Malignant solitary fibrous tumors: a clinicopathological and molecular genetic analysis

Abstract

Objective: To explore the clinicopathological features, immunophenotype and molecular genetic characteristics of malignant solitary fibrous tumor (MSFT). Methods: Seven cases of MSFT were collected from the First Affiliated Hospital of Zhengzhou University from July 2018 to December 2020. Immunohistochemistry, RNA-based NGS and DNA-based NGS were performed. Results Among the 7 patients, there were 5 males and 2 females with a median age of 53 years (37-69 years). Two tumors located at skull base, and one in the tentorium of cerebellum, parietal occipital region, occipital area, chest and buttock respectively. The maximum diameter of the tumor was 2.5-20.0 cm. Microscopically, typical hemangiopericomatoid structures were noted; the tumor was cellular, fusiform or oval, very pleomorphic, with necrosis and high mitotic figures (>4/10 HPF). In some cases, classical solitary fibrous tumor morphology and dedifferentiated region were observed. Immunohistochemically, the tumor was positive for CD34 (6/7), STAT6 (7/7), bcl-2 (7/7), but negative for S-100 (7/7); CKpan or EMA was positive to varying degrees; mutated p53 was noted (3/7); Ki-67 positive index was more than 10%. NAB2-STAT6 gene fusion was typically detected in all the 7 cases. In 4 cases, ZNF415-FGFR1, COPG1-MET, IPO11-LRRC70_ncRNA-PLAG1 and Clorf198-CD274 (PD-L1) gene fusions were also detected. NOTCH1 mutation was found in 7 cases and TP53 mutation in 4 cases. TERT promoter mutations were not detected in all the cases. Conclusions: MSFT is rare and needs to be differentiated from many other spindle cell tumors. Especially when tumors express epithelial markers, they are easily misdiagnosed as sarcomatoid carcinoma and synovial sarcoma, etc. Immunohistochemistry and molecular detection of NAB2-STAT6 gene fusion have important diagnostic values. NOTCH1 and TP53 mutations may be associated with the progression of MSFT. Some patients have FGFR1 gene fusion and MET gene fusion, which may be potential therapeutic targets.