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

Abstract

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