NAB2-STAT6 Gene Fusion Research Articles

Solitary fibrous tumor of the adrenal gland \u2013 its biological behavior and report of a new case

IntroductionA solitary fibrous tumor (SFT) is an uncommon neoplasm of mesenchymal and probably fibroblastic origin, occurring mainly in the extremities, and pleura. However, a primary involvement of endocrine organs is rare and even exceptional when found in the adrenal gland. Hereby, we describe the 10th report of an adrenal SFT.Case presentationA 77-year old man was diagnosed with a lesion in the right adrenal gland during a urologic indicated computed tomography (CT). No symptoms and laboratory anomalies were reported indicating any endocrine activity. Follow up CT-scans showed progressive growth of the nodule for which the patient underwent laparoscopic right adrenalectomy. Histological examination showed a hypercellular spindle cell neoplasm with elongated nuclei and a low mitotic index. The vessels were arranged in a hemangiopericytoma-like pattern with a slight sclerosing appearance. Immunohistochemistry showed a positive staining of neoplastic cells for STAT6, CD-34 and Bcl-2. Translocation analysis using RT-PCR showed no NAB2-STAT6 fusion. The specimen was confirmed as a hypercellular variant of an adrenal SFT.DiscussionSFT is a rare neoplasm when occurring in the adrenal gland. Differential diagnosis can be broad because of no defined pathognomonic morphological characteristics. However, NAB2-STAT6 gene fusions are considered a molecular hallmark of SFTs. Therefore, STAT6 immunohistochemistry is a valuable diagnostic tool in differentiating between SFT and histologic mimics. After diagnosing SFT, its biological behavior is difficult to predict. SFTs are mostly benign tumors. Nonetheless, a histological benign-appearing SFT can show malignant clinical characteristics impeding assessment of proper follow up. However, malignancy has not been previously reported in any adrenal SFT case report.

Gene Expression in Solitary Fibrous Tumors (SFTs) Correlates with Anatomic Localization and NAB2-STAT6 Gene Fusion Variants

Solitary fibrous tumors (SFTs) harbor recurrent NAB2-STAT6 gene fusions, promoting constitutional up-regulation of oncogenic early growth response 1 (EGR1)-dependent gene expression. SFTs with the most common canonical NAB2 exon 4-STAT6 exon 2 fusion variant are often located in the thorax (pleuropulmonary) and are less cellular with abundant collagen. In contrast, SFTs with NAB2 exon 6-STAT6 exon 16/17 fusion variants typically display a cellular round to ovoid cell morphology and are often located in the deep soft tissue of the retroperitoneum and intra-abdominal pelvic region or in the meninges. Here, we employed next-generation sequencing-based gene expression profiling to identify significant differences in gene expression associated with anatomic localization and NAB2-STAT6 gene fusion variants. SFTs with the NAB2 exon 4-STAT6 exon 2 fusion variant showed a transcriptional signature enriched for genes involved in DNA binding, gene transcription, and nuclear localization, whereas SFTs with the NAB2 exon 6-STAT6 exon 16/17 fusion variants were enriched for genes involved in tyrosine kinase signaling, cell proliferation, and cytoplasmic localization. Specific transcription factor binding motifs were enriched among differentially expressed genes in SFTs with different fusion variants, implicating co-transcription factors in the modification of chimeric NGFI-A binding protein 2 (NAB2)-STAT6-dependent deregulation of EGR1-dependent gene expression. In summary, this study establishes a potential molecular biologic basis for clinicopathologic differences in SFTs with distinct NAB2-STAT6 gene fusion variants.

Recurrence of Solitary Fibrous Tumor/Hemangiopericytoma Could Be Predicted by Ki-67 Regardless of Its Origin.

Since the discovery of the NAB2-STAT6 gene fusion in 2013, solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) have been considered the same disease. STAT6 nuclear stain is approved as a highly sensitive and specific marker to diagnose SFT/HPC from other tumors with similar histology. As the next step, detection of fusion variants that may predict clinical malignancy of SFT/HPC has been attempted. However, no fusion variants with a clear relation to malignancy have been identified. In this study, the clinical and histological backgrounds of 23 Japanese patients diagnosed with SFT/HPC from 2000 to 2019 at Kochi University Hospital were examined to identify factors potentially related to recurrence. A significant relationship to recurrence was detected for mitosis ≥ 1/10 HPF (400×), necrosis, and Ki-67>5%. These findings indicate that a deliberate investigation of histological features such as mitosis and necrosis is crucial for the clinical observation of SFT/ HPC patients. In addition, Ki-67 was revealed to be a useful parameter to predict recurrence in SFT/HPC patients.

