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==Overview==
==Overview==
Atypical teratoid rhabdoid tumor is comprised of [[Malignant rhabdoid tumor|rhabdoid tumor]] [[Cell (biology)|cells]] and varying amounts of small undifferentiated [[Primitive neuroectodermal tumor|primitive neuroectodermal tumor (PNET)]]-like [[Mesenchymal stem cell|mesenchymal]], and/or [[Epithelium|epithelial]] differentiated [[tumor]] [[Cell (biology)|cells]]. [[Gene]] involved in the [[pathogenesis]] of atypical teratoid rhabdoid tumor include ''[[SMARCB1]]'' (''hSNF5/INI-1''), a [[tumor suppressor gene]]. Atypical teratoid rhabdoid tumor may be associated with rhabdoid predisposition syndrome. On [[gross pathology]], atypical teratoid rhabdoid tumor is characterized by an encapsulated, grayish, friable mass which is moderately [[vascular]]. On [[microscopic]] [[Histopathology|histopathological]] [[analysis]], atypical teratoid rhabdoid tumor is characterized by round blue [[tumor]] [[Cell (biology)|cells]] of high [[Cell (biology)|cellularity]] composed of atypical [[cells]] with eccentric [[Cell nucleus|nuclei]], small [[Nucleolus|nucleoli]], and abundant amounts of [[eosinophilic]] [[cytoplasm]] with frequent [[mitotic]] figures. Atypical teratoid rhabdoid tumor is demonstrated by positivity to [[tumor markers]] such as [[Epithelium|epithelial]] [[membrane]] [[antigen]], [[vimentin]], and [[actin|smooth muscle actin]].


==Pathogenesis==
== Pathophysiology ==
*Atypical teratoid rhabdoid tumor is a primitive neuroectodermal tumor (PNET). The tumor cells are derived from the [[neuroectoderm]], but have not developed and differentiated in the way a normal neuron would, and so the cells appear "primitive".
 
*Atypical teratoid rhabdoid tumor was until relatively recently classed as [[medulloblastoma]], although both are clinically and histologically different.
===Pathogenesis===
*Atypical teratoid rhabdoid tumor is comprised of [[Malignant rhabdoid tumor|rhabdoid tumor]] [[Cell (biology)|cells]] and varying amounts of small undifferentiated [[Primitive neuroectodermal tumor|primitive neuroectodermal tumor (PNET)]]-like [[Mesenchymal stem cell|mesenchymal]], and/or [[Epithelium|epithelial]] differentiated [[tumor]] [[Cell (biology)|cells]].<ref name="SlavcChocholous2014">{{cite journal|last1=Slavc|first1=Irene|last2=Chocholous|first2=Monika|last3=Leiss|first3=Ulrike|last4=Haberler|first4=Christine|last5=Peyrl|first5=Andreas|last6=Azizi|first6=Amedeo A.|last7=Dieckmann|first7=Karin|last8=Woehrer|first8=Adelheid|last9=Peters|first9=Christina|last10=Widhalm|first10=Georg|last11=Dorfer|first11=Christian|last12=Czech|first12=Thomas|title=Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992-2012|journal=Cancer Medicine|volume=3|issue=1|year=2014|pages=91–100|issn=20457634|doi=10.1002/cam4.161}}</ref>


==Genetics==
==Genetics==
*Gene involved in the pathogenesis of atypical teratoid rhomboid tumor include:<ref name="GinnGajjar2012">{{cite journal|last1=Ginn|first1=Kevin F.|last2=Gajjar|first2=Amar|title=Atypical Teratoid Rhabdoid Tumor: Current Therapy and Future Directions|journal=Frontiers in Oncology|volume=2|year=2012|issn=2234-943X|doi=10.3389/fonc.2012.00114}}</ref>
*[[Gene]] involved in the [[pathogenesis]] of atypical teratoid rhabdoid tumor include ''[[SMARCB1]]'' (''hSNF5/INI-1''), a [[tumor suppressor gene]].<ref name="GinnGajjar2012">{{cite journal|last1=Ginn|first1=Kevin F.|last2=Gajjar|first2=Amar|title=Atypical Teratoid Rhabdoid Tumor: Current Therapy and Future Directions|journal=Frontiers in Oncology|volume=2|year=2012|issn=2234-943X|doi=10.3389/fonc.2012.00114}}</ref>
*Atypical teratoid rhabdoid tumor is characterized by loss of the long arm of [[chromosome 22]], which results in loss of the ''hSNF5/INI-1'' [[gene]].
*''INI1'', a member of the [[SWI/SNF]] [[chromatin]] remodeling complex, is important in the maintenance of the [[Spindle apparatus|mitotic spindle]] and [[cell cycle]] control.


