Glioma pathophysiology: Difference between revisions

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==Overview==
==Overview==
The pathogenesis of cerebral glioma involves invasion of the tumor cells into the adjacent normal brain tissue. Although in certain areas the margin of the tumor may seem to be macroscopically well defined from the brain, there are always microscopic nests of tumor cells extending well out into the brain.<ref name=aaa>Pathology of glioma. http://www.surgwiki.com/wiki/Intracranial_tumours,_infection_and_aneurysms#MANAGEMENT</ref> Genes involved in the pathogenesis of glioma include ''ERCC1'', ''[[ERCC2]]'', ''[[XRCC1]]'', ''MGMT'', ''IDH1'', ''[[IDH2]]'', ''[[p53]]'', ''[[EGFR]]'', ''[[TSC1]]'', ''[[TSC2]]'', ''[[RB1]]'', ''[[APC]]'', ''hMLH1'', ''hMSH2'', ''[[PMS2]]'', ''[[PTEN]]'', ''[[NF1]]'', and ''NF2''.<ref name=ddd>Pathology of glioma. Wikipedia. https://en.wikipedia.org/wiki/Glioma</ref><ref name="pmid16932614">{{cite journal| author=Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M| title=Epidemiology and molecular pathology of glioma. | journal=Nat Clin Pract Neurol | year= 2006 | volume= 2 | issue= 9 | pages= 494-503; quiz 1 p following 516 | pmid=16932614 | doi=10.1038/ncpneuro0289 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16932614  }} </ref> The gross and histopathological appearance of glioma varies with the tumor grade and type.<ref name=aaa>Pathology of pilocytic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php/Pilocytic_astrocytoma</ref><ref name=fff>Pathology of gliomas. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref><ref name=bbb>Pathology of anaplastic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php?title=Neuropathology_tumours&redirect=no#Infiltrative_astrocytomas</ref><ref name=ccc>Pathology of glioblastoma. Libre Pathology. http://librepathology.org/wiki/index.php/Glioblastoma</ref><ref name=vvv>Pathology of ependymoma. Libre Pathology. http://librepathology.org/wiki/index.php/Ependymoma</ref>
The pathogenesis of cerebral glioma involves invasion of the tumor cells into the adjacent normal brain tissue. Although in certain areas the margin of the tumor may seem to be macroscopically well defined from the brain, there are always microscopic nests of tumor cells extending well out into the brain.<ref name=aaa>Pathology of glioma. http://www.surgwiki.com/wiki/Intracranial_tumours,_infection_and_aneurysms</ref> Genes involved in the pathogenesis of glioma include ''ERCC1'', ''[[ERCC2]]'', ''[[XRCC1]]'', ''MGMT'', ''IDH1'', ''[[IDH2]]'', ''[[p53]]'', ''[[EGFR]]'', ''[[TSC1]]'', ''[[TSC2]]'', ''[[RB1]]'', ''[[APC]]'', ''hMLH1'', ''hMSH2'', ''[[PMS2]]'', ''[[PTEN]]'', ''[[NF1]]'', and ''NF2''.<ref name=ddd>Pathology of glioma. Wikipedia. https://en.wikipedia.org/wiki/Glioma</ref><ref name="pmid16932614">{{cite journal| author=Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M| title=Epidemiology and molecular pathology of glioma. | journal=Nat Clin Pract Neurol | year= 2006 | volume= 2 | issue= 9 | pages= 494-503; quiz 1 p following 516 | pmid=16932614 | doi=10.1038/ncpneuro0289 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16932614  }} </ref> The gross and histopathological appearance of glioma varies with the tumor grade and type.<ref name=ppp>Pathology of pilocytic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php/Pilocytic_astrocytoma</ref><ref name=fff>Pathology of gliomas. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref><ref name=bbb>Pathology of anaplastic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php?title=Neuropathology_tumours&redirect=no#Infiltrative_astrocytomas</ref><ref name=ccc>Pathology of glioblastoma. Libre Pathology. http://librepathology.org/wiki/index.php/Glioblastoma</ref><ref name=vvv>Pathology of ependymoma. Libre Pathology. http://librepathology.org/wiki/index.php/Ependymoma</ref>


