Rhabdomyosarcoma pathophysiology: Difference between revisions

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{{Rhabdomyosarcoma}}
{{Rhabdomyosarcoma}}
{{CMG}};{{AE}} {{PSK}}
{{CMG}}; {{AE}} {{S.M}}
==Overview==
==Overview==
Rhabdomyosarcoma arises from the skeletal muscle cells. Development of alveolar rhabdomyosarcoma is result of specific [[genetic mutations]]. The pathogenesis of rhabdomyosarcoma include t(2;13) and t(1;13) [[Chromosomal translocation|chromosomal translocations]]. The microscopic pathology of rhabdomyosarcoma depends on the histological subtype.
The origin of [[rhabdomyosarcoma]] is straited [[muscle cells]].The presentation sites of rhabdomyosarcoma are [[head]] and [[neck]], [[extremities]], [[Genitourinary tract]], [[trunk]], [[orbit]], [[retroperitoneum]], [[bladder]], [[vagina]], [[nasopharynx]], and [[middle ear]].The exact [[pathogenesis]] of [[rhabdomyosarcoma]] is unclear. However, there is causal association between MET [[proto-oncogene]] and [[macrophage]] migration inhibitory factor (MIF) and it is thought that [[P53]] is related to [[oncogenic]] [[transformation]] and [[tumor]] progression. Multiple gene mutations are related to rhabdomyosarcoma such as [[loss of heterozygosity]] of 11p15, [[TP53]], [[NRAS]], [[KRAS]], [[HRAS]], PIK3CA, CTNNB1, FGFR4, and translocation in [[PAX3]] or [[PAX7]] genes with [[FOXO1]]. [[Immunohistochemistry]] can identify some specific proteins related to rhabdomyosarcoma such as [[desmin]], [[actin]], [[myogenin]], and [[myoglobin]]. The other [[histologic]] procedure is [[transmission electron microscopy]] (TEM) which can be used for poorly differentiated or undifferentiated [[tumors]] and myofilaments, actin, desmin, myotubular intermediate [[filaments]], and rudimentary Z-band material. [[Fusion protein]] is identified by [[Reverse transcription polymerase chain reaction|reverse transcriptase polymerase chain reaction]] and [[Fluorescence in situ hybridization|fluorescent in situ hybridization]].


