Background: Small round blue-cell tumors (SRBCTs) of soft tissue, which mainly include rhabdomyosarcoma (RMS), synovial sarcoma (SS), and Ewing's sarcoma/peripheral primitive neuroectodermal tumors (EWS/ pPNETs), are malignancies with overlapping morphological and immunohistochemical characteristics. Immunohistochemistry is one of the most prevalent and convenient methods for pathological diagnosis; however, differentiation between SRBCT subtypes in the absence of valid diagnostic markers is still very challenging. The purpose of the present study was to investigate diagnostic immunohistochemistry for subtyping soft tissue SRBCTs.
Methods: Seventeen RMS, 25 SS, and 14 EWS/pPNETs were investigated. Reverse transcription RT-PCR and immunohistochemistry was performed to determine a diagnosis. Also, the expression of CD99, FLI1, PAX5, myogenin, and Keratin/EMA was assessed between subtypes. The sensitivity and specificity test was performed to evaluate their diagnostic significance.
Results: The sensitivity and specificity of the target markers were evaluated as follows. FLI1 and CD99 expression displayed strong associations in EWS/pPNETs, with OR (95% CI) and p values of 3.82 (1.23 - 11.94), p = 0.021 and 123.50 (12.63 - infinity), p < 0.001, respectively. Keratin/EMA expression did not support the diagnosis of EWS/pPNETs [OR (95% CI) = 0.06 (0.01 - 0.53), p = 0.011]. Myogenin expression displayed strong association with RMS, with high sensitivity and specificity of 94.1% and 100%, respectively. Membrane expression of CD99 did not support the diagnosis of RMS [OR (95% CI) = 0.09 (0.01 - 0.75), p = 0.026]. Keratin/EMA expression strongly indicated SS [OR (95% CI) = 345.00 (29.44 - infinity), p = 0.00011. A ROC curve value of 0.94 indicated that keratin/EMA expression might be a promising biomarker for SS, while separate expression of FLI1 and CD99 did not support the diagnosis of SS. Similarly, myogenin expression in RMS might be a promising biomarker for RMS with a ROC curve value of 0.97.
Conclusions: Diagnosis of SRBCTs should be based on a comprehensive analysis involving morphology and immunoreactivity to a panel of markers.
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