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NAB2‐STAT6 gene fusion and STAT6 immunoexpression in extrathoracic solitary fibrous tumors: the association between fusion variants and locations

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm harboring NAB2‐STAT6 fusion, which drives STAT6 nuclear relocation. For extrathoracic SFTs, the clinical relevance of this molecular hallmark remains obscure. We assessed STAT6 immunoexpression for 61 extrathoracic SFTs exclusive of the meninges and head and neck, and 25 had analyzable RNAs to distinguish fusion variants by RT–PCR. The immunohistochemical and molecular findings were correlated with clincopathological features and disease‐free survival (DFS). Twenty‐eight males and 33 females had SFTs in the body cavities (n = 31), extremities (n = 17), and trunk (n = 13), categorized into 53 non‐malignant and 8 malignant tumors. The vast majority (n = 57, 93%) exhibited distinctive STAT6 nuclear expression, including malignant ones. The common fusion variants were NAB2ex6‐STAT6ex16/17 in 13 SFTs and NAB2ex4‐STAT6ex2 in 8, while miscellaneous variants were detected only in 4 SFTs in the limbs and trunk but not in any body cavity‐based cases (P = 0.026). The worse DFS was univariately associated with malignant histology (P = 0.04) but unrelated to tumor size, location, or fusion variant. Conclusively, extrathoracic SFTs mostly harbor NAB2ex6‐STAT6ex16/17, followed by NAB2ex4‐STAT6ex2. Miscellaneous variants are significantly rare in SFTs within the body cavities. The clinical aggressiveness of extrathoraic SFTs is associated with malignant histology but unrelated to the NAB2‐STAT6 fusion variants.