Analysis of NAB2-STAT6 Gene Fusion in 17 Cases of Meningeal Solitary Fibrous Tumor/Hemangiopericytoma

Abstract

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a mesenchymal tumor that can affect virtually any region of the body. SFT/HPC of the thoracic cavity and soft tissue has been histologically considered a single biological entity termed SFT; in fact, NAB2-STAT6 gene fusion was recently identified in both diseases. In contrast, meningeal SFT and HPC still need to be investigated in detail with regard to gene fusion variants. The aim of this study was to verify the frequency of NAB2-STAT6 fusion and the relationship between fusion variants and clinicopathologic findings of SFT/HPC, especially meningeal SFT/HPC. We examined the NAB2-STAT6 fusion by reverse transcription polymerase chain reaction with 4 cases of meningeal SFT and 13 cases of meningeal HPC. NAB2-STAT6 fusion transcripts were identified in 12 of 17 cases, including NAB2ex6-STAT6ex17 (4/17, 24%), NAB2ex6-STAT6ex16 and NAB2ex4-STAT6ex2 (3/17, 18%, respectively), and NAB2ex5-STAT6ex16 (2/17, 12%). Three cases showed a pseudopapillary pattern, and 2 of them carried NAB2ex6-STAT6ex17. In addition, our meta-analysis revealed that the major fusion variant in meningeal SFT/HPC was NAB2ex6-STAT6ex16/17 (29/54, 54%), which was also common in soft tissue and intraperitoneum/retroperitoneum but rare in thoracic SFT. Fusion variant significantly correlated with age and histologic diagnosis in meningeal SFT/HPC but not with prognosis. Our results represented that meningeal SFT and HPC were in a single biological spectrum with NAB2-STAT6 gene fusion as was nonmeningeal SFT and further confirmed the organ-specific tumorigenic process and morphologic differences on the basis of fusion variants in meningeal SFT/HPC.

Solitary fibrous tumour of the female genital tract: a clinicopathological analysis of 25 cases

“…However, there is tremendous variability in both breakpoints, making detection of fusion transcripts challenging. In fact, there are instances in which STAT6 IHC is positive without a detectable NAB2–STAT6 fusion, presumably because of limitations of the reverse transcription polymerase chain reaction assay . Conversely, during the inversion and translocation events, it is conceivable that the locus recognised by the STAT6 antibody may be lost.…”

Clinicopathological differences between variants of the NAB2–STAT6 fusion gene in solitary fibrous tumors of the meninges and extra-central nervous system

“…Because of the difference in terminology of SFT/HPC between meninges and other sites, it is difficult to compare the histology in all primary sites. While there were some reports that there was no statistical correlation between the histological variants and the NAB2-STAT6 fusion gene variants [25,26,28,31], Barthelmeb reported that there was a significant correlation between NAB2-STAT6 fusion gene and histological feature; fibrous SFT, cellular SFT and HPC in intrathoracic region, head and neck, and soft tissue and that most tumors with NAB2 exon 4-STAT6 exon 2/3 fusion are classical fibrous pleuropulmonary SFTs with a benign appearance, and most tumors with NAB2 exon 6-STAT6 exon 16/17 are cellular SFT and HPCs in the retroperitoneum and pelvis with cellular appearance, increased mitotic activity [12]. Based on Fritchie's study of meningeal SFTs, there was no significant difference between histology and NAB2-STAT6 fusion gene, while there was a significant difference between histology and tumor with/without NAB2 exon 4-STAT6 exon 3 fusion [32].…”

“…To clarify the feature by NAB2/STAT6 fusion gene variants in meningeal SFTs/HPCs, it is important that These data were cases obtained from the following references: [11,12,17,18,20,21,23,24,26,27,32] a Other variants of SFTs/HPCs with recurrence included NAB2 exon 2-STAT6 exon 2, NAB2 exon 2-STAT6 exon 6, NAB2 intron 6-STAT6 exon 17, and NAB2 exon 7-STAT6 exon 18; other variants of SFTs/HPCs without recurrence included NAB2 exon 2-STAT6 exon 2, NAB2 exon 3-STAT6 exon 19, and NAB2 exon 5-STAT6 exon 18…”

A case of giant cell‐rich solitary fibrous tumor in the external auditory canal

“…As with conventional SFT, tumor cells react with CD34, vimentin, and Bcl‐2, whereas S‐100 protein, smooth muscle actin, desmin, and cytokeratin are negative . In addition, STAT6 nuclear immunoreactivity, which is the consequence of NAB2‐STAT6 fusion, is the most useful diagnostic marker for SFT, and the sensitivity and specificity have been reported to be 86–100% and 96–100%, respectively . Our case presented a well‐circumscribed mass composed of CD34‐ and STAT6‐positive spindle cells in a collagenous background and scattered multinucleate giant cells, leading to the pathological diagnosis of giant cell‐rich SFT.…”