Sarcomatoid Squamous Cell Carcinoma and Its Mimics: A Meta-Analysis of Institutional Cases and Published Reports

Background/Objective: Sarcomatoid squamous cell carcinoma (sSCC) is a rare tumor that resembles atypical fibroxanthoma/pleomorphic dermal sarcoma (AFX/PDS) and spindle cell/dedifferentiated melanoma histologically. Methods: Immunohistochemistry was performed on 51 sSCCs from 46 patients, 26 AFX/PDS from 24 patients, and 15 spindle cell/dedifferentiated melanoma from 15 patients. Twenty-nine studies comprising 307 sSCCs, 636 AFX/PDS, and 168 spindle cell/dedifferentiated melanomas were included in the pooled analysis. Results: p63 showed the highest pooled sensitivity for sSCC (0.89), followed by keratin AE1/AE3 (0.87), keratin MNF116 (0.87), keratin 903 (0.85), p40 (0.82), and keratin 5/6 (0.72). Evidence regarding pooled diagnostic performance was limited for several markers. Among the best-supported markers for sSCC, p63 demonstrated a pooled OR of 42.36 (95% CI 13.95-128.61), sensitivity of 0.82, and specificity of 0.94; p40 showed a pooled OR of 50.27 (95% CI 13.91-181.70), sensitivity of 0.90, and specificity of 0.85; and keratin 5/6 had a pooled OR of 108.60 (95% CI 27.10-435.20), sensitivity of 0.94, and specificity of 0.93. For AFX/PDS, CD10 showed a pooled OR of 10.64 (95% CI 2.96-38.19), sensitivity of 0.73, and specificity of 0.80. For spindle cell/dedifferentiated melanoma, S100 showed a pooled OR of 161.23 (95% CI 24.55-1058.69), sensitivity of 0.95, and specificity of 0.94 (95% CI 0.85-0.97), while SOX10 yielded a pooled OR of 121.27 (95% CI 6.33-2323.34). Conclusions: A panel comprising p63 or p40, keratin 5/6, CD10, CD163 or CD68, and SOX10 or S100 may aid in distinguishing sSCC from AFX/PDS and spindle cell/dedifferentiated melanoma.