Surgical therapy and next-generation sequencing-based genetic alteration analysis of malignant solitary fibrous tumor of the pleura

BACKGROUND: Solitary fibrous tumor of the pleura (SFTP) is a rare pleural neoplasm arising from mesenchymal cells, accounting for <5% of pleural neoplasms. Approximately 10% of cases of SFTP demonstrate malignant potential, leading to local recurrence after radical surgery and subsequent metastasis. METHODS: A large malignant-like mass was found in the left thoracic cavity of a 61-year-old woman. Following radical resection of the mass, the patient was diagnosed with malignant SFTP by histologic and immunohistochemical analyses. In addition, a next-generation sequencing-based mutation test was used to reveal the mutational profile of the tumor. The genetic alteration panel was analyzed with reference to public data on the ClinVar and COSMIC databases, after which the public SFTP data were analyzed for frequency of altered genes. Finally, through overlay of the abovementioned two sets, the genetic alteration accounting for SFTP initiation was anticipated to be identified. RESULTS: In the mutation panel of our malignant SFTP group, kinase insert domain receptor (KDR) and fms-related tyrosine kinase 1 (FLT1) scored high in pathogenesis but had only a medium frequency; the NAB2–STAT6 fusion appeared to be the dominant genetic alteration in public SFTP samples. CONCLUSION: The high frequency of NAB2–STAT6 fusion indicates its prominent role in SFTP, while somatic mutations such as FLT1-R593W and KDR-V297I may also contribute to the malignant angiogenic phenotype. The present study affirmed the heterogeneity of SFTP, and more sophisticated classification methods will be needed to explore its underlying mechanisms. SUMMARY: We believe that improvement in the prognosis of SFTP relies on early diagnosis, margin-free resection, and long-term follow-up. Through genetic analysis, it appears that both NAB2–STAT6 fusion and somatic mutations such as FLT1-R593W and KDR-V297I contribute to SFTP development.