A Cristina Vargas1, Christina I 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 A Bhadri3,5, Fiona Maclean2, S Fiona Bonar2,7,12, Richard A Scolyer1,3, Rooshdiya Z Karim1,3, Stanley W McCarthy1,3, Annabelle Mahar1, Sandra A O'Toole1,3,11. 1. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. 2. Douglass Hanly Moir Pathology, Macquarie Park, NSW, Australia. 3. Sydney Medical School, University of Sydney, Sydney, NSW, Australia. 4. School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia. 5. Chris O'Brien Lifehouse, Camperdown, NSW, Australia. 6. Orthopaedic Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. 7. Macquarie University, North Ryde, NSW, Australia. 8. The Children's Hospital, Westmead, NSW, Australia. 9. North Shore Private Hospital, St Leonards, NSW, Australia. 10. Radiology/Medical Imaging, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. 11. The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. 12. School of Medicine, Notre Dame University, Sydney, NSW, Australia.
Abstract
AIMS: Recurrent Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangements characterize a select group of bone and soft tissue tumours. In our routine diagnostic practice with fluorescence in-situ hybridization (FISH), we have occasionally observed EWSR1 gene rearrangements in tumours not associated classically with EWSR1 translocations. This study aimed to review our institutional experience of this phenomenon and also to highlight the occurrence of unusual EWSR1 FISH signals (i.e. 5' centromeric region or 3' telomeric region signals) that do not fulfil the published diagnostic criteria for rearrangements. METHODS AND RESULTS: Using an EWSR1 break-apart probe, we performed FISH assays on formalin-fixed paraffin-embedded tissue sections from 135 bone and soft tissue specimens as part of their routine diagnostic work-up. EWSR1 gene rearrangements were identified in 51% of cases, 56% of which also showed an abnormal FISH signal pattern (in addition to classically rearranged signals). However, atypical FISH signals were present in 45% of the non-rearranged cases. In addition, we observed tumours unrelated to those described classically as EWSR1-associated that were technically EWSR1-rearranged in 6% of cases. Borderline levels of rearrangement (affecting 10-30% of lesional cells) were present in an additional 17% of these cases. CONCLUSIONS: While our study confirmed that FISH is a sensitive and specific tool in the diagnosis of EWSR1-associated tumours, atypical FISH signals and classical rearrangement in entities other than EWSR1-associated tumours can occur. Therefore, it is essential that the FISH result not be used as an isolated test, but must be evaluated in the context of clinical features, imaging, pathological and immunohistochemical findings.
AIMS: Recurrent Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangements characterize a select group of bone and soft tissue tumours. In our routine diagnostic practice with fluorescence in-situ hybridization (FISH), we have occasionally observed EWSR1 gene rearrangements in tumours not associated classically with EWSR1 translocations. This study aimed to review our institutional experience of this phenomenon and also to highlight the occurrence of unusual EWSR1 FISH signals (i.e. 5' centromeric region or 3' telomeric region signals) that do not fulfil the published diagnostic criteria for rearrangements. METHODS AND RESULTS: Using an EWSR1 break-apart probe, we performed FISH assays on formalin-fixed paraffin-embedded tissue sections from 135 bone and soft tissue specimens as part of their routine diagnostic work-up. EWSR1 gene rearrangements were identified in 51% of cases, 56% of which also showed an abnormal FISH signal pattern (in addition to classically rearranged signals). However, atypical FISH signals were present in 45% of the non-rearranged cases. In addition, we observed tumours unrelated to those described classically as EWSR1-associated that were technically EWSR1-rearranged in 6% of cases. Borderline levels of rearrangement (affecting 10-30% of lesional cells) were present in an additional 17% of these cases. CONCLUSIONS: While our study confirmed that FISH is a sensitive and specific tool in the diagnosis of EWSR1-associated tumours, atypical FISH signals and classical rearrangement in entities other than EWSR1-associated tumours can occur. Therefore, it is essential that the FISH result not be used as an isolated test, but must be evaluated in the context of clinical features, imaging, pathological and immunohistochemical findings.
Authors: Michael Liew; Leslie R Rowe; Phillipe Szankasi; Christian N Paxton; Todd Kelley; Reha M Toydemir; Mohamed E Salama Journal: Ann Lab Med Date: 2018-11 Impact factor: 3.464