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Soft tissue tumors: Embryonal rhabdomyosarcoma

Identity

Phylum Soft Tissue Tumors:Skeletal Muscle tumors:Embryonal rhabdomyosarcoma
Note Embryonal rhabdomyosarcoma (ERMS) refers to one subtype of the rhabdomyosarcoma family of soft tissue tumors. These are mesenchymal tumours related to the skeletal muscle lineage.

Classification

    ERMS is one of two subtypes of rhabdomyosarcoma. The other major subtype is alveolar rhabdosarcoma (ARMS). Within the ERMS subtype, there are two histopathologic variants with superior outcome, botryoid and spindle cell. Another proposed histologic variant is anaplastic ERMS. There are no genetic subtypes of ERMS with clinical significance.

Clinics and Pathology

Embryonic origin In many cases, ERMS occurs in regions without abundant or in some cases, regions without any detectable skeletal muscle. Therefore, the relationship of ERMS to skeletal muscle is not clear. However, it is postulated that ERMS is derived from mesenchymal precursors of mesodermal origin.
Epidemiology ERMS accounts for 70-80% of all RMS tumors, and usually occurs in young children (median age of 6.5 years). ERMS represents ~4% of all malignancies among children and adolescents, and has an annual incidence of ~4 per million.
Clinics ERMS often occurs in the head and neck region, genitourinary tract, and retroperitoneum. This tumor often presents as a painless mass, but in other cases, may be discovered from symptoms produced by compression of structures at the primary site. A small fraction of ERMS (10%) will have metastatic disease at the time of diagnosis, with the most frequent site of metastasis being the lungs. The standard treatment for ERMS is a combination of surgery, radiation, and intensive chemotherapy.
Pathology The term embryonal RMS was coined to indicate the microcopic similarity of the tumor cells to developing skeletal myocytes. The tumors cells show variable myogenic differentiation, from small round cells to larger oblong cells with eosinophilic cytoplasm. In the most differentiated cells, there is a strap-like appearance, occasionally with cross striations and multinucleation. From an architectural standpoint, these tumors classically have variable cellularity, with hypercellular areas alternating with hypocellular areas containing a loose myxoid stroma.
Spindle cell RMS has dense whorls or bundles of spindle-shaped cells resembling smooth muscle. These tumors often occur in the paratesticular region of children and the head and neck region of adults. Botryoid RMS usually occurs in the lumen of a hollow internal organ, such as the urinary bladder or vagina. This form of RMS has the gross appearance of multiple polypoid nodules, and the microscopic appearance of a dense cambium layer of tumor cells under an intact epithelial surface.
Anaplasia is recognized by the presence of large, lobated hyperchromatic nuclei and atypical mitoses. Anaplastic cells can be found in a focal or diffuse distribution.
 
Histopathology of ERMS (hematoxylin-eosin, original magnification: 100X; courtesy of Dr. Linda Ernst).
Prognosis Patients with ERMS tumors have a better outcome than patients with ARMS tumors. The 4-year failure free survival rates for patients with localized and metastastic ARMS are 85% and 35%, respectively. Other risk factors that influence outcome of ERMS include age, primary site, size of primary tumor, extent of local spread, and the presence of nodal and distal metastases. Based on these other factors, patients with ERMS tumors with limited extent of disease or in a favorable site (orbit, superficial head and neck, biliary tree, vagina, and paratestis) have a 85-95% probability of long-term survival. It should be also noted that though metastastic disease is a poor prognostic sign, patients with metastatic ERMS under 10 years of age have a survival rate of 40-50%, thus far exceeding the survival rate for metastatic ARMS.

Genetics

Note Though most cases of ERMS occur sporadically without an apparent genetic predisposition, a subset of ERMS occurs in association with the several genetic syndromes, including:
  • Neurofibromatosis type I (NF1)
  • Costello syndrome (HRAS)
  • Cytogenetics

    Cytogenetics
    Morphological
    In contrast to the recurrent chromosomal translocations found in ARMS, ERMS does not have recurrent structural chromosome rearrangements, but rather has frequent chromosome gains. The most notable gains in ERMS were chromosomes 2, 8, 11, 12, 13, and 20.
    Comparative genomic hybridization studies indicated that usual ERMS tumors had a low frequency of amplification (6-10%) but anaplastic ERMS tumors had a higher frequency of amplification (67%).
    Cytogenetics Molecular There is frequently a loss of one of the two parental alleles at one or more contiguous chromosomal 11 loci in the tumor cells. The smallest chromosomal region of consistent allelic loss is 11p15.5. Multiple genes are present in this region and demonstrate expression that is epigenetically regulated in a parent-of-origin-specific fashion by genomic imprinting. It is postulated that one allele of a tumor suppressor gene in this region is physiologically inactivated by imprinting and the second allele is removed by the allelic loss event, and thus both alleles of the tumor suppressor are inactivated to promote an oncogenic effect.
    Allelic loss of imprinted region at 11p15.5 in ERMS. In the 11p15.5 chromosomal region, there is parent-of-origin-specific expression (imprinting) of multiple genes, such that red indicates an expressed allele and blue indicates an unexpressed allele. In many cases of ERMS and other tumors, the maternal alleles in the 11p15.5 region (and variable amounts of contiguous regions) are lost by one of a variety of genomic mechanisms in a process termed allelic loss, loss of heterozygosity, or conversion to homozygosity.

    Genes involved and Proteins

    Gene Name IGF2
    Location 11p15.5
    Protein Growth factor.

    Gene Name H19
    Location 11p15.5
    Protein Non-coding RNA.

    Gene Name CDKN1C
    Location 11p15.5
    Protein Kinase inhibitor.

