Visceral Clear Cell Sarcoma of Soft Tissue with Confirmation by EWS-ATF1 Fusion Detection

• Published in: Ultrastructural pathology 2006, Vol.30 (1-2), p.111-118
• Main Authors: Granville, Laura, Hicks, John, Popek, Edwina, Dishop, Megan, Tatevian, Nina, Lopez-Terrada, Dolores
• Format: Article
• Language: English
• Subjects: Adolescent; Anemia, Iron-Deficiency - diagnosis; Biomarkers, Tumor - metabolism; clear cell sarcoma of soft tissues; Cytogenetic Analysis; cytogenetics; Diagnosis, Differential; DNA, Neoplasm - analysis; EWS-ATF1; Fatal Outcome; Humans; immunocytochemistry; Intestinal Neoplasms - genetics; Intestinal Neoplasms - metabolism; Intestinal Neoplasms - pathology; Male; malignant melanoma of soft parts; Melanoma - diagnosis; Melanoma - secondary; molecular pathology; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Sarcoma, Clear Cell - genetics; Sarcoma, Clear Cell - metabolism; Sarcoma, Clear Cell - pathology; Sequence Analysis, DNA; Soft Tissue Neoplasms - genetics; Soft Tissue Neoplasms - metabolism; Soft Tissue Neoplasms - pathology; t(12; 22)(q13; q12); Transcription Factors - genetics; Transcription Factors - metabolism; ultrastructure; visceral clear cell sarcoma
• ISSN: 0191-3123; 1521-0758
• DOI: 10.1080/01913120500406400

Clear cell sarcoma of soft tissue (CCS-ST) is a rare malignant neoplasm characterized by a tumor-defining translocation [t(12;22) (q13;q12)], resulting in the EWS-ATF1 gene fusion. An extremely limited number of visceral CCS-ST cases have been reported in the literature. Here the authors report a visceral CCS-ST in a Hispanic adolescent male with a large infiltra-tive mass involving the small bowel. The tumor was evaluated by light microscopy, immunocytochemistry, electron microscopy, cytogenetics, and molecular genetics. The tumor cells were strongly positive for S-100 protein, but negative for HMB-45. Rare premelanosomes were identified only after an extensive search with electron microscopy. Cytogenetics showed a characteristic t(12;22)(q13;q12) for CCS-ST with isochromosome 18q and trisomy 22. An EWS exon 8 sense primer and an antisense ATF1 primer were employed for detection of the CCS-ST tumor-defining EWS-ATF1 translocation, using reverse transcriptase-polymerase chain reaction techniques (RT-PCR), and the fusion gene breakpoint underwent DNA sequencing. This tumor is exceptional, because it is the first visceral CCS-ST that has been confirmed by RT-PCR and DNA sequencing. This case also illustrates the necessity of a multimodal approach to tumor diagnosis, and the utility of cytogenetics and molecular pathology in confirming the diagnosis of CCS-ST and eliminating conventional metastatic or primary visceral malignant melanoma as a consideration.