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Soft Tissues: Extraskeletal myxoid chondrosarcoma

Written2000-07Jérome Couturier
Department of Pathology, Institut Curie, Paris, France
Updated2004-09Masanori Hisaoka, Hiroshi Hashimoto
Department of Pathology & Oncology, School of Medicine, University of Occupational & Environmental Health, Japan

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ICD-Topo C470-C476,C478-C479,C490-C496,C498-C499 CONNECTIVE & SOFT TISSUE
ICD-Morpho 9231/3 Extraskeletal myxoid chondrosarcoma ("chordoid" type)
Atlas_Id 5025
Phylum Soft Tissues::Extrasqueletal myxoid chondrosarcoma

Clinics and Pathology

Disease Malignant tumour of soft tissue origin, distinct from the primary skeletal chondrosarcoma with myxoid alteration.
Epidemiology It is a rare tumour: 2.3% of soft tissue sarcomas in a Japanese series; mean ages reported in various series range from 46 to 57 years, this tumour being exceptional in children and adolescents; males are affected about twice as often as females.
Clinics Location: deep soft tissues of the lower extremities in about 75% of the cases, especially the thigh, the popliteal fossa, and the buttock; occasionally, a bone involvement may exist, as a minor component.
  • Macroscopic findings: the tumour presents as lobulated or multinodular mass, generally well circumscribed by a distinct fibrous capsule.The size of the tumour at the time of diagnosis may vary from 1 to about 20 cm (mean size: about 7 cm).
  • Histology: typically, tumour nodules are composed of round or slightly elongated cells, with minimal features of chondroblasts, separated by mucoid substance; differentiated cartilage cells are rare; histological diagnosis may be very difficult, especially in highly cellular forms devoid of myxoid matrix.
  • Tumour cells generally show positivity for vimentin, S-100 protein, occasionally for EMA, and negativity for cytokeratin.
  • a subset of tumours display neural or neuroendocrine differentiation as shown by positive immunohistochemical reactivities to neural or neuroendocrine markers such as neuron-specific enolase, synaptophysin, chromogranin A, and PGP9.5; tumours are mostly negative for markers (collagen type II, X, proteoglycan aggrecan) for the chondrocytic cell lineage.
  • ultrastructurally, at least one third of the tumours demonstrate microtubular aggregates within dilated rough endoplasmic reticulum; neurosecretory granules (80-170 nm diameter) are occasionally identified
  • Treatment Treatment: surgical excision, with adjuvant chemotherapy in case of lymph nodes or metastasi.


  • Cytogenetic studies have demonstrated the presence of a recurrent translocation t(9;22)(q22;q12); it results in the fusion of the EWSR1 gene on chromosome 22 with NR4A3 (TEC, CHN, or NOR1) gene on chromosome 9.
  • Recently, a variant translocation t(9;17)(q22;q11) and t(9;15)(q22;q21) have been identified, fusing the gene NR4A3 to gene TAF15 (TAF2N, TAFII68, or RBP56) and gene TCF12 (HTF4), respectively.
  • a variant fusion gene, TFG -NR4A3, has also been identified recently.
  • Left: t(9;22)(q22;q12) G- banding; right: EWSR1 FISH of formalin-fixed paraffin-embedded section showing EWSR1 rearrangement - Courtesy Gail Aldrete and Charles D. Bangs.
    Variants -

    Genes involved and Proteins

    Gene Name NR4A3
    Location 9q22
    Dna / Rna transcripts: 2.6 kb and 3.7 kb
    Protein Orphan nuclear receptor; signaling mediator; activate the c-fos promoter; role in growth and differentiation processes of hematopoietic tissues.

    Gene Name EWSR1
    Location 22q12
    Dna / Rna 17 exons; 2.4 kb mRNA.
    Protein RNA-binding protein; transcription repressor.

    Gene Name TAF15
    Location 17q11.1-q11.2
    Dna / Rna 16 exons; alternative splicing; 2.2 kb bp mRNA.
    Protein RNA-binding protein; part of theTFIID and RNA polymerase II complex.

