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Soft Tissues: Rhabdomyosarcoma

Written2009-01Jennifer Reichek, Frederic G Barr
Department of Pathology, Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
This article is an update of :
1998-03Jérome Couturier
Department of Pathology, Institut Curie, Paris, France

(Note : for Links provided by Atlas : click)


Atlas_Id 5004
Phylum Soft Tissues::Rhabdomyosarcoma
WHO/OMS Classification Soft Tissues
Note Rhabdomyosarcoma (RMS) refers to a family of mesenchymal tumours related to the skeletal muscle lineage.


    The two main histopathologic subtypes of rhabdomyosarcoma are :
  • Embryonal rhabdomyosarcoma (ERMS)
  • Alveolar rhabdomyosarcoma (ARMS)
  • Clinics and Pathology

    Embryonic origin RMS is postulated to be derived from mesodermal tissues.
    Epidemiology RMS is the most common pediatric soft tissue sarcoma, representing ~5% of all malignancies among children and adolescents. The annual incidence is 4-5 per million. ERMS accounts for 70-80% of all RMS, and usually occurs in young children (median age of 6.5 years). ARMS accounts for the remaining 20-30% of RMS, and more often occurs in older children and young adults (median age of 12 years).
    Clinics RMS often presents as a painless mass. In other cases, the tumor may be discovered from symptoms produced by compression of structures at the primary site, such as diplopia (double vision) caused by RMS in the orbital region. The two histopathologic subtypes tend to occur at different sites. ERMS often occurs in the head and neck region, genitourinary tract, and retroperitoneum whereas ARMS often occurs in the extremities. All types of RMS are treated with a combination of surgery, radiation therapy, and intensive chemotherapy.
  • In ERMS, the tumor cells range from small round cells to large elongated cells, and exhibit varying degrees of myogenic differentiation. There is often varying cell density with highly cellular areas alternating with low cellular areas in a loose myxoid stroma.
  • In ARMS, tumor cells are small with a round nucleus and scant cytoplasm. Aggregates of these tumors cells often become discohesive and produce spaces, reminiscent of lung alveoli.
  • An anaplastic RMS subset is recognized by large, lobated hyperchromatic nuclei and atypical mitoses. Anaplasia is more prevalent in ERMS and can be found as a focal or diffuse feature in the tumor.
  • The tumor cells of both subtypes of RMS variably express muscle specific proteins (such as desmin, myoglobin, muscle-specific actin, or the myogenic transcription factors MyoD and myogenin) that can be detected by immunohistochemistry.
    Histopathology of rhabdomyosarcoma subtypes. A. Embryonal subtype. B. Alveolar subtype. (hematoxylin-eosin, original magnification: 100X; courtesy of Dr. Linda Ernst)
    Prognosis Factors that influence the selection of therapy and the outcome of patients include primary site (orbit, superficial head and neck, biliary tree, vagina, and paratestis are considered favorable), size of primary tumor, extent of local spread, presence of nodal and distal metastases, and histologic subtype. Of the two histologic subtypes, ARMS has a poorer prognosis than ERMS.


    Note Most cases of RMS occur sporadically without an apparent genetic predisposition. However, a small subset of RMS is associated with the following known genetic syndromes:
  • Hereditary retinoblastoma syndrome (RB1)
  • Li-Fraumeni syndrome (TP53)
  • Neurofibromatosis type I (NF1)
  • Costello syndrome (HRAS)
  • Beckwith-Wiedemann syndrome (11p15 genes)
  • Nevoid basal cell carcinoma syndrome (PTCH)
  • Rubinstein-Taybi syndrome (CREBBP).
  • Cytogenetics

    Studies of cytogenetics and other acquired genetic changes in ERMS and ARMS have revealed significant genetic differences between these two subtypes.

  • Most ARMS cases are distinguished from ERMS and other solid tumors by the presence of one of two recurrent chromosomal translocations, which generate related fusion genes.
    - t(2;13)(q35;q14) generates PAX3 - FOXO1 in ~60% of ARMS cases
    - t(1;13)(p36;q14) generates PAX7 - FOXO1 in ~20% of ARMS cases

  • ERMS does not have recurrent structural chromosome rearrangements, but rather has frequent chromosome gains and losses. In addition, ERMS has a much higher frequency of loss of one of the two alleles of many chromosome 11 loci, particularly in the 11p15.5 region.
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    This paper should be referenced as such :
    Reichek J, Barr FG
    Soft Tissues: Rhabdomyosarcom
    Atlas Genet Cytogenet Oncol Haematol. in press
    On line version :
    History of this paper:
    Reichek, J ; Barr, FG. Soft tissue tumors: Rhabdomyosarcoma. Atlas Genet Cytogenet Oncol Haematol. 2009;13(12):989-991.

