Signal Transducer and Activator of Transcription 6 (STAT6) is a transcription factor in the Jak/STAT signal transduction pathway responsible for mediating IL-4 immune signaling. STAT6 was recently suggested to be a reliable marker to distinguish solitary fibrous tumors from other soft tissue neoplasms. Gene fusions are common in solitary fibrous tumors. Recent next generation sequencing studies demonstrated the presence of a NAB2-STAT6 fusion, formed by an intrachromosomal inversion fusing two neighboring genes on chromosome 12q13, in 55-100% of solitary fibrous tumors, regardless of tumor morphology or anatomical site. Analysis is further complicated due to the difficulty in detecting this fusion by fluorescence in situ hybridization (FISH).

Solitary fibrous tumors are classically characterized by CD34 positive spindle cells. However, approximately 5-10% of these tumors are negative for CD34, posing challenges for differential diagnosis. By immunohistochemistry, nuclear STAT6 expression can discriminate solitary fibrous tumors from its morphological mimics in the meninges, including meningioma, glioblastoma, gliosarcoma, haemangioblastoma, schwannoma and haemangioma. A recent study by Cheah, et al. using the rabbit monoclonal STAT6 antibody (Clone YE361) observed expression in all solitary fibrous tumors (54/54) tested, regardless of histology, anatomical site or CD34 status. Morphological mimics of solitary fibrous tumors were negative, demonstrating 100% specificity.