Diagnosis and treatment of solitary fibrous tumors of the thyroid gland: the importance of an appropriate diagnostic approach.

Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics

Late recurrence of renal solitary fibrous tumour in the contralateral kidney

AimsTo characterise clinicopathological features and clinical outcomes of the genitourinary tract solitary fibrous tumours, incorporating NAB2-STAT6 gene fusion status.MethodsThe presence of the molecular hallmark NAB2-STAT6 gene fusion and for the...

STAT6 is expressed in vulvovaginal mesenchymal neoplasms other than solitary fibrous tumour

A solitary fibrous tumor (SFT) is a rare mesenchymal tumor with a high risk of local recurrence and a metastatic potential.1 Because of the rarity of the disease, the data regarding possible nonsurgical treatment options are limited. Until recently, most extensive reports regarding nonsurgical SFT treatment were based on case reports.2 Surgery remains the leading treatment option, and currently, the disease is being surgically managed similarly to soft-tissue sarcomas.3 Sadly, although a combination therapy has been already applied in clinical practice to soft-tissue sarcomas,4 additional therapies such as immunotherapy, have gained only minimal interest in SFTs. In the past few years, however, several new principles concerning the therapy of SFTs have evolved. We read with a great interest the recent study by Haas et al,5 who revealed the major potential of perioperative radiotherapy in the local control of the disease. The authors performed a retrospective analysis across 7 sarcoma centers by collecting data on 549 patients with SFTs who underwent either surgery alone or surgery together with peri/postoperative radiotherapy. To date, this is the largest study regarding the nonsurgical treatment of SFTs. The authors concluded that perioperative radiotherapy should be considered as a treatment option for this rare disease and thus broke the frequently cited claim of the inefficacy of radiotherapy for SFTs. Although the effectivity of standard cytotoxic chemotherapeutic regimens still remains questionable,6 an effort has been made through the past few years to discover different approaches in the treatment of SFTs. Some of these promising approaches, however, have not yet been tested in clinical trials. This is presumably due to the rarity of the disease. Only a small number of targeted therapies have been tested and further occasionally applied in clinical practice.3 The approved targeted therapies selectively target specific molecular pathways that may be involved in angiogenesis or tumorigenesis.3 So far, the most promising targeted therapy for malignant SFTs seems to be bevacizumab, a humanized recombinant antibody against vascular endothelial growth factor (VEGF), together with temozolomide, an alkylating chemotherapeutic. This therapy shows a partial response in 79% of patients.7 Pazopanib has been tested as an anti-VEGF receptor agent in the treatment of SFTs, however, it showed mild antitumor activity only in nondedifferentiated cases.8 On the other hand, sunitinib, a tyrosine kinase inhibitor, showed activity and long-lasting responses in the treatment of SFTs.9 Moreover, the pretreatment status of PDGFRB and/or VEGFR2, evaluated by immunostaining, was not predictive of a response. This suggests that sunitinib may be a promising treatment option for all patients with SFTs.9 Although different immunotherapeutic approaches, such as adoptive cell transfer, checkpoint inhibition, and chimeric antigen receptor T-cell therapy, have already been tested in soft-tissue sarcomas,4 only an anti–PD-L1 checkpoint inhibitor has been used in SFT therapy.10 A single case report by Boothe et al10 illustrates a major effect of anti–PD-L1 therapy in a patient with chemo-refractory and radiation-refractory SFT. The patient had a low PD-L1 expression status (5%) but presented a prompt and nearly complete response to an anti–PD-L1 antibody. The study itself reveals the large potential of checkpoint immunotherapy in SFT treatment. Although SFTs present rare diseases and may have a benign biological nature, local recurrence and metastatic behavior are also highly prevalent. Based on the limited data, we aim to highlight that similarly to soft-tissue sarcomas, radiotherapy, targeted therapy, and immunotherapy should become part of therapeutic algorithms in SFTs. Moreover, clinical testing of other immune checkpoint inhibitors is urgently needed, and only close interdisciplinary cooperation between surgical and nonsurgical institutions can introduce patients with SFTs to novel immunotherapeutic approaches, such as adoptive T-cell transfer and chimeric antigen receptor T-cell immunotherapy. No specific funding was disclosed. The authors made no disclosures.

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

Purpose: Tumors previously diagnosed as solitary fibrous tumors (SFT) and hemangiopericytomas (HPC) are characterized by the NAB2-STAT6 fusion gene, leading to nuclear STAT6 expression, and are now considered part of one SFT/HPC tumor entity by the 2016 World Health Organization Classification of Tumors of the Central Nervous System. We present the first primary choroidal SFT/HPC with the diagnosis confirmed by STAT6 expression. Procedures: A 51-year-old man underwent enucleation for a choroidal mass, which revealed a spindle cell neoplasm involving the optic nerve, without extrascleral extension. Immunohistochemical stains for S-100, melan-A, tyrosinase, and HMB45 were all negative; however, detection of monosomy 3 by FISH favored a choroidal spindle cell melanoma. Four years later, he presented with hepatic metastases of a spindle cell tumor, and a year later with an epithelioid malignancy involving the calvarium. Results: The calvarial tumor showed nuclear STAT6 immunoreactivity, supporting the diagnosis of SFT/HPC. Retrospectively, the choroidal and hepatic masses were also found to demonstrate nuclear STAT6 expression, supporting the diagnosis of a primary choroidal SFT/HPC with metachronous metastases to the liver and calvarium. Conclusions: This case highlights the significance of considering SFT/HPC in the diagnosis of intraocular spindle cell tumors and the importance of STAT6 immunohistochemistry in the evaluation of such tumors.

Investigations on the NAB2-STAT6 fusion gene in solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) have increased since its discovery in 2013. Although several SFTs reported without NAB2-STAT6 fusion gene analysis, we reviewed 546 SFTs/HPCs with NAB2-STAT6 fusion gene analysis in this study and investigated differences between the gene variants. In total, 452 cases tested positive for the NAB2-STAT6 fusion gene, with more than 40 variants being detected. The most frequent of these were NAB2 exon 6-STAT6 exon 16/17/18 and NAB2 exon 4-STAT6 exon 2/3, with the former occurring most frequently in SFTs in meninges, soft tissues, and head and neck; the latter predominated in SFTs in the pleura and lung. There was no difference between the histology of SFTs and fusion gene variants. A follow-up analysis of SFTs showed that 51 of 202 cases had a recurrence, with 18 of 53 meningeal SFTs having a local recurrence and/or metastasis within 0-19years. In meninges and soft tissue, SFTs with the NAB2 exon 6-STAT6 exon 16/17/18 tended to recur more frequently than SFTs with the NAB2 exon 4-STAT6 exon 2/3. Clinicopathological data, including yearly follow-ups, are required for meningeal SFTs/HPCs to define the correlation of variants of NAB2-STAT6 fusion gene.

Solitary fibrous tumors are mesenchymal lesions that arise at a variety of sites, most commonly the pleura. Most patients are asymptomatic at diagnosis, with lesions being detected incidentally. Nevertheless, some patients present due to symptoms from local tumor compression (eg. of the airways and pulmonary parenchyma). Furthermore, radiological methods are not always conclusive in making a diagnosis, and thus, pathological analysis is often required. In the past three decades, immunohistochemical techniques have provided a gold standard in solitary fibrous tumor diagnosis. The signature marker of solitary fibrous tumor is the presence of the NAB2-STAT6 fusion that can be reliably detected with a STAT6 antibody. While solitary fibrous tumors are most often benign, they can be malignant in 10-20% