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<meta name="DC.Description" content="Given the recent advances in molecular pathogenesis of tumors, with better correlation with tumor behavior and prognosis, major changes were made to the new 2021 World Health Organization (WHO) classification of CNS tumors, including updated criteria for diagnosis of glioblastoma (GBM). Diagnosis of GBM now requires absence of isocitrate dehydrogenase and histone 3 mutations (IDH-wild-type and H3-wild-type) as the basic cornerstone, with elimination of the IDH-mutant category. The requirements for diagnosis were conventionally histopathological, based on the presence of pathognomonic features such as microvascular proliferation and necrosis. However, even if these histologic features are absent, many lower-grade (WHO grade 2/3) diffuse astrocytic gliomas behave clinically similar to GBM (grade 4). The 2021 WHO classification introduced new molecular criteria that can be used to upgrade the diagnosis of such histologically lower-grade, IDH-wild-type, astrocytomas to GBM. The 3 molecular criteria include: concurrent gain of whole chromosome 7 and loss of whole chromosome 10 (+7/–10); telomerase reverse transcriptase promoter mutation; and epidermal growth factor receptor amplification. Given these changes, it is now strongly recommended to have molecular analysis of WHO grade 2/3 diffuse astrocytic, IDH-wild-type, gliomas in adult patients, as identification of any of the above mutations allows for upgrading the tumor to WHO grade 4 (“molecular GBM”) with important prognostic implications. Despite an early stage, there is active ongoing research on the unique MR imaging features of molecular GBM. This paper highlights the differences between “molecular” and “histopathological” GBM, with the aim of providing a basic understanding about these changes.

cIMPACT-NOW
:   Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO
CNS5
:   2021 WHO classification of CNS tumors
EGFR
:   epidermal growth factor receptor
GBM
:   glioblastoma
GFAP
:   glial fibrillary acidic protein
GSEA
:   gene set enrichment analysis
IDH
:   isocitrate dehydrogenase
MGMT
:   methylguanine-DNA methyltransferase
MVP
:   microvascular proliferation
NGS
:   next-generation sequencing
TERT
:   telomerase reverse transcriptase
TMZ
:   temozolomide
WHO
:   World Health Organization" />
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&lt;p&gt;Given the recent advances in molecular pathogenesis of tumors, with better correlation with tumor behavior and prognosis, major changes were made to the new 2021 World Health Organization (WHO) classification of CNS tumors, including updated criteria for diagnosis of glioblastoma (GBM). Diagnosis of GBM now requires absence of isocitrate dehydrogenase and histone 3 mutations (IDH-wild-type and H3-wild-type) as the basic cornerstone, with elimination of the IDH-mutant category. The requirements for diagnosis were conventionally histopathological, based on the presence of pathognomonic features such as microvascular proliferation and necrosis. However, even if these histologic features are absent, many lower-grade (WHO grade 2/3) diffuse astrocytic gliomas behave clinically similar to GBM (grade 4). The 2021 WHO classification introduced new molecular criteria that can be used to upgrade the diagnosis of such histologically lower-grade, IDH-wild-type, astrocytomas to GBM. The 3 molecular criteria include: concurrent gain of whole chromosome 7 and loss of whole chromosome 10 (+7/–10); telomerase reverse transcriptase promoter mutation; and epidermal growth factor receptor amplification. Given these changes, it is now strongly recommended to have molecular analysis of WHO grade 2/3 diffuse astrocytic, IDH-wild-type, gliomas in adult patients, as identification of any of the above mutations allows for upgrading the tumor to WHO grade 4 (“molecular GBM”) with important prognostic implications. Despite an early stage, there is active ongoing research on the unique MR imaging features of molecular GBM. This paper highlights the differences between “molecular” and “histopathological” GBM, with the aim of providing a basic understanding about these changes.&lt;/p&gt;" />
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<meta name="twitter:title" content="Molecular GBM versus Histopathological GBM: Radiology-Pathology-Genetic Correlation and the New WHO 2021 Definition of Glioblastoma" />
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<meta name="twitter:description" content="Given the recent advances in molecular pathogenesis of tumors, with better correlation with tumor behavior and prognosis, major changes were made to the new 2021 World Health Organization (WHO) classification of CNS tumors, including updated criteria for diagnosis of glioblastoma (GBM). Diagnosis of GBM now requires absence of isocitrate dehydrogenase and histone 3 mutations (IDH-wild-type and H3-wild-type) as the basic cornerstone, with elimination of the IDH-mutant category. The requirements for diagnosis were conventionally histopathological, based on the presence of pathognomonic features such as microvascular proliferation and necrosis. However, even if these histologic features are absent, many lower-grade (WHO grade 2/3) diffuse astrocytic gliomas behave clinically similar to GBM (grade 4). The 2021 WHO classification introduced new molecular criteria that can be used to upgrade the diagnosis of such histologically lower-grade, IDH-wild-type, astrocytomas to GBM. The 3 molecular criteria include: concurrent gain of whole chromosome 7 and loss of whole chromosome 10 (+7/–10); telomerase reverse transcriptase promoter mutation; and epidermal growth factor receptor amplification. Given these changes, it is now strongly recommended to have molecular analysis of WHO grade 2/3 diffuse astrocytic, IDH-wild-type, gliomas in adult patients, as identification of any of the above mutations allows for upgrading the tumor to WHO grade 4 (“molecular GBM”) with important prognostic implications. Despite an early stage, there is active ongoing research on the unique MR imaging features of molecular GBM. This paper highlights the differences between “molecular” and “histopathological” GBM, with the aim of providing a basic understanding about these changes.

