Subependymal giant cell astrocytoma pathophysiology: Difference between revisions

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__NOTOC__
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{{Subependymal giant cell astrocytoma}}
{{Subependymal giant cell astrocytoma}}
{{CMG}}{{AE}}{{SR}}
{{CMG}}{{AE}} {{IO}}, {{SR}}


==Overview==
==Overview==
Subependymal giant cell astrocytoma is believed to arise from a [[subependymal|subependymal nodule]] present in the ventricular wall of a patient with [[tuberous sclerosis]].<ref name=Pathogenesisofsega1>Pathology of subependymal giant cell astrocytoma. Dr. Bruno Di Muzio and Dr. Jeremy Jones et al. Radiopaedia 2015. http://radiopaedia.org/articles/subependymal-giant-cell-astrocytoma. Accessed on November 2, 2015</ref><ref name="pmid25977907">{{cite journal| author=Jung TY, Kim YH, Jung S, Baek HJ, Lee KH| title=The clinical characteristics of subependymal giant cell astrocytoma: five cases. | journal=Brain Tumor Res Treat | year= 2015 | volume= 3 | issue= 1 | pages= 44-7 | pmid=25977907 | doi=10.14791/btrt.2015.3.1.44 | pmc=PMC4426277 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25977907  }} </ref> Genes involved in the pathogenesis of subependymal giant cell astrocytoma include ''[[TSC1]]'' and ''[[TSC2]]''. Subependymal giant cell astrocytomas are almost exclusively associated with [[tuberous sclerosis complex]], which is an autosomal dominant disorder.<ref name="RothRoach2013">{{cite journal|last1=Roth|first1=Jonathan|last2=Roach|first2=E. Steve|last3=Bartels|first3=Ute|last4=Jóźwiak|first4=Sergiusz|last5=Koenig|first5=Mary Kay|last6=Weiner|first6=Howard L.|last7=Franz|first7=David N.|last8=Wang|first8=Henry Z.|title=Subependymal Giant Cell Astrocytoma: Diagnosis, Screening, and Treatment. Recommendations From the International Tuberous Sclerosis Complex Consensus Conference 2012|journal=Pediatric Neurology|volume=49|issue=6|year=2013|pages=439–444|issn=08878994|doi=10.1016/j.pediatrneurol.2013.08.017}}</ref> On gross pathology, subependymal giant cell astrocytoma is characterized by a large, fleshy, well-circumscribed intraventricular mass in the wall of the lateral ventricle near the [[foramen of Monro]], that does not invade into the periventricular parenchyma.<ref name=grosspathologyofsega>Final Diagnosis-Subependymal giant cell astrocytoma. upmc.edu 2015. http://path.upmc.edu/cases/case179/dx.html. Accessed on November 4, 2015</ref><ref name=grossfeaturesofsega>Gross features of subependymal giant cell astrocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Subependymal_giant_cell_astrocytoma. Accessed on November 2, 2015</ref> On microscopic histopathological analysis, subependymal giant cell astrocytoma is characterized by three types of cells (fibrillated elongated spindle cells, swollen gemistocytic-like cells, and giant ganglion-like cells) with nuclear pseudoinclusions and rosettes, perivascular inflammatory cells, and glassy [[eosinophilic]] cytoplasm.<ref name=MicroscopicpathologyofSEGA1>Microscopic features of subependymal giant cell astrocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Subependymal_giant_cell_astrocytoma. Accessed on November 2, 2015</ref><ref name="OuyangZhang2014">{{cite journal|last1=Ouyang|first1=Taohui|last2=Zhang|first2=Na|last3=Benjamin|first3=Thomas|last4=Wang|first4=Long|last5=Jiao|first5=Jiantong|last6=Zhao|first6=Yiqing|last7=Chen|first7=Jian|title=Subependymal giant cell astrocytoma: current concepts, management, and future directions|journal=Child's Nervous System|volume=30|issue=4|year=2014|pages=561–570|issn=0256-7040|doi=10.1007/s00381-014-2383-x}}</ref> Subependymal giant cell astrocytoma is demonstrated by positivity to [[tumor marker]]s such as [[GFAP]], [[vimentin]], [[S-100 protein|S-100]], [[neurofilament]], and [[synaptophysin]].<ref name=Immunohistochemistryofsega1>IHC features of subependymal giant cell astrocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Subependymal_giant_cell_astrocytoma. Accessed on October 2, 2015</ref><ref name="pmid8546029">{{cite journal| author=Hirose T, Scheithauer BW, Lopes MB, Gerber HA, Altermatt HJ, Hukee MJ et al.| title=Tuber and subependymal giant cell astrocytoma associated with tuberous sclerosis: an immunohistochemical, ultrastructural, and immunoelectron and microscopic study. | journal=Acta Neuropathol | year= 1995 | volume= 90 | issue= 4 | pages= 387-99 | pmid=8546029 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8546029  }} </ref><ref name="pmid25977907">{{cite journal| author=Jung TY, Kim YH, Jung S, Baek HJ, Lee KH| title=The clinical characteristics of subependymal giant cell astrocytoma: five cases. | journal=Brain Tumor Res Treat | year= 2015 | volume= 3 | issue= 1 | pages= 44-7 | pmid=25977907 | doi=10.14791/btrt.2015.3.1.44 | pmc=PMC4426277 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25977907  }} </ref><ref name="pmid8928613">{{cite journal| author=Lopes MB, Altermatt HJ, Scheithauer BW, Shepherd CW, VandenBerg SR| title=Immunohistochemical characterization of subependymal giant cell astrocytomas. | journal=Acta Neuropathol | year= 1996 | volume= 91 | issue= 4 | pages= 368-75 | pmid=8928613 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8928613  }} </ref>
Subependymal giant cell astrocytoma is almost exclusively associated with [[tuberous sclerosis complex]], which is an [[autosomal dominant]] disorder. It is associated with inactivation of the [[tumor suppressor genes]], [[TSC1]] and/or [[TSC2]]. It is also believed to arise from a [[subependymal|subependymal nodule]] present in the ventricular wall of a patient with [[tuberous sclerosis]]. Some of the common findings seen on microscopic pathology include [[pleomorphic]] multinuleated [[eosinophilic]] cells, streams of elongated tumor cells with abundant [[cytoplasm]], and clustered cells arranged in a perivascular pseudopallisading pattern. On [[immunohistochemistry]], the [[tumor]] cells are positive for [[glial fibrillary acidic protein]], [[microtubule-associated protein 2]], [[synaptophysin]], [[S-100]], [[neurofilament]], and [[neuron-specific enolase]].


