Subependymal giant cell astrocytoma pathophysiology: Difference between revisions
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*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> | *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]]. | *''[[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. | *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> | ||
===Associated Conditions=== | ===Associated Conditions=== | ||
Revision as of 23:56, 3 November 2015
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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
Pathophysiology
Pathogenesis
- Subependymal giant cell astrocytoma is believed to arise from a subependymal nodule present in the ventricular wall of a patient with tuberous sclerosis.[1]
Genetic
- Development of subependymal giant cell astrocytoma is the result of multiple genetic mutations.
- Genes involved in the pathogenesis of subependymal giant cell astrocytoma include:[2]
- Both the genes, TSC1 and TSC2, are tumor suppressor genes.[2]
- TSC1 is located on chromosome 9q34 and TSC2 is located on chromosome 16p13.
- Protein products of the TSC1 and TSC2 genes, hamartin and tuberin, respectively, form a heterodimer that suppresses the 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.[3][2]
Associated Conditions
- Subependymal giant cell astrocytomas are almost exclusively associated with tuberous sclerosis complex, which is an autosomal dominant disorder.[2]
- Subependymal giant cell astrocytomas are characteristic brain tumors that occur in 10% to 20% of tuberous sclerosis patients.
Gross Pathology
- On gross pathology, subependymal giant cell astrocytoma is characterized by:
- Subependymal giant cell astrocytoma typically arises at the caudothalamic groove adjacent to the foramen of Monro.[2]
- Other common intracranial sites associated with subependymal giant cell astrocytoma include:[2]
Gallery
-
![Gross specimen of subependymal giant cell astrocytoma showing a large fleshy mass in the midline and producing marked dilatation of the lateral ventricles.[4]](/images/9/90/Subependymal_giant_cell_astrocytoma_gross_appearance_1.jpg)
Gross specimen of subependymal giant cell astrocytoma showing a large fleshy mass in the midline and producing marked dilatation of the lateral ventricles.[4]
![Gross specimen of subependymal giant cell astrocytoma showing a large fleshy mass in the midline and producing marked dilatation of the lateral ventricles.[4]](/index.php/File:Subependymal_giant_cell_astrocytoma_gross_appearance_1.jpg)
Microscopic pathology
On microscopic histopathological analysis, subependymal giant cell astrocytoma is characterized by:[5]
- Giant cells with nuclear atypia ("bizarre cells", "ganglioid cells")
- Vesicular nuclei
- Nuclear pseudoinclusions
- Glassy eosinophilic cytoplasm
- Elongated cells in a fibrillary background
- Abundant mast cells
- Lymphocytic infiltrates
- 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.[6]
Gallery
-
![Typical histology of subependymal giant cell astrocytoma with differentiated giant cells.[7]](/images/c/c1/Subependymal_giant_cell_astrocytoma_microscopic_appearance_1.jpg)
Typical histology of subependymal giant cell astrocytoma with differentiated giant cells.[7]
![Typical histology of subependymal giant cell astrocytoma with differentiated giant cells.[7]](/index.php/File:Subependymal_giant_cell_astrocytoma_microscopic_appearance_1.jpg)
Immunohistochemistry
Subependymal giant cell astrocytoma is demonstrated by positivity to tumor markers such as:[8][9][3]
- GFAP +ve (50%)
- Vimentin +ve (100%)
- S-100 +ve (100%)
- Neurofilament +/-ve (ganglionic component)
- Synaptophysin +/-ve (ganglionic component)
- TTF-1
- MIB-1 (1-5%)
- MAP-2 +ve
- Class III beta-tubulin +ve
- Calbindin 28-kD +ve
- Somatostatin +ve
- Met-enkephalin +ve
- 5-hydroxytryptamine +ve
- Beta-endorphin +ve
- Neuropeptide Y +ve
Gallery
-
![Immunohistochemistry staining of a supependymal giant cell astrocytoma showing positivity to GFAP.[7]](/images/6/69/Subependymal_giant_cell_astrocytoma_microscopic_appearance_4.jpg)
Immunohistochemistry staining of a supependymal giant cell astrocytoma showing positivity to GFAP.[7]
![Immunohistochemistry staining of a supependymal giant cell astrocytoma showing positivity to GFAP.[7]](/index.php/File:Subependymal_giant_cell_astrocytoma_microscopic_appearance_4.jpg)
Reference
- ↑ 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 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.
- ↑ 3.0 3.1 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.
- ↑ 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
- ↑ 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
- ↑ Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A; et al. (2007). "The 2007 WHO classification of tumours of the central nervous system". Acta Neuropathol. 114 (2): 97–109. doi:10.1007/s00401-007-0243-4. PMC 1929165. PMID 17618441.
- ↑ 7.0 7.1 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
- ↑ 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.