NAB2-STAT6 Fusion Research Articles

STAT6-targeting antisense oligonucleotides against solitary fibrous tumor

Solitary fibrous tumor (SFT) is a rare, non-hereditary soft tissue sarcoma which is thought to originate from fibroblastic mesenchymal stem cells. The etiology of SFT is thought to be due to an environmental intrachromosomal gene fusion between NAB2 and STAT6 genes on chromosome 12. Wherein the activation domain of STAT6 is fused with the DNA-binding domain of NAB2 resulting in the oncogenesis of SFT. All NAB2-STAT6 fusion variations discovered in SFTs contain the C-terminal of STAT6 transcript, and thus can serve as target site for antisense oligonucleotides (ASOs)-based therapies. Indeed, our in vitro studies show the STAT6 3’-untranslated region (UTR)-targeting ASO (ASO 993523) was able to reduce expression of NAB2-STAT6 fusion transcripts in multiple SFT cell models with high efficiency (IC50: 116-300 nM). Encouragingly, In vivo treatment of SFT patient-derived xenograft (PDX) mouse models with ASO 993523 resulted in acceptable tolerability profiles, reduced expression of NAB2-STAT6 fusion transcripts in xenograft tissues (21.9%), and importantly, reduced tumor growth (32.4% decrease in tumor volume compared to the untreated control). Taken together, our study established ASO 993523 as a potential agent for the treatment of SFTs.

Solitary Fibrous Tumor of the Pancreas: Analysis of 9 Cases With Literature Review.

Solitary fibrous tumor (SFT) has been increasingly reported in various anatomic sites. However, it is still extremely rare in the pancreas. Herein, we present the first series of primary pancreatic SFTs. Nine cases of primary pancreatic SFTs were analyzed. The mean age was 60 years (36 to 76y) with no sex predilection. Six tumors were in the head, 3 were in the tail. On imaging studies, tumors were described as a hypervascular mass, 2 revealed cystic areas, and 3 were favored to be neuroendocrine tumors. On biopsy, 2 cases were diagnosed as atypical spindle cell tumor; one was misdiagnosed as suspicious for sarcoma, and another case as metastatic renal cell carcinoma. Two were diagnosed as low-grade sarcoma and low-grade stromal tumor on frozen sections. Grossly, tumors were well-demarcated with a median size of 4cm (0.9 to 15cm). Microscopically, they were composed of ovoid to spindle tumor cells with no significant mitotic activity and were arranged in alternating hypercellular and hypocellular areas. Staghorn-like vessels and entrapped pancreatic parenchyma were also detected within all tumors. Tumor cells revealed diffuse/strong nuclear STAT6 expression in 7 of 8, CD34 in 7 of 9, and bcl-2 in 4 of 4 tested cases. One tested tumor harbored NAB2 - STAT6 fusion. Eight patients with available follow-up data were free of disease at a mean follow-up of 76 months (3 to 189mo). SFT should be considered in the differential diagnoses of mesenchymal neoplasms of the pancreas. Immunohistochemical nuclear STAT6 expression is a characteristic feature of SFT. Primary pancreatic SFTs seem to have favorable biological behavior in our series.

Reduction of Tumor Growth with RNA-Targeting Treatment of the NAB2-STAT6 Fusion Transcript in Solitary Fibrous Tumor Models.

Solitary fibrous tumor (SFT) is a rare soft-tissue sarcoma. This nonhereditary cancer is the result of an environmental intrachromosomal gene fusion between NAB2 and STAT6 on chromosome 12, which fuses the activation domain of STAT6 with the repression domain of NAB2. Currently there is not an approved chemotherapy regimen for SFTs. The best response on available pharmaceuticals is a partial response or stable disease for several months. The purpose of this study is to investigate the potential of RNA-based therapies for the treatment of SFTs. Specifically, in vitro SFT cell models were engineered to harbor the characteristic NAB2-STAT6 fusion using the CRISPR/SpCas9 system. Cell migration as well as multiple cancer-related signaling pathways were increased in the engineered cells as compared to the fusion-absent parent cells. The SFT cell models were then used for evaluating the targeting efficacies of NAB2-STAT6 fusion-specific antisense oligonucleotides (ASOs) and CRISPR/CasRx systems. Our results showed that fusion specific ASO treatments caused a 58% reduction in expression of fusion transcripts and a 22% reduction in cell proliferation after 72 h in vitro. Similarly, the AAV2-mediated CRISPR/CasRx system led to a 59% reduction in fusion transcript expressions in vitro, and a 55% reduction in xenograft growth after 29 days ex vivo.