==Pathophysiology==
==Pathophysiology==
===Pathogenesis===
===Pathogenesis===
*Subependymal giant cell astrocytoma is believed to arise from a [[subependymal|subependymal nodule]] present in the ventricular wall of a patient with [[tuberous sclerosis]].<ref name=Pathogenesisofsega1>Pathology of subependymal giant cell astrocytoma. Dr. Bruno Di Muzio and Dr. Jeremy Jones et al. Radiopaedia 2015. http://radiopaedia.org/articles/subependymal-giant-cell-astrocytoma. Accessed on November 2, 2015</ref><ref name="pmid25977907">{{cite journal| author=Jung TY, Kim YH, Jung S, Baek HJ, Lee KH| title=The clinical characteristics of subependymal giant cell astrocytoma: five cases. | journal=Brain Tumor Res Treat | year= 2015 | volume= 3 | issue= 1 | pages= 44-7 | pmid=25977907 | doi=10.14791/btrt.2015.3.1.44 | pmc=PMC4426277 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25977907  }} </ref>
*Subependymal giant cell astrocytoma is a rare, [[benign tumor]] predominantly associated with [[tuberous sclerosis complex]], although a few cases have been reported in patients without evidence of [[tuberous sclerosis]].<ref name="BeaumontGodzik2015">{{cite journal|last1=Beaumont|first1=Thomas L.|last2=Godzik|first2=Jakub|last3=Dahiya|first3=Sonika|last4=Smyth|first4=Matthew D.|title=Subependymal giant cell astrocytoma in the absence of tuberous sclerosis complex: case report|journal=Journal of Neurosurgery: Pediatrics|volume=16|issue=2|year=2015|pages=134–137|issn=1933-0707|doi=10.3171/2015.1.PEDS13146}}</ref>
*Subependymal giant cell astrocytoma has both glial and neuronal components.<ref name="pmid23391693">{{cite journal| author=Jóźwiak S, Nabbout R, Curatolo P, participants of the TSC Consensus Meeting for SEGA and Epilepsy Management| title=Management of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC): Clinical recommendations. | journal=Eur J Paediatr Neurol | year= 2013 | volume= 17 | issue= 4 | pages= 348-52 | pmid=23391693 | doi=10.1016/j.ejpn.2012.12.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23391693 }} </ref>
*It is classified as a WHO grade I [[central nervous system]] tumor.
*The various risk factors that may lead to the transformation of a subependymal nodule into a subependymal giant cell astrocytic tumor include:<ref name="OuyangZhang2014">{{cite journal|last1=Ouyang|first1=Taohui|last2=Zhang|first2=Na|last3=Benjamin|first3=Thomas|last4=Wang|first4=Long|last5=Jiao|first5=Jiantong|last6=Zhao|first6=Yiqing|last7=Chen|first7=Jian|title=Subependymal giant cell astrocytoma: current concepts, management, and future directions|journal=Child's Nervous System|volume=30|issue=4|year=2014|pages=561–570|issn=0256-7040|doi=10.1007/s00381-014-2383-x}}</ref>
*It is of glioneuronal origin and typically arises from the caudothalamic groove adjacent to the foramen of monro.<ref name="RothRoach2013">{{cite journal|last1=Roth|first1=Jonathan|last2=Roach|first2=E. Steve|last3=Bartels|first3=Ute|last4=Jóźwiak|first4=Sergiusz|last5=Koenig|first5=Mary Kay|last6=Weiner|first6=Howard L.|last7=Franz|first7=David N.|last8=Wang|first8=Henry Z.|title=Subependymal Giant Cell Astrocytoma: Diagnosis, Screening, and Treatment. Recommendations From the International Tuberous Sclerosis Complex Consensus Conference 2012|journal=Pediatric Neurology|volume=49|issue=6|year=2013|pages=439–444|issn=08878994|doi=10.1016/j.pediatrneurol.2013.08.017}}</ref><ref name="LouisOhgaki2007">{{cite journal|last1=Louis|first1=David N.|last2=Ohgaki|first2=Hiroko|last3=Wiestler|first3=Otmar D.|last4=Cavenee|first4=Webster K.|last5=Burger|first5=Peter C.|last6=Jouvet|first6=Anne|last7=Scheithauer|first7=Bernd W.|last8=Kleihues|first8=Paul|title=The 2007 WHO Classification of Tumours of the Central Nervous System|journal=Acta Neuropathologica|volume=114|issue=2|year=2007|pages=97–109|issn=0001-6322|doi=10.1007/s00401-007-0243-4}}</ref>