==Pathophysiology==
==Pathophysiology==


===Pathogenesis===
===Pathogenesis===
*The pathogenesis of cerebral glioma involves invasion of the tumor cells into the adjacent normal brain tissue. Although in certain areas the margin of the tumor may seem to be macroscopically well defined from the brain, there are always microscopic nests of tumor cells extending well out into the brain.<ref name=aaa>Pathology of glioma. http://www.surgwiki.com/wiki/Intracranial_tumours,_infection_and_aneurysms#MANAGEMENT</ref>
*The pathogenesis of cerebral glioma involves invasion of the tumor cells into the adjacent normal brain tissue. Although in certain areas the margin of the tumor may seem to be macroscopically well defined from the brain, there are always microscopic nests of tumor cells extending well out into the brain.<ref name=aaa>Pathology of glioma. http://www.surgwiki.com/wiki/Intracranial_tumours,_infection_and_aneurysms</ref>
*Astrocytic projections interact with vessels and act as additional elements of the [[blood brain barrier]] (BBB). The tumors take advantage of the blood brain barrier to ensure survival and continuous growth.  
*Astrocytic projections interact with vessels and act as additional elements of the [[blood brain barrier]] (BBB). The tumors take advantage of the blood brain barrier to ensure survival and continuous growth.  
*Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue.
*Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue.
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===Associated Conditions===
===Associated Conditions===
Gliomas may be associated with:<ref name="pmid16932614">{{cite journal| author=Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M| title=Epidemiology and molecular pathology of glioma. | journal=Nat Clin Pract Neurol | year= 2006 | volume= 2 | issue= 9 | pages= 494-503; quiz 1 p following 516 | pmid=16932614 | doi=10.1038/ncpneuro0289 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16932614  }} </ref><ref name=aaa>{{cite journal|last=Reuss|first=D|author2=von Deimling, A|title=Hereditary tumor syndromes and gliomas.|journal=Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer|year=2009|volume=171|pages=83–102|pmid=19322539|doi=10.1007/978-3-540-31206-2_5}}</ref>
Gliomas may be associated with:<ref name="pmid16932614">{{cite journal| author=Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M| title=Epidemiology and molecular pathology of glioma. | journal=Nat Clin Pract Neurol | year= 2006 | volume= 2 | issue= 9 | pages= 494-503; quiz 1 p following 516 | pmid=16932614 | doi=10.1038/ncpneuro0289 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16932614  }} </ref><ref name=xxx>{{cite journal|last=Reuss|first=D|author2=von Deimling, A|title=Hereditary tumor syndromes and gliomas.|journal=Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer|year=2009|volume=171|pages=83–102|pmid=19322539|doi=10.1007/978-3-540-31206-2_5}}</ref>
*[[Neurofibromatosis type 1]]
*[[Neurofibromatosis type 1]]
*[[Neurofibromatosis type 2]]
*[[Neurofibromatosis type 2]]
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===Gross Pathology===
===Gross Pathology===
The gross pathological appearance of glioma varies with the tumor grade and type. Common findings are listed below:<ref name=aaa>Pathology of pilocytic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php/Pilocytic_astrocytoma</ref><ref name=fff>Pathology of gliomas. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref><ref name=bbb>Pathology of anaplastic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php?title=Neuropathology_tumours&redirect=no#Infiltrative_astrocytomas</ref><ref name=ccc>Pathology of glioblastoma. Libre Pathology. http://librepathology.org/wiki/index.php/Glioblastoma</ref><ref name=vvv>Pathology of ependymoma. Libre Pathology. http://librepathology.org/wiki/index.php/Ependymoma</ref>
The gross pathological appearance of glioma varies with the tumor grade and type. Common findings are listed below:<ref name=ppp>Pathology of pilocytic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php/Pilocytic_astrocytoma</ref><ref name=fff>Pathology of gliomas. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref><ref name=bbb>Pathology of anaplastic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php?title=Neuropathology_tumours&redirect=no#Infiltrative_astrocytomas</ref><ref name=ccc>Pathology of glioblastoma. Libre Pathology. http://librepathology.org/wiki/index.php/Glioblastoma</ref><ref name=vvv>Pathology of ependymoma. Libre Pathology. http://librepathology.org/wiki/index.php/Ependymoma</ref>


