EWS-ATF1 fusion transcripts in gastrointestinal tumors previously diagnosed as malignant melanoma

Clear cell sarcoma (CCS) is classically a deep soft tissue tumor associated with tendons or aponeuroses, although cases of primary CCS of the gastrointestinal (GI) tract have recently been reported. Because it is difficult to distinguish CCS from metastatic melanoma based on morphology, immunohistochemical profile, and ultrastructural features, it is possible that some GI tumors diagnosed as metastatic melanoma actually represent primary GI CCS. Because the EWS-ATF1 fusion transcript and the associated t(12;22)(q13;q12) translocation occur in CCS but not cutaneous melanoma, we investigated the use of molecular-based testing for discriminating CCS from metastatic melanoma (MM) in GI tumors.

Patients with GI tumors diagnosed as MM were identified from departmental files. The tumors were tested for the EWS-ATF1 fusion transcript by RT-PCR and for t(12;22)(q13;q12) by fluorescence in situ hybridization.

Detailed review of medical records revealed that 16 (80%) of the 20 had a documented history of cutaneous melanoma. Two cases (10%) harbored the EWS-ATF1 fusion transcript, and fluorescence in situ hybridization confirmed the presence of t(12;22) in both cases. Of the 2 positive tumors, 1 developed in a patient who had no history of cutaneous melanoma, and the other developed in a patient with a remote history of vulvar melanoma.

Based on molecular genetic findings, a subset of GI tumors diagnosed as MM by routine histopathologic evaluation represents CCS.