**Diameter above 5 mm
*The inactivation of the [[tumor suppressor genes]] [[TSC1]] (on [[chromosome]] 9q34) and/or [[TSC2]] (on [[chromosome]] 16p13) results in the formation of subependymal giant cell astrocytoma in people with [[tuberous sclerosis]].<ref name="BeaumontGodzik2015">{{cite journal|last1=Beaumont|first1=Thomas L.|last2=Godzik|first2=Jakub|last3=Dahiya|first3=Sonika|last4=Smyth|first4=Matthew D.|title=Subependymal giant cell astrocytoma in the absence of tuberous sclerosis complex: case report|journal=Journal of Neurosurgery: Pediatrics|volume=16|issue=2|year=2015|pages=134–137|issn=1933-0707|doi=10.3171/2015.1.PEDS13146}}</ref>
**Incomplete [[calcification]] at the perimonro region
*[[TSC1]] and [[TSC2]] encodes the proteins [[tuberin]] and [[hamartin]], respectively. The [[tuberin]]/[[hamartin]] complex suppresses [[Ras]] [[homolog]] enriched in [[brain]] (RHES) which functions as a direct activator of the mammalian target of rapamycin (mTOR). The complex also inhibits cyclin-dependent kinase inhibitor 1B, which regulates [[cell cycle]] progression. The activation of mTOR and progression of the [[cell cycle]] from the loss of upstream inhibition leads to protein translation, cell growth, and proliferation.<ref name="BeaumontGodzik2015">{{cite journal|last1=Beaumont|first1=Thomas L.|last2=Godzik|first2=Jakub|last3=Dahiya|first3=Sonika|last4=Smyth|first4=Matthew D.|title=Subependymal giant cell astrocytoma in the absence of tuberous sclerosis complex: case report|journal=Journal of Neurosurgery: Pediatrics|volume=16|issue=2|year=2015|pages=134–137|issn=1933-0707|doi=10.3171/2015.1.PEDS13146}}</ref>
**Enhancement after [[gadolinium]] administration
*It is believed that a subependymal nodule, which are common [[brain]] masses seen in [[tuberous sclerosis]], can transform to subependymal giant cell astrocytoma.
*It is commonly located in the ventricles but a few may have extraventricular locations.<ref name="RothRoach2013">{{cite journal|last1=Roth|first1=Jonathan|last2=Roach|first2=E. Steve|last3=Bartels|first3=Ute|last4=Jóźwiak|first4=Sergiusz|last5=Koenig|first5=Mary Kay|last6=Weiner|first6=Howard L.|last7=Franz|first7=David N.|last8=Wang|first8=Henry Z.|title=Subependymal Giant Cell Astrocytoma: Diagnosis, Screening, and Treatment. Recommendations From the International Tuberous Sclerosis Complex Consensus Conference 2012|journal=Pediatric Neurology|volume=49|issue=6|year=2013|pages=439–444|issn=08878994|doi=10.1016/j.pediatrneurol.2013.08.017}}</ref>
*Subependymal giant cell astrocytoma is a major cause of [[tuberous sclerosis]] complex-related [[morbidity]] and [[mortality]] during the pediatrics age, as it is seen in 10 to 20% of these patients.<ref name="pmid25977907">{{cite journal| author=Jung TY, Kim YH, Jung S, Baek HJ, Lee KH| title=The clinical characteristics of subependymal giant cell astrocytoma: five cases. | journal=Brain Tumor Res Treat | year= 2015 | volume= 3 | issue= 1 | pages= 44-7 | pmid=25977907 | doi=10.14791/btrt.2015.3.1.44 | pmc=4426277 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25977907  }} </ref>
*It is believed to arise from a [[subependymal|subependymal nodule]] but this is controversial because subependymal giant cell astrocytomas are located in the caudothalamic groove while subependymal nodules are located in the ependymal lining of the lateral ventricles along the caudate nucleus.<ref name="pmid25977907">{{cite journal| author=Jung TY, Kim YH, Jung S, Baek HJ, Lee KH| title=The clinical characteristics of subependymal giant cell astrocytoma: five cases. | journal=Brain Tumor Res Treat | year= 2015 | volume= 3 | issue= 1 | pages= 44-7 | pmid=25977907 | doi=10.14791/btrt.2015.3.1.44 | pmc=PMC4426277 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25977907 }} </ref>
*On [[immunohistochemistry]], the [[tumor]] cells test positive for the [[glial fibrillary acidic protein]] and [[microtubule-associated protein 2]].<ref name="pmid25977907">{{cite journal| author=Jung TY, Kim YH, Jung S, Baek HJ, Lee KH| title=The clinical characteristics of subependymal giant cell astrocytoma: five cases. | journal=Brain Tumor Res Treat | year= 2015 | volume= 3 | issue= 1 | pages= 44-7 | pmid=25977907 | doi=10.14791/btrt.2015.3.1.44 | pmc=4426277 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25977907  }} </ref>


