| Disease | Soft tissue tumour, presenting as a slow growing mass intimately associated with tendons and aponeuroses, in young adults. |
| Note | To be distinguished from clear cell sarcoma of the kidney, to which it is unrelated. |
| Embryonic origin | mesoderm |
| Epidemiology | rare sarcoma affecting primarily young adults |
| Clinics | slowly growing tumour mass, causing pain or tenderness, particularly frequently (up to 95% of the cases) situated in the extremities, with a predilection for the foot and the ankle. |
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| Cellular smear almost exclusively showing dispersed spindle cells. Their oval nuclei are only slightly irregular and contain a large nucleolus. The cytoplasm is rather scant (MGG, 400x) (Courtesy of Dr. J. Willems, Onze-Lieve-Vrouw Ziekenhuis Aalst, Belgium). |
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| Pathology | Polygonal or spindle shaped cells with abundant eosinophilic or clear cytoplasm displaying a uniform, nested to fascicular growth pattern, delineated by fibrous septa. Melanin deposits can be demonstrated using specific stains, but is more readily detectable by immunoreactivity against melanoma antigens (e.g. S100 and HMB45) in the vast majority of the cases. |
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| Left to right: A: Typical clear cell sarcoma with eosinophilic cytoplasm (H&E, 400x); B: A reticulin meshwork surrounds the individual nests (reticulin, 200x); C: Strong S100 immunoreactivity, a consistent feature (S100, 400x). |
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| Treatment | radical surgical resection, adjuvant radiotherapy should be considered in incomplete resections, large (>5 cm) tumours and/or high grade lesions. Clear cell sarcomas seems to display little sensitivity to conventional soft tissue sarcoma multi-agent chemotherapy protocols. |
| Evolution | special attention should be paid to the occurrence of late recurrences (median time to recurrence: 4.2 years). |
| Prognosis | Generally, clear cell sarcoma is characterised by an adverse prognosis, only 40 to 50% of the patients being long-term survivors. As recurrences may occur late, 5-year survival rates tend to misjudge prognosis. Established prognostic features include: tumour size, necrosis and local recurrence. |
Cytogenetics
Morphological | The cytogenetic hallmark of clear cell sarcoma is the presence of the t(12;22)(q13;q12). This translocation has been described in the majority of reported clear cell sarcoma cases, not however in other malignancies. The translocation is readily identifiable with G-, R- or Q-banding. |
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| The t(12;22)(q13;q12), as identified by G-banding. |
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| Cytogenetics Molecular | Fluorescence in situ hybridisation based approaches can be used to demonstrate the t(12;22), using chromosome painting probes or to demonstrate EWSR1 and ATF1 gene rearrangement, using gene specific probes. Although the t(12;22) has been reported as the sole chromosomal aberration in clear cell sarcoma, most cases display additional cytogenetic anomalies, including +7, +8 and structural and numerical aberrations of chromosome 22. |
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| dual colour in situ hybridisation the EWS cosmid G9 (green) and the ATF1 CCS2.2 cosmid (red) demonstrating a juxtaposition of 5' EWS to 3' ATF1 sequences, indicating the presence of a EWS/ATF1 genomic fusion (arrowheads). |
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| Probes | EWSR1 probes: 5' EWSR1: G9 cosmid; 3' ATF1 probe: CCS2.2 |
| Variants | No variant translocations, creating EWSR1/ATF1 fusion transcripts, have been described. |
| Molecular diagnosis of clear cell sarcoma: detection of EWS-ATF1 and MITF-M transcripts and histopathological and ultrastructural analysis of 12 cases. |
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| Cytogenetic findings in clear cell sarcoma of tendons and aponeuroses. Malignant melanoma of soft parts. |
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| PMID 2009504 |
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| Malignant melanoma of soft parts. A reassessment of clear cell sarcoma. |
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| PMID 6614306 |
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| EWS-ATF-1 chimeric protein in soft tissue clear cell sarcoma associates with CREB-binding protein and interferes with p53-mediated trans-activation function. |
| Fujimura Y, Siddique H, Lee L, Rao VN, Reddy ES |
| Oncogene. 2001 ; 20 (46) : 6653-6659. |
| PMID 11709699 |
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| Clear cell sarcoma of soft tissues. Mayo Clinic experience with 35 cases. |
| Lucas DR, Nascimento AG, Sim FH |
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| PMID 1463095 |
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| Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses. |
| Panagopoulos I, Mertens F, Dbiec-Rychter M, Isaksson M, Limon J, Kardas I, Domanski HA, Sciot R, Perek D, Crnalic S, Larsson O, Mandahl N |
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| PMID 11992546 |
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| PMID 10599094 |
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| Malignant melanoma of the soft parts (clear-cell sarcoma): confirmation of EWS and ATF-1 gene fusion caused by a t(12;22) translocation. |
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| PMID 9160316 |
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| PMID 8401579 |
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