    Gene Name TCF12
    Location 15q21
    Dna / Rna 370 kb; 21 exons; 4 kb mRNA.
    Protein Transcription factor; a basic helix-loop-helix protein.

    Gene Name TFG
    Location 3q11-q12
    Dna / Rna 39.51 kb; 8 exons; 1.9 kb mRNA
    Protein Putative signal transducer; positive regulator of I-kappaB kinase/NF-kappaB cascade.

    Result of the chromosomal anomaly

    Fusion Protein
  • The EWSR1/NR4A3(TEC,CHN) gene fusion encodes a fusion protein in which the C-terminal RNA-binding domain of EWSR1 (EWS) is replaced by the entire NR4A3 (TEC) protein. NR4A3 (TEC) is a member of the steroid/thyroid receptor gene superfamily; the EWSR1/NR4A3 (EWS/TEC) fusion protein is a potent transcriptional activator.
  • The TAF15(TAF2N, TAGII68 or RBP56) / NR4A3(TEC) fusion, in which exon 6 of TAF15 (TAF2N,TAFII68, or RBP56) is fused to the entire coding region of NR4A3 (TEC), is structurally and functionally very similar to the EWSR1/NR4A3 (EWS/TEC) fusion.
  • In the TCF12/NR4A3 fusion, the first 108 amino acids of the N terminus of TCF12 are fused in-frame upstream of the entire NR4A3 sequence.
  • The TFG/NR4A3 fusion, in which exon 6 of TFG is fused to the entire coding region of NR4A3.


    Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype.
    Aigner T, Oliveira AM, Nascimento AG
    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2004 ; 17 (2) : 214-221.
    PMID 14657948
    Skeletal and extraskeletal myxoid chondrosarcoma: a comparative clinicopathologic, ultrastructural, and molecular study.
    Antonescu CR, Argani P, Erlandson RA, Healey JH, Ladanyi M, Huvos AG
    Cancer. 1998 ; 83 (8) : 1504-1521.
    PMID 9781944
    Identification of a novel fusion gene involving hTAFII68 and CHN from a t(9;17)(q22;q11.2) translocation in an extraskeletal myxoid chondrosarcoma.
    Attwooll C, Tariq M, Harris M, Coyne JD, Telford N, Varley JM
    Oncogene. 1999 ; 18 (52) : 7599-7601.
    PMID 10602520
    Extraskeletal myxoid chondrosarcoma: multimodal diagnosis and identification of a new cytogenetic subgroup characterized by t(9;17)(q22;q11).
    Bjerkehagen B, Dietrich C, Reed W, Micci F, Saeter G, Berner A, Nesland JM, Heim S
    Virchows Archiv : an international journal of pathology. 1999 ; 435 (5) : 524-530.
    PMID 10592057
    Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma.
    Clark J, Benjamin H, Gill S, Sidhar S, Goodwin G, Crew J, Gusterson BA, Shipley J, Cooper CS
    Oncogene. 1996 ; 12 (2) : 229-235.
    PMID 8570200
    Enzinger FM, Weiss S
    Soft Tissue Tumors 3rd ed..
    Myxoid chondrosarcoma with a translocation involving chromosomes 9 and 22.
    Hinrichs SH, Jaramillo MA, Gumerlock PH, Gardner MB, Lewis JP, Freeman AE
    Cancer genetics and cytogenetics. 1985 ; 14 (3-4) : 219-226.
    PMID 3967207
    TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma.
    Hisaoka M, Ishida T, Imamura T, Hashimoto H
    Genes, chromosomes & cancer. 2004 ; 40 (4) : 325-328.
    PMID 15188455
    The EWS/TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator.
    Labelle Y, Bussiè J, Courjal F, Goldring MB
    Oncogene. 1999 ; 18 (21) : 3303-3308.
    PMID 10359536
    Fusion of the RBP56 and CHN genes in extraskeletal myxoid chondrosarcomas with translocation t(9;17)(q22;q11).
    Panagopoulos I, Mencinger M, Dietrich CU, Bjerkehagen B, Saeter G, Mertens F, Mandahl N, Heim S
    Oncogene. 1999 ; 18 (52) : 7594-7598.
    PMID 10602519
    Skeletal and extraskeletal myxoid chondrosarcoma: related or distinct tumors?
    Rubin BP, Fletcher JA
    Advances in anatomic pathology. 1999 ; 6 (4) : 204-212.
    PMID 10410173
    Fusion of the EWS-related gene TAF2N to TEC in extraskeletal myxoid chondrosarcoma.
    Sjögren H, Meis-Kindblom J, Kindblom LG, Aman P, Stenman G
    Cancer research. 1999 ; 59 (20) : 5064-5067.
    PMID 10537274