:::::::::::{| style="border: 0px; font-size: 90%; margin: 3px; width:650px"
==Genetics==
|valign=top|
[[Genes]] involved in the [[pathogenesis]] of subependymal giant cell astrocytoma include:<ref name="pmid21465222">{{cite journal| author=Campen CJ, Porter BE| title=Subependymal Giant Cell Astrocytoma (SEGA) Treatment Update. | journal=Curr Treat Options Neurol | year= 2011 | volume= 13 | issue= 4 | pages= 380-5 | pmid=21465222 | doi=10.1007/s11940-011-0123-z | pmc=3130084 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21465222  }} </ref>
|+
*[[TSC1]]
! style="background: #4479BA; width: 800px;" | {{fontcolor|#FFF|Subependymal giant cell astrocytoma}}
*[[TSC2]]
! style="background: #4479BA; width: 800px;" | {{fontcolor|#FFF|Subependymal nodule}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" |
*Large-sized
| style="padding: 5px 5px; background: #DCDCDC;" |
*Small-sized
|-
| style="padding: 5px 5px; background: #DCDCDC;" |
*Tumor mass grows in size
| style="padding: 5px 5px; background: #DCDCDC;" |
*Remains stable in size
|-
| style="padding: 5px 5px; background: #DCDCDC;" |
*Mass effect
| style="padding: 5px 5px; background: #DCDCDC;" |
*No mass effect
|-
| style="padding: 5px 5px; background: #DCDCDC;" |
*Located in the caudothalamic groove
| style="padding: 5px 5px; background: #DCDCDC;" |
*Located in the ependymal lining of the lateral ventricles along the caudate nucleus
|-
| style="padding: 5px 5px; background: #DCDCDC;" |
*No calcification
| style="padding: 5px 5px; background: #DCDCDC;" |
*Calcification present
|-
| style="padding: 5px 5px; background: #DCDCDC;" |
*Contrast enhancement present
| style="padding: 5px 5px; background: #DCDCDC;" |
*Nonenhancing lesions
|}