    Other genes implicated (Data extracted from papers in the Atlas)

    Genes FGFR1 FOXO1 PAX3 SPRY1 YBX1

    Translocations implicated (Data extracted from papers in the Atlas)

    External links

    Mitelman databaseTopo ( Soft_tissue ) - Mitelman database (CGAP - NCBI)
    COSMICHisto = - Site = soft_tissue (COSMIC)
    arrayMapTopo ( C47,C49) Morph ( 8910/3) - arrayMap (Zurich)

    Bibliography

    Rhabdomyosarcoma complicating multiple neurofibromatosis.
    McKeen EA, Bodurtha J, Meadows AT, Douglass EC, Mulvihill JJ.
    J Pediatr. 1978 Dec;93(6):992-3.
    PMID 102756
     
    Chromosomal localization of the human rhabdomyosarcoma locus by mitotic recombination mapping.
    Scrable HJ, Witte DP, Lampkin BC, Cavenee WK.
    Nature. 1987 Oct 15-21;329(6140):645-7.
    PMID 3657988
     
    Chromosomal analysis of sixteen human rhabdomyosarcomas.
    Wang-Wuu S, Soukup S, Ballard E, Gotwals B, Lampkin B.
    Cancer Res. 1988 Feb 15;48(4):983-7.
    PMID 3338090
     
    Gains, losses, and amplification of genomic material in rhabdomyosarcoma analyzed by comparative genomic hybridization.
    Weber-Hall S, Anderson J, McManus A, Abe S, Nojima T, Pinkerton R, Pritchard-Jones K, Shipley J.
    Cancer Res. 1996 Jul 15;56(14):3220-4.
    PMID 8764111
     
    Allelotype of pediatric rhabdomyosarcoma.
    Visser M, Sijmons C, Bras J, Arceci RJ, Godfried M, Valentijn LJ, Voute PA, Baas F.
    Oncogene. 1997 Sep;15(11):1309-14.
    PMID 9315099
     
    Soft Tissue Sarcomas.
    Gurney JG, Young JL, Roffers SD, Smith MA, Bunin GR.
    In L. A. Ries, M. A. Smith, J. G. Gurney, M. Linet, T. Tamra, J. L. Young, and G. R. Bunin (ed.), Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975-1995. NIH Pub. No. 99-4649, Bethesda, MD. 1999; p. 111-124.
     
    Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease.
    Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS.
    J Clin Oncol. 2001 Jun 15;19(12):3091-102.
    PMID 11408506
     
    Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes.
    Bridge JA, Liu J, Qualman SJ, Suijkerbuijk R, Wenger G, Zhang J, Wan X, Baker KS, Sorensen P, Barr FG.
    Genes Chromosomes Cancer. 2002 Mar;33(3):310-21.
    PMID 11807989
     
    Molecular pathogenesis of rhabdomyosarcoma.
    Xia SJ, Pressey JG, Barr FG.
    Cancer Biol Ther. 2002 Mar-Apr;1(2):97-104.
    PMID 12170781
     
    Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma--a report from the Intergroup Rhabdomyosarcoma Study IV.
    Breneman JC, Lyden E, Pappo AS, Link MP, Anderson JR, Parham DM, Qualman SJ, Wharam MD, Donaldson SS, Maurer HM, Meyer WH, Baker KS, Paidas CN, Crist WM.
    J Clin Oncol. 2003 Jan 1;21(1):78-84.
    PMID 12506174
     
    Myogenin and MyoD1 expression in paediatric rhabdomyosarcomas.
    Sebire NJ, Malone M.
    J Clin Pathol. 2003 Jun;56(6):412-6. Review
    PMID 12783965
     
    Neurofibromatosis in children with Rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma study IV.
    Sung L, Anderson JR, Arndt C, Raney RB, Meyer WH, Pappo AS.
    J Pediatr. 2004 May;144(5):666-8.
    PMID 15127010
     
    Germline mutations in HRAS proto-oncogene cause Costello syndrome.
    Aoki Y, Niihori T, Kawame H, Kurosawa K, Ohashi H, Tanaka Y, Filocamo M, Kato K, Suzuki Y, Kure S, Matsubara Y.
    Nat Genet. 2005 Oct;37(10):1038-40. Epub 2005 Sep 18.
    PMID 16170316
     
    Tumor predisposition in Costello syndrome.
    Gripp KW.
    Am J Med Genet C Semin Med Genet. 2005 Aug 15;137C(1):72-7. Review
    PMID 16010679
     
    Rhabdomyosarcomas in adults and children: an update.
    Parham DM, Ellison DA.
    Arch Pathol Lab Med. 2006 Oct;130(10):1454-65.
    PMID 17090187
     
    Rhabdomyosarcoma and the undifferentiated sarcomas.
    Wexler LH, Meyer WH, Helman LJ.
    In P. A. Pizzo and D. G. Poplack (ed.), Principles and Practice of Pediatric Oncology, 2006. Fifth ed. Lippincott Williams & Wilkins, Philadelphia; p. 971-1001.
     
    Prevalence and clinical impact of anaplasia in childhood rhabdomyosarcoma : a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.
    Qualman S, Lynch J, Bridge J, Parham D, Teot L, Meyer W, Pappo A.
    Cancer. 2008 Dec 1;113(11):3242-7.
    PMID 18985676
     
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    Contributor(s)

    Written01-2009Frederic G Barr
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA

    Citation

    This paper should be referenced as such :
    Barr, FG
    Soft tissue tumors: Embryonal rhabdomyosarcoma
    Atlas Genet Cytogenet Oncol Haematol. 2009;13(12):986-988.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Tumors/EmbryoRhabdomyoID5193.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Tue Aug 26 15:53:15 CEST 2014


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