    This paper should be referenced as such :
    Hisaoka, M ; Hashimoto, H
    Soft tissue tumors: Extraskeletal myxoid chondrosarcoma
    Atlas Genet Cytogenet Oncol Haematol. 2004;8(4):334-335.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :
    History of this paper:
    Couturier, J. Soft tissue tumors: Extraskeletal myxoid chondrosarcoma. Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):145-146.

    Other genes implicated (Data extracted from papers in the Atlas) [ 7 ]

    Genes EWSR1 PLAGL1 TAF15 TCF12 NR4A3 NR4A3 TFG

    Translocations implicated (Data extracted from papers in the Atlas)

     t(3;9)(q12;q22) TFG/NR4A3
     t(9;15)(q22;q21) TCF12/NR4A3
     t(9;17)(q22;q11) AF15/NR4A3
     t(9;22)(q22;q12) EWSR1/NR4A3

    External links

    Mitelman database t(3;9)(q12;q22) TFG/NR4A3 [Case List]    t(3;9)(q12;q22) TFG/NR4A3 [Association List] Mitelman database (CGAP - NCBI)
    Mitelman database t(9;15)(q22;q21) TCF12/NR4A3 [Case List]    t(9;15)(q22;q21) TCF12/NR4A3 [Association List] Mitelman database (CGAP - NCBI)
    Mitelman database t(9;17)(q22;q11) AF15/NR4A3 [Case List]    t(9;17)(q22;q11) AF15/NR4A3 [Association List] Mitelman database (CGAP - NCBI)
    Mitelman database t(9;22)(q22;q12) EWSR1/NR4A3 [Case List]    t(9;22)(q22;q12) EWSR1/NR4A3 [Association List] Mitelman database (CGAP - NCBI)
    arrayMap Topo ( C47,C49) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
    Mitelman databaseEWSR1/NR4A3[MCList]    EWSR1 (22q12.2) NR4A3 (9q22.33)   t(9;22)(q31;q12)
    TICdbEWSR1/NR4A3    EWSR1 (22q12.2) NR4A3 (9q22.33)
    COSMIC_fusionTAF15 (17q12) NR4A3 (9q22.33)    [fusion589] [fusion657] [fusion658] [fusion957] [fusion958] [fusion959]
    TICdbTAF15/NR4A3    TAF15 (17q12) NR4A3 (9q22.33)
    COSMIC_fusionTCF12 (15q21.3) NR4A3 (9q22.33)    [fusion754] [fusion755]
    Mitelman databaseTCF12/NR4A3[MCList]    TCF12 (15q21.3) NR4A3 (9q22.33)   t(9;15)(q31;q21)
    COSMIC_fusionTFG (3q12.2) NR4A3 (9q22.33)    [fusion1187] [fusion610]
    Mitelman databaseTFG/NR4A3[MCList]    TFG (3q12.2) NR4A3 (9q22.33)   t(3;9)(q12;q31)
    TICdbTFG/NR4A3    TFG (3q12.2) NR4A3 (9q22.33)
    Disease databaseSoft Tissues: Extraskeletal myxoid chondrosarcoma
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Wed May 3 17:27:58 CEST 2017

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