**[[SMARCB1]]
==Associated Conditions==
*Atypical teratoid rhabdoid tumor may be associated with rhabdoid predisposition [[syndrome]].<ref name="SlavcChocholous2014">{{cite journal|last1=Slavc|first1=Irene|last2=Chocholous|first2=Monika|last3=Leiss|first3=Ulrike|last4=Haberler|first4=Christine|last5=Peyrl|first5=Andreas|last6=Azizi|first6=Amedeo A.|last7=Dieckmann|first7=Karin|last8=Woehrer|first8=Adelheid|last9=Peters|first9=Christina|last10=Widhalm|first10=Georg|last11=Dorfer|first11=Christian|last12=Czech|first12=Thomas|title=Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992-2012|journal=Cancer Medicine|volume=3|issue=1|year=2014|pages=91–100|issn=20457634|doi=10.1002/cam4.161}}</ref>


==Gross Pathology==
*On [[gross pathology]], atypical teratoid rhabdoid tumor is characterized by an encapsulated, grayish, friable mass which is moderately [[vascular]].<ref name="pmid22135607">{{cite journal| author=Chan KH, Mohammed Haspani MS, Tan YC, Kassim F| title=A case report of atypical teratoid/rhabdoid tumour in a 9-year-old girl. | journal=Malays J Med Sci | year= 2011 | volume= 18 | issue= 3 | pages= 82-6 | pmid=22135607 | doi= | pmc=PMC3216225 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22135607  }} </ref>
*Common [[Cranium|intracranial]] sites associated with atypical teratoid rhabdoid tumor include:<ref name="locationatrt1">Location of Atypical teratoid/rhabdoid tumour. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/atypical-teratoidrhabdoid-tumour. Accessed on December 14, 2015</ref>


[[genetics|Genetic]] similarities have been found within rhabdoid tumors.  In particular the [[Chromosome|chromosomal]] [[22q11.2 deletion syndrome|22 deletion]] is very common in AT/RTs.  The [[chromosome 22]] area contains the hSNF5/INI1 [[gene]] that appears to function as a classic [[tumor suppressor]] gene.<ref>
{| style="border: 0px; font-size: 90%; margin: 3px; width:1000px align=center"
{{cite journal |author=Chung-Lan Kao, Shih-Hwa Chiou, Yann-Jang Chen, Sher Singh, Han-Tso Lin, Ren-Shyan Liu, Chih-Wen Lo, Chi-Chang Yang, Chin-Wen Chi, Chen-hsen Lee and Tai-Tong Wong |title=Increased expression of osteopontin gene in atypical teratoid/rhabdoid tumor of the central nervous system |journal=Modern Pathology |volume=18 |issue= 6 |pages=769–778 |year=2005 |accessdate = 2008-05-05 |url=http://www.nature.com/modpathol/journal/v18/n6/full/3800270a.html}}</ref> Most rhabdoid tumors have INI1 deletions whether they occur in the CNS, kidney or elsewhere.  This [[mutation]] is viewed as the "first hit" which predisposes children to malignancies.  INI1/hSNF5, a component of the [[chromatin]] remodeling SWI/SNF complex, is a critical tumor suppressor biallelically inactivated in rhabdoid tumors. Identification of INI1 as a tumor suppressor has facilitated accurate diagnosis of rhabdoid tumors.
| valign="top" |
|+
The rate of [[transcription (genetics)|transcription]] for SWI/SNF and [[Histone deacetylase|HDAC]] complexes seem to be regulated by the INI1 gene.  The SWI/SNF complex plays a role in chromatin remodeling.  AT/RT is the first pediatric brain tumor for which a candidate tumor suppressor gene has been identified. A mutation or deletion in the INI1/hSNF5 gene occurs in the majority of AT/RT tumors.  Up to 90% of AT/RT cases involve chromosome 22 deletion.  This is mainly point mutations on the hSNF5/INI1 gene (i.e., one can diagnosis AT/RT without a chromsome 22 deletion elsewhere).  The [[SWI/SNF|hSNF5/INI1]] gene regulates 15 or so proteins in the chromintin structure.  In addition, the OPN gene has a higher expression in AT/RT tumors. It is increasingly believed that the reason that all of the AT/RT cancers are not associated with the hSNF5/INI1 gene is that there are 14 additional proteins in the chromintin structure that are controlled by other genes.  There are also some emerging mouse models of the AT/RT cancer as well as experimental cell lines derived from tumors.  Despite these advances, the function of the gene is not yet understood. There is not enough known about the function of INI1, either as an independent modulator of gene expression or through its association with the [[SWI/SNF]] complex, to be able to use specific targeted biological agents for treatment.<ref>http://cancerres.aacrjournals.org/content/62/1/323.abstract</ref>  Prospective clinical and biologic trials are greatly needed to understand the efficacy of therapeutic interventions, as well as the role of the gene.
! style="background: #4479BA; width: 800px;" | {{fontcolor|#FFF|Infratentorial}}
! style="background: #4479BA; width: 800px;" | {{fontcolor|#FFF|Supratentorial}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" |
*[[Cerebellum]]
*[[Brain stem]]
| style="padding: 5px 5px; background: #DCDCDC;" |
*[[cerebrum|Cerebral hemispheres]]
*[[Pineal gland]]
*[[Septum pellucidum]]
*[[Hypothalamus]]
|}