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===Microscopic Pathology===
===Microscopic Pathology===
The histopathological appearance of glioma varies with the tumor grade and type, with increasing cellular [[atypia]], [[mitoses]], [[endothelial cell]] proliferation, and [[necrosis]]. Common findings are listed below:<ref name=aaa>Pathology of pilocytic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php/Pilocytic_astrocytoma</ref><ref name=fff>Pathology of gliomas. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref><ref name=bbb>Pathology of anaplastic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php?title=Neuropathology_tumours&redirect=no#Infiltrative_astrocytomas</ref><ref name=ccc>Pathology of glioblastoma. Libre Pathology. http://librepathology.org/wiki/index.php/Glioblastoma</ref><ref name=vvv>Pathology of ependymoma. Libre Pathology. http://librepathology.org/wiki/index.php/Ependymoma</ref>
The histopathological appearance of glioma varies with the tumor grade and type, with increasing cellular [[atypia]], [[mitoses]], [[endothelial cell]] proliferation, and [[necrosis]]. Common findings are listed below:<ref name=ppp>Pathology of pilocytic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php/Pilocytic_astrocytoma</ref><ref name=fff>Pathology of gliomas. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref><ref name=bbb>Pathology of anaplastic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php?title=Neuropathology_tumours&redirect=no#Infiltrative_astrocytomas</ref><ref name=ccc>Pathology of glioblastoma. Libre Pathology. http://librepathology.org/wiki/index.php/Glioblastoma</ref><ref name=vvv>Pathology of ependymoma. Libre Pathology. http://librepathology.org/wiki/index.php/Ependymoma</ref>


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====Gallery====
[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<br>
<br>