Rare variants of solitary fibrous tumor

ObjectiveSome cases of solitary fibrous tumor (SFT) exhibit unusual histologic features that may cause diagnostic difficulty, such as fascicular monotonous spindle cells accompanied by hyalinized blood vessels and numerous evenly distributed mast cells, and features mimicking myxoid liposarcoma. Awareness of these features is important for reaching correct diagnosis of similar cases. MethodsThree cases of SFT with the above unusual features were retrieved from our consult files for review, including H&E slides and immunohistochemical stains. In addition, FISH analysis for SS18-SSX (SYT), DDIT3 and MDM2 were performed. Furthermore, formalin-fixed paraffin-embedded (FFPE) tissue sections were tested for 8 fusion variants of NAB2-STAT6 by qualitative endpoint reverse-transcriptase (RT)-PCR. ResultsNeoplastic cells from all 3 cases are positive for CD34, CD99, and STAT6 immunohistochemically. In addition, the tumors are positive for NAB2-STAT6 fusion gene. Mast cells from the first case possess nonneoplastic phenotype and are positive for CD117 and tryptase staining but negative for CD25. ConclusionsThe three cases studied here represent rare types of SFT, which differ from classical “pattern-less” pattern of SFT. Correct diagnosis required a combination of CD34 and STAT6 immunostaining and NAB2-STAT6 fusion gene analysis.

STAT6 Expression in Solitary Fibrous Tumor and Histologic Mimics: a Single Institution Experience.

STAT6 stain has proved to be a good surrogate marker for the genetic alteration (NAB2-STAT6 gene fusion) in solitary fibrous tumor (SFT). This study aims to validate the use of STAT6 rabbit monoclonal antibody in differentiating SFT from its histologic mimics. Forty-five cases of SFT and 110 cases from 9 other spindle cell tumors were collected for STAT6 immunostaining. Positive nuclear STAT6 staining was present in all 45 SFT cases (100% sensitivity). No nuclear staining was identified in other spindle cell neoplasms (0/13, dedifferentiated liposarcoma; 0/17, synovial sarcoma; 0/16, malignant peripheral nerve sheath tumors; 0/25, undifferentiated pleomorphic sarcoma; 0/10, dermatofibrosarcoma protuberans; 0/9, low-grade fibromyxoid sarcoma; 0/6, angiofibroma; 0/5, deep fibromatosis; 0/9, gastrointestinal tumor). The STAT6 staining in SFT was usually diffuse (5+ in 19 cases; 4+ in 17 cases) and strong (40 cases). Monoclonal STAT6 stain is highly sensitive and specific for SFTs and particularly useful in the diagnosis of difficult SFT cases.

NAB2-STAT6 fusion protein mediates cell proliferation and oncogenic progression via EGR-1 regulation

Solitary fibrous tumors are rare mesenchymal tumors derived from soft tissues and vascular walls. NAB2-STAT6 fusion gene serves as a marker gene for this disease and consists of the truncated repressor domain of NGFI-A-Binding protein 2 (NAB2) and the intact activation domain of STAT6. In this study, we found that EGR-1 and the proliferation-related EGR-1 target gene IGF2 were upregulated in NIH-3T3 cells transfected with NAB2-STAT6. Additionally, p-Rb (Ser795) and cyclin D1 levels were upregulated, and cell proliferation was also enhanced. We identified that treatment with the IGF2 inhibitor reduced cell proliferation in NIH-3T3 cells transfected with NAB2-STAT6. The oncogenic progression was enhanced in NIH-3T3 cells transfected with NAB2-STAT6 compared with those transfected with the empty vector. Taken together, our study suggests that the NAB2-STAT6 fusion gene is associated with cell proliferation through EGR-1 transcriptional expression and IGF2 can be a drug target for the treatment of solitary fibrous tumors.