===Pathophysiology===
==Pathophysiology==


==Histology==
===Histology===


* The origin of rhabdomyosarcoma is muscle cells.
* The origin of [[rhabdomyosarcoma]] is straited [[muscle cells]].<ref name="pmid9407933">{{cite journal| author=Barr FG| title=Molecular genetics and pathogenesis of rhabdomyosarcoma. | journal=J Pediatr Hematol Oncol | year= 1997 | volume= 19 | issue= 6 | pages= 483-91 | pmid=9407933 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9407933  }} </ref>
* The presentation sites of rhabdomyosarcoma are:
* The presentation sites of rhabdomyosarcoma are:
** Head and neck (28%)
** [[Head]] and [[neck]] (28%)
** Extremities (24%)
** [[Extremities]] (24%)
** Genitourinary tract (18%)
** [[Genitourinary tract]] (18%)
** Trunk (11%)
** [[Trunk]] (11%)
**Orbit (7%)
**[[Orbit]] (7%)
**Retroperitoneum (6%)
**[[Retroperitoneum]] (6%)
**Other sites such as bladder, vagina, nasopharynx, and middle ear (3%)
**Other sites such as [[bladder]], [[vagina]], [[nasopharynx]], and [[middle ear]] (3%)
* Round or spindle-shaped [[muscle cells]] are present in [[embryonal rhabdomyosarcoma]] (ERMS).<ref name="pmid10666368">{{cite journal| author=Dias P, Chen B, Dilday B, Palmer H, Hosoi H, Singh S et al.| title=Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass. | journal=Am J Pathol | year= 2000 | volume= 156 | issue= 2 | pages= 399-408 | pmid=10666368 | doi=10.1016/S0002-9440(10)64743-8 | pmc=1850049 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10666368  }} </ref>
* [[Alveolar]] architecture with small round [[undifferentiated]] cells which are separated by dense hyalinized [[fibrous]] [[septa]] are present in [[alveolar rhabdomyosarcoma]] ([[ARMS]]).
* Despite all muscle [[differentiation]] markers [[expression]] in [[ARMS]], mature muscle characteristics is not seen in [[ARMS]] [[histology]].
===Pathogenesis===
*The exact [[pathogenesis]] of [[rhabdomyosarcoma]] is unclear.<ref name="pmid16651427">{{cite journal| author=Taulli R, Scuoppo C, Bersani F, Accornero P, Forni PE, Miretti S et al.| title=Validation of met as a therapeutic target in alveolar and embryonal rhabdomyosarcoma. | journal=Cancer Res | year= 2006 | volume= 66 | issue= 9 | pages= 4742-9 | pmid=16651427 | doi=10.1158/0008-5472.CAN-05-4292 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16651427  }} </ref>
*Distruption of [[skeletal muscle]] progenitor cell growth and related differentiation may cause [[rhabdomyosarcoma]].<ref name="pmid16651427" />
*There is causal association between MET [[proto-oncogene]] and [[macrophage]] migration inhibitory factor (MIF).<ref name="pmid20861157">{{cite journal| author=Tarnowski M, Grymula K, Liu R, Tarnowska J, Drukala J, Ratajczak J et al.| title=Macrophage migration inhibitory factor is secreted by rhabdomyosarcoma cells, modulates tumor metastasis by binding to CXCR4 and CXCR7 receptors and inhibits recruitment of cancer-associated fibroblasts. | journal=Mol Cancer Res | year= 2010 | volume= 8 | issue= 10 | pages= 1328-43 | pmid=20861157 | doi=10.1158/1541-7786.MCR-10-0288 | pmc=2974061 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20861157  }} </ref>
*It is thought that [[P53]] is related to [[oncogenic]] [[transformation]] and [[tumor]] progression.<ref name="pmid20682800">{{cite journal| author=Xu J, Timares L, Heilpern C, Weng Z, Li C, Xu H et al.| title=Targeting wild-type and mutant p53 with small molecule CP-31398 blocks the growth of rhabdomyosarcoma by inducing reactive oxygen species-dependent apoptosis. | journal=Cancer Res | year= 2010 | volume= 70 | issue= 16 | pages= 6566-76 | pmid=20682800 | doi=10.1158/0008-5472.CAN-10-0942 | pmc=2922473 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20682800  }} </ref>
===Genetics===
===Genetics===
====Alveolar rhabdomyosarcoma====
