Gastrointestinal Melanoma or Clear Cell Sarcoma? Molecular Evaluation of 7 Cases Previously Diagnosed as Malignant Melanoma

Abstract

Clear cell sarcoma (CCS) is a rare tumor classically associated with the tendons and aponeuroses of distal extremities of young adults. CCS and malignant melanoma (MM) share immunohistochemical profiles and ultrastructural features, but classic CCS has characteristic morphology with low mitotic activity and minimal pleomorphism. Occasional cases show pleomorphism, high mitotic index, and/or melanin pigmentation, making CCS indistinguishable from MM based on morphology. However, CCS is genetically distinct owing to its consistent association with a t(12;22)(q13;q12) chromosomal translocation, leading to the formation of the EWS/ATF1 fusion transcript. This translocation has never been documented in cutaneous melanoma, and thus is regarded as specific for CCS. Recent evidence suggests that primary "malignant melanomas" in unusual anatomic sites, most notably the gastrointestinal (GI) tract, may be CCS. This is supported by 11 cases of primary GI CCS with the t(12;22) translocation. We used reverse-transcription polymerase chain reaction and fluorescence in situ hybridization to examine whether a proportion of cases diagnosed as MM of the GI tract in patients without a history of cutaneous MM actually represent primary GI CCS. In total, we examined 7 cases: Four with no prior history of MM, 2 with histories of cutaneous MM, and 1 with an anal MM. All 4 cases for which there was no history of cutaneous/mucosal MM harbored the EWS/ATF1 fusion transcript. We report the largest series of GI CCS and have shown that molecular studies may be warranted in cases that otherwise seem to represent MM of unusual primary locations.

Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts)

“…Both EWSR1-ATF1 and EWSR1-CREB1 are known to occur in gastrointestinal clear cell sarcomas. 5,6,8,10 However, the prevalence of chimeric transcript types in gastrointestinal clear cell sarcomas at this site remains uncertain given the rare nature of this tumor.…”

“…[1][2][3] Occasionally, primary clear cell sarcoma can arise in visceral organs including the gastrointestinal tract. 1,[4][5][6][7][8][9][10] It is one of the few sarcomas with a high propensity for lymph node metastases with frequencies of up to 50% reported. [1][2][3] Histologically, clear cell sarcoma is characterized by polygonal to spindled cells arranged in nests and fascicles with clear to eosinophillic granular cytoplasm and prominent nucleoli.…”

“…[1][2][3] Interestingly, clear cell sarcomas of the gastrointestinal origin can be negative for specific melanocytic markers. 5,6,[8][9][10] In addition, 50% of traditional extremity clear cell sarcomas can harbor pigment. 3 This can sometimes make the distinction between clear cell sarcoma and melanoma difficult, especially in situations in which there is no clear in situ component identified or in metastatic melanomas of unknown primary.…”

Clear Cell Sarcoma–like Tumor of the Gastrointestinal Tract: An Evolving Entity

“…Spindling of cells is a rarer feature, as are large epithelioid cells 5 and pleomorphism (Figure 3), 19 which can also occur in gastrointestinal CCS with EWSR1-ATF1 fusion transcripts. 20 Architecturally, cells are most often arranged in diffuse sheets or more ill-defined nests (Figures 2 through 4), without the well-formed nests typical of CCS. Clear cell sarcoma-like tumors of the gastrointestinal tract often also show, at least focally, pseudoalveolar ( Figure 5), pseudopapillary, microcystic, fascicular, or trabecular growth patterns, and abortive rosettelike structures have been described.…”

“…However, 6 of 7 cases of conventional CCS of the gastrointestinal tract were found to contain melanin where there was an active search for pigmentation. [20][21][22][23] Most CCSLGTs show extensive areas of tumor necrosis and often show high mitotic activity. 13 …”