Soft tissue tumors comprise a great variety of common and rare entities with overlapping features. Their diagnosis is based on the evaluation of several histological parameters which are difficult to assess on small incisional biopsies. Useful diagnostic markers in the field of soft tissue tumors include: 1) molecular biomarkers detecting pathogenetically relevant, distinctive alterations; 2) immunohistochemical surrogate biomarkers of pathogenetically relevant, distinctive molecular alterations; 3) highly specific immunohistochemical biomarkers indicating tumor differentiation. Their introduction in clinical practice has revolutionized the pre-operative diagnosis of soft tissue tumors. Cytology has long been considered inadequate as a first-line approach in this setting. However, since the implementation of new immunohistochemical and molecular tests with high diagnostic specificity, fine needle aspiration cytology (FNAC) is starting to gain acceptance for the pre-operative assessment of soft tissue tumors. FNAC represents a versatile, poorly expensive and well-tolerated diagnostic strategy with relevant advantages over histological biopsies. Moreover, evidences suggest that, in expert hands, FNAC can also aim at a definite diagnosis, especially if a cell block is prepared, allowing the application of multiple ancillary techniques.
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