*According to [[microarray]] and targeted [[sequencing]], following [[genomic]] characteristics are attributed to [[Rhabdomyosarcoma]] (RMS):<ref name="pmid2798419">{{cite journal| author=Scrable H, Cavenee W, Ghavimi F, Lovell M, Morgan K, Sapienza C| title=A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting. | journal=Proc Natl Acad Sci U S A | year= 1989 | volume= 86 | issue= 19 | pages= 7480-4 | pmid=2798419 | doi= | pmc=298088 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2798419  }} </ref><ref name="pmid10918230">{{cite journal| author=Taylor AC, Shu L, Danks MK, Poquette CA, Shetty S, Thayer MJ et al.| title=P53 mutation and MDM2 amplification frequency in pediatric rhabdomyosarcoma tumors and cell lines. | journal=Med Pediatr Oncol | year= 2000 | volume= 35 | issue= 2 | pages= 96-103 | pmid=10918230 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10918230  }} </ref><ref name="pmid2680062">{{cite journal| author=Stratton MR, Fisher C, Gusterson BA, Cooper CS| title=Detection of point mutations in N-ras and K-ras genes of human embryonal rhabdomyosarcomas using oligonucleotide probes and the polymerase chain reaction. | journal=Cancer Res | year= 1989 | volume= 49 | issue= 22 | pages= 6324-7 | pmid=2680062 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2680062  }} </ref><ref name="pmid22142829">{{cite journal| author=Shukla N, Ameur N, Yilmaz I, Nafa K, Lau CY, Marchetti A et al.| title=Oncogene mutation profiling of pediatric solid tumors reveals significant subsets of embryonal rhabdomyosarcoma and neuroblastoma with mutated genes in growth signaling pathways. | journal=Clin Cancer Res | year= 2012 | volume= 18 | issue= 3 | pages= 748-57 | pmid=22142829 | doi=10.1158/1078-0432.CCR-11-2056 | pmc=3271129 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22142829  }} </ref><ref name="pmid19809159">{{cite journal| author=Taylor JG, Cheuk AT, Tsang PS, Chung JY, Song YK, Desai K et al.| title=Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models. | journal=J Clin Invest | year= 2009 | volume= 119 | issue= 11 | pages= 3395-407 | pmid=19809159 | doi=10.1172/JCI39703 | pmc=2769177 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19809159  }} </ref><ref name="pmid8098985">{{cite journal| author=Barr FG, Galili N, Holick J, Biegel JA, Rovera G, Emanuel BS| title=Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. | journal=Nat Genet | year= 1993 | volume= 3 | issue= 2 | pages= 113-7 | pmid=8098985 | doi=10.1038/ng0293-113 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8098985  }} </ref>
Specific genetic abnormalities have been identified, that are specific for alveolar rhabdomyosarcomas. They include t(2;13) and t(1;13) [[Chromosomal translocation|chromosomal translocations]] resulting in ''PAX3-FKHR'' and ''PAX7-FKHR'' gene fusions.
**[[Loss of heterozygosity]] of 11p15.
** [[Mutations]] in [[TP53]]
** [[Mutations]] in [[NRAS]]
** [[Mutations]] in [[KRAS]]
** [[Mutations]] in [[HRAS]]
** [[Mutations]] in PIK3CA
** [[Mutations]] in CTNNB1 
** [[Mutations]] in FGFR4
** [[Translocations]] in [[PAX3]] or [[PAX7]] genes with [[FOXO1]]
*Specific genetic changes in different types of [[rhabdomyosarcoma]]:
*[[Alveolar rhabdomyosarcoma]]:<ref name="pmid22454413">{{cite journal| author=Missiaglia E, Williamson D, Chisholm J, Wirapati P, Pierron G, Petel F et al.| title=PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in rhabdomyosarcoma and significantly improves current risk stratification. | journal=J Clin Oncol | year= 2012 | volume= 30 | issue= 14 | pages= 1670-7 | pmid=22454413 | doi=10.1200/JCO.2011.38.5591 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22454413  }} </ref><ref name="pmid20663909">{{cite journal| author=Cao L, Yu Y, Bilke S, Walker RL, Mayeenuddin LH, Azorsa DO et al.| title=Genome-wide identification of PAX3-FKHR binding sites in rhabdomyosarcoma reveals candidate target genes important for development and cancer. | journal=Cancer Res | year= 2010 | volume= 70 | issue= 16 | pages= 6497-508 | pmid=20663909 | doi=10.1158/0008-5472.CAN-10-0582 | pmc=2922412 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20663909  }} </ref>
**[[Translocation]] of FKHR [[gene]] on [[Chromosome 13 (human)|chromosome 13]] with the [[PAX3]] [[gene]] on [[chromosome 2]] or the [[PAX7]] [[gene]] on [[chromosome 1]]
**[[PAX7]] [[Translocations|translocation]] occur in younger patients with longer event-free [[survival rate]]
*[[Embryonal rhabdomyosarcoma]]:<ref name="pmid94079332" />
** Particular [[gene]] changes are not clear
**[[Loss of heterozygosity]] from the 11p15 region
** Hyperdiploid [[gene]]
** Lack of [[gene]] [[amplification]]


