Clear cell sarcoma of soft tissue (
malignant melanoma of soft parts) is a
soft tissue sarcoma with melanocytic differentiation that typically occurs in the tendons and aponeuroses of young adults. As demonstrated by cytogenetics and
reverse-transcriptase polymerase chain reaction, between 70% and over 90% of
clear cell sarcomas have a t(12;22) translocation, fusing the EWS and ATF1 genes on chromosomes 22q12 and 12q13, respectively. Identification of this translocation distinguishes
clear cell sarcoma from histologic mimics, most importantly conventional
malignant melanoma. We report our experience with a commercially available, dual-color, break-apart fluorescence in situ hybridization (FISH) probe, which allows detection of EWS (22q12) gene rearrangement in
formalin-fixed,
paraffin-embedded tissues. Histologically and immunophenotypically well-characterized cases of
clear cell sarcoma (n = 10) and
malignant melanoma (n = 32) were evaluated with a 22q12 dual-color, break-apart probe (Vysis, Downer's Grove, IL, USA), which spans the known common breakpoints in the EWS gene on chromosome 22 (introns 7-10). Signals from
tumor cell nuclei were counted under a fluorescence microscope and the presence of red-green break-apart signals was recorded. Of the
clear cell sarcoma cases, seven of 10 showed evidence of an EWS gene rearrangement with a mean of 81.6% positive cells per sample (range: 60-95%). All cases of
malignant melanoma (n = 32) showed virtually absent break-apart signals in the EWS gene (less than 4% cells per case). FISH detects EWS gene rearrangement in a substantial proportion of
clear cell sarcomas, with excellent specificity. Importantly, EWS FISH is negative in
malignant melanoma, a clinically dissimilar
tumor, which may closely mimic
clear cell sarcoma histologically and immunohistochemically. As the studied probe can be utilized in routinely processed tissue, FISH provides an excellent alternative to
reverse-transcriptase polymerase chain reaction in cases where fresh tissue is unavailable.