Clear Cell Sarcoma


Clear cell sarcomas (a.k.a. malignant melanoma of soft parts) are rare tumours that mainly occur in young adults with the peak incidence in the third and fourth decades.  The tumours are small, slow growing masses that may be tender or painful. These tumours arise in the deep soft tissue of the extremities and are often associated with tendons or aponeuroses; often without skin involvement.

At least 90% of cases harbour a t(12;22)(q13;q12) that results in the fusion of the 5’portion of EWSR1 on chromosome 22 and the 3’ portion of ATF1 on chromosome 12.  The fusion protein deregulates promoters harbouring an ATF1 binding site. A variant t(2;22) involving EWSR1 and CREB1 is seen in up to 6% of cases.


  1. Completed CGL Cytogenetic Solid Tumour testing requisition form [link]
  2. FFPE Tumour specimen (see Specimen Guidelines, Cytogenetics test type)
  3. A minimum of 10% tumour content and at least 200 nuclei is required


Results are reported within fourteen days from receipt of specimen and completed requisition form.  


  • Specimens are reported as Positive for a rearrangement, Negative for a rearrangement.
  • Up to 90-95% of clear cell sarcomas will have an EWSR1 rearrangement identified by this assay.
  • The majority of clear cell sarcomas will have an EWSR1ATF1 fusion, however, this fusion is also identified in angiomatoid fibrous histiocytomas


FISH analysis is performed on the provided FFPE specimen using the EWSR1 (22q12) dual colour, break-apart probe (Vysis) and an “in house” dual colour, break-apart probe (RP11-112N23/RP11-812E7, RP11-165G10/RP11-624H10) to ATF1 (12q13).


  1. Song JS1, Choi J, Kim JH, Jang SJ, Cho KJ. Diagnostic utility of EWS break-apart fluorescence in situ hybridization in distinguishing between non-cutaneous melanoma and clear cell sarcoma.  2010. Pathol Int.60:608-13.
  2. Antonescu CR1, Nafa K, Segal NH, Dal Cin P, Ladanyi M.  EWS-CREB1: a recurrent variant fusion in clear cell sarcoma–association with gastrointestinal location and absence of melanocytic differentiation. 2006. Clin Cancer Res 12:5356-62.
  3. Rossi S1, Szuhai K, Ijszenga M et al. EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma. 2007 Clin Cancer Res13:7322-8.