Chitinase 3-like 1 induces cancer cell migration in solitary fibrous tumors

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor that is diagnosed through the detection of the NAB2-STAT6 fusion gene. SFT rarely progresses to malignant tumors; however, metastasis is exhibited in approximately 20% of patients with SFT. In this study, we found that chitinase 3-like 1 (CHI3L1), which induces cancer cell migration, was upregulated in NIH-3T3 cells that were transfected with the NAB2-STAT6 fusion gene. Moreover, the expression levels of the migration markers MMP2 and MMP9 were increased and the p-Akt level was also upregulated. In addition, it was observed that when CHI3L1 siRNA was transfected into NAB2-STAT6-transfected cells, cell migration and proliferation were reduced. Therefore, this study demonstrated that CHI3L1 activates Akt signaling to induce cell migration.

Trabectedin Is Active against Two Novel, Patient-Derived Solitary Fibrous Pleural Tumor Cell Lines and Synergizes with Ponatinib.

Solitary fibrous tumor of the pleura (SFT) is a rare disease. Besides surgery combined with radiotherapy in nondisseminated stages, curative options are currently absent. Out of fourteen primo-cell cultures, established from surgical SFT specimens, two showed stable in vitro growth. Both cell models harbored the characteristic NAB2-STAT6 fusion and were further investigated by different preclinical methods assessing cell viability, clone formation, and protein regulation upon single-drug treatment or in response to selected treatment combinations. Both fusion-positive cell models showed-in line with the clinical experience and the literature-a low to moderate response to most of the tested cytotoxic and targeted agents. However, the multi-tyrosine kinase inhibitors ponatinib and dasatinib, as well as the anti-sarcoma compound trabectedin, revealed promising activity against SFT growth. Furthermore, both cell models spontaneously presented strong FGFR downstream signaling targetable by ponatinib. Most interestingly, the combination of either ponatinib or dasatinib with trabectedin showed synergistic effects. In conclusion, this study identified novel trabectedin-based treatment combinations with clinically approved tyrosine kinase inhibitors, using two newly established NAB2-STAT6 fusion-positive cell models. These findings can be the basis for anti-SFT drug repurposing approaches in this rare and therapy-refractory disease.

Malignant solitary fibrous tumor of the pleura: A narrative review of clinical characteristics, diagnosis and therapeutic options

Solitary fibrous tumor of the pleura (SFTP) is a rare mesenchymal neoplasm that originates from CD34+ dendritic stromal cells. While the majority of SFTPs are considered benign, an estimated 10%-20% are malignant. Malignant SFTP (MSFTP) is highly invasive and has propensities for local recurrence and distant metastasis. In recent years, an increasing number of MSFTPs have been reported. However, the diagnosis of MSFTP can be difficult owing to a lack of typical clinical manifestations and imaging features. To facilitate its diagnosis, the clinical, imaging, and histopathological characteristics of MSFTP are reviewed herein, followed by the clinical management such as surgery, radiotherapy, chemotherapy, targeted drugs and immunotherapy. Detection of NAB2-STAT6 fusion and expression of nuclear STAT6 can facilitate the diagnosis of SFTP. Furthermore, the recurrence risk stratification and prediction models of MSFTP as well as progress will be discussed. An improved understanding of these factors may contribute to more efficient diagnosis and management of MSFTP patients.