[[Image:Pilocytic astrocytoma 1.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. As illustrated, many lesions are composed largely of spongy tissue rich in microcysts. Characteristic of [[pilocytic astrocytoma]]s in general, the lesion is largely a solid mass of neoplastic cells without an obvious background of infiltrated brain.|250px]]
<div align="left">
[[Image:Pilocytic astrocytoma 2.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. The perivascular radiating processes in some lesions can create a likeness to an [[ependymoma]]. Note the spongy background unusual for [[ependymoma]]s.|250px]]
<gallery heights="225" widths="225">
[[Image:Pilocytic astrocytoma 3.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. Other [[pilocytic astrocytoma]]s are solid, rather than microcystic, and may be lobular.|250px]]
Image:Pilocytic astrocytoma 1.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. As illustrated, many lesions are composed largely of spongy tissue rich in microcysts. Characteristic of [[pilocytic astrocytoma]]s in general, the lesion is largely a solid mass of neoplastic cells without an obvious background of infiltrated brain.
[[Image:Pilocytic astrocytoma 4.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. Rosenthal fibers, usually confined to the solid rather than spongy regions are found in many pilocytic [[astrocytoma]]s, but are not requisite for the diagnosis.|250px]]
Image:Pilocytic astrocytoma 2.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. The perivascular radiating processes in some lesions can create a likeness to an [[ependymoma]]. Note the spongy background unusual for [[ependymoma]]s.
[[Image:Pilocytic astrocytoma 15.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. Rosenthal fibers are extremely abundant in some lesions. Particularly in the [[cerebellum]], it can be difficult to distinguish such solid, paucicellular, highly fibrillar [[pilocytic astrocytoma]]s from reactive gliosis with abundant Rosenthal fiber formation.|250px]]
Image:Pilocytic astrocytoma 3.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. Other [[pilocytic astrocytoma]]s are solid, rather than microcystic, and may be lobular.
[[Image:Pilocytic astrocytoma 16.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. A loose array of polar cells creates an additional variant of pilocytic [[astrocytoma]].|250px]]
Image:Pilocytic astrocytoma 4.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. Rosenthal fibers, usually confined to the solid rather than spongy regions are found in many pilocytic [[astrocytoma]]s, but are not requisite for the diagnosis.
[[Image:Pilocytic astrocytoma 7.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. Some pilocytic [[astrocytoma]]s are traversed by prominent collagenous septa.|250px]]
Image:Pilocytic astrocytoma 15.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. Rosenthal fibers are extremely abundant in some lesions. Particularly in the [[cerebellum]], it can be difficult to distinguish such solid, paucicellular, highly fibrillar [[pilocytic astrocytoma]]s from reactive gliosis with abundant Rosenthal fiber formation.
[[Image:Pilocytic astrocytoma 8.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. Unusual pilocytic [[astrocytoma]]s have an extensive mucinous background without microcysts.|250px]]
Image:Pilocytic astrocytoma 16.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. A loose array of polar cells creates an additional variant of pilocytic [[astrocytoma]].
[[Image:Comparison.jpg|CNS: Comparison of normal [[optic nerve]] and [[pilocytic astrocytoma]] of the [[optic nerve]]. These two figures compare, at the same magnification, the normal [[optic nerve]] (left) with one containing a [[pilocytic astrocytoma]] (right). The [[neoplasm]] enlarges the compartments of the [[nerve]] and extends in collar-like fashion into the [[subarachnoid]] space.|250px]]
Image:Pilocytic astrocytoma 7.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. Some pilocytic [[astrocytoma]]s are traversed by prominent collagenous septa.
[[Image:Pilocytic astrocytoma 9.jpg|CNS: [[Pilocytic astrocytoma]]; The "hair cells" for which this lesion is named are readily seen.|250px]]
Image:Pilocytic astrocytoma 8.jpg|CNS: [[Pilocytic astrocytoma]]: variations in histologic appearance. Unusual pilocytic [[astrocytoma]]s have an extensive mucinous background without microcysts.
[[Image:Pilocytic astrocytoma 10.jpg|CNS: [[Pilocytic astrocytoma]]; Nuclear hyperchromasia and [[pleomorphism]] are common. Note the typical cellular elongation, and, at the center of the illustration, the [[eosinophil]]ic granular body that populates [[pilocytic astrocytoma]]s and certain other slowly growing gliomas.|250px]]
Image:Comparison.jpg|CNS: Comparison of normal [[optic nerve]] and [[pilocytic astrocytoma]] of the [[optic nerve]]. These two figures compare, at the same magnification, the normal [[optic nerve]] (left) with one containing a [[pilocytic astrocytoma]] (right). The [[neoplasm]] enlarges the compartments of the [[nerve]] and extends in collar-like fashion into the [[subarachnoid]] space.
[[Image:Pilocytic astrocytoma 11.jpg|CNS: [[Pilocytic astrocytoma]]; Intracytoplasmic Rosenthal fibers are prominent in some pilocytic [[neoplasm]]s.|250px]]
Image:Pilocytic astrocytoma 9.jpg|CNS: [[Pilocytic astrocytoma]]; The "hair cells" for which this lesion is named are readily seen.
