Introduction: FISH is increasingly utilised in the diagnosis and classification of bone and soft tissue neoplasms where recurrent translocations or copy number changes are a defining diagnostic feature.

Materials and Methods: We reviewed our retrospective experience of FISH in soft tissue and bone neoplasms over the past 5 years performed on FFPE tissue sections using standard commercial break-apart and amplification probes.

Results: 500 FISH tests were performed. MDM2 FISH was performed in 178 cases; 35% were amplified mostly well-differentiated liposarcomas / atypical lipomatous tumours (n=49, 79%), with rare de-differentiated liposarcomas and low grade osteosarcomas. 130 EWSR1 FISH assays were performed in 130 cases; 51% were Ewing sarcoma, 8% clear cell sarcomas and 8% extraskeletal myxoid chondrosarcomas with rare sclerosing epithelioid fibrosarcoma, desmoplastic small round blue cell tumour and angiomatoid fibrous histiocytomas. EWSR1 FISH showed atypical patterns in 39%. Ninety six SS18 assays were performed; 36% were rearranged in monophasic or biphasic synovial sarcomas. Atypical signal patterns were seen in 6% of SS18 assays. The remaining FISH assays performed include DDIT3, FUS, PDGFB, USP6, ALK and TFE3.

Discussion: FISH is now an essential tool for the accurate classification of many bone and soft tissue sarcomas but atypical patterns may be seen and close correlation with clinical, imaging and histological features is required.