Subependymal giant cell astrocytoma pathophysiology: Difference between revisions
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*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> | *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> | ||
*TSC1 and TSC2 encodes the proteins tuberin and hamartin, respectively. The tuberin/harmatin 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> | *TSC1 and TSC2 encodes the proteins tuberin and hamartin, respectively. The tuberin/harmatin 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> | ||
*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> | *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> | *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> | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]
Overview
Subependymal giant cell astrocytoma is believed to arise from a subependymal nodule present in the ventricular wall of a patient with tuberous sclerosis.[1][2] Genes involved in the pathogenesis of subependymal giant cell astrocytoma include TSC1 and TSC2. Subependymal giant cell astrocytoma is almost exclusively associated with tuberous sclerosis complex, which is an autosomal dominant disorder.[3] 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.[4][5] 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.[6][7] Subependymal giant cell astrocytoma is demonstrated by positivity to tumor markers such as GFAP, vimentin, S-100, neurofilament, and synaptophysin.[2][8][9][10]
Pathophysiology
Pathogenesis
- 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.[11]
- It is classified as a WHO grade I central nervous system tumor.
- It is of glioneuronal origin and typically arises from the caudothalamic groove adjacent to the foramen of monro.[3][12]
- 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.[11]
- TSC1 and TSC2 encodes the proteins tuberin and hamartin, respectively. The tuberin/harmatin 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.[11]
- 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.[3]
- 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.[2]
- It is believed to arise from a 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.[2]
- On Immunohistochemistry, the tumor cells test positive for the glial fibrillary acidic protein and microtubule-associated protein 2.[2]
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Genetics
Genes involved in the pathogenesis of subependymal giant cell astrocytoma include:[13]
- TSC1
- TSC2
Associated Conditions
Conditions associated with subependymal giant cell astrocytoma include:[13]
- Tuberous sclerosis
Gross Pathology
Microscopic Pathology
On microscopic histopathological analysis, subependymal giant cell astrocytoma is characterized by:[2][6][7][14][11][15][15]
- Pleomorphic multinuleated eosinophilic cells
- Streams of elongated tumor cells with abundant cytoplasm
- Clustered cells arranged in a perivascular pseudopallisading pattern
- Evenly distributed granular chromatin
- Frequent binucleation and multinucleation
- 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 positive on immunohistochemistry for glial fibrillary acidic protein, microtubule-associated protein 2, synaptophysin, S-100, neurofilament, and neuron-specific enolase.
References
- ↑ 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
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 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.
- ↑ 3.0 3.1 3.2 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.
- ↑ Final Diagnosis-Subependymal giant cell astrocytoma. upmc.edu 2015. http://path.upmc.edu/cases/case179/dx.html. Accessed on November 4, 2015
- ↑ 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
- ↑ 6.0 6.1 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.
- ↑ 7.0 7.1 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
- ↑ 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
- ↑ Hirose T, Scheithauer BW, Lopes MB, Gerber HA, Altermatt HJ, Hukee MJ; et al. (1995). "Tuber and subependymal giant cell astrocytoma associated with tuberous sclerosis: an immunohistochemical, ultrastructural, and immunoelectron and microscopic study". Acta Neuropathol. 90 (4): 387–99. PMID 8546029.
- ↑ Lopes MB, Altermatt HJ, Scheithauer BW, Shepherd CW, VandenBerg SR (1996). "Immunohistochemical characterization of subependymal giant cell astrocytomas". Acta Neuropathol. 91 (4): 368–75. PMID 8928613.
- ↑ 11.0 11.1 11.2 11.3 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.
- ↑ 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.
- ↑ 13.0 13.1 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.
- ↑ 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.
- ↑ 15.0 15.1 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.