Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis (malignant melanoma of soft parts)

Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft p arts) and conventional malignant melanoma may demonstrate significant morph ologic overlap at the light microscopic and ultrastructural level. Conseque ntly, the clinically relevant distinction between primary clear cell sarcom a and metastatic melanoma in the absence of a known primary cutaneous, muco sal or ocular tumour may occasionally cause diagnostic problems, A balanced translocation, t(12;22)(q13;q13), which can be detected, amongst others, u sing the reverse transcriptase polymerase chain reaction (RT-PCR) or fluore scent in situ hybridization (FISH), has been identified in a high percentag e (50-75%) of clear cell sarcomas and is presumed to be tumour specific. Wh ether this chromosomal rearrangement is present in malignant melanoma has, to date, not as yet been studied by molecular genetic or molecular cytogene tic techniques, Using RT-PCR and FISH, a series of metastases from 25 known cutaneous melanomas and 8 melanoma cell lines (5 uveal and 3 cutaneous) we re screened for the t(12;22)(q13;q13) translocation, Primers for RT-PCR wer e chosen based upon published breakpoint sequences. The Cosmids G9 and CCS2 .2, corresponding to the 5' region of EWS and 3' region of ATF-1 respective ly, were used as probes, The translocation was not identified in any of the melanomas or melanoma cell lines analysed in this study; in contrast this translocation was identified in 3 out of 5 clear cell sarcomas using these techniques, This allows distinction between translocation positive cases of clear cell sarcoma and malignant melanoma at a molecular genetic level. Co nsequently, in diagnostically challenging cases, this represents a valuable tool for the clinicopathologic differentiation between these two entities, with an important impact on patient management and prognosis. (C) 2001 Can cer Research Campaign.