==Microscopic Pathology==
==Associated conditions==
Characteristic features on microscopic analysis are variable depending on the rhabdomyosarcoma subtype:<ref name=Librepathology>{{cite web | title = librepathology| url =http://librepathology.org/wiki/index.php/Rhabdomyosarcoma#cite_ref-PST14feb11_2-0}}</ref>
===Immunohistochemistry===
===Alveolar Rhabdomyosarcoma===
* Through [[immunohistochemistry]], muscle specific proteins can be identified in RMS.<ref name="pmid10666368">{{cite journal| author=Dias P, Chen B, Dilday B, Palmer H, Hosoi H, Singh S et al.| title=Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass. | journal=Am J Pathol | year= 2000 | volume= 156 | issue= 2 | pages= 399-408 | pmid=10666368 | doi=10.1016/S0002-9440(10)64743-8 | pmc=1850049 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10666368  }} </ref>
*Characterized by Alveolus-like pattern.
* RMS stains positive for following [[proteins]]:
*Fibrous septae lined by tumor cells.
** [[Polyclonal]] [[desmin]] (99%)
**Cells may "fall-off" the septa, i.e. be detached/scattered in the alveolus-like space.
** Muscle-specific [[actin]] (95%)
**Space between fibrous septae may be filled with tumor, called solid variant of alveolar rhabdomyosarcoma.
** [[Myogenin]] or [[myogenic]] differentiation 1 ( MyoD1) (95%)
*Rhabdomyoblasts: Essentially diagnostic cells with [[Nucleus|eccentric nucleus]] and moderate amount of intensely eosinophilic cytoplasm.
*** Expressed more in [[ARMS]] rather than ERMS
*Nuclear pleomorphism
*** Associated with poorer [[prognosis]]
*[[Mitoses]]
** [[Myoglobin]] (78%)
{| align
===Transmission electron microscopy===
|-valign="top"
* [[Transmission electron microscopy]] (TEM) can be used for poorly differentiated or undifferentiated [[tumors]].<ref name="pmid12110339">{{cite journal| author=Hicks J, Flaitz C| title=Rhabdomyosarcoma of the head and neck in children. | journal=Oral Oncol | year= 2002 | volume= 38 | issue= 5 | pages= 450-9 | pmid=12110339 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12110339  }} </ref><ref name="pmid11353062">{{cite journal| author=Parham DM| title=Pathologic classification of rhabdomyosarcomas and correlations with molecular studies. | journal=Mod Pathol | year= 2001 | volume= 14 | issue= 5 | pages= 506-14 | pmid=11353062 | doi=10.1038/modpathol.3880339 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11353062  }} </ref>
| [[Image:800px-Alveolar rhabdomyosarcoma - intermed mag.jpg|thumb|350px|Alveolar Rhabdomyosarcoma- intermediate magnification]]
* Presence of following proteins are associated with [[TEM]] features of RMS:
| [[Image:800px-Alveolar rhabdomyosarcoma - very high mag.jpg|thumb|350px|Alveolar Rhabdomyosarcoma - high magnification]]
** Myofilaments
|}
** [[Desmin]] and [[actin]] [[filaments]]
** Myotubular intermediate [[filaments]]
** Rudimentary Z-band material
===Reverse transcriptase polymerase chain reaction (RT-PCR)===
===Fluorescent in situ hybridization (FISH) ===
*By using [[RT-PCR]] and [[FISH]], features of [[fusion protein]] are identified in [[ARMS]].<ref name="pmid12951587">{{cite journal| author=Helman LJ, Meltzer P| title=Mechanisms of sarcoma development. | journal=Nat Rev Cancer | year= 2003 | volume= 3 | issue= 9 | pages= 685-94 | pmid=12951587 | doi=10.1038/nrc1168 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12951587  }} </ref>


====Embryonal Rhabdomyosarcoma====
==Gross Pathology==
*Randomly arranged small cells
*Myxoid matrix
*Strap cells: Tadpole like morphology
*Rhabdomyoblasts: Essentially diagnostic cells with [[Nucleus|eccentric nucleus]] and moderate amount of intensely eosinophilic cytoplasm


====Botryoid Rhabdomyosarcoma====
{| class="wikitable"
*Malignant cells in an abundant myxoid stroma.
|+
*Non-proliferating layer deep to the surface called "Cambium layer".
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Gross findings
*Cambium layer is defined as cellular region deep to epithelial component.
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Gross pathology
|-
| style="background:#DCDCDC;" align="left" + |
* Clusters of edematous and grape-like masses
* Protrusion into [[lumen]] of hollow [[organs]]
| style="background:#F5F5F5;" + |
|-
| style="background:#DCDCDC;" align="left" + |
* Poorly circumscribed [[mass]]
* white and infiltrative
* soft or firm [[mass]]
| style="background:#F5F5F5;" + |[[File:Embryonal rhabdomyosarcoma.jpg|thumb|none|300px| Gross feature of orbital embryonal rhabdomyosarcoma [http://www.pathologyoutlines.com/topic/softtissueembryonalrhabdo.html Source: Contributed by Mark R. Wick, M.D., from Pathologyoutlines]]]
|-
| style="background:#DCDCDC;" align="left" + |
*Fleshy [[tumor]]
*Tan gray color [[tumor]]
| style="background:#F5F5F5;" + |[[File:Alveolar rhabdomyosarcoma.jpg|thumb|none|300px| Gross pathology of alveolar rhabdomyosarcoma [http://www.pathologyoutlines.com/wick/softtissue/rhabdomyosarcomaalveolartypeleggross.jpg Source:Courtesy of Mark R. Wick, M.D., from Pathologyoutlines]]]
|}