==Mircoscopic Pathology==
==Microscopic Pathology==
AT/RT and rhabdoid tumor share the term "rhabdoid" because under a microscope both tumors resemble [[rhabdomyosarcoma]].
*On [[microscopic]] [[Histopathology|histopathological]] [[analysis]], atypical teratoid rhabdoid tumor is characterized by the round blue [[tumor]] [[Cell (biology)|cells]] of high [[Cellular|cellularity]] composed of atypical [[Cell (biology)|cells]] with eccentric [[Cell nucleus|nuclei]], small [[Nucleolus|nucleoli]], and abundant amounts of [[eosinophilic]] [[cytoplasm]] with frequent [[Mitosis|mitotic]] figures.<ref name="SlavcChocholous2014">{{cite journal|last1=Slavc|first1=Irene|last2=Chocholous|first2=Monika|last3=Leiss|first3=Ulrike|last4=Haberler|first4=Christine|last5=Peyrl|first5=Andreas|last6=Azizi|first6=Amedeo A.|last7=Dieckmann|first7=Karin|last8=Woehrer|first8=Adelheid|last9=Peters|first9=Christina|last10=Widhalm|first10=Georg|last11=Dorfer|first11=Christian|last12=Czech|first12=Thomas|title=Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992-2012|journal=Cancer Medicine|volume=3|issue=1|year=2014|pages=91–100|issn=20457634|doi=10.1002/cam4.161}}</ref>
The tumor [[histology]] is jumbled small and large cells.  The [[Tissue (biology)|tissue]] of this tumor contains many different types of cells including the rhabdoid cells, large spindled cell, [[Epithelial reticular cells|epithelial]] and mesencymal cells and areas resembling [[primitive neuroectodermal tumor]] (PNET). As much as 70% of the tumor may be made up of PNET-likw cells. [[Ultrastructure]] characteristic whorls of [[intermediate filament]]s in the rhabdoid tumors (as with rhabdoid tumors in any area of the body).  Ho and associates found sickle shaped embracing cells, previously unreported, in all of 11 cases of AT/RT.
*According to the ''[[World Health Organization|WHO]] [[classification]]'' ''of [[Tumor|tumors]] of the [[central nervous system]]'', atypical teratoid rhabdoid tumor is [[Classification|classified]] into a [[World Health Organization|WHO]] [[Grading (tumors)|grade]] IV [[tumor]].


