Soft tissue tumors: Extraskeletal 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.
Pathology	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.

Cytogenetics

Cytogenetics Morphological

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.

Variants

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Genes involved and Proteins

Gene Name	NR4A3 (TEC)
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	TAF2N
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
Description	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.

Bibliography

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

-

Enzinger FM, Weiss S

Soft Tissue Tumors 3rd ed..

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

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

The EWS/TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator.

Labelle Y, BussiˆŪres 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.

Sjˆgren H, Meis-Kindblom J, Kindblom LG, Aman P, Stenman G

Cancer research. 1999 ; 59 (20) : 5064-5067.

PMID 10537274

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

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

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Contributor(s)

Written	07-2000	Jérome Couturier
		Department of Pathology, Institut Curie, Paris, France
Updated	09-2004	Masanori Hisaoka, Hiroshi Hashimoto
		Department of Pathology & Oncology, School of Medicine, University of Occupational & Environmental Health, Japan

Citation

This paper should be referenced as such :

Couturier J . Soft tissue tumors: Extraskeletal myxoid chondrosarcoma. Atlas Genet Cytogenet Oncol Haematol. July 2000 . URL : http://AtlasGeneticsOncology.org/Genes/ExtraMyxChondroID5025.html

Hisaoka M, Hashimoto H . Soft tissue tumors: Extraskeletal myxoid chondrosarcoma. Atlas Genet Cytogenet Oncol Haematol. Septem ber 2004 . URL : http://AtlasGeneticsOncology.org/Genes/ExtraMyxChondroID5025.html

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