====Spindlecell Rhabdomyosarcoma====
==Microscopic Pathology==
*Vesicular growth pattern
{| class="wikitable"
*[[Spindle cells]]
|+
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Pathologic findings
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Microscopic pathology
|-
| style="background:#DCDCDC;" align="left" + |
The [[microscopic]] features of [[ARMS]] are:<ref name="pmid15536621">{{cite journal| author=Hostein I, Andraud-Fregeville M, Guillou L, Terrier-Lacombe MJ, Deminière C, Ranchère D et al.| title=Rhabdomyosarcoma: value of myogenin expression analysis and molecular testing in diagnosing the alveolar subtype: an analysis of 109 paraffin-embedded specimens. | journal=Cancer | year= 2004 | volume= 101 | issue= 12 | pages= 2817-24 | pmid=15536621 | doi=10.1002/cncr.20711 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15536621  }} </ref>
* Ovoid to round [[tumor]] cells are packed with fibrovascular septae 
* [[Tumor]] [[cells]] have club-shaped [[appearance]] 
* [[Tumor]] [[cells]] are divided by pseudo-alveolar spaces, slightly like [[pulmonary]] [[alveoli]]
* Rhabdomyoblasts are shed into pseudo-alveolar areas
* Presence of more than 50% [[alveolar]] components
| style="background:#F5F5F5;" + |[[Image:800px-Alveolar rhabdomyosarcoma - intermed mag.jpg|thumb|none|300px|Alveolar Rhabdomyosarcoma- intermediate magnification [https://commons.wikimedia.org/wiki/File:Alveolar_rhabdomyosarcoma_-_intermed_mag.jpg Source: Nephron,from Wikimedia Commons]]]
|-
| style="background:#DCDCDC;" align="left" + |
The [[microscopic]] features of ERMS are:<ref name="pmid94079332" /><ref name="pmid9724344">{{cite journal| author=Qualman SJ, Coffin CM, Newton WA, Hojo H, Triche TJ, Parham DM et al.| title=Intergroup Rhabdomyosarcoma Study: update for pathologists. | journal=Pediatr Dev Pathol | year= 1998 | volume= 1 | issue= 6 | pages= 550-61 | pmid=9724344 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9724344  }} </ref>
* Rhabdomyoblasts arranged in sheets and large nests
* Different stages of cell [[morphogenesis]]
* Positive stains are [[desmin]], [[actin]], [[myogenin]], and MyoD1
* Infrequent intermixed [[fusiform]] [[cells]]
* No [[alveolar]] architectural pattern
* Typical rhabdomyoblast has [[eosinophilic]] [[cytoplasm]] with poorly formed myofilaments
| style="background:#F5F5F5;" + |[[File:Embryonal rhabdomyosarcoma.jpeg|thumb|none|300px| Microscopic pathology of embryonal rhabdomyosarcoma [http://www.pathologyoutlines.com/topic/softtissueembryonalrhabdo.html Source: Contributed by Mark R. Wick, M.D., from Pathologyoutlines]]]
|-
| style="background:#DCDCDC;" align="left" + |
*The [[microscopic]] features of [[botryoid rhabdomyosarcoma]]:<ref name="pmid26357564">{{cite journal| author=Neha B, Manjunath AP, Girija S, Pratap K| title=Botryoid Rhabdomyosarcoma of the Cervix: Case report with review of the literature. | journal=Sultan Qaboos Univ Med J | year= 2015 | volume= 15 | issue= 3 | pages= e433-7 | pmid=26357564 | doi=10.18295/squmj.2015.15.03.022 | pmc=4554283 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26357564  }} </ref>
** [[Botryoid rhabdomyosarcoma]] grows beneath an [[epithelial]] surface
** Rhabdomyoblasts adhere to [[dense]] subepithelial which is called cambrium layer
**[[Malignant]] [[cells]] are found in myoxid [[stroma]]
| style="background:#F5F5F5;" + |[[ File:Botryoid rhabdomyosarcoma.jpg|thumb|none|300px| Microscopic feature of botryoid rhabdomyosarcoma [http://www.pathologyoutlines.com/topic/softtissuebotyroidembryrhabdo.html, from Pathologyoutlines]]]
|-
| style="background:#DCDCDC;" align="left" + |
The [[microscopic]] features of [[anaplastic rhabdomyosarcoma]] are:<ref name="pmid24382691">{{cite journal| author=Hettmer S, Archer NM, Somers GR, Novokmet A, Wagers AJ, Diller L et al.| title=Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers. | journal=Cancer | year= 2014 | volume= 120 | issue= 7 | pages= 1068-75 | pmid=24382691 | doi=10.1002/cncr.28507 | pmc=4173134 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24382691  }} </ref>
* Presence of large hyperchromatic [[nuclei]]
* Atypical bizarre [[mitotic]] features
* Threefold larger [[nuclear]] size
| style="background:#F5F5F5;" + |[[File:Analastic rhabdomyosarcoma.jpg|thumb|none|300px| Microscopic feature of anaplastic rhabdomyosarcoma [http://www.pathologyoutlines.com/images/softtissue/06_33A.jpg, from Pathologyoutlines]]]
|}


==References==
==References==

Latest revision as of 16:38, 27 May 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shadan Mehraban, M.D.[2]

Overview

The origin of rhabdomyosarcoma is straited muscle cells.The presentation sites of rhabdomyosarcoma are head and neck, extremities, Genitourinary tract, trunk, orbit, retroperitoneum, bladder, vagina, nasopharynx, and middle ear.The exact pathogenesis of rhabdomyosarcoma is unclear. However, there is causal association between MET proto-oncogene and macrophage migration inhibitory factor (MIF) and it is thought that P53 is related to oncogenic transformation and tumor progression. Multiple gene mutations are related to rhabdomyosarcoma such as loss of heterozygosity of 11p15, TP53, NRAS, KRAS, HRAS, PIK3CA, CTNNB1, FGFR4, and translocation in PAX3 or PAX7 genes with FOXO1. Immunohistochemistry can identify some specific proteins related to rhabdomyosarcoma such as desmin, actin, myogenin, and myoglobin. The other histologic procedure is transmission electron microscopy (TEM) which can be used for poorly differentiated or undifferentiated tumors and myofilaments, actin, desmin, myotubular intermediate filaments, and rudimentary Z-band material. Fusion protein is identified by reverse transcriptase polymerase chain reaction and fluorescent in situ hybridization.

