Fluorescence in Situ Hybridization (FISH) for Differential Diagnosis of Soft Tissue Sarcomas

Introduction:Soft tissue sarcomas are rare tumors comprising 1 percent of solid malignancies. The latest edition of WHO soft tissue pathology lists 94 benign and malignant soft tissue tumors. Many of these show a large degree of morphological overlap. Immunohistochemistry has been shown to be reliable in many cases for differential diagnosis of lesions, although cytogenetic tests are considered the gold standard for many entities.Fluorescence in-situ hybridization (FISH) is a cytogenetic technique that uses fluorescent probes that bind to only those parts of the chromosome which have a high degree of sequence complementarity. Many soft tissue tumors show recurrent genetic mutations that are now being used as diagnostic markers. Knowledge of the molecular identity allows prediction of behavior, prognosis and treatment response. Objective:The aim of this study was to identify genetic mutations in soft tissue sarcomas using FISH testing and to assess correlations with histological diagnosis. Material and methods:A total of 25 cases of different soft tissue sarcomas diagnosed on histology with the help of immunohistochemical staining and for which FISH studies were requested were included in this study. Three pathologists with a special interest in soft tissue sarcomas reviewed the cases. FISH tests for EWS, the X:18 translocation, FOXO1 and MDM2 were respectively applied for 8 cases of Ewing sarcoma, 8 cases of synovial sarcoma, 2 cases of rhabdomyosarcoma and 7 cases of dedifferentiated liposarcoma and atypical lipomatous tumors/well differentiated liposarcomas. Results:EWS gene fusion was detected in 7 out of 8 cases of Ewing sarcoma and the X:18 translocation was positive in 3 of the 8 cases of synovial sarcoma. FOXO1 was not detected in either of the two rhabdomyosarcomas. MDM2 by FISH was detected in only one out of 5 cases of atypical lipomatous tumors and 1 out of 2 dedifferentiated liposarcomas. Conclusion: FISH is a useful adjunct in the diagnostic assessment of different types of soft tissue sarcomas. It is easy to set up, is relatively inexpensive and has the ability to diagnose sarcomas with great accuracy, especially in cases which can not be accurately classified even after thorough histological and immunohistochemical evaluation. It may play a very important role in the accurate diagnosis and correct management of patients.