P11.68.A Hemangiopericytoma, case series and clinic-pathological analysis

Abstract Background Hemangiopericytoma (HPC) is an extremely rare aggressive tumor of mesenchymal origin, which constitutes less than 1% of primary tumors of the central nervous system. Typically it occurs in young adults (mean age at diagnosis 30-50 years). Initially described as gemmangiomas, was first called hemangiopericytoma in 1942 but it was considered as a variant of meningioma until 1993 when it was finally recognized as a distinct clinical-pathological entity by the World Health Organization (WHO). In 2016, there was the unification of both HPC and Solitary Fibrous Tumor (SFT) in a single spectrum of rare and thick mesenchymal tumors due to the identification, in both tumoral types, of a molecular alteration called NAB2-STAT6 fusion. Material and Methods The present study is a case series of patients that received a pathological diagnosis of SFT/HPC at our Institute from 1981 to 2020. Clinical data included: demographic data, tumor characteristics and treatment modality. Hystological diagnosis and immunohistochemistry allowed to confirm diagnosis, based on the 2016 WHO classification. Haematoxylin staining was completed with immunohistochemistry with primary antibodies for STAT 6 and evaluation of presence of tumor necrosis. Statistical analysis was conducted considering age at first diagnosis, treatment modality, extent of tumor resection, presence of necrosis in histological analysis compared to PFS-1, OS and relapses number. Results The case series was composed by 82 patients (46 men and 36 women) with median age of 43 (± 20) that accede to our Institute from 1981 to 2020. Our statistical analysis showed significative correlation between age, extend of tumor resection and presence of necrosis with OS and relapses number. Conclusion Hemangiopericytoma is a very rare cerebral tumors, and for this reason large case series are not disposable in literature. In our study we collected all disposable data of every patient with pathological diagnosis of SFT/HPC acceded to our hospital in the long period of 39 years in the aim to verify the presence of significative correlations. We observed strong correlation between tumor resection and presence of necrosis in tumor tissue with prognosis parameters (OS and number of relapses). This result it could be important to conduct the decisional process about treatment after surgical resection, considering also pathological features, rather than only surgical resection.

Analysis of clinicopathological features and NAB2-STAT6 fusion variants of meningeal solitary fibrous tumor with ectopic salivary gland components in the cerebellopontine angle.

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that can occur at any location. Since the identification of specific NAB2-STAT6 fusion in SFTs, the fusion gene variants, NAB2 exon 4-STAT6 exon 2/3 and NAB2 exon 5/6/7-STAT6 exon 16/17/18, have been reported to be associated with clinicopathological features, and the latter variant is predominant in meningeal SFTs. SFTs developing in the salivary glands are rare, and more rarely, those involving ectopic salivary glands (ESGs) have been reported in the cerebellopontine angle (CPA); however, their characteristics remain not well understood. In this study, we performed a clinicopathological and molecular analysis of 3 cases of meningeal SFT with ESGs. All cases presented with an extra-axial mass in the CPA, which is a rarer location for intracranial ESGs compared to the sellar region. Histologically, except for the presence of ESGs, there was no significant difference between current cases and ordinary SFTs. The ESGs demonstrated no cellular atypia, and although the spindle tumor cells were immunopositive for STAT6, the ESGs were negative in all cases, supporting that the ESGs are non-neoplastic components. In 1 case, ESGs were found only in the primary tumor and disappeared in recurrence/dissemination. Of note, molecular analysis identified NAB2 exon 4-STAT6 exon 2 in all cases. In conclusion, our results suggest that ESGs particularly in the CPA may be associated with SFTs and that meningeal SFTs with ESGs may be associated with the minor fusion variant of NAB2-STAT6 in the intracranial lesions.

Novel Therapeutic Options for Solitary Fibrous Tumor: Antiangiogenic Therapy and Beyond.