[[Image:Malignant ependymoma.jpg|Brain: [[Malignant]] [[ependymoma]]: Micro med mag H&E tumor cells.|250px]]
Image:Pilocytic astrocytoma 10.jpg|CNS: [[Pilocytic astrocytoma]]; Nuclear hyperchromasia and [[pleomorphism]] are common. Note the typical cellular elongation, and, at the center of the illustration, the [[eosinophil]]ic granular body that populates [[pilocytic astrocytoma]]s and certain other slowly growing gliomas.
[[Image:Oligodendroglioma 2.jpg|CNS: [[Oligodendroglioma]]; Occasional [[oligodendroglioma]]s contain cells with minute, refractile [[eosinophil]]ic bodies representing miniature Rosenthal fibers.|250px]]
Image:Pilocytic astrocytoma 11.jpg|CNS: [[Pilocytic astrocytoma]]; Intracytoplasmic Rosenthal fibers are prominent in some pilocytic [[neoplasm]]s.
[[Image:Oligodendroglioma 1.jpg|CNS: [[Oligodendroglioma]]; The cells of some [[oligodendroglioma]]s acquire sufficient [[cytoplasm]] and process formation to become decidedly astrocytic, but their nuclei retain the roundness, uniformity, and chromatin distribution typical of [[oligodendroglioma]].|250px]]
Image:Malignant ependymoma.jpg|Brain: [[Malignant]] [[ependymoma]]: Micro med mag H&E tumor cells.
[[Image:Anaplastic oligodendroglioma.jpg|[[Anaplastic]] [[oligodendroglioma]]: [[Anaplastic]] [[oligodendroglioma]]s are highly cellular and associated with vascular proliferation.|250px]]
Image:Oligodendroglioma 2.jpg|CNS: [[Oligodendroglioma]]; Occasional [[oligodendroglioma]]s contain cells with minute, refractile [[eosinophil]]ic bodies representing miniature Rosenthal fibers.
[[Image:Oligodendroglioma frozen.jpg|CNS: [[Oligodendroglioma]] (frozen section); [[Oligodendroglioma]]s in frozen sections lack the distinctive halos so often seen in permanent sections. Cellular monomorphism and infiltration of [[cerebral cortex]] with perineuronal satellitosis suggest the correct diagnosis.|250px]]
Image:Oligodendroglioma 1.jpg|CNS: [[Oligodendroglioma]]; The cells of some [[oligodendroglioma]]s acquire sufficient [[cytoplasm]] and process formation to become decidedly astrocytic, but their nuclei retain the roundness, uniformity, and chromatin distribution typical of [[oligodendroglioma]].
[[Image:Clear cell ependymoma.jpg|CNS: Clear cell [[ependymoma]]; Perinuclear clearing similar to that seen in [[oligodendroglioma]]s is a prominent feature of the clear cell variant. Note the vague perivascular pseudorosettes. The lesion was a discrete occipital intraventricular mass.|250px]]
Image:Anaplastic oligodendroglioma.jpg|[[Anaplastic]] [[oligodendroglioma]]: [[Anaplastic]] [[oligodendroglioma]]s are highly cellular and associated with vascular proliferation.
[[Image:Glioblastoma multiforme 1.jpg|CNS: [[Glioblastoma multiforme]]; Brain: [[Glioblastoma multiforme]]. Grade I-Ii: Micro med mag with H&E, [[tumor]] well shown|250px]]
Image:Oligodendroglioma frozen.jpg|CNS: [[Oligodendroglioma]] (frozen section); [[Oligodendroglioma]]s in frozen sections lack the distinctive halos so often seen in permanent sections. Cellular monomorphism and infiltration of [[cerebral cortex]] with perineuronal satellitosis suggest the correct diagnosis.
[[Image:Glioblastoma multiforme 2.jpg|CNS: [[Glioblastoma multiforme]] arising in an [[astrocytoma]]. At higher magnification, gemistocytic [[astrocytoma]] with microcystic change is apparent at the bottom of the illustration and cellular nodules of [[glioblastoma multiforme]] are seen at the top. The 6-year history of symptoms attested to the initially low-grade nature of this astrocytic tumor.|250px]]
Image:Clear cell ependymoma.jpg|CNS: Clear cell [[ependymoma]]; Perinuclear clearing similar to that seen in [[oligodendroglioma]]s is a prominent feature of the clear cell variant. Note the vague perivascular pseudorosettes. The lesion was a discrete occipital intraventricular mass.
[[Image:Glioblastoma multiforme 103.jpg|CNS: [[Glioblastoma multiforme]]; Characteristic of most [[glioblastoma]]s are small cells with elongated nuclei and bipolar processes. As here, the [[chromatin]] is generally not markedly dense nor are nucleoli usually prominent.|250px]]
Image:Glioblastoma multiforme 1.jpg|CNS: [[Glioblastoma multiforme]]; Brain: [[Glioblastoma multiforme]]. Grade I-Ii: Micro med mag with H&E, [[tumor]] well shown
[[Image:Glioblastoma multiforme 104.jpg|CNS: [[Glioblastoma multiforme]]; Vascular proliferation, a common feature of glioblastoma, produces tufts which often grow directionally. Here, as is often the case, they are oriented toward a focus of necrosis (top right).|250px]]
Image:Glioblastoma multiforme 2.jpg|CNS: [[Glioblastoma multiforme]] arising in an [[astrocytoma]]. At higher magnification, gemistocytic [[astrocytoma]] with microcystic change is apparent at the bottom of the illustration and cellular nodules of [[glioblastoma multiforme]] are seen at the top. The 6-year history of symptoms attested to the initially low-grade nature of this astrocytic tumor.
[[Image:Glioblastoma multiforme 105.jpg|CNS: [[Glioblastoma multiforme]]; At high magnification, the neovascular tuft is a mass which, as can be confirmed by immunohistochemistry, is formed of both endothelial cells and smooth muscle cells (pericytes).|250px]]
Image:Glioblastoma multiforme 103.jpg|CNS: [[Glioblastoma multiforme]]; Characteristic of most [[glioblastoma]]s are small cells with elongated nuclei and bipolar processes. As here, the [[chromatin]] is generally not markedly dense nor are nucleoli usually prominent.
