Rhabdomyosarcoma pathophysiology: Difference between revisions
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{{CMG}}; {{AE}} {{S.M}} | {{CMG}}; {{AE}} {{S.M}} | ||
==Overview== | ==Overview== | ||
==Pathophysiology== | ==Pathophysiology== | ||
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===Histology=== | ===Histology=== | ||
* 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 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> | * 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 | * [[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. | * Despite all muscle [[differentiation]] markers [[expression]] in [[ARMS]], mature muscle characteristics is not seen in [[ARMS]] [[histology]]. | ||
===Pathogenesis=== | ===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> | *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" /> | *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> | *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> | *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=== | ||
*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> | *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> | ||
**Loss of heterozygosity of 11p15. | **[[Loss of heterozygosity]] of 11p15. | ||
** Mutations in TP53 | ** [[Mutations]] in [[TP53]] | ||
** Mutations in NRAS | ** [[Mutations]] in [[NRAS]] | ||
** Mutations in KRAS | ** [[Mutations]] in [[KRAS]] | ||
** Mutations in HRAS | ** [[Mutations]] in [[HRAS]] | ||
** Mutations in PIK3CA | ** [[Mutations]] in PIK3CA | ||
** Mutations in CTNNB1 | ** [[Mutations]] in CTNNB1 | ||
** Mutations in FGFR4 | ** [[Mutations]] in FGFR4 | ||
** Translocations in PAX3 or PAX7 genes with FOXO1 | ** [[Translocations]] in [[PAX3]] or [[PAX7]] genes with [[FOXO1]] | ||
*Specific genetic changes in different types of rhabdomyosarcoma: | *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> | *[[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 with the PAX3 gene on chromosome 2 or the PAX7 gene on chromosome 1 | **[[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 translocation occur in younger patients with longer event-free survival rate | **[[PAX7]] [[Translocations|translocation]] occur in younger patients with longer event-free [[survival rate]] | ||
*Embryonal rhabdomyosarcoma:<ref name="pmid94079332" /> | *[[Embryonal rhabdomyosarcoma]]:<ref name="pmid94079332" /> | ||
** Particular gene changes are not clear | ** Particular [[gene]] changes are not clear | ||
** | **[[Loss of heterozygosity]] from the 11p15 region | ||
** Hyperdiploid gene | ** Hyperdiploid [[gene]] | ||
** Lack of gene amplification | ** Lack of [[gene]] [[amplification]] | ||
==Associated conditions== | ==Associated conditions== | ||
===Immunohistochemistry=== | ===Immunohistochemistry=== | ||
* 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> | * 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> | ||
* RMS stains positive for following proteins: | * RMS stains positive for following proteins: | ||
** Polyclonal desmin (99%) | ** [[Polyclonal]] [[desmin]] (99%) | ||
** Muscle-specific actin (95%) | ** Muscle-specific [[actin]] (95%) | ||
** Myogenin or myogenic differentiation 1 ( MyoD1) (95%) | ** [[Myogenin]] or [[myogenic]] differentiation 1 ( MyoD1) (95%) | ||
*** Expressed more in ARMS rather than ERMS | *** Expressed more in [[ARMS]] rather than ERMS | ||
*** Associated with poorer prognosis | *** Associated with poorer [[prognosis]] | ||
** Myoglobin (78%) | ** [[Myoglobin]] (78%) | ||
===Transmission electron microscopy=== | ===Transmission electron microscopy=== | ||
* 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> | * [[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> | ||
* | * Presence of following proteins are associated with [[TEM]] features of RMS: | ||
** Myofilaments | ** Myofilaments | ||
** Desmin and actin filaments | ** [[Desmin]] and [[actin]] [[filaments]] | ||
** Myotubular intermediate filaments | ** Myotubular intermediate [[filaments]] | ||
** Rudimentary Z-band material | ** Rudimentary Z-band material | ||
===Reverse transcriptase polymerase chain reaction (RT-PCR)=== | ===Reverse transcriptase polymerase chain reaction (RT-PCR)=== | ||
===Fluorescent in situ hybridization (FISH) === | ===Fluorescent in situ hybridization (FISH) === | ||
*By using RT-PCR and FISH, features of fusion | *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> | ||
==Gross Pathology== | ==Gross Pathology== | ||
Line 78: | Line 77: | ||
| style="background:#DCDCDC;" align="left" + | | | style="background:#DCDCDC;" align="left" + | | ||
* Clusters of edematous and grape-like masses | * Clusters of edematous and grape-like masses | ||
* Protrusion into lumen of hollow organs | * Protrusion into [[lumen]] of hollow [[organs]] | ||
| style="background:#F5F5F5;" + |[[File:Gross pathology of rhabdomyosarcoma.jpeg|thumb|none|300px|Gross feature of embryonal rhabdomyosarcoma of the nasopharynx (botryoid type) [https://www.humpath.com/rhinopharyngeal-embryonal, from flickr]]] | | style="background:#F5F5F5;" + |[[File:Gross pathology of rhabdomyosarcoma.jpeg|thumb|none|300px|Gross feature of embryonal rhabdomyosarcoma of the nasopharynx (botryoid type) [https://www.humpath.com/rhinopharyngeal-embryonal, from flickr]]] | ||
|- | |- | ||
| style="background:#DCDCDC;" align="left" + | | | style="background:#DCDCDC;" align="left" + | | ||
* Poorly circumscribed mass | * Poorly circumscribed [[mass]] | ||
* white and infiltrative | * white and infiltrative | ||
* soft or firm mass | * 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:#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" + | | | style="background:#DCDCDC;" align="left" + | | ||
*Fleshy tumor | *Fleshy [[tumor]] | ||