Simple SummaryIn the latest WHO classification, solitary fibrous tumors (SFTs) are now subdivided into benign SFT (intermediate category (locally aggressive)), SFT NOS (intermediate category (rarely metastasizing)), and malignant SFT. Thanks to recent progress in molecular characterization, the identification of the NAB2–STAT6 fusion oncogene has emerged as a specific cytogenetic hallmark for SFT. Despite these recent advances in classification and understanding of the molecular pathophysiology of SFT, there are no consensus clinical guidelines regarding systemic treatment. Several new therapeutic options are of interest in this subtype of sarcoma considered as refractory to classical chemotherapy. In case of advanced disease, antiangiogenic therapy might be viewed as the best therapeutic option.SFT is an ultrarare mesenchymal ubiquitous tumor, with an incidence rate <1 case/million people/year. The fifth WHO classification published in April 2020 subdivided SFT into three categories: benign (locally aggressive), NOS (rarely metastasizing), and malignant. Recurrence can occur in up to 10–40% of localized SFTs, and several risk stratification models have been proposed to predict the individual risk of metastatic relapse. The Demicco model is the most widely used and is based on age at presentation, tumor size, and mitotic count. Total en bloc resection is the standard treatment of patients with a localized SFT; in case of advanced disease, the clinical efficacy of conventional chemotherapy remains poor. In this review, we discuss new insights into the biology and the treatment of patients with SFT. NAB2–STAT6 oncogenic fusion, which is the pathognomonic hallmark of SFT, is supposedly involved in the overexpression of vascular endothelial growth factor (VEGF). These specific biological features encouraged the successful assessment of antiangiogenic drugs. Overall, antiangiogenic therapies showed a significant activity toward SFT in the advanced/metastatic setting. Nevertheless, these promising results warrant additional investigation to be validated, including randomized phase III trials and biological translational analysis, to understand and predict mechanisms of efficacy and resistance. While the therapeutic potential of immunotherapy remains elusive, the use of antiangiogenics as first-line treatment should be considered.

A mesenchymal chondrosarcoma with aberrant nuclear expression of STAT6: a potential diagnostic pitfall

STAT6 is usually considered to be a very sensitive and specific immunomarker for diagnosis of solitary fibrous tumor (SFT), being a surrogate of the NAB2-STAT6 fusion gene identified in most cases of this tumor. STAT6 expression has also been reported in rare cases of other soft tissue tumors, such as low-grade fibromyxoid sarcoma, myxoid/round cell liposarcoma, dedifferentiated liposarcoma and deep fibrous histiocytoma. The aim of this study was to report, for the first time, a case of mesenchymal chondrosarcoma showing diffuse aberrant immunohistochemical expression of STAT6. Molecular biology, showing the HEY1-NCOA2 fusion gene, was crucial to rule out SFT.

Case Report of a Rare Intracranial Tumour

A meningeal Solitary Fibrous Tumour (SFT), also called hemangiopericytoma is a fibroblastic type of mesenchymal tumour. These tumours often show a rich, well-branched vascular pattern that encompasses a histological spectrum of tumours which was previously classified separately as meningeal SFT and haemangiopericytoma. Discovery of NAB2-STAT6 fusion in a vast majority of haemangiopericytomas and solitary fibrous tumours indicates a possibility of morphological continuum. Herein, authors report a case 65-year-old female known case of hypertension and type II diabetes mellitus, presented with complaint of headache since 2 months and left side weakness since 3 weeks. On clinical examination, she was found to have motor weakness of left upper limb and lower limb with no sensory deficit. Magnetic resonance imaging showed an extra axial, right frontoparietal convexity, solidly enhancing tumour with transosseous invasion and the imaging features were suggestive of atypical meningioma. After craniotomy, immunohistochemical evaluation showed tumour cells were strongly positive for CD34 and STAT-6 exhibited the characteristic nuclear localization.The case was reported as Solitary fibrous tumour/Haemangiopericytoma-Grade II. The patient was advised adjuvant radiotherapy but deferred treatment. Regular follow-up after 2 years post surgery has shown that the patient is disease free.

Solitary fibrous tumor/hemangiopericytoma

Solitary fibrous tumor(SFT)/hemangiopericytoma(HPC)is a rare mesenchymal tumor with propensity for recurrence and metastasis. Although SFT and HPC were initially considered to be distinct entities, the identification of NAB2-STAT6 fusion as a definitive molecular alteration in both tumors has led to their integration into one disease entity, for both meningeal and non-meningeal lesions. This fusion leads to a nuclear relocation of the STAT6 protein and is detectable with immunohistochemistry. STAT6 immunohistochemistry has been shown to have excellent sensitivity and specificity for histological diagnosis. Although these discoveries have improved the diagnosis of SFT/HPC, the association of the NAB2-STAT6 fusion status with phenotype and prognosis remains unclear, and accurate prognostic factors have not been established. This comprehensive review provides current knowledge on the clinical, histological, and molecular characteristics of SFT/HPC.

Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study

Solitary fibrous tumors (SFT) are mesenchymal neoplasms with a favorable prognosis usually originating from the visceral pleura. Rarely, they may occur at various extrapleural sites and show malignant behavior coupled with dedifferentiation. NAB2-STAT6 fusion gene and STAT6 nuclear expression are biomarkers for diagnosis of SFT in addition to CD34, Bcl-2, and CD99. Furthermore, several reports have shown specific NAB2-STAT6 fusion variants and loss of STAT6 protein expression are associated with malignancy. We report a rare case of retroperitoneal SFT which rapidly progressed to death within 35 days after admission. Autopsy found a primary tumor containing both benign and malignant histologies, with multiple metastatic sites similar to the malignant, dedifferentiated tumor. STAT6 was detected in the primary differentiated tumor but not in the primary dedifferentiated tumor or lung/liver metastases. However, the NAB2-STAT6 fusion gene (NAB2ex6/STAT6ex16 variant) was detected in the primary tumor and lung/liver metastases. Intriguingly, fusion gene expression at the transcriptional level was downregulated in the dedifferentiated tumors compared to the differentiated tumor. We further performed target DNA sequencing and found gene mutations in TP53, FLT3, and AR in the dedifferentiated tumors, with TP53 mutations especially found among them. We demonstrate that downregulation of NAB2-STAT6 fusion gene at the transcriptional level is associated with malignant SFT for the first time. Moreover, the present study supports the idea that TP53 mutations promote malignancy in SFTs.

Determination of biological behavior of solitary fibrous tumors: correlation of expression of Ki-67, TPX2 and TERT mRNA subunit level and NAB2-STAT6 fusion compared to morphological aspects of SFTs.

We present a retrospective study of 65 cases of solitary fibrous tumors (SFTs) of several localizations including the most common site of origin in the pleura and lungs. SFTs are mesenchymal fibroblastic tumors with an unpredictable biological potential ranging from benign to malignant. We investigated morphologic characteristics, proliferation activity evaluated by immunohistochemical expression of Ki-67 antigen, and the existence of NAB2-STAT6 fusion gene together with Ki-67, TPX2, and TERT mRNA expression levels. The aim was to define relationships between proliferation activity and biological potential and progression of the disease. We measured Ki-67, TPX2, and TERT mRNA levels using quantitative real-time reverse transcription PCR (RQ-RT-PCR). We observed a significant association between increased Ki-67 and TERT mRNA levels and the SFTs with malignant potential. Also, we investigated the effect of TERT promoter mutation on telomerase activation and patient outcome in our SFT cohort. We verified that TERT promoter mutation was frequent (36.6%) and present in a majority of malignant SFTs and SFTs with uncertain biological behavior. TERT promoter mutation alone predicted the disease recurrence.

Skull Base Tumors: Neuropathology and Clinical Implications.

Tumors that arise in and around the skull base comprise a wide range of common and rare entities. Recent studies have advanced our understanding of their pathogenesis, which in some cases, have significantly influenced clinical practice. The genotype of meningiomas is strongly associated with their phenotype, including histologic subtype and tumor location, and clinical outcome. A single molecular alteration, NAB2-STAT6 fusion, has redefined the category of solitary fibrous tumors to include the previous entity hemangiopericytomas. Schwannomas, both sporadic and familial, are characterized by near ubiquitous alterations in NF2 , with additional mutations in SMARCB1 or LZTR1 in schwannomatosis. In pituitary adenohypophyseal tumors, cell lineage transcription factors such as SF-1, T-PIT, and PIT-1 are now essential for classification, providing a more rigorous taxonomy for tumors that were previously considered null cell adenomas. The pituicyte lineage transcription factor TTF-1 defines neurohypophyseal tumors, which may represent a single nosological entity with a spectrum of morphologic manifestations (ie, granular cell tumor, pituicytoma, and spindle cell oncocytoma). Likewise, the notochord cell lineage transcription factor brachyury defines chordoma, discriminating them from chondrosarcomas. The identification of nonoverlapping genetic drivers of adamantinomatous craniopharyngiomas and papillary craniopharyngiomas indicates that these are distinct tumor entities and has led to successful targeted treatment of papillary craniopharyngiomas using BRAF and/or mitogen-activated protein kinase inhibitors. Similarly, dramatic therapeutic responses have been achieved in patients with Langerhans cell histiocytosis, both with BRAF -mutant and BRAF -wildtype tumors. Familiarity with the pathology of skull base tumors, their natural history, and molecular features is essential for optimizing patient care.