===Genetic===
==Associated Conditions==
*Development of subependymal giant cell astrocytoma is the result of multiple genetic mutations.
Conditions associated with subependymal giant cell astrocytoma include:<ref name="pmid21465222">{{cite journal| author=Campen CJ, Porter BE| title=Subependymal Giant Cell Astrocytoma (SEGA) Treatment Update. | journal=Curr Treat Options Neurol | year= 2011 | volume= 13 | issue= 4 | pages= 380-5 | pmid=21465222 | doi=10.1007/s11940-011-0123-z | pmc=3130084 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21465222 }} </ref>
*Genes involved in the pathogenesis of subependymal giant cell astrocytoma include:<ref name="RothRoach2013">{{cite journal|last1=Roth|first1=Jonathan|last2=Roach|first2=E. Steve|last3=Bartels|first3=Ute|last4=Jóźwiak|first4=Sergiusz|last5=Koenig|first5=Mary Kay|last6=Weiner|first6=Howard L.|last7=Franz|first7=David N.|last8=Wang|first8=Henry Z.|title=Subependymal Giant Cell Astrocytoma: Diagnosis, Screening, and Treatment. Recommendations From the International Tuberous Sclerosis Complex Consensus Conference 2012|journal=Pediatric Neurology|volume=49|issue=6|year=2013|pages=439–444|issn=08878994|doi=10.1016/j.pediatrneurol.2013.08.017}}</ref>
:*''[[TSC1]]''
:*''[[TSC2]]''
*Both the genes, ''[[TSC1]]'' and ''[[TSC2]]'', are [[tumor suppressor genes]].<ref name="RothRoach2013">{{cite journal|last1=Roth|first1=Jonathan|last2=Roach|first2=E. Steve|last3=Bartels|first3=Ute|last4=Jóźwiak|first4=Sergiusz|last5=Koenig|first5=Mary Kay|last6=Weiner|first6=Howard L.|last7=Franz|first7=David N.|last8=Wang|first8=Henry Z.|title=Subependymal Giant Cell Astrocytoma: Diagnosis, Screening, and Treatment. Recommendations From the International Tuberous Sclerosis Complex Consensus Conference 2012|journal=Pediatric Neurology|volume=49|issue=6|year=2013|pages=439–444|issn=08878994|doi=10.1016/j.pediatrneurol.2013.08.017}}</ref>
*''[[TSC1]]'' is located on [[chromosome 9|chromosome 9q34]] and ''[[TSC2]]'' is located on [[chromosome 16|chromosome 16p13]].
*Protein products of the ''[[TSC1]]'' and ''[[TSC2]]'' genes, [[hamartin]] and [[tuberin]], respectively, form a [[heterodimer]] that suppresses the [[mammalian target of rapamycin|mammalian target of rapamycin (mTOR)]], a major cell growth and proliferation controller. In [[tuberous sclerosis complex]] (TSC), increased mTOR activation leads to disorganized cellular overgrowth, abnormal differentiation, increased protein translation, and the formation of tumors.<ref name="pmid25977907">{{cite journal| author=Jung TY, Kim YH, Jung S, Baek HJ, Lee KH| title=The clinical characteristics of subependymal giant cell astrocytoma: five cases. | journal=Brain Tumor Res Treat | year= 2015 | volume= 3 | issue= 1 | pages= 44-7 | pmid=25977907 | doi=10.14791/btrt.2015.3.1.44 | pmc=PMC4426277 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25977907 }} </ref><ref name="RothRoach2013">{{cite journal|last1=Roth|first1=Jonathan|last2=Roach|first2=E. Steve|last3=Bartels|first3=Ute|last4=Jóźwiak|first4=Sergiusz|last5=Koenig|first5=Mary Kay|last6=Weiner|first6=Howard L.|last7=Franz|first7=David N.|last8=Wang|first8=Henry Z.|title=Subependymal Giant Cell Astrocytoma: Diagnosis, Screening, and Treatment. Recommendations From the International Tuberous Sclerosis Complex Consensus Conference 2012|journal=Pediatric Neurology|volume=49|issue=6|year=2013|pages=439–444|issn=08878994|doi=10.1016/j.pediatrneurol.2013.08.017}}</ref>
*Other genes that may be involved in the pathogenesis of subependymal giant cell astrocytoma include:<ref name="OuyangZhang2014">{{cite journal|last1=Ouyang|first1=Taohui|last2=Zhang|first2=Na|last3=Benjamin|first3=Thomas|last4=Wang|first4=Long|last5=Jiao|first5=Jiantong|last6=Zhao|first6=Yiqing|last7=Chen|first7=Jian|title=Subependymal giant cell astrocytoma: current concepts, management, and future directions|journal=Child's Nervous System|volume=30|issue=4|year=2014|pages=561–570|issn=0256-7040|doi=10.1007/s00381-014-2383-x}}</ref>
**[[Annexin A1|ANXA1]]
**[[GPNMB]]
**[[Lactotransferrin|LTF]]
**[[Rho family of GTPases|RND3]]
**[[S100A11]]
**[[SFRP4]]
**[[Pentraxins|NPTX1]]