Pathophysiology

Histology

Pathogenesis

Genetics

Associated conditions

Immunohistochemistry

Transmission electron microscopy

Reverse transcriptase polymerase chain reaction (RT-PCR)

Fluorescent in situ hybridization (FISH)

Gross Pathology

Gross findings Gross pathology
  • Clusters of edematous and grape-like masses
  • Protrusion into lumen of hollow organs
  • Poorly circumscribed mass
  • white and infiltrative
  • soft or firm mass
Gross feature of orbital embryonal rhabdomyosarcoma Source: Contributed by Mark R. Wick, M.D., from Pathologyoutlines
Gross pathology of alveolar rhabdomyosarcoma Source:Courtesy of Mark R. Wick, M.D., from Pathologyoutlines

Microscopic Pathology

Pathologic findings Microscopic pathology

The microscopic features of ARMS are:[18]

Alveolar Rhabdomyosarcoma- intermediate magnification Source: Nephron,from Wikimedia Commons

The microscopic features of ERMS are:[14][19]

Microscopic pathology of embryonal rhabdomyosarcoma Source: Contributed by Mark R. Wick, M.D., from Pathologyoutlines
Microscopic feature of botryoid rhabdomyosarcoma from Pathologyoutlines

The microscopic features of anaplastic rhabdomyosarcoma are:[21]

  • Presence of large hyperchromatic nuclei
  • Atypical bizarre mitotic features
  • Threefold larger nuclear size
Microscopic feature of anaplastic rhabdomyosarcoma from Pathologyoutlines