INNV-24. METASTATIC HEMANGIOPERICYTOMA TO THE LIVER: DEFINING THE IMPORTANCE OF NAB-STAT2 FUSION

Abstract BACKGROUND Meningeal hemangiopericytoma (HPC) is a rare and aggressive vascular tumor which typically occurs in younger adults and has a tendency for local recurrence with delayed metastases outside the CNS. HPC is considered a variant of solitary fibrous tumor (SFT), and is associated with the presence of the fusion oncoprotein NAB2-STAT6. This fusion results in over-expression of the EGR1 gene and results in tumorigenesis. CASE REPORT We present a case of a 49 y/o female with a remote history of left occipital lobe HPC, initially treated with resection and radiotherapy in 2007, who presented with symptoms of right upper quadrant abdominal pain. She was found to have a hypervascular 7 cm mass in the right upper lobe of the liver on magnetic resonance imaging (MRI) studies and subsequently underwent hepatectomy for removal of the mass. Histopathological findings revealed metastatic HPC with features consistent with her primary meningeal tumor that was removed over 13 years agoearlier. Presence of the NAB2-STAT6 fusion was confirmed by targeted genomic analysis. MRI revealed a small focus of nodular enhancement abutting the confluence of the superior sagittal sinus and transverse sinus. This was considered her source of disease and possible dissemination. She was treated with stereotactic radiosurgery to target the lesion. DISCUSSION Given the rarity and often remote medical history of the primary intracranial HPC, this report suggests that 1) long term follow up of HPC is essential and 2) detection of the NAB2-STAT6 fusion can identify and confirm recurrent HPC at metastatic sites. In regards to the latter, distinguishing HPCs from other more benign spindle cell tumors that may mimic SFT (such as fibroblastic meningiomas) is also of therapeutic significance as HPCs typically require adjuvant treatment, (i.e. radiotherapy) as opposed to surgical resection alone.

Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors.

Simple SummaryA solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that can arise at any body location. Local or distant recurrences occur in a significant proportion of cases, but these recurrences are difficult to predict using clinical or pathological features. A specific genetic alteration, the gene fusion NAB2-STAT6, is considered to be the defining driver mutation, and different fusion variants seem to account for specific clinical and pathological features, but their prognostic value remains controversial. We inspected a series of 83 SFTs with a high rate of recurrence to evaluate the clinical significance of several potential biomarkers in addition to gene fusion. Our findings confirm previous observations and uncover novel associations of molecular alterations with clinical features, adding additional evidence for their potential application as molecular biomarkers that are helpful to predict the course of the disease.Risk stratification of solitary fibrous tumor (SFT) patients based on clinicopathological features has limited efficacy, especially in predicting late relapse or metastasis. The hallmark alteration of SFT is the gene fusion NAB2-STAT6, whose prognostic value remains controversial. As biological knowledge of this entity has increased in recent years, new molecular alterations have emerged that could be helpful to refine current risk models. Here, we evaluated NAB2-STAT6 fusion variants and other molecular alterations in a series of 83 SFTs that are enriched in progressing cases. Gene fusion variants were identified by targeted RNA-seq in the whole series, whereas TERT promoter (pTERT) mutations were inspected by Sanger sequencing in a subset of 18 cases. Immunohistochemical assays were performed to assess BCOR and NTRK expression as well as P53 mutation status in 45, 44, and 44 cases, respectively. While confirming the associations of gene fusion variants with clinicopathological parameters, our results do not prove their prognostic value. Pan-TRK immunoexpresion correlated with recurrence/progression, P53 staining associated with higher mitotic counts, and pTERT mutations were enriched in cases with fatal outcome. An intriguing correlation was found for BCOR protein expression with gene fusion variants, size, and tumor location.