===Associated Conditions===
==Immunohistochemistry==
* Rhabdoid predisposition syndrome <ref>http://atlasgeneticsoncology.org//Kprones/rhabdKpronID10051.htm </ref>
*Atypical teratoid rhabdoid tumor is demonstrated by positivity to [[tumor markers]], such as:<ref name="ihcatrt1">Markers of Atypical teratoid/rhabdoid tumour. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/atypical-teratoidrhabdoid-tumour. Accessed on December 14, 2015</ref><ref name="pmid16687525">{{cite journal| author=Meyers SP, Khademian ZP, Biegel JA, Chuang SH, Korones DN, Zimmerman RA| title=Primary intracranial atypical teratoid/rhabdoid tumors of infancy and childhood: MRI features and patient outcomes. | journal=AJNR Am J Neuroradiol | year= 2006 | volume= 27 | issue= 5 | pages= 962-71 | pmid=16687525 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16687525  }} </ref>
:*[[Epithelium|Epithelial]] [[membrane]] [[antigen]]
:*[[Vimentin]]
:*[[actin|Smooth muscle actin]]
:*[[GFAP]]
:*[[Cytokeratin]]
:*[[Neurofilament]]
:*[[Desmin]]


==References==
==References==
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Latest revision as of 17:24, 16 May 2019

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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

Atypical teratoid rhabdoid tumor is comprised of rhabdoid tumor cells and varying amounts of small undifferentiated primitive neuroectodermal tumor (PNET)-like mesenchymal, and/or epithelial differentiated tumor cells. Gene involved in the pathogenesis of atypical teratoid rhabdoid tumor include SMARCB1 (hSNF5/INI-1), a tumor suppressor gene. Atypical teratoid rhabdoid tumor may be associated with rhabdoid predisposition syndrome. On gross pathology, atypical teratoid rhabdoid tumor is characterized by an encapsulated, grayish, friable mass which is moderately vascular. On microscopic histopathological analysis, atypical teratoid rhabdoid tumor is characterized by round blue tumor cells of high cellularity composed of atypical cells with eccentric nuclei, small nucleoli, and abundant amounts of eosinophilic cytoplasm with frequent mitotic figures. Atypical teratoid rhabdoid tumor is demonstrated by positivity to tumor markers such as epithelial membrane antigen, vimentin, and smooth muscle actin.

Pathophysiology

Pathogenesis

Genetics

Associated Conditions

  • Atypical teratoid rhabdoid tumor may be associated with rhabdoid predisposition syndrome.[1]

Gross Pathology

  • On gross pathology, atypical teratoid rhabdoid tumor is characterized by an encapsulated, grayish, friable mass which is moderately vascular.[3]
  • Common intracranial sites associated with atypical teratoid rhabdoid tumor include:[4]
Infratentorial Supratentorial

Microscopic Pathology

Immunohistochemistry

  • Atypical teratoid rhabdoid tumor is demonstrated by positivity to tumor markers, such as:[5][6]

References

  1. ↑ 1.0 1.1 1.2 Slavc, Irene; Chocholous, Monika; Leiss, Ulrike; Haberler, Christine; Peyrl, Andreas; Azizi, Amedeo A.; Dieckmann, Karin; Woehrer, Adelheid; Peters, Christina; Widhalm, Georg; Dorfer, Christian; Czech, Thomas (2014). "Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992-2012". Cancer Medicine. 3 (1): 91–100. doi:10.1002/cam4.161. ISSN 2045-7634.
  2. ↑ Ginn, Kevin F.; Gajjar, Amar (2012). "Atypical Teratoid Rhabdoid Tumor: Current Therapy and Future Directions". Frontiers in Oncology. 2. doi:10.3389/fonc.2012.00114. ISSN 2234-943X.
  3. ↑ Chan KH, Mohammed Haspani MS, Tan YC, Kassim F (2011). "A case report of atypical teratoid/rhabdoid tumour in a 9-year-old girl". Malays J Med Sci. 18 (3): 82–6. PMC 3216225. PMID 22135607.
  4. ↑ Location of Atypical teratoid/rhabdoid tumour. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/atypical-teratoidrhabdoid-tumour. Accessed on December 14, 2015
  5. ↑ Markers of Atypical teratoid/rhabdoid tumour. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/atypical-teratoidrhabdoid-tumour. Accessed on December 14, 2015
  6. ↑ Meyers SP, Khademian ZP, Biegel JA, Chuang SH, Korones DN, Zimmerman RA (2006). "Primary intracranial atypical teratoid/rhabdoid tumors of infancy and childhood: MRI features and patient outcomes". AJNR Am J Neuroradiol. 27 (5): 962–71. PMID 16687525.

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