[[Image:Glioblastoma multiforme 106.jpg|CNS: [[Glioblastoma multiforme]]; In many instances, [[necrosis]] is surrounded by a distinctive collar of cells, which are often smaller than those in surrounding neoplastic tissue. The phenomenon is referred to as pseudopalisading.|250px]]
Image:Glioblastoma multiforme 104.jpg|CNS: [[Glioblastoma multiforme]]; Vascular proliferation, a common feature of glioblastoma, produces tufts which often grow directionally. Here, as is often the case, they are oriented toward a focus of necrosis (top right).
[[Image:Cerebrospinal dissemination of glioblastoma multiforme 1.jpg|CNS: Cerebrospinal dissemination of glioblastoma multiforme; As seen at low (left) and high (right) magnification, the small undifferentiated-appearing cells of this glioblastoma are drop metastases colonizing the nerve roots of the cauda equina.|250px]]
Image:Glioblastoma multiforme 105.jpg|CNS: [[Glioblastoma multiforme]]; At high magnification, the neovascular tuft is a mass which, as can be confirmed by immunohistochemistry, is formed of both endothelial cells and smooth muscle cells (pericytes).
[[Image:Cerebrospinal dissemination of glioblastoma multiforme 2.jpg|CNS: Cerebrospinal dissemination of glioblastoma multiforme; As seen at low (left) and high (right) magnification, the small undifferentiated-appearing cells of this glioblastoma are drop metastases colonizing the nerve roots of the cauda equina.|250px]]
Image:Glioblastoma multiforme 106.jpg|CNS: [[Glioblastoma multiforme]]; In many instances, [[necrosis]] is surrounded by a distinctive collar of cells, which are often smaller than those in surrounding neoplastic tissue. The phenomenon is referred to as pseudopalisading.
[[Image:Glioblastoma multiforme 116.jpg|CNS: [[Glioblastoma multiforme]]; Higher magnification reveals the small cell nature of such tumors.|250px]]
Image:Cerebrospinal dissemination of glioblastoma multiforme 1.jpg|CNS: Cerebrospinal dissemination of glioblastoma multiforme; As seen at low (left) and high (right) magnification, the small undifferentiated-appearing cells of this glioblastoma are drop metastases colonizing the nerve roots of the cauda equina.
[[Image:Glioblastoma multiforme 117.jpg|CNS: [[Glioblastoma multiforme]]; Some glioblastomas are especially infiltrative of the cerebral cortex where subpial, perivascular, and perineuronal accumulations are prominent.|250px]]
Image:Cerebrospinal dissemination of glioblastoma multiforme 2.jpg|CNS: Cerebrospinal dissemination of glioblastoma multiforme; As seen at low (left) and high (right) magnification, the small undifferentiated-appearing cells of this glioblastoma are drop metastases colonizing the nerve roots of the cauda equina.
[[Image:Glioblastoma multiforme 126.jpg|CNS: [[Glioblastoma multiforme]]; Although this densely cellular and largely undifferentiated lesion technically merits a diagnosis of [[anaplastic]] [[astrocytoma]], it is, for practical purposes, a glioblastoma.|250px]]
Image:Glioblastoma multiforme 116.jpg|CNS: [[Glioblastoma multiforme]]; Higher magnification reveals the small cell nature of such tumors.
[[Image:Glioblastoma multiforme malignant astrocytoma 1.jpg|Brain: [[Glioblastoma multiforme]] [[malignant]] [[astrocytoma]]|250px]]
Image:Glioblastoma multiforme 117.jpg|CNS: [[Glioblastoma multiforme]]; Some glioblastomas are especially infiltrative of the cerebral cortex where subpial, perivascular, and perineuronal accumulations are prominent.
[[Image:Glioblastoma multiforme pallisading.jpg|Brain: [[Glioblastoma multiforme]]; pallisading|250px]]
Image:Glioblastoma multiforme 126.jpg|CNS: [[Glioblastoma multiforme]]; Although this densely cellular and largely undifferentiated lesion technically merits a diagnosis of [[anaplastic]] [[astrocytoma]], it is, for practical purposes, a glioblastoma.
[[Image:Glioblastoma multiforme vascular proliferation.jpg|Brain: [[Glioblastoma multiforme]]; vascular proliferation|250px]]
Image:Glioblastoma multiforme malignant astrocytoma 1.jpg|Brain: [[Glioblastoma multiforme]] [[malignant]] [[astrocytoma]]
[[Image:Glioblastoma multiforme extravasated blood.jpg|Brain: [[Glioblastoma multiforme]]; Plump and juicy [[endothelial cell]]s, extravasated blood|250px]]
Image:Glioblastoma multiforme pallisading.jpg|Brain: [[Glioblastoma multiforme]]; pallisading
[[Image:Glioblastoma multiforme perivascular lymphocytes.jpg|Brain: [[Glioblastoma multiforme]]; perivascular [[lymphocyte]]s|250px]]
Image:Glioblastoma multiforme vascular proliferation.jpg|Brain: [[Glioblastoma multiforme]]; vascular proliferation
[[Image:Glioblastoma multiforme thrombosed vessel.jpg|Brain: [[Glioblastoma multiforme]]; thrombosed vessel|250px]]
Image:Glioblastoma multiforme extravasated blood.jpg|Brain: [[Glioblastoma multiforme]]; Plump and juicy [[endothelial cell]]s, extravasated blood
[[Image:Hemosiderin in glioblastoma.jpg|Brain: [[Glioblastoma multiforme]]; [[Hemosiderin]] in glioblastoma|250px]]
Image:Glioblastoma multiforme perivascular lymphocytes.jpg|Brain: [[Glioblastoma multiforme]]; perivascular [[lymphocyte]]s
Image:Glioblastoma multiforme thrombosed vessel.jpg|Brain: [[Glioblastoma multiforme]]; thrombosed vessel
Image:Hemosiderin in glioblastoma.jpg|Brain: [[Glioblastoma multiforme]]; [[Hemosiderin]] in glioblastoma
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==References==
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Latest revision as of 01:45, 27 November 2017

Glioma Microchapters

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Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Glioma from other Diseases

Epidemiology and Demographics

Risk Factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Sujit Routray, M.D. [3]

Overview

The pathogenesis of cerebral glioma involves invasion of the tumor cells into the adjacent normal brain tissue. Although in certain areas the margin of the tumor may seem to be macroscopically well defined from the brain, there are always microscopic nests of tumor cells extending well out into the brain.[1] Genes involved in the pathogenesis of glioma include ERCC1, ERCC2, XRCC1, MGMT, IDH1, IDH2, p53, EGFR, TSC1, TSC2, RB1, APC, hMLH1, hMSH2, PMS2, PTEN, NF1, and NF2.[2][3] The gross and histopathological appearance of glioma varies with the tumor grade and type.[4][5][6][7][8]

Pathophysiology

Pathogenesis

  • The pathogenesis of cerebral glioma involves invasion of the tumor cells into the adjacent normal brain tissue. Although in certain areas the margin of the tumor may seem to be macroscopically well defined from the brain, there are always microscopic nests of tumor cells extending well out into the brain.[1]
  • Astrocytic projections interact with vessels and act as additional elements of the blood brain barrier (BBB). The tumors take advantage of the blood brain barrier to ensure survival and continuous growth.
  • Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue.
  • Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema.[9]

Genetics

Genes involved in the pathogenesis of glioma include:[2][3]

Associated Conditions

Gliomas may be associated with:[3][10]

Gross Pathology

The gross pathological appearance of glioma varies with the tumor grade and type. Common findings are listed below:[4][5][6][7][8]

Type of glioma Gross pathological features

Pilocytic astrocytoma

1. Well-circumscribed cystic tumor
2. Solid mural nodule
3. Commonly located in the cerebellum

Low-grade astrocytoma

1. Poorly demarcated tumor
2. Tumor mass causing enlargement of the involved portion of the brain and blurring of anatomical landmarks
3. Commonly located in the cerebral hemisphere

