A Comparison of Clear Cell Sarcoma to Jaw and Salivary Tumors Bearing EWS Fusions.

OBJECTIVE: To review tumors identified as "clear cell sarcoma" in order to determine similarities to the rare EWS fusion positive jaw and salivary gland tumors clear cell odontogenic carcinoma (CCOC) and clear cell carcinoma of the salivary gland (CCC). METHODS: PubMed was used to collect all reports of clear cell sarcoma (CCS). Search parameters were "clear cell sarcoma" and "CCS." References in the publications were screened and cross-referenced. Data extracted included demographic characteristics, presenting signs and symptoms, radiographic findings, histological and immunohistochemical features and known molecular/genetic aberrations. RESULTS: Clear cell sarcoma has several similarities to CCOC and CCC. All three tumor types have similar histologic appearances including the presence of clear cells, as well as similar genetic profiles in that all harbor an EWSR1-CREB family fusions. Additionally, these tumors appear in soft tissue as well as bone, and can have a prolonged clinical course. CCS can appear anywhere in the body, including the head and neck region. All three tumors appear to have a predilection to women, although CCS may have a slight younger age of onset as compared to CCOC and CCC (3rd vs 5th decade of life, respectively). CONCLUSION: Gaining a better understanding of the similarities and differences between these three tumors may lead to a better understanding of each one.

Detection of EWSR1 fusions in CCOC by targeted RNA-seq.

OBJECTIVE: To describe the application of a targeted RNA sequencing assay to detect fusion transcripts in formalin-fixed paraffin-embedded (FFPE), non-decalcified samples of clear cell odontogenic carcinoma (CCOC) and related tumors, and to add to knowledge of the genetic drivers of CCOC. STUDY DESIGN: Five FFPE tissues, including intraosseous CCOC (n = 3), clear cell carcinoma of the salivary gland (CCC, n = 1), and Ewing sarcoma (ES, n = 1), were analyzed by targeted RNA-seq to detect fusions. RESULTS: The 3 intraosseous CCOC samples harbored EWSR1 translocations: EWSR1-ATF1 (n = 2) and EWSR1-CREM (n = 1); the CCC sample contained an EWSR1-ATF1 fusion; and the ES sample contained an EWSR1-FLI1 fusion detected by RNA-seq. CONCLUSIONS: These results demonstrate that targeted RNA-seq is a valuable tool to detect fusions in FFPE samples of rare tumors such as CCOC and CCC. The results also confirm the observations that CCOC is driven by fusions between EWSR1 and CREB family transcription factors, including ATF1 and CREM. To our knowledge, this is the second report of CCOC with an EWSR1-CREM translocation.