The Significance of Cytoplasmic STAT6 Positivity and High p53/p16 Expression as a Novel Predictor of Histological/Clinical Malignancy in NAB2::STAT6 Fusion-Positive Orbital Solitary Fibrous Tumors.

Orbital solitary fibrous tumor (SFT) is an extremely rare variant of systemic SFTs. However, the relationship between the biological/clinical characteristics, histological malignancies, and known oncogenes of systemic SFTs has not yet been elucidated. Therefore, we investigated these features and explored the prognostic factors of orbital SFTs by analyzing a series of orbital SFT cases. Six orbital SFT and one meningeal SFT were analyzed for comparison. NAB2::STAT6 variants were identified in five of the six orbital SFTs cases and one meningeal SFT case. There was no correlation between the exon composition of NAB2::STAT6 variants and the time of relapse after surgery or histological malignancy. Nuclear STAT6 staining by immunohistochemistry was observed in all cases, whereas cytosolic STAT6 staining was confirmed in three orbital SFT cases. The presence of histological malignancies and positive cytosolic STAT6 staining were mutually exclusive. The diffuse strong expressions of p53 and p16 were confirmed only in a case with the worst clinical course. No TERT promoter mutations were observed in any of these cases. Our study suggests that positivity of cytosolic STAT6 staining and high p53/p16 expression may be a predictor of histological/clinical malignancy in orbital SFT. Further evidence is necessary to confirm our results.