Ana Cristina Vargas1, Christina Selinger1, Laveniya Satgunaseelan1,2, Wendy A Cooper1,3,4, Ruta Gupta1,3, Paul Stalley5,6,7,8,9, Wendy Brown10, Judy Soper10, Julie Schatz10, Richard Boyle5,6,7,8,9, David M Thomas11, Martin H N Tattersall3,5, Vivek Bhadri3,5, Fiona Maclean2, Sally Fiona Bonar2,8,12, Richard A Scolyer1,3, Rooshdiya Z Karim1,3, Stanley W McCarthy1,3, Annabelle Mahar1, Sandra A O'Toole1,3,11. 1. Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. 2. Douglass Hanly Moir Pathology, Macquarie Park, New South Wales, Australia. 3. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. 4. School of Medicine, University of Western Sydney, Campbelltown, New South Wales, Australia. 5. Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. 6. Orthopaedic Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. 7. Macquarie University, New South Wales, Australia. 8. Westmead Kids, Sydney, New South Wales, Australia. 9. North Shore Private Hospital, St Leonards, New South Wales, Australia. 10. Radiology/Medical Imaging, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. 11. The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia. 12. School of Medicine, Notre Dame University, Sydney, New South Wales, Australia.
Abstract
AIM: Fluorescence in situ hybridization (FISH) is an important ancillary tool for the classification of bone/soft tissue (BST) tumors. The aim of this study was to evaluate the contribution of FISH to the final classification of common BST entities in the molecular pathology department of the Royal Prince Alfred Hospital (RPAH), which is one of the most important referral centers for the management of sarcomas in Australia. METHODS: All routine diagnostic FISH tests performed on BST formalin-fixed paraffin embedded (FFPE) tissue specimens at the RPAH in a 5-year period (February, 2010-November, 2015) were reviewed. FISH analyses presented in this study include commercial break-apart probes (SS18, FUS, DDIT3, FUS, USP6, PDGFB, TFE3 and ALK) and a single enumeration (MDM2) probe. RESULTS: There were 434 interpretable FISH assays on BST samples including MDM2 (n=180), SS18 (n=97), FUS (n=64), DDIT3 (n=37), USP6 (n=30), PDGFB (n=13), TFE3 (n=8) and ALK (n=5). Discrepancies between the histopathological diagnosis and the FISH results were seen in 12% of the cases. In this subset of discordant cases, FISH contributed to the re-classification of 7% of cases originally diagnosed as synovial sarcoma (SS18) and 6% of adipocytic neoplasms (MDM2) based on the presence or absence of the expected gene alteration. CONCLUSION: Our study confirms that paraffin FISH is a sensitive and specific ancillary tool in the diagnosis of BST neoplasms when used in the appropriate clinicopathological context. These findings highlight the need for further ancillary molecular tools in the diagnosis and characterization of challenging cases.
AIM: Fluorescence in situ hybridization (FISH) is an important ancillary tool for the classification of bone/soft tissue (BST) tumors. The aim of this study was to evaluate the contribution of FISH to the final classification of common BST entities in the molecular pathology department of the Royal Prince Alfred Hospital (RPAH), which is one of the most important referral centers for the management of sarcomas in Australia. METHODS: All routine diagnostic FISH tests performed on BST formalin-fixed paraffin embedded (FFPE) tissue specimens at the RPAH in a 5-year period (February, 2010-November, 2015) were reviewed. FISH analyses presented in this study include commercial break-apart probes (SS18, FUS, DDIT3, FUS, USP6, PDGFB, TFE3 and ALK) and a single enumeration (MDM2) probe. RESULTS: There were 434 interpretable FISH assays on BST samples including MDM2 (n=180), SS18 (n=97), FUS (n=64), DDIT3 (n=37), USP6 (n=30), PDGFB (n=13), TFE3 (n=8) and ALK (n=5). Discrepancies between the histopathological diagnosis and the FISH results were seen in 12% of the cases. In this subset of discordant cases, FISH contributed to the re-classification of 7% of cases originally diagnosed as synovial sarcoma (SS18) and 6% of adipocytic neoplasms (MDM2) based on the presence or absence of the expected gene alteration. CONCLUSION: Our study confirms that paraffin FISH is a sensitive and specific ancillary tool in the diagnosis of BST neoplasms when used in the appropriate clinicopathological context. These findings highlight the need for further ancillary molecular tools in the diagnosis and characterization of challenging cases.