References

  1. ↑ Barr FG (1997). "Molecular genetics and pathogenesis of rhabdomyosarcoma". J Pediatr Hematol Oncol. 19 (6): 483–91. PMID 9407933.
  2. ↑ 2.0 2.1 Dias P, Chen B, Dilday B, Palmer H, Hosoi H, Singh S; et al. (2000). "Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass". Am J Pathol. 156 (2): 399–408. doi:10.1016/S0002-9440(10)64743-8. PMC 1850049. PMID 10666368.
  3. ↑ 3.0 3.1 Taulli R, Scuoppo C, Bersani F, Accornero P, Forni PE, Miretti S; et al. (2006). "Validation of met as a therapeutic target in alveolar and embryonal rhabdomyosarcoma". Cancer Res. 66 (9): 4742–9. doi:10.1158/0008-5472.CAN-05-4292. PMID 16651427.
  4. ↑ Tarnowski M, Grymula K, Liu R, Tarnowska J, Drukala J, Ratajczak J; et al. (2010). "Macrophage migration inhibitory factor is secreted by rhabdomyosarcoma cells, modulates tumor metastasis by binding to CXCR4 and CXCR7 receptors and inhibits recruitment of cancer-associated fibroblasts". Mol Cancer Res. 8 (10): 1328–43. doi:10.1158/1541-7786.MCR-10-0288. PMC 2974061. PMID 20861157.
  5. ↑ Xu J, Timares L, Heilpern C, Weng Z, Li C, Xu H; et al. (2010). "Targeting wild-type and mutant p53 with small molecule CP-31398 blocks the growth of rhabdomyosarcoma by inducing reactive oxygen species-dependent apoptosis". Cancer Res. 70 (16): 6566–76. doi:10.1158/0008-5472.CAN-10-0942. PMC 2922473. PMID 20682800.
  6. ↑ Scrable H, Cavenee W, Ghavimi F, Lovell M, Morgan K, Sapienza C (1989). "A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting". Proc Natl Acad Sci U S A. 86 (19): 7480–4. PMC 298088. PMID 2798419.
  7. ↑ Taylor AC, Shu L, Danks MK, Poquette CA, Shetty S, Thayer MJ; et al. (2000). "P53 mutation and MDM2 amplification frequency in pediatric rhabdomyosarcoma tumors and cell lines". Med Pediatr Oncol. 35 (2): 96–103. PMID 10918230.
  8. ↑ Stratton MR, Fisher C, Gusterson BA, Cooper CS (1989). "Detection of point mutations in N-ras and K-ras genes of human embryonal rhabdomyosarcomas using oligonucleotide probes and the polymerase chain reaction". Cancer Res. 49 (22): 6324–7. PMID 2680062.
  9. ↑ Shukla N, Ameur N, Yilmaz I, Nafa K, Lau CY, Marchetti A; et al. (2012). "Oncogene mutation profiling of pediatric solid tumors reveals significant subsets of embryonal rhabdomyosarcoma and neuroblastoma with mutated genes in growth signaling pathways". Clin Cancer Res. 18 (3): 748–57. doi:10.1158/1078-0432.CCR-11-2056. PMC 3271129. PMID 22142829.
  10. ↑ Taylor JG, Cheuk AT, Tsang PS, Chung JY, Song YK, Desai K; et al. (2009). "Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models". J Clin Invest. 119 (11): 3395–407. doi:10.1172/JCI39703. PMC 2769177. PMID 19809159.
  11. ↑ Barr FG, Galili N, Holick J, Biegel JA, Rovera G, Emanuel BS (1993). "Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma". Nat Genet. 3 (2): 113–7. doi:10.1038/ng0293-113. PMID 8098985.
  12. ↑ Missiaglia E, Williamson D, Chisholm J, Wirapati P, Pierron G, Petel F; et al. (2012). "PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in rhabdomyosarcoma and significantly improves current risk stratification". J Clin Oncol. 30 (14): 1670–7. doi:10.1200/JCO.2011.38.5591. PMID 22454413.
  13. ↑ Cao L, Yu Y, Bilke S, Walker RL, Mayeenuddin LH, Azorsa DO; et al. (2010). "Genome-wide identification of PAX3-FKHR binding sites in rhabdomyosarcoma reveals candidate target genes important for development and cancer". Cancer Res. 70 (16): 6497–508. doi:10.1158/0008-5472.CAN-10-0582. PMC 2922412. PMID 20663909.
  14. ↑ 14.0 14.1
  15. ↑ Hicks J, Flaitz C (2002). "Rhabdomyosarcoma of the head and neck in children". Oral Oncol. 38 (5): 450–9. PMID 12110339.
  16. ↑ Parham DM (2001). "Pathologic classification of rhabdomyosarcomas and correlations with molecular studies". Mod Pathol. 14 (5): 506–14. doi:10.1038/modpathol.3880339. PMID 11353062.
  17. ↑ Helman LJ, Meltzer P (2003). "Mechanisms of sarcoma development". Nat Rev Cancer. 3 (9): 685–94. doi:10.1038/nrc1168. PMID 12951587.
  18. ↑ Hostein I, Andraud-Fregeville M, Guillou L, Terrier-Lacombe MJ, Deminière C, Ranchère D; et al. (2004). "Rhabdomyosarcoma: value of myogenin expression analysis and molecular testing in diagnosing the alveolar subtype: an analysis of 109 paraffin-embedded specimens". Cancer. 101 (12): 2817–24. doi:10.1002/cncr.20711. PMID 15536621.
  19. ↑ Qualman SJ, Coffin CM, Newton WA, Hojo H, Triche TJ, Parham DM; et al. (1998). "Intergroup Rhabdomyosarcoma Study: update for pathologists". Pediatr Dev Pathol. 1 (6): 550–61. PMID 9724344.
  20. ↑ Neha B, Manjunath AP, Girija S, Pratap K (2015). "Botryoid Rhabdomyosarcoma of the Cervix: Case report with review of the literature". Sultan Qaboos Univ Med J. 15 (3): e433–7. doi:10.18295/squmj.2015.15.03.022. PMC 4554283. PMID 26357564.
  21. ↑ Hettmer S, Archer NM, Somers GR, Novokmet A, Wagers AJ, Diller L; et al. (2014). "Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers". Cancer. 120 (7): 1068–75. doi:10.1002/cncr.28507. PMC 4173134. PMID 24382691.

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