    Other genes implicated (Data extracted from papers in the Atlas) [ 33 ]


    Translocations implicated (Data extracted from papers in the Atlas)

     t(1;13)(p36;q14) PAX7/FOXO1
     t(2;13)(q35;q14) PAX3/FOXO1
     t(2;2)(p23;q36) PAX3/NCOA1
     t(2;8)(q36;q13) PAX3/NCOA2
     t(4;22)(q35;q12) EWSR1/DUX4
     t(6;8)(p21;q13) SRF/NCOA2
     t(8;11)(q13;p15) TEAD1/NCOA2
     t(8;13)(p11;q14) FOXO1/FGFR1
     t(X;2)(q13;q36) PAX3/FOXO4

    External links

    Mitelman database t(1;13)(p36;q14) [CaseList]     t(1;13)(p36;q14) [Transloc - MCList]   PAX7/FOXO1 Fusion - MCList]
    COSMIC[ PAX7 ]   [ FOXO1 ]
    Mitelman database t(2;13)(q35;q14) [CaseList]     t(2;13)(q35;q14) [Transloc - MCList]   PAX3/FOXO1 Fusion - MCList]
    COSMIC[ PAX3 ]   [ FOXO1 ]
    Mitelman database t(2;2)(p23;q36) [CaseList]     t(2;2)(p23;q36) [Transloc - MCList]   PAX3/NCOA1 Fusion - MCList]
    COSMIC[ PAX3 ]   [ NCOA1 ]
    Mitelman database t(2;8)(q36;q13) [CaseList]     t(2;8)(q36;q13) [Transloc - MCList]   PAX3/NCOA2 Fusion - MCList]
    COSMIC[ PAX3 ]   [ NCOA2 ]
    Mitelman database t(4;22)(q35;q12) [CaseList]     t(4;22)(q35;q12) [Transloc - MCList]   EWSR1/DUX4 Fusion - MCList]
    COSMIC[ EWSR1 ]   [ DUX4 ]
    Mitelman database t(6;8)(p21;q13) [CaseList]     t(6;8)(p21;q13) [Transloc - MCList]   SRF/NCOA2 Fusion - MCList]
    COSMIC[ SRF ]   [ NCOA2 ]
    Mitelman database t(8;11)(q13;p15) [CaseList]     t(8;11)(q13;p15) [Transloc - MCList]   TEAD1/NCOA2 Fusion - MCList]
    COSMIC[ TEAD1 ]   [ NCOA2 ]
    Mitelman database t(8;13)(p11;q14) [CaseList]     t(8;13)(p11;q14) [Transloc - MCList]   FOXO1/FGFR1 Fusion - MCList]
    COSMIC[ FOXO1 ]   [ FGFR1 ]
    Mitelman database t(X;2)(q13;q36) [CaseList]     t(X;2)(q13;q36) [Transloc - MCList]   PAX3/FOXO4 Fusion - MCList]
    COSMIC[ PAX3 ]   [ FOXO4 ]
    arrayMap arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
    Mitelman databasePAX3/FOXO1[MCList]    PAX3 (2q36.1) FOXO1 (13q14.11)   
    Mitelman databasePAX3/FOXO1[MCList]    PAX3 (2q36.1) FOXO1 (13q14.11)   t(1;13)(p36;q14)
    Mitelman databasePAX3/FOXO4[MCList]    PAX3 (2q36.1) FOXO4 (Xq13.1)   t(X;2)(q13;q36)
    COSMIC_fusionPAX3 (2q36.1) NCOA1 (2p23.3)    [fusion1042] [fusion1043] [fusion289] [fusion290]
    Mitelman databasePAX3/NCOA1[MCList]    PAX3 (2q36.1) NCOA1 (2p23.3)   t(2;2)(p23;q36)
    TICdbPAX3/NCOA1    PAX3 (2q36.1) NCOA1 (2p23.3)
    COSMIC_fusionPAX3 (2q36.1) NCOA2 (8q13.3)    [fusion1040] [fusion1041]
    Mitelman databasePAX3/NCOA2[MCList]    PAX3 (2q36.1) NCOA2 (8q13.3)   t(2;8)(q36;q13)
    TICdbPAX3/NCOA2    PAX3 (2q36.1) NCOA2 (8q13.3)
    COSMIC_fusionPAX7 (1p36.13) FOXO1 (13q14.11)    [fusion287] [fusion288] [fusion344]
    Mitelman databasePAX7/FOXO1[MCList]    PAX7 (1p36.13) FOXO1 (13q14.11)   
    Mitelman databasePAX7/FOXO1[MCList]    PAX7 (1p36.13) FOXO1 (13q14.11)   t(1;13)(p36;q14)
    Mitelman databaseSRF/NCOA2[MCList]    SRF (6p21.1) NCOA2 (8q13.3)   t(6;8)(p21;q13)
    Mitelman databaseTEAD1/NCOA2[MCList]    TEAD1 (11p15.3) NCOA2 (8q13.3)   t(8;11)(q13;p15)
    Disease databaseSoft Tissues: Rhabdomyosarcoma
    REVIEW articlesautomatic search in PubMed
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