*Tan gray color 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]]] | | 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]]] | ||
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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> | 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 | * Ovoid to round [[tumor]] cells are packed with fibrovascular septae | ||
* Tumor cells have club-shaped appearance | * [[Tumor]] [[cells]] have club-shaped [[appearance]] | ||
* Tumor cells are divided by pseudo-alveolar spaces, slightly like pulmonary alveoli | * [[Tumor]] [[cells]] are divided by pseudo-alveolar spaces, slightly like [[pulmonary]] [[alveoli]] | ||
* Rhabdomyoblasts are shed into pseudo-alveolar areas | * Rhabdomyoblasts are shed into pseudo-alveolar areas | ||
* Presence of more than 50% alveolar components | * 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:#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" + | | | 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> | 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 | * Rhabdomyoblasts arranged in sheets and large nests | ||
* Different stages of cell morphogenesis | * Different stages of cell [[morphogenesis]] | ||
* Positive stains are desmin, actin, myogenin, and MyoD1 | * Positive stains are [[desmin]], [[actin]], [[myogenin]], and MyoD1 | ||
* Infrequent intermixed fusiform cells | * Infrequent intermixed [[fusiform]] [[cells]] | ||
* No alveolar architectural pattern | * No [[alveolar]] architectural pattern | ||
* Typical rhabdomyoblast has eosinophilic cytoplasm with poorly formed myofilaments | * 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:#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" + | | | 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> | *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 | ** [[Botryoid rhabdomyosarcoma]] grows beneath an [[epithelial]] surface | ||
** Rhabdomyoblasts adhere to dense subepithelial which is called cambrium layer | ** Rhabdomyoblasts adhere to [[dense]] subepithelial which is called cambrium layer | ||
**Malignant cells are found in myoxid stroma | **[[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:#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" + | | | 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> | 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 | * Presence of large hyperchromatic [[nuclei]] | ||
* Atypical bizarre mitotic features | * Atypical bizarre [[mitotic]] features | ||
* Threefold larger nuclear size | * 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]]] | | 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]]] | ||
|} | |} |
Revision as of 17:27, 8 February 2019
Rhabdomyosarcoma Microchapters |
Diagnosis |
---|
Treatment |
Case Studies |
Rhabdomyosarcoma pathophysiology On the Web |
American Roentgen Ray Society Images of Rhabdomyosarcoma pathophysiology |
Risk calculators and risk factors for Rhabdomyosarcoma pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shadan Mehraban, M.D.[2]
Overview
Pathophysiology
Histology
- The origin of rhabdomyosarcoma is straited muscle cells.[1]
- The presentation sites of rhabdomyosarcoma are:
- Head and neck (28%)
- Extremities (24%)
- Genitourinary tract (18%)
- Trunk (11%)
- Orbit (7%)
- Retroperitoneum (6%)
- Other sites such as bladder, vagina, nasopharynx, and middle ear (3%)
- Round or spindle-shaped muscle cells are present in embryonal rhabdomyosarcoma (ERMS).[2]
- 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.[3]
- Distruption of skeletal muscle progenitor cell growth and related differentiation may cause rhabdomyosarcoma.[3]
- There is causal association between MET proto-oncogene and macrophage migration inhibitory factor (MIF).[4]
- It is thought that P53 is related to oncogenic transformation and tumor progression.[5]
Genetics
- According to microarray and targeted sequencing, following genomic characteristics are attributed to Rhabdomyosarcoma (RMS):[6][7][8][9][10][11]
- Specific genetic changes in different types of rhabdomyosarcoma:
- Alveolar rhabdomyosarcoma:[12][13]
- Translocation of FKHR gene on chromosome 13 with the PAX3 gene on chromosome 2 or the PAX7 gene on chromosome 1
- PAX7 translocation occur in younger patients with longer event-free survival rate
- Embryonal rhabdomyosarcoma:[14]
- Particular gene changes are not clear
- Loss of heterozygosity from the 11p15 region
- Hyperdiploid gene
- Lack of gene amplification
Associated conditions
Immunohistochemistry
- Through immunohistochemistry, muscle specific proteins can be identified in RMS.[2]
- RMS stains positive for following proteins:
Transmission electron microscopy
- Transmission electron microscopy (TEM) can be used for poorly differentiated or undifferentiated tumors.[15][16]
- Presence of following proteins are associated with TEM features of RMS:
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.[17]
Gross Pathology
Gross findings | Gross pathology |
---|---|
Microscopic Pathology
Pathologic findings | Microscopic pathology |
---|---|
The microscopic features of ARMS are:[18] |
|
The microscopic features of ERMS are:[14][19]
|
|
|
|
The microscopic features of anaplastic rhabdomyosarcoma are:[21] |
References
- ↑ Barr FG (1997). "Molecular genetics and pathogenesis of rhabdomyosarcoma". J Pediatr Hematol Oncol. 19 (6): 483–91. PMID 9407933.
- ↑ 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.
- ↑ 3.0 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 14.0 14.1
- ↑ Hicks J, Flaitz C (2002). "Rhabdomyosarcoma of the head and neck in children". Oral Oncol. 38 (5): 450–9. PMID 12110339.
- ↑ 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.
- ↑ Helman LJ, Meltzer P (2003). "Mechanisms of sarcoma development". Nat Rev Cancer. 3 (9): 685–94. doi:10.1038/nrc1168. PMID 12951587.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.