Diagnostic challenges in spindle cell sarcomas: integrating morphology, immunohistochemistry and fish

Soft tissue sarcomas are rare, accounting for approximately 1% of all malignancies and comprising more than 50 histological subtypes. Spindle cell morphology represents a particularly challenging subset due to significant morphological overlap and frequent reliance on ancillary techniques. In this retrospective study, 90 spindle cell tumours referred for second-opinion evaluation were analysed. Initial diagnoses based on morphology were reassessed using histomorphological review, targeted immunohistochemistry (IHC), and selective molecular analysis (FISH). Diagnostic revision was observed in 55 of 90 cases (61.1%). Histomorphological reassessment alone was sufficient in 5 cases, while IHC contributed to diagnostic change in 26 cases. Molecular analysis using FISH, applied selectively, contributed to reclassification in 7 cases (18%), particularly in synovial sarcoma, fibrosarcoma, low-grade fibromyxoid sarcoma, and dedifferentiated liposarcoma. Diagnostic discrepancies were mainly attributed to the morphological similarity of spindle cell sarcomas, limited initial ancillary testing, and incomplete clinical information. These findings highlight that spindle cell tumours remain diagnostically challenging and demonstrate that an integrated approach combining morphology, IHC, and selective molecular testing significantly improves diagnostic accuracy. Second-opinion evaluation in specialised centres plays a critical role in optimising diagnosis and guiding clinical management.