===Associated Conditions===
*[[Tuberous sclerosis]]
*Subependymal giant cell astrocytomas are almost exclusively associated with [[tuberous sclerosis complex]], which is an autosomal dominant disorder.<ref name="RothRoach2013">{{cite journal|last1=Roth|first1=Jonathan|last2=Roach|first2=E. Steve|last3=Bartels|first3=Ute|last4=Jóźwiak|first4=Sergiusz|last5=Koenig|first5=Mary Kay|last6=Weiner|first6=Howard L.|last7=Franz|first7=David N.|last8=Wang|first8=Henry Z.|title=Subependymal Giant Cell Astrocytoma: Diagnosis, Screening, and Treatment. Recommendations From the International Tuberous Sclerosis Complex Consensus Conference 2012|journal=Pediatric Neurology|volume=49|issue=6|year=2013|pages=439–444|issn=08878994|doi=10.1016/j.pediatrneurol.2013.08.017}}</ref>
*Subependymal giant cell astrocytomas are characteristic brain tumors that occur in 10% to 20% of [[tuberous sclerosis]] patients.


===Gross Pathology===
==Microscopic Pathology==
*On gross pathology, subependymal giant cell astrocytoma is characterized by a large, fleshy, well-circumscribed intraventricular mass in the wall of the lateral ventricle near the [[foramen of Monro]], that does not invade into the periventricular parenchyma.<ref name=grosspathologyofsega>Final Diagnosis-Subependymal giant cell astrocytoma. upmc.edu 2015. http://path.upmc.edu/cases/case179/dx.html. Accessed on November 4, 2015</ref><ref name=grossfeaturesofsega>Gross features of subependymal giant cell astrocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Subependymal_giant_cell_astrocytoma. Accessed on November 2, 2015</ref>
On microscopic histopathological analysis, subependymal giant cell astrocytoma is characterized by:<ref name="pmid25977907">{{cite journal| author=Jung TY, Kim YH, Jung S, Baek HJ, Lee KH| title=The clinical characteristics of subependymal giant cell astrocytoma: five cases. | journal=Brain Tumor Res Treat | year= 2015 | volume= 3 | issue= 1 | pages= 44-7 | pmid=25977907 | doi=10.14791/btrt.2015.3.1.44 | pmc=4426277 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25977907  }} </ref><ref name="OuyangZhang2014">{{cite journal|last1=Ouyang|first1=Taohui|last2=Zhang|first2=Na|last3=Benjamin|first3=Thomas|last4=Wang|first4=Long|last5=Jiao|first5=Jiantong|last6=Zhao|first6=Yiqing|last7=Chen|first7=Jian|title=Subependymal giant cell astrocytoma: current concepts, management, and future directions|journal=Child's Nervous System|volume=30|issue=4|year=2014|pages=561–570|issn=0256-7040|doi=10.1007/s00381-014-2383-x}}</ref><ref name="MicroscopicpathologyofSEGA1">Microscopic features of subependymal giant cell astrocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Subependymal_giant_cell_astrocytoma. Accessed on November 2, 2015</ref><ref name="pmid2067610">{{cite journal| author=Shepherd CW, Scheithauer BW, Gomez MR, Altermatt HJ, Katzmann JA| title=Subependymal giant cell astrocytoma: a clinical, pathological, and flow cytometric study. | journal=Neurosurgery | year= 1991 | volume= 28 | issue= 6 | pages= 864-8 | pmid=2067610 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2067610  }} </ref><ref name="BeaumontGodzik2015">{{cite journal|last1=Beaumont|first1=Thomas L.|last2=Godzik|first2=Jakub|last3=Dahiya|first3=Sonika|last4=Smyth|first4=Matthew D.|title=Subependymal giant cell astrocytoma in the absence of tuberous sclerosis complex: case report|journal=Journal of Neurosurgery: Pediatrics|volume=16|issue=2|year=2015|pages=134–137|issn=1933-0707|doi=10.3171/2015.1.PEDS13146}}</ref><ref name="pmid27013816">{{cite journal| author=Nasit J, Vaghsiya V, Hiryur S, Patel S| title=Intraoperative Squash Cytologic Features of Subependymal Giant Cell Astrocytoma. | journal=J Lab Physicians | year= 2016 | volume= 8 | issue= 1 | pages= 58-61 | pmid=27013816 | doi=10.4103/0974-2727.176231 | pmc=4785769 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27013816  }} </ref><ref name="pmid27013816">{{cite journal| author=Nasit J, Vaghsiya V, Hiryur S, Patel S| title=Intraoperative Squash Cytologic Features of Subependymal Giant Cell Astrocytoma. | journal=J Lab Physicians | year= 2016 | volume= 8 | issue= 1 | pages= 58-61 | pmid=27013816 | doi=10.4103/0974-2727.176231 | pmc=4785769 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27013816  }} </ref>
*Subependymal giant cell astrocytoma typically arises at the caudothalamic groove adjacent to the [[foramen of Monro]].<ref name="RothRoach2013">{{cite journal|last1=Roth|first1=Jonathan|last2=Roach|first2=E. Steve|last3=Bartels|first3=Ute|last4=Jóźwiak|first4=Sergiusz|last5=Koenig|first5=Mary Kay|last6=Weiner|first6=Howard L.|last7=Franz|first7=David N.|last8=Wang|first8=Henry Z.|title=Subependymal Giant Cell Astrocytoma: Diagnosis, Screening, and Treatment. Recommendations From the International Tuberous Sclerosis Complex Consensus Conference 2012|journal=Pediatric Neurology|volume=49|issue=6|year=2013|pages=439–444|issn=08878994|doi=10.1016/j.pediatrneurol.2013.08.017}}</ref>
*[[Pleomorphic]] multinuleated [[eosinophilic]] cells
*Other common intracranial sites associated with subependymal giant cell astrocytoma include:<ref name="RothRoach2013">{{cite journal|last1=Roth|first1=Jonathan|last2=Roach|first2=E. Steve|last3=Bartels|first3=Ute|last4=Jóźwiak|first4=Sergiusz|last5=Koenig|first5=Mary Kay|last6=Weiner|first6=Howard L.|last7=Franz|first7=David N.|last8=Wang|first8=Henry Z.|title=Subependymal Giant Cell Astrocytoma: Diagnosis, Screening, and Treatment. Recommendations From the International Tuberous Sclerosis Complex Consensus Conference 2012|journal=Pediatric Neurology|volume=49|issue=6|year=2013|pages=439–444|issn=08878994|doi=10.1016/j.pediatrneurol.2013.08.017}}</ref>
*Streams of elongated [[tumor]] cells with abundant [[cytoplasm]]
:*[[Fornix of brain|Fornix]]
*Clustered cells arranged in a perivascular pseudopallisading pattern
:*[[Hypothalamus]]
*Evenly distributed granular [[chromatin]]
:*[[Basal ganglia]]
*Frequent binucleation and multinucleation
:*[[Genu of internal capsule|Genu of the internal capsule]]
*[[Vesicular]] [[nuclei]]
*Occasional distinct to prominent [[nucleoli]]
*On rare occasions, there can be atypical features such as vascular [[endothelial]] proliferations, [[mitosis]], and [[necrosis]]
*Tumor cells are positive on [[immunohistochemistry]] for [[glial fibrillary acidic protein]], [[microtubule-associated protein 2]], [[synaptophysin]], [[S-100]], [[neurofilament]], and [[neuron-specific enolase


====Gallery====
[[File:SEGA histology.jpg|400px|thumb|left|Histology showing subependymal giant cell astrocytoma[https://commons.wikimedia.org/wiki/File:SEGA_HE.jpg source:wikimedia commons]]]<br style="clear:left" />
<gallery>
[[File:SEGA histology 2.jpg|400px|thumb|left|histological picture showing presence of neurofilaments on immunohistochemical staining[https://commons.wikimedia.org/wiki/File:SEGA_NF.jpg source:wikimedia commons ]]]<br style="clear:left" />
Image:Subependymal giant cell astrocytoma gross appearance 1.jpg|<sub>Gross specimen of subependymal giant cell astrocytoma showing a large fleshy mass in the midline and producing marked dilatation of the lateral ventricles.<ref name=grossfeaturesofsega>Gross features of subependymal giant cell astrocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Subependymal_giant_cell_astrocytoma. Accessed on November 2, 2015</ref></sub>
[[File:SEGA GFAP.jpg|400px|thumb|left|Histological picture showing immunohistochemical staining for the presence of GFAP[https://commons.wikimedia.org/wiki/File:SEGA_GFAP.jpg source: wikimedia commons ]]]<br style="clear:left" />


