Soft tissue tumors: Malignant melanoma of soft parts

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Soft tissue tumors: Malignant melanoma of soft parts

Identity

Other names

Clear cell sarcoma of soft parts

Classification

this tumour, initially described by Enzinger as "clear cell sarcoma of tendons and aponeuroses", is of uncertain origin, but its immunohistochemical profile shows its melanocytic nature; however it has no genetic relationship with the cutaneous malignant melanoma

Clinics and Pathology

Embryonic origin	being of melanocytic origin, this tumour should be classified as a neuroectodermal tumour
Etiology	unknown
Epidemiology	it is a very rare tumour representing a minority of all soft tissue sarcomas
Clinics	the malignant melanoma of soft parts (MMSP) preferentially occurs in young adults, between ages of 20 and 40 years; the tumour develops mainly in the extremities, especially the legs (foot, knee, heel, ankle); it is usually deeply seated, and often bound to tendons and aponeuroses
Pathology	the tumours show compact nests and strands of round or fusiform cells with a clear cytoplasm, separated by fibrocollagenous tissue often connected to adjacent tendons or aponeuroses; mitotic index is generally low; the cells of nearly all cases express S-100 protein and the melanoma-associated antigen HMB45
Treatment	the treatment protocols vary greatly according to the intitutions; however, the melanoma of soft parts is a highly malignant tumour which requires surgical excision combined with radiotherapy and/or chemotherapy
Evolution	many patients develop recurrences and regional and distant metastases, in lymph nodes, lung, and bones; in the series of Enzinger, the average time between diagnosis and recurrence was 2.6 years, between diagnosis and metastasis, 3.5 years
Prognosis	the prognosis is poor; in the series of 115 patients studied by Enzinger, 46% had died; of the 62 living patients, 21 experienced one or more recurrences, and 7 had a metastatic disease

Cytogenetics

Cytogenetics
Morphological

this tumour is characterised by the presence of a chromosome translocation t(12;22)(q13;q12), which involves genes ATF-1, on chromosome 12, and EWS, on chromosome 22

Genes involved and Proteins

Gene Name	EWSR1
Location	22q12
Protein	RNA binding protein

Gene Name	ATF-1
Location	12q13
Protein	transcription factor

Result of the chromosomal anomaly

Fusion Protein
Description	the chimaeric protein is composed of the N-terminal domain of EWS linked to the bZIP domain of ATF-1
Oncogenesis	binds to ATF sites present in cAMP-responsive promoters via the ATF1 bZIP domain and activates transcription constitutively, dependent on the activation domain (EAD) present in EWSR1

Bibliography

Soft tissue tumors.

Enzinger FM, Weiss SW

3rd ed..

EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts.

Zucman J, Delattre O, Desmaze C, Epstein AL, Stenman G, Speleman F, Fletchers CD, Aurias A, Thomas G

Nature genetics. 1993 ; 4 (4) : 341-345.

PMID 8401579

The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator.

Fujimura Y, Ohno T, Siddique H, Lee L, Rao VN, Reddy ES

Oncogene. 1996 ; 12 (1) : 159-167.

PMID 8552387