Solitary fibrous tumor – clinicopathologic, immunohistochemical and molecular analysis of 28 cases

Abstract

BackgroundSolitary fibrous tumor is a mesenchymal tumor of fibroblastic type, which can affect any region of the body. Recently, a recurrent gene fusion NAB2-STAT6 has been identified as molecular hallmark. The NAB2-STAT6 fusion leads to EGR1 activation and transcriptional deregulation of EGR1-dependent target genes and is a driving event in initiation of SFT. In this study, we report the clinicopathologic and RT-PCR findings and evaluated expression of STAT6 and EGR1 protein in a cohort of 28 SFTs.Methods28 patients with a median age of 54 years were included with SFTs originating at different sites, most occurring in the lung and pleura (9, 32%), 5 in soft tissues of the lower extremities (18%) and 5 in the head and neck (18%). For detection of the NAB2-STAT6 fusion gene, RT-PCR was performed using RNA extracted from formalin-fixed and paraffin-embedded tissues. Immunohistochemistry was performed on all cases with antibodies against STAT6 and EGR1.ResultsAll patients were treated by surgery, 3 with adjuvant chemo- or radiotherapy. Follow-up data of 18 patients could be obtained of which 2 patients died of metastatic disease 13 months and 52 years after first diagnosis. Sixteen patients have no evidence of disease with a median follow up of 29.5 months (range 7 – 120 months). NAB2-STAT6 fusion transcripts were found in 19/28 cases (68%). The most common fusion was between NAB2 exon 4 and STAT6 exon 3 (11/19, 58%), mainly occurring in pleuropulmonary lesions. All cases showed strong nuclear expression of STAT6 (28/28, 100%) while EGR1 showed low-level variable nuclear expression in all samples, comparable with the EGR1 expression results of the control group.ConclusionsThe identification of the NAB2-STAT6 fusion in SFTs can provide important diagnostic information, especially in cases with aberrant morphology or when biopsy material is limited. STAT6 immunohistochemistry is another useful tool in diagnosing SFT. EGR1 immunohistochemistry indicates low-level protein expression in accordance with EGR1 activation due to distorted NAB2 activity.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_224

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

“…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…”

Endobronchial fibroma in a pneumoconiosis patient with a history of tuberculosis: A case report and literature review

“…S-100 protein immunoreaction products, which do not appear in fibroma, are seen in the Schwann cells of neurofibroma (27). Angiofibroma, which has numerous thin-walled vessels surrounded by fibrous stroma, may be distinguished from fibroma by the appearance of small branching capillaries with CD34 protein immunoreactivity (24). An endobronchial leiomyoma with a proliferation of spindle cells in a whorl pattern may also be challenging to differentiate from fibromas; however, the desmin and actin immunoreaction products seen in the spindle cells of endobronchial leiomyoma tumors may aid this differential diagnosis (28).…”

“…Microscopically, a large number of inflammatory cells surrounded by collagen are always present in inflammatory pseudotumors (2). Solitary fibrous tumors (SFTs) also resemble fibromas; however, SFTs typically have a patternless architecture of alternating hypo-and hypercellular regions of spindle-shaped cells (2,24). A Positivity for CD34, CD99 and BCL-2 proteins in immunohistochemistry may be useful in forming a diagnosis of SFT (24).…”

“…Solitary fibrous tumors (SFTs) also resemble fibromas; however, SFTs typically have a patternless architecture of alternating hypo-and hypercellular regions of spindle-shaped cells (2,24). A Positivity for CD34, CD99 and BCL-2 proteins in immunohistochemistry may be useful in forming a diagnosis of SFT (24). Pulmonary adenofibroma, a rare benign biphasic tumor involving epithelial and stromal components, with stromal composition of haphazardly arranged bland spindle-cell fibroblastic proliferation and regions of hyalinization, may be distinguished from fibromas by the characteristic appearance of club-shaped and papillary structures (2).…”

Giant solitary fibrous tumor from the lesser omentum causing a gastric outlet obstruction: A case report

“…Microscopically, the tumor is composed of spindle cells with a patternless architecture composed of hyalinized collagen separating areas of hyper-and hypocellularity. Immunohistochemistry is the only way to confirm a diagnosis of SFT [9]. Our patient was positive for CD 34 reactivity, as is the case in 95% of SFT.…”