</gallery>
==References==
 
===Microscopic pathology===
On microscopic histopathological analysis, subependymal giant cell astrocytoma is characterized by:<ref name=MicroscopicpathologyofSEGA1>Microscopic features of subependymal giant cell astrocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Subependymal_giant_cell_astrocytoma. Accessed on November 2, 2015</ref><ref name="OuyangZhang2014">{{cite journal|last1=Ouyang|first1=Taohui|last2=Zhang|first2=Na|last3=Benjamin|first3=Thomas|last4=Wang|first4=Long|last5=Jiao|first5=Jiantong|last6=Zhao|first6=Yiqing|last7=Chen|first7=Jian|title=Subependymal giant cell astrocytoma: current concepts, management, and future directions|journal=Child's Nervous System|volume=30|issue=4|year=2014|pages=561–570|issn=0256-7040|doi=10.1007/s00381-014-2383-x}}</ref>
*Three types of cells
**Fibrillated elongated spindle cells
**Swollen gemistocytic-like cells
**Giant ganglion-like cells with [[atypia|nuclear atypia]]
*Nuclear pseudoinclusions and rosettes
*Perivascular inflammatory cells ([[lymphocytes|lymphocytic infiltrate]])
*[[Calcification]]
*[[Vesicular]] nuclei
*[[Nuclear]] pseudoinclusions
*Glassy [[eosinophilic]] cytoplasm
*Elongated cells in a fibrillary background
*[[Mast cell|Abundant mast cells]]
*Endothelial proliferation
*[[Necrosis]]
 
According to the ''WHO classification of tumors of the central nervous system'', subependymal giant cell astrocytoma is classified into a ''WHO grade I'' tumor.<ref name="pmid17618441">{{cite journal| author=Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A et al.| title=The 2007 WHO classification of tumours of the central nervous system. | journal=Acta Neuropathol | year= 2007 | volume= 114 | issue= 2 | pages= 97-109 | pmid=17618441 | doi=10.1007/s00401-007-0243-4 | pmc=PMC1929165 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17618441  }} </ref>
 
====Gallery====
<gallery>
File:Subependymal giant cell astrocytoma microscopic appearance 1.jpg|<sub>Typical histology of subependymal giant cell astrocytoma with differentiated giant cells.<ref name=microfeaturesofsgca>Microscopic images of subependymal giant cell astrocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Subependymal_giant_cell_astrocytoma. Accessed on November 2, 2015</ref></sub>
 
</gallery>
 
===Immunohistochemistry===
Subependymal giant cell astrocytoma is demonstrated by positivity to [[tumor marker]]s such as:<ref name=Immunohistochemistryofsega1>IHC features of subependymal giant cell astrocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Subependymal_giant_cell_astrocytoma. Accessed on October 2, 2015</ref><ref name="pmid8546029">{{cite journal| author=Hirose T, Scheithauer BW, Lopes MB, Gerber HA, Altermatt HJ, Hukee MJ et al.| title=Tuber and subependymal giant cell astrocytoma associated with tuberous sclerosis: an immunohistochemical, ultrastructural, and immunoelectron and microscopic study. | journal=Acta Neuropathol | year= 1995 | volume= 90 | issue= 4 | pages= 387-99 | pmid=8546029 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8546029  }} </ref><ref name="pmid25977907">{{cite journal| author=Jung TY, Kim YH, Jung S, Baek HJ, Lee KH| title=The clinical characteristics of subependymal giant cell astrocytoma: five cases. | journal=Brain Tumor Res Treat | year= 2015 | volume= 3 | issue= 1 | pages= 44-7 | pmid=25977907 | doi=10.14791/btrt.2015.3.1.44 | pmc=PMC4426277 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25977907  }} </ref><ref name="pmid8928613">{{cite journal| author=Lopes MB, Altermatt HJ, Scheithauer BW, Shepherd CW, VandenBerg SR| title=Immunohistochemical characterization of subependymal giant cell astrocytomas. | journal=Acta Neuropathol | year= 1996 | volume= 91 | issue= 4 | pages= 368-75 | pmid=8928613 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8928613  }} </ref><ref name="OuyangZhang2014">{{cite journal|last1=Ouyang|first1=Taohui|last2=Zhang|first2=Na|last3=Benjamin|first3=Thomas|last4=Wang|first4=Long|last5=Jiao|first5=Jiantong|last6=Zhao|first6=Yiqing|last7=Chen|first7=Jian|title=Subependymal giant cell astrocytoma: current concepts, management, and future directions|journal=Child's Nervous System|volume=30|issue=4|year=2014|pages=561–570|issn=0256-7040|doi=10.1007/s00381-014-2383-x}}</ref>
*[[GFAP]] +ve (50%)
*[[Vimentin]] +ve (100%)
*[[S-100 protein|S-100]] +ve (100%)
*[[Neurofilament]] +/-ve (ganglionic component)
*[[Synaptophysin]] +/-ve (ganglionic component)
*[[TTF1 (gene)|TTF-1]]
*[[MIB1|MIB-1]] (1-5%)
*[[Microtubule-associated protein|MAP-2]] +ve
*[[Tubulin|Class III beta-tubulin]] +ve
*[[Calbindin|Calbindin 28-kD]] +ve
*[[Somatostatin]] +ve
*[[Met-enkephalin]] +ve
*[[5-hydroxytryptamine]] +ve
*[[Beta-endorphin]] +ve
*[[Neuropeptide Y]] +ve
*[[Serotonin]] +ve
*[[Neuron-Specific Enolase (NSE)|Neuron-specific enolase]]
*[[Substance P]]
*[[Neural cell adhesion molecule]]
 