NOVEL USE OF EBUS-IFB TO DIAGNOSE SOLITARY FIBROUS TUMORS OF THE PLEURA

TOPIC: Procedures TYPE: Fellow Case Reports INTRODUCTION: Endobronchial ultrasound-guided intranodal forceps biopsy (EBUS-IFB) is a novel technique that allows higher yield sampling than fine-needle aspiration (FNA) [1]. We present a case of the EBUS-IFB technique utilized to diagnose a posterior mediastinal solitary fibrous tumor of the pleura. CASE PRESENTATION: A 50-year-old male with tobacco dependence and asbestos exposure presented intoxicated and complained of assault, prompting trauma evaluation. CT chest found an incidental 7.4 cm heterogeneously enhanced mass within the right upper posterior hemithorax abutting the mediastinum. The patient endorsed chronic back pain, cough, and weight loss. Our approach consisted of EBUS-FNA with a 19 gauge needle followed by EBUS-IFB. Immunohistochemistry demonstrated CD34, Vimentin, and signal transducer and activator of transcription 6 (STAT6) protein positive neoplastic cells with a final diagnosis of solitary fibrous tumors of the pleura. DISCUSSION: Solitary fibrous tumors are rare mesenchymal tumors (SFTP) with fibroblastic differentiation characterized by NAB2-STAT6 gene fusion on chromosome 12. NAB2-STAT6 fusion protein drives the nuclear entry of STAT6 protein, facilitating the discrimination between solitary fibrous tumors and histologically similar tumors. EBUS-FNA does not produce high yield results for SFTP [2]. In our case, small mini-forceps were passed into a targeted mass following EBUS-FNA needle puncture, and we obtained adequate tissue to make a successful diagnosis. To our knowledge, this is the first case EBUS-IFB applied to a posterior mediastinal SFTP. CONCLUSIONS: Our case demonstrates the novel use of EBUS-IFB to diagnose paraspinal SFTP. This technique provides a less invasive alternative from surgical biopsy to aid in the diagnosis of SFTP. REFERENCE #1: J Thorac Dis. 2019 Sep;11(9):4049-4058. REFERENCE #2: Curr Opin Pulm Med. 2012 Jul;18(4):339-46 DISCLOSURES: No relevant relationships by Kenneth D'Souza, source=Web Response No relevant relationships by Reiichiro Obata, source=Web Response no disclosure on file for Muhammad Perwaiz

Molecular description of meningeal solitary fibrous tumors/hemangiopericytomas compared to meningiomas: two completely separate entities.

Meningeal solitary fibrous tumors (SFT), like all SFT, are defined by NAB2-STAT6 fusion and share clinicopathologic similarities with meningiomas, the most frequent meningeal tumors. Our aim is to establish the molecular identity of meningeal SFT and seek molecular prognostic factors. RNA sequencing and whole exome sequencing were performed in STAT6-positive SFT and grade 2-3 meningiomas, and data concerning other soft tissues tumors was obtained from the local database. Uniform manifold approximation and projection, individual gene expression and Gene Set Enrichment Analysis were performed. RNA clustering shows that SFT share a common molecular signature, different from any other type of tumoral tissue. Meningeal SFT aggregate with other SFT, with no clinical or histological subgroup. Comparison of genes expressions suggests significant over-expressions of ZIC2, ZIC3, ZIC5, GABBR2, TP53 in CNS-SFT. The pathogenic TP53 c.743G>T variant, previously undescribed in SFT, was found in one sample of meningeal SFT during malignant progression. Meningeal SFT are molecular counterparts of extra-meningeal SFT, completely separate from meningiomas. They might develop from the same tissues and benefit from the same treatments as SFT.

Solitary fibrous tumor: molecular hallmarks and treatment for a rare sarcoma.

Solitary fibrous tumor (SFT) is a rare soft tissue sarcoma subtype which mainly affects adults in the fifth and sixthdecades of life. Originally part of a spectrum of tumors called hemangiopericytomas, classification has been refined such that SFTs nowrepresent a distinct subtype. The identification of NAB2-STAT6 fusion in virtually all SFTs has further aided to define this rare subgroup. SFTs have a spectrum of behavior from benign to malignant, with evidence suggesting risk of metastases related to age at diagnosis, extent of necrosis, mitotic rate and tumor size. The standard treatment for localized disease is surgical excision with or without radiotherapy. Retrospective and prospective evidence suggests antiangiogenic treatment is effective for unresectable disease. Further translational work is required to understand the biology driving the differential behavior and identify more effective treatments for patients with metastatic disease.