histologically, all of these 17 tumors were low-grade diffuse astrocytomas. Nevertheless, 10/17 patients experienced early malignant progression. Other methylation classes included diffuse midline glioma, H3 K27M-mutant, diffuse astrocytoma, IDH-mutant, pilocytic astrocytoma, and normal or reactive brain tissue (total n = 8). In conclusion, no convincing diffuse astrocytoma, IDH-wildtype, was identified. Most IDH-wildtype tumors showing histopathological and radiological features of low-grade diffuse astrocytoma exhibit molecular and clinical features of high-grade glioma and may represent an early stage of primary glioblastoma. Our findings have implications for the biology, classification and neuropathological diagnosis of diffuse astrocytoma, IDH-wildtype in adults.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Astrocytoma</subject><subject>Astrocytoma - classification</subject><subject>Astrocytoma - diagnosis</subject><subject>Astrocytoma - genetics</subject><subject>Brain Neoplasms - classification</subject><subject>Brain Neoplasms - diagnosis</subject><subject>Brain Neoplasms - genetics</subject><subject>Diagnosis</subject><subject>Disease Progression</subject><subject>DNA Methylation</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Glioblastoma - classification</subject><subject>Glioblastoma - diagnosis</subject><subject>Glioblastoma - genetics</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Isocitrate dehydrogenase</subject><subject>Isocitrate Dehydrogenase - biosynthesis</subject><subject>Isocitrate Dehydrogenase - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular Diagnostic Techniques</subject><subject>Mutation - genetics</subject><subject>Young Adult</subject><issn>0022-3069</issn><issn>1554-6578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp90M9LwzAUB_AgipvTk3cZCCJo3cuvtfE2nD8GAy-Kx5C26daZNTNplf33ZnQqCHpJQvjkvZcvQscYrjAIOlhUuhpUZg2Y7KAu5pxFQx4nu6gLQEhEYSg66MD7BQAIEGwfdYhgjFHMukiMy6JovO6PfO1stq7tUl32J-OH6KU0eb1e6ev-qD8uvbfmvaxm4ahmlfWlP0R7hTJeH233Hnq-u326eYimj_eTm9E0yjgWJCIkpglXqcohZwmmw1zjlAkGCWGKpkUssMBFhgXkKSNZzDPgmoZrpcWQ8Zz20Hlbd-XsW6N9LZelz7QxqtK28ZKEX7KEJpAEevqLLmzjqjBdUDyAsJAfNVNGy7IqbO1UtikqRzFAIsKQENRFqzJnvXe6kCtXLpVbSwxyk7vc5C7b3IM-2XZu0qXOv-1X0AEMWvBhTa2dfzXNh3ZyrpWp53-UPGtf2Gb1b-9PtzGYzQ</recordid><startdate>201806</startdate><enddate>201806</enddate><creator>Hasselblatt, Martin</creator><creator>Jaber, Mohammed</creator><creator>Reuss, David</creator><creator>Grauer, Oliver</creator><creator>Bibo, Annkatrin</creator><creator>Terwey, Stephanie</creator><creator>Schick, Uta</creator><creator>Ebel, Heinrich</creator><creator>Niederstadt, Thomas</creator><creator>Stummer, Walter</creator><creator>von Deimling, Andreas</creator><creator>Paulus, Werner</creator><general>Oxford University Press</general><general>by American Association of Neuropathologists, Inc</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>201806</creationdate><title>Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis</title><author>Hasselblatt, Martin ; Jaber, Mohammed ; Reuss, David ; Grauer, Oliver ; Bibo, Annkatrin ; Terwey, Stephanie ; Schick, Uta ; Ebel, Heinrich ; Niederstadt, Thomas ; Stummer, Walter ; von Deimling, Andreas ; Paulus, Werner</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5192-227385abad0d48136de1b4940824a3bf79191fc190db42c75c05e3f79ae9645d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Astrocytoma</topic><topic>Astrocytoma - 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Academic</collection><jtitle>Journal of neuropathology and experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hasselblatt, Martin</au><au>Jaber, Mohammed</au><au>Reuss, David</au><au>Grauer, Oliver</au><au>Bibo, Annkatrin</au><au>Terwey, Stephanie</au><au>Schick, Uta</au><au>Ebel, Heinrich</au><au>Niederstadt, Thomas</au><au>Stummer, Walter</au><au>von Deimling, Andreas</au><au>Paulus, Werner</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis</atitle><jtitle>Journal of neuropathology and experimental neurology</jtitle><addtitle>J Neuropathol Exp Neurol</addtitle><date>2018-06</date><risdate>2018</risdate><volume>77</volume><issue>6</issue><spage>422</spage><epage>425</epage><pages>422-425</pages><issn>0022-3069</issn><eissn>1554-6578</eissn><abstract>Abstract
The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review. DNA methylation status and copy number profiles were assessed by Infinium HumanMethylation450k BeadChip. Only 25/212 patients harbored tumors without IDH1/IDH2 hotspot mutations and without contrast enhancement. By DNA methylation profiling, 10/25 tumors were classified as glioblastoma, IDH-wildtype, and an additional 7 cases could not be classified using methylome analysis, but showed genetic characteristics of glioblastoma. Histologically, all of these 17 tumors were low-grade diffuse astrocytomas. Nevertheless, 10/17 patients experienced early malignant progression. Other methylation classes included diffuse midline glioma, H3 K27M-mutant, diffuse astrocytoma, IDH-mutant, pilocytic astrocytoma, and normal or reactive brain tissue (total n = 8). In conclusion, no convincing diffuse astrocytoma, IDH-wildtype, was identified. Most IDH-wildtype tumors showing histopathological and radiological features of low-grade diffuse astrocytoma exhibit molecular and clinical features of high-grade glioma and may represent an early stage of primary glioblastoma. Our findings have implications for the biology, classification and neuropathological diagnosis of diffuse astrocytoma, IDH-wildtype in adults.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>29444314</pmid><doi>10.1093/jnen/nly012</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Aged, 80 and over Astrocytoma Astrocytoma - classification Astrocytoma - diagnosis Astrocytoma - genetics Brain Neoplasms - classification Brain Neoplasms - diagnosis Brain Neoplasms - genetics Diagnosis Disease Progression DNA Methylation Female Genetic aspects Glioblastoma - classification Glioblastoma - diagnosis Glioblastoma - genetics Health aspects Humans Immunohistochemistry Isocitrate dehydrogenase Isocitrate Dehydrogenase - biosynthesis Isocitrate Dehydrogenase - genetics Male Middle Aged Molecular Diagnostic Techniques Mutation - genetics Young Adult |
| title | Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis |
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