Anaplastic astrocytoma

1. Spongy or gelationous mass
2. Ill defined borders
3. Microcysts
4. Calcification
5. Commonly located in frontal lobe, temporal lobe, brain stem, or spinal cord

Glioblastoma multiforme

1. Poorly-marginated, diffusely infiltrating tumor
2. Firm or gelatinous in consistency
3. Central necrotic core
4. Commonly located in the frontal and temporal lobe

Oligodendroglioma

1. Well circumscribed tumor
2. Pinkish-white in color
3. Mucinous changes
4. Commonly located in the frontal lobe, followed by parietal and temporal lobes

Ependymoma

1. Well-differentiated tumor
2. Exophytic pattern of growth
3. Commonly located at the fourth ventricle and filum terminale


Gallery

Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

Microscopic Pathology

The histopathological appearance of glioma varies with the tumor grade and type, with increasing cellular atypia, mitoses, endothelial cell proliferation, and necrosis. Common findings are listed below:[4][5][6][7][8]

Type of glioma Histopathological features

Pilocytic astrocytoma

1. Low cellularity without mitoses or anaplasia
2. Classically biphasic
  • Fibrillar
  • Microcystic
3. Hair-like fibers best observed on smear or with GFAP
4. Rosenthal fibers
5. Eosinophilic granular bodies
6. Microvascular proliferation
7. Focal pseudopalisading necrosis

Low-grade astrocytoma

1. Stellate, spindle-shaped tumor cells with fiber like processes
2. Large eosinophilic cytoplasmic mass
3. Forms microcysts

Anaplastic astrocytoma

1. Astrocytic tumor cells with:

Glioblastoma multiforme

1. Astrocytic tumor cells with:

Oligodendroglioma

1. Diffusely growing tumor
2. Highly cellular lesion resembling fried eggs with:

Ependymoma

1. Tadpole-shaped cells resembling an ice cream cone
2. Nuclear features monotonous, i.e. "boring"
  • Little variation in size, shape, and staining
3. Rosettes: circular nuclear free zones/cells arranged in a pseudoglandular fashion (2 types)
  • Perivascular pseudorosettes: tumor cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumor cells) surrounding blood vessel (nucleus-free zone). More common than ependymal rosette but less specific
  • Ependymal rosette (true ependymal rosette): rosette has an empty space at the centre


Gallery

Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

References

  1. 1.0 1.1 Pathology of glioma. http://www.surgwiki.com/wiki/Intracranial_tumours,_infection_and_aneurysms
  2. 2.0 2.1 Pathology of glioma. Wikipedia. https://en.wikipedia.org/wiki/Glioma
  3. 3.0 3.1 3.2 Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M (2006). "Epidemiology and molecular pathology of glioma". Nat Clin Pract Neurol. 2 (9): 494–503, quiz 1 p following 516. doi:10.1038/ncpneuro0289. PMID 16932614.
  4. 4.0 4.1 4.2 Pathology of pilocytic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php/Pilocytic_astrocytoma
  5. 5.0 5.1 5.2 Pathology of gliomas. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
  6. 6.0 6.1 6.2 Pathology of anaplastic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php?title=Neuropathology_tumours&redirect=no#Infiltrative_astrocytomas
  7. 7.0 7.1 7.2 Pathology of glioblastoma. Libre Pathology. http://librepathology.org/wiki/index.php/Glioblastoma
  8. 8.0 8.1 8.2 Pathology of ependymoma. Libre Pathology. http://librepathology.org/wiki/index.php/Ependymoma
  9. Dubois LG, Campanati L, Righy C, D'Andrea-Meira I, Spohr TC, Porto-Carreiro I; et al. (2014). "Gliomas and the vascular fragility of the blood brain barrier". Front Cell Neurosci. 8: 418. doi:10.3389/fncel.2014.00418. PMC 4264502. PMID 25565956.
  10. Reuss, D; von Deimling, A (2009). "Hereditary tumor syndromes and gliomas". Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer. 171: 83–102. doi:10.1007/978-3-540-31206-2_5. PMID 19322539.


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