====Gallery====
<gallery>
Image:Subependymal giant cell astrocytoma microscopic appearance 4.jpg|<sub>Immunohistochemistry staining of a supependymal giant cell astrocytoma showing positivity to GFAP.<ref name=microfeaturesofsgca>Microscopic images of subependymal giant cell astrocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Subependymal_giant_cell_astrocytoma. Accessed on November 2, 2015</ref></sub>
 
</gallery>
 
==Reference==
{{reflist|2}}
{{reflist|2}}


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Latest revision as of 15:47, 8 November 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ifeoma Odukwe, M.D. [2], Sujit Routray, M.D. [3]

Overview

Subependymal giant cell astrocytoma is almost exclusively associated with tuberous sclerosis complex, which is an autosomal dominant disorder. It is associated with inactivation of the tumor suppressor genes, TSC1 and/or TSC2. It is also believed to arise from a subependymal nodule present in the ventricular wall of a patient with tuberous sclerosis. Some of the common findings seen on microscopic pathology include pleomorphic multinuleated eosinophilic cells, streams of elongated tumor cells with abundant cytoplasm, and clustered cells arranged in a perivascular pseudopallisading pattern. On immunohistochemistry, the tumor cells are positive for glial fibrillary acidic protein, microtubule-associated protein 2, synaptophysin, S-100, neurofilament, and neuron-specific enolase.

Pathophysiology

Pathogenesis

Genetics

Genes involved in the pathogenesis of subependymal giant cell astrocytoma include:[5]

Associated Conditions

Conditions associated with subependymal giant cell astrocytoma include:[5]

Microscopic Pathology

On microscopic histopathological analysis, subependymal giant cell astrocytoma is characterized by:[4][6][7][8][1][9][9]

Histology showing subependymal giant cell astrocytomasource:wikimedia commons


histological picture showing presence of neurofilaments on immunohistochemical stainingsource:wikimedia commons


Histological picture showing immunohistochemical staining for the presence of GFAPsource: wikimedia commons


References

  1. ↑ 1.0 1.1 1.2 1.3 Beaumont, Thomas L.; Godzik, Jakub; Dahiya, Sonika; Smyth, Matthew D. (2015). "Subependymal giant cell astrocytoma in the absence of tuberous sclerosis complex: case report". Journal of Neurosurgery: Pediatrics. 16 (2): 134–137. doi:10.3171/2015.1.PEDS13146. ISSN 1933-0707.
  2. ↑ 2.0 2.1 Roth, Jonathan; Roach, E. Steve; Bartels, Ute; Jóźwiak, Sergiusz; Koenig, Mary Kay; Weiner, Howard L.; Franz, David N.; Wang, Henry Z. (2013). "Subependymal Giant Cell Astrocytoma: Diagnosis, Screening, and Treatment. Recommendations From the International Tuberous Sclerosis Complex Consensus Conference 2012". Pediatric Neurology. 49 (6): 439–444. doi:10.1016/j.pediatrneurol.2013.08.017. ISSN 0887-8994.
  3. ↑ Louis, David N.; Ohgaki, Hiroko; Wiestler, Otmar D.; Cavenee, Webster K.; Burger, Peter C.; Jouvet, Anne; Scheithauer, Bernd W.; Kleihues, Paul (2007). "The 2007 WHO Classification of Tumours of the Central Nervous System". Acta Neuropathologica. 114 (2): 97–109. doi:10.1007/s00401-007-0243-4. ISSN 0001-6322.
  4. ↑ 4.0 4.1 4.2 4.3 Jung TY, Kim YH, Jung S, Baek HJ, Lee KH (2015). "The clinical characteristics of subependymal giant cell astrocytoma: five cases". Brain Tumor Res Treat. 3 (1): 44–7. doi:10.14791/btrt.2015.3.1.44. PMC 4426277. PMID 25977907.
  5. ↑ 5.0 5.1 Campen CJ, Porter BE (2011). "Subependymal Giant Cell Astrocytoma (SEGA) Treatment Update". Curr Treat Options Neurol. 13 (4): 380–5. doi:10.1007/s11940-011-0123-z. PMC 3130084. PMID 21465222.
  6. ↑ Ouyang, Taohui; Zhang, Na; Benjamin, Thomas; Wang, Long; Jiao, Jiantong; Zhao, Yiqing; Chen, Jian (2014). "Subependymal giant cell astrocytoma: current concepts, management, and future directions". Child's Nervous System. 30 (4): 561–570. doi:10.1007/s00381-014-2383-x. ISSN 0256-7040.
  7. ↑ Microscopic features of subependymal giant cell astrocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Subependymal_giant_cell_astrocytoma. Accessed on November 2, 2015
  8. ↑ Shepherd CW, Scheithauer BW, Gomez MR, Altermatt HJ, Katzmann JA (1991). "Subependymal giant cell astrocytoma: a clinical, pathological, and flow cytometric study". Neurosurgery. 28 (6): 864–8. PMID 2067610.
  9. ↑ 9.0 9.1 Nasit J, Vaghsiya V, Hiryur S, Patel S (2016). "Intraoperative Squash Cytologic Features of Subependymal Giant Cell Astrocytoma". J Lab Physicians. 8 (1): 58–61. doi:10.4103/0974-2727.176231. PMC 4785769. PMID 27013816.


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