MYH9-USP6 Fusion Transcript in Nodular Fasciitis: An Institutional Review
David B Swanson, Elliott B Cohen, Lily Ramyar, Rita A Kandel, Brendan C Dickson. Mount Sinai Hospital, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada
Background: Nodular fasciitis (NF) is a benign, self-limiting proliferation of fibroblasts and myofibroblasts. The rapid growth, rich cellularity, and brisk mitotic activity that can be present in these lesions may pose a diagnostic challenge in the context of limited sampling, as with needle core biopsies. In a recent report, a majority of cases of NF were shown to harbor a stable translocation between ubiquitin specific peptidase 6 (USP6) on chromosome 17 and myosin heavy chain 9 (MYH9) on chromosome 22. The purpose of this study was to perform an institutional review of cases diagnosed as NF to assess for the presence of the MYH9-USP6 fusion product.
Design: Ribonucleic acid was extracted from archival formalin-fixed, paraffin-embedded tissue from 22 cases of NF and 26 cases of non-NF soft tissue tumors (including: benign fibrous histiocytoma, Ewing family tumor, ischemic fasciitis, myositis ossificans, myxofibrosarcoma, myxoid liposarcoma, non-ossifying fibroma, proliferative myositis, solitary fibrous tumor, and synovial sarcoma). Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using primers specific for the breakpoint between exon 1 of MYH9 and exon 2 of USP6.
Results: The MYH9-USP6 fusion transcript was identified in 19 of 22 (86%) NF cases. No fusion product was detected in any of the 26 non-NF cases (0%). All PCR products were verified by direct sequencing analysis. In comparing the morphology of lesions with and without the translocation, there were no conspicuous differences.
Conclusions: This study confirms the presence and specificity of the MYH9-USP6 gene fusion in NF, and these results demonstrate this can be exploited in a diagnostic assay suitable for use on formalin-fixed, paraffin-embedded tissue. It is possible that cases of NF that were negative for the fusion product have breakpoints not identified by this assay; this requires confirmation by fluorescence in situ hybridization. Recurrent chromosomal translocations characterize numerous malignant, and far fewer benign soft tissue tumors; NF is the only lesion, however, that frequently is associated with spontaneous regression. Further research is necessary into the pathogenesis of this unique self-limiting neoplasm, and the contribution, if any, of the fusion product in limiting growth of these lesions.
Category: Bone & Soft Tissue
Monday, March 19, 2012 1:00 PM
Poster Session II # 22, Monday Afternoon