cIMPACT-NOW
:   Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO
CNS5
:   2021 WHO classification of CNS tumors
EGFR
:   epidermal growth factor receptor
GBM
:   glioblastoma
GFAP
:   glial fibrillary acidic protein
GSEA
:   gene set enrichment analysis
IDH
:   isocitrate dehydrogenase
MGMT
:   methylguanine-DNA methyltransferase
MVP
:   microvascular proliferation
NGS
:   next-generation sequencing
TERT
:   telomerase reverse transcriptase
TMZ
:   temozolomide
WHO
:   World Health Organization" />
<meta name="og-title" property="og:title" content="Molecular GBM versus Histopathological GBM: Radiology-Pathology-Genetic Correlation and the New WHO 2021 Definition of Glioblastoma" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/early/2024/07/11/ajnr.A8225" />
<meta name="og-site-name" property="og:site_name" content="American Journal of Neuroradiology" />
<meta name="og-description" property="og:description" content="Given the recent advances in molecular pathogenesis of tumors, with better correlation with tumor behavior and prognosis, major changes were made to the new 2021 World Health Organization (WHO) classification of CNS tumors, including updated criteria for diagnosis of glioblastoma (GBM). Diagnosis of GBM now requires absence of isocitrate dehydrogenase and histone 3 mutations (IDH-wild-type and H3-wild-type) as the basic cornerstone, with elimination of the IDH-mutant category. The requirements for diagnosis were conventionally histopathological, based on the presence of pathognomonic features such as microvascular proliferation and necrosis. However, even if these histologic features are absent, many lower-grade (WHO grade 2/3) diffuse astrocytic gliomas behave clinically similar to GBM (grade 4). The 2021 WHO classification introduced new molecular criteria that can be used to upgrade the diagnosis of such histologically lower-grade, IDH-wild-type, astrocytomas to GBM. The 3 molecular criteria include: concurrent gain of whole chromosome 7 and loss of whole chromosome 10 (+7/–10); telomerase reverse transcriptase promoter mutation; and epidermal growth factor receptor amplification. Given these changes, it is now strongly recommended to have molecular analysis of WHO grade 2/3 diffuse astrocytic, IDH-wild-type, gliomas in adult patients, as identification of any of the above mutations allows for upgrading the tumor to WHO grade 4 (“molecular GBM”) with important prognostic implications. Despite an early stage, there is active ongoing research on the unique MR imaging features of molecular GBM. This paper highlights the differences between “molecular” and “histopathological” GBM, with the aim of providing a basic understanding about these changes.

cIMPACT-NOW
:   Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO
CNS5
:   2021 WHO classification of CNS tumors
EGFR
:   epidermal growth factor receptor
GBM
:   glioblastoma
GFAP
:   glial fibrillary acidic protein
GSEA
:   gene set enrichment analysis
IDH
:   isocitrate dehydrogenase
MGMT
:   methylguanine-DNA methyltransferase
MVP
:   microvascular proliferation
NGS
:   next-generation sequencing
TERT
:   telomerase reverse transcriptase
TMZ
:   temozolomide
WHO
:   World Health Organization" />
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    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">July 2024,  </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A8225 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-108867--61299566753" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">Amit Agarwal </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Radiology (A.A., A.D., V.G., N.S.), Mayo Clinic, Jacksonville, Florida</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Amit%2BAgarwal%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Agarwal%20A&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AAmit%2BAgarwal%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0001-9139-8007" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Amit Agarwal</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">Mark A. Edgar </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Department of Laboratory Medicine and Pathology (Neuropathology) (M.A.E.), Mayo Clinic, Jacksonville, Florida</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Mark%2BA.%2BEdgar%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Edgar%20MA&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AMark%2BA.%2BEdgar%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">Amit Desai </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Radiology (A.A., A.D., V.G., N.S.), Mayo Clinic, Jacksonville, Florida</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Amit%2BDesai%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Desai%20A&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AAmit%2BDesai%2B" rel="nofollow" class="" 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href="/lookup/external-ref?access_num=Gupta%20V&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AVivek%2BGupta%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0002-4298-7179" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Vivek Gupta</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">Neetu Soni </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Radiology (A.A., A.D., V.G., N.S.), Mayo Clinic, Jacksonville, Florida</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Neetu%2BSoni%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Soni%20N&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ANeetu%2BSoni%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0003-2082-1634" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Neetu Soni</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">Girish Bathla </div><div class="author-tooltip-affiliation"><span 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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Amit</span> <span class="nlm-surname">Agarwal</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Mark A.</span> <span class="nlm-surname">Edgar</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Amit</span> <span class="nlm-surname">Desai</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Vivek</span> <span class="nlm-surname">Gupta</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Neetu</span> <span class="nlm-surname">Soni</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Girish</span> <span class="nlm-surname">Bathla</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Jul 2024, </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A8225 </span></div>
  
  
  
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