59. Dedifferentiated solitary fibrous tumour arising from the bladder: A case report

Background: Solitary fibrous tumour (SFT) is a rare mesenchymal tumour of fibroblastic differentiation. They most commonly arise in the pleura, but have a wide anatomical distribution. Conventional SFTs are circumscribed, spindle cell neoplasms with characteristic histomorphology including patternless architecture, dense collagen and prominent haemangiopericytoma-like ‘staghorn’ vessels. Conventional SFTs express CD34, Bcl2 and STAT6, but are negative for S100, keratin and desmin. Molecular profiling has shown consistent 12q chromosomal abnormality resulting in NAB2-STAT6 fusion. The NAB2-STAT6 gene fusion product is reliably identified on STAT6 immunohistochemistry, which has proven both a highly sensitive and specific marker for SFTs. Most SFTs are clinically benign, however up to 15% may show features of malignancy including increased mitoses (>4 per 10 HPF), necrosis and infiltrative margins. In addition, areas of dedifferentiation may occur, characterised by sharply demarcated areas of hypercellularity and pleomorphism with loss of morphological features of conventional SFT. Dedifferentiated areas may lose the typical immunohistochemical profile of conventional SFT, including loss of CD34 and STAT6. Aim: To report a case of dedifferentiated SFT in the bladder and review the current literature. Method: A 39-year-old male presented with one month history of urinary frequency and abdominal pain. CT and MRI showed a large heterogenous necrotic mass in the posterior bladder wall. An en bloc tumour resection and cystoprostatectomy was performed. Results: Macroscopic examination showed a 15 cm circumscribed tumour arising from the superior bladder. Microscopy revealed a spindle cell tumour arising from the bladder muscularis propria with areas of conventional SFT adjacent to vast areas of dedifferentiation with malignant features including hypercellularity, pleomorphism, increased mitoses (40 per 10 HPF) and necrosis. Immunohistochemistry showed positive staining for STAT6, CD34 and Bcl2 in both conventional and dedifferentiated areas. Conclusion: This is a unique case of a dedifferentiated SFT of the bladder in a young patient.

Meningioma-like Tumor of the Skin Revisited: A Distinct CD34+ Dermal Tumor With an Expanded Histologic Spectrum.

The term meningioma-like tumor of the skin (MLTS) was coined in 1993 to designate a particular whorled spindle cell superficial cutaneous tumor. No additional confirmed cases of this entity have been reported to date. Some authors have speculated that these cases might be cellular neurothekeomas. In order to delineate the histologic spectrum and the immunophenotype of this unusual tumor, we studied 5 cases, 2 previously unreported and the 3 original cases. The immunohistochemical findings of case 5, however, were limited to those from the original study. Clinically, the tumor presented as a reddish papule, plaque, or nodule, located in the extremities or trunk. The patient often referred to a recent growth of a longstanding lesion. Histologically, the characteristic whorled spindle and stellate dendritic cell population, commonly in a perivascular arrangement, and variable myxoid component, were consistently found in all cases. A prominent microvasculature was also a constant finding. The presence of large deciduoid cells was conspicuous in one case. A reticular pattern of multivacuolated cells giving a chordoma-like appearance was evident in another case. Tumor cells were diffusely positive for CD34 in all 4 cases studied, and negative for S-100, EMA, NKI-C3, CD68, and smooth muscle markers. No complete loss of retinoblastoma protein was found. No brachyury immunostaining was found in the case with chordoid features. No EWSR1 or NAB2-STAT6 gene fusions were found. From these findings, we demonstrate that MLTS is a distinct CD34 spindle cell benign dermal tumor, unrelated to cellular neurothekeoma, and exhibiting myxoid, deciduoid, or chordoma-like features.

Solitary fibrous tumor.

Solitary fibrous tumor (SFT) is a rare tumor of mesenchymal origin that account for less than 2% of all soft tissue masses. Initially identified in the pleura, SFT has been identified in multiple anatomic locations and can arise anywhere in the body. The varying histologic features along with non-specific means of identification have led SFT to be associated with several different names. Over the last several decades, sustained advances through research and technology have led to more reliable methods for differentiating this distinct soft tissue tumor. Advances specifically in immunohistochemistry and molecular diagnostics have identified CD34 as the most consistent marker in SFT, however even this lacks specificity to conclusively narrow down the broad differential for exact identification. More recently the discovery of the NAB2-STAT6 fusion gene has led to more precise diagnosis of SFT. Like many other soft tissue tumors, surgical management is the mainstay of treatment for SFT with emphasis on obtaining tumor-negative margins. Radiation therapy and chemotherapy regimens have not demonstrated global effectiveness, and thus no standardized treatments have been identified. Given the rarity of SFT and current supportive evidence for therapies, management should be focused on tumor extirpation. Nonetheless, individualized therapy, determined within a multidisciplinary setting should be considered.

1642P - Determination of biological behavior of solitary fibrous tumors

Background: Solitary fibrous tumor (SFT) is an uncommon neoplasm of pleural and extrapleural site of origin formed by cells with fibroblastic features. This tumor exhibits a spectrum of biological behavior and can occur at any age with the peak in the sixth and seventh decade of life. Most of these tumors grow slowly and their clinical behavior is mostly benign; however, up to 20 % of patients develop local recurrences and/or distant metastases. Methods: We performed a retrospective study of 54 cases of SFTs. We investigated morphologic characteristics, proliferation activity evaluated using Ki-67 immunostain and existence of NAB2-STAT6 fusion gene together with Ki-67, TPX2, and hTERT mRNA expression levels. The aim was to define relationships between proliferation activity and biological potential and progression of the disease. Recently, several alterations within the TERT gene have been detected in human tumors. The most frequent alteration in the TERT gene, somatic promoter mutation, has been described. We measured Ki-67, TPX2, and hTERT mRNA levels using quantitative real-time reverse transcription PCR (RQ-RT-PCR). Determination of hot spot promoter mutation in TERT was analyzed. Results: NAB2-STAT6 fusion transcript was found in 46/54 cases (85%) of amplifiable samples. The mRNA expression of Ki-67 correlated with local recurrences (p = 0.025) and biological behavior of the tumor (p = 0.0027), but did not correlate with the type of the NAB2/STAT6 fusion (0.24). The level of Ki-67 mRNA correlated with IHC established results (p = 0.02). The TPX2 mRNA expression did not correlate with local recurrences (p = 0.26) nor with biological behavior of the tumor (p = 0.062). The mRNA hTERT expression correlated well with biological behavior of the tumor (p < 0.0001). The majority of SFTs with benign behavior were without detectable expression of hTERT mRNA. A majority of the patients with hTERT expression had also somatic promoter mutation C228T or less frequently C250T. We observed a significant association between increased Ki-67 and hTERT mRNA levels and the SFTs with malignant potential. Conclusions: Detection of hTERT mRNA expression and its promoter mutation at routine practice might lead to a better estimation of a biological potential of SFTs. Legal entity responsible for the study: Ministry of Health, Czech Republic. Funding: Supported by the Project (Ministry of Health, Czech Republic) for conceptual development of research organization 00064203 (University Hospital Motol, Prague, Czech Republic). Disclosure: All authors have declared no conflicts of interest.

Grading of meningeal solitary fibrous tumors/hemangiopericytomas: analysis of the prognostic value of the Marseille Grading System in a cohort of 132 patients

The finding that meningeal solitary fibrous tumors (SFTs) and meningeal hemangiopericytomas (HPCs) are both characterized by NAB2-STAT6 gene fusion has pushed their inclusion in the WHO 2016 Classification of tumors of the central nervous system (CNS) as different manifestations of the same entity. Given that the clinical behavior of the CNS SFT/HPC spectrum ranges from benign to malignant, it is presently unclear whether the grading criteria are still adequate. Here, we present the results of a study that analyzed the prognostic value of an updated version of the Marseille Grading System (MGS) in a retrospectively assembled cohort of 132 primary meningeal SFTs/HPCs with nuclear overexpression of STAT6. The median patient follow-up was 64 months (range 4-274 months); 73 cases (55%) were MGS I, 50 cases (38%) MGS II and 9 cases (7%) were MGS III. Progression-free survival (PFS) and disease-specific survival (DSS) were investigated using univariate analysis: the prognostic factors for PFS included MGS, extent of surgery, radiotherapy, chemotherapy and mitotic activity ≥5/10 high-power field (HPF). Moreover, MGS, radiotherapy, mitotic activity ≥5/10 HPF, and necrosis were the prognostic factors measured for DSS. In multivariate analysis, extent of surgery, mitotic activity ≥5/10 HPF, MGS I and MGS III were the independent prognostic factors measured for PFS while necrosis, MGS III and radiotherapy were the independent prognostic factors for DSS. In conclusion, our results show that assessing the malignancy risk of SFT/HPC should not rely on one single criterion like mitotic activity. Therefore, MGS is useful as it combines the value of different criteria. In particular, the combination of a high mitotic activity and necrosis (MGS III) indicates a particularly poor prognosis.

Telomerase promoter mutations and copy number alterations in solitary fibrous tumours

AimsSolitary fibrous tumour (SFT) is an infrequently metastasising mesenchymal tumour defined by the NAB2–STAT6 fusion gene. Activating mutations in the telomerase reverse transcriptase (hTERT) gene promoter has been reported to...

Extrapleural solitary fibrous tumor: A distinct entity from pleural solitary fibrous tumor. An update on clinical, molecular and diagnostic features.

Solitary fibrous tumor (SFT) is a mesenchymal neoplasm that was originally described to be localized in the pleura, but thereafter, this has been reported in several anatomic sites. Although the etiology of the neoplasm remains largely unknown, the pathogenesis seems to be related to an NAB2-STAT6 fusion gene due to paracentric inversion on chromosome 12q13. The diagnosis of extrapleural SFT is challenging, owing to its rarity, and requires an integrated approach that includes specific clinical, histological, immunohistochemical, and even molecular findings. Histologically, extrapleural SFT shares morphological features same as those of the pleural SFT because it is characterized by a patternless distribution of both oval- and spindle-shaped cells in a variable collagen stroma. In addition, morphological variants of mixoid, fat-forming, and giant cell-rich tumors are described. A correct diagnosis is mandatory for a proper therapy and management of the patients with extrapleural SFT, as extrapleural SFT is usually more aggressive than pleural form, particularly cases occurring in the mediastinum, retroperitoneum, pelvis, and meninges. Although SFT is usually considered as a clinically indolent neoplasm, the prognosis is substantially unpredictable and only partially related to morphological features. In this context, cellularity, neoplastic borders, cellular atypias, and mitotic activity can show a wide range of variability. We review extrapleural SFT by discussing diagnostic clues, differential diagnosis, recent molecular findings, and prognostic factors.

Reappraisal of morphological and immunohistochemical spectrum of intracranial and spinal solitary fibrous tumors/hemangiopericytomas with impact on long-term follow-up.

Hemangiopericytomas (HPCs) and solitary fibrous tumors (SFTs) are unique entities in the central nervous system (CNS) and even rarer in the spine with propensity to recurrence and metastasis. Both these tumors were detected to share the NAB2-STAT6 fusion gene with frequent morphologic overlap that necessitated the need for the combined term SFT/HPC in the CNS by the World Health Organization (WHO) in 2016. This study aims to describe the clinical outcome of intracranial and spinal SFT/HPCs based on detailed histomorphologic and immunohistochemical features. A retrospective analysis of these tumors was conducted over a period of 10 years from January 2006 to January 2017 at our institute. Based on the elaborative assessment of morphology and immunohistochemistry, these tumors were categorized into three grades as per WHO criteria. A total of 13 cases were encountered involving mainly extra-axial and supratentorial regions. Among intracranial HPCs, anaplastic subtypes constituted significantly higher proportion (39%) when compared with peripheral HPCs. Peculiar morphological patterns like micropapillae and pseudoangiomatous arrangement of tumor cells were observed in high-grade tumors. A panel of immunomarkers were used to confirm the diagnosis and rule out other mimickers. Gross total resection was achieved in 54% (7/13) of the cases with local recurrence observed in 31% (4/13). Grade II tumors showed recurrence in 28% cases. No case showed distant metastasis. To conclude, not just clinical parameters but morphologic features such as unusual patterns, mitosis, and proliferative index also play a pivotal role in predicting the clinical behaviour of SFT/HPC.

Solitary Fibrous Tumors in Pediatric Patients: A Rare and Potentially Overdiagnosed Neoplasm, Confirmed by STAT6 Immunohistochemistry.

Pathological diagnosis of solitary fibrous tumor (SFT) in the pediatric population is challenging, as it occurs uncommonly in this age-group and resembles other spindle cell neoplasms. SFT contains a NAB2-STAT6 fusion gene, which can be reliably detected using STAT6 immunohistochemistry. Positive staining is highly sensitive and specific. We sought to investigate the utility of STAT6 immunohistochemistry, to show how commonly SFT was historically recognized at 3 academic pediatric institutions, to reclassify them when appropriate, and to demonstrate features of major mimics of SFT. Our series included cases with a previous diagnosis of SFT or for which SFT was among key considerations, from 3 major academic pediatric hospitals seen over the past 30 years. Of 18 tumors identified, only 3 tumors from 2 patients demonstrated positive STAT6 staining as well as the typical histology and immunophenotype seen in SFT. The remaining 15 tumors were reclassified based on morphology, additional immunohistochemistry and fluorescence in situ hybridization as desmoid-type fibromatosis (3 tumors), nerve sheath/neural tumors (3 tumors), low-grade fibromyxoid sarcoma, medallion-like dermal fibroma, poorly differentiated Sertoli cell tumor, nodular/proliferative fasciitis, calcifying fibrous tumor, aneurysmal bone cyst of soft tissue, STAT6-negative SFT with adipocytic differentiation, undifferentiated small round blue cell tumor, and scar (1 tumor each). Our study confirms that SFT is rare in the pediatric population and that it is potentially overdiagnosed. STAT6 immunohistochemistry is recommended to confirm the diagnosis of SFT in the pediatric population.

Risk assessment in solitary fibrous tumors: validation and refinement of a risk stratification model

Solitary fibrous tumors are an uncommon sarcoma type characterized by NAB2–STAT6 gene fusion. While solitary fibrous tumors metastasize in 5–25% of cases, it has historically been challenging to determine which specific tumor and patient characteristics predict aggressive behavior. We previously reported on a novel risk stratification scheme for solitary fibrous tumors incorporating patient age, tumor size, and mitotic activity to predict risk of metastasis. Herein we validate this risk stratification scheme in an independent, lower-risk population of 79 patients with primary non-meningeal solitary fibrous tumors, and propose incorporating tumor necrosis as a fourth variable to further improve the risk score. Fifty-seven percent of cases were considered low risk, 29% intermediate risk, and 14% high risk for metastasis. Of 50 patients with sufficient clinical follow-up data, no metastases developed in the low-risk patients (n=23), while there was a 7% 10-year metastatic risk in the intermediate risk group (n=17), and a 49% 5-year metastatic risk for the high-risk patients (n=10). When tumor necrosis was added as a fourth variable to the model, predictive power was enhanced. Under the revised stratification, the proportion of tumors identified as low risk increased to 66%, with no metastasis at 10 years, intermediate risk cases comprised 24% with 10% risk of metastasis at 10 years, and high risk comprised 10% of cases with 73% risk of metastasis at 5 years. In Kaplan–Meier analysis, this fourth-variable stratification provided significant discrimination between the risk groups (P=0.0005). These findings confirmed the clinical utility of our previously published risk stratification model and support the inclusion of necrosis as a fourth variable in the model.

A case of meningeal myxoid solitary fibrous tumor/hemangiopericytoma with unique NAB2-STAT6 fusion gene and symptomatic intratumoral hemorrhage

We experienced a case of meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) with symptomatic intratumoral hemorrhage in a 67-year-old Japanese woman. Her chief complaints were sudden onset of motor aphasia and right hemiparesis. Brain computed tomography showed the hemorrhagic mass adjacent to the superior sagittal sinus. The mass was resected and pathological examination of the specimen revealed a tumor that is rich in vessels and accompanied with intratumoral hemorrhage. Short spindle tumor cells were proliferating with myxoid stroma. Tumor cells appeared to be arranged around the vessels and sometimes attached to the vessel wall directly. Although hyalinization of the vessel wall was observed, neither patternless pattern nor staghorn vessels were seen. Immunohistochemistry revealed that the tumor cells were positive for both CD34 and nuclear STAT6. Moreover, gene analyses revealed unique NAB2-STAT6 fusion. Immunohistochemical findings and fusion-gene analyses enabled us to make the definite diagnosis of meningeal myxoid SFT/HPC. The present case showed the three unique features such as clinically symptomatic intratumoral hemorrhage at the onset, rare variant of myxoid SFT/HPC, and unique NAB2-STAT6 fusion.

A malignant solitary fibrous tumour arising from the first lumbar vertebra and mimicking an osteosarcoma: a case report

BackgroundA solitary fibrous tumour (SFT) is an unusual neoplasm typically found in soft tissues. Although SFTs can arise in the bones, they very rarely arise in the vertebral arch. Here, we describe a case of a SFT that arose in the vertebral arch of the first lumbar (L1) spinal vertebrae and mimicked osteosarcoma.Case presentationA 49-year-old woman presented with a 2-month history of lower back pain and a lumbar region mass. Magnetic resonance imaging demonstrated a heterogeneously enhanced mass in the L1 vertebral arch. The patient received neoadjuvant chemotherapy, followed by a surgical procedure comprising an anterior spinal fusion and en bloc resection. Histologically, our initial diagnosis was osteosarcoma. The postoperative course was uneventful, and the patient received adjuvant chemotherapy. However, the tumour metastasised to the lung 5 years after the first surgery, and a second surgery was performed for lung tumour resection. The histology of the metastatic lung tumour appeared similar to that of the malignant SFT, and the specimen from the first surgery was re-examined. Immunohistochemically, the tumour was positive for STAT6. Reverse transcription-polymerase chain reaction revealed a NAB2-STAT6 fusion gene, thus confirming our final diagnosis of malignant SFT. The patient died of disease progression 8 years after the first surgery; however, there was no evidence of local recurrence.ConclusionsMalignant SFT in the vertebral arch is extremely rare and very difficult to distinguish histologically an osteoid from lace-like collagen. STAT6 immunostaining is useful for distinguishing malignant SFTs from other neoplasms. Although it is difficult to completely resect a SFT arising from the spine, we demonstrated the feasibility of an en bloc resection of spinal tumours arising from posterior elements, without local recurrence.

Validation of nuclear STAT6 immunostaining as a diagnostic marker of meningeal solitary fibrous tumor (SFT)/hemangiopericytoma.

NAB2-STAT6 gene fusion is a molecular characteristic of solitary fibrous tumors (SFT) and hemangiopericytoma, underscoring their definition as one diagnostic entity. NAB2-STAT6 fusion is associated with nuclear relocation of STAT6 protein that can be detected by immunohistochemistry. We evaluated the diagnostic value of STAT6 expression in meningeal tumors. 77 meningeal tumors (17/77 (22.0%) SFT/hemangiopericytoma, 11/77 meningothelial meningioma, 10/77 atypical meningioma 8/77 chordoid meningioma, 9/77 fibroblastic meningioma, 10/77 transitional meningioma, 3/77 rhabdoid meningioma and 9/77 anaplastic meningioma) were included. STAT6 immunohistochemistry was performed on FFPE specimens using a fully automated slide-staining system and anti-STAT6 antibody SC-20:sc621. Two independent observers analyzed all specimens blinded to histological diagnoses, and a third observer was consulted in case of discordancy. STAT6 immunohistochemistry yielded an exclusively nuclear immunostaining signal. 16/17 (94%) SFT/hemangiopericytoma specimens presented with clear-cut, wide-spread, and moderate to strong staining in tumor cell nuclei and were rated as STAT6-positive. In only 1 SFT case with weak and focal nuclear STAT6 immunostaining signal, STAT6 expression was rated discordant (observer 1: STAT6-negative, observers 2 and 3: STAT6-positive). All non-SFT/hemangiopericytoma cases were unanimously rated as STAT6-negative. In 76/77 (98.7%) cases the evaluation of STAT6 immunostaining results was in agreement among observers. STAT6 immunohistochemistry is a robust method to verify diagnosis of SFT/hemangiopericytoma and should therefore be included in the diagnostic work-up of meningeal tumors. In singular cases, weak and focal STAT6 expression may lead to false-negative evaluation and may prompt further molecular work-up. .

Extrapleural solitary fibrous tumour with malignant histological features: a case report and review of current and emerging prognostic factors

Solitary fibrous tumour (SFT) is a mesenchymal neoplasm, historically considered to be a tumour of the pleura with limited metastatic potential. Over time, evidence has shown that SFTs are anatomically ubiquitous, possess a NAB2-STAT6 gene fusion, and can behave aggressively, resulting in local recurrence, metastasis and death. Attempts have subsequently been made to identify factors that can be used to predict which tumours will behave aggressively. We report a case of a 57 year old woman presenting with a longstanding pelvic mass, which was resected and a diagnosis of malignant solitary fibrous tumour was made, based on the features of increased mitotic activity and tumour necrosis, as per the 2013 WHO classification of tumours of soft tissue and bone. A review of recent literature shows increased mitotic rate is the feature most consistently reported to correlate with a poor outcome. Other features such as older patient age, larger tumour size, site of primary tumour and tumour necrosis are reported by some authors to correlate with aggressive behaviour. There may be a future role for molecular based prognostic indicators, with an initial investigation into the molecular alterations in SFT suggesting there are specific genotypes of NAB2-STAT6 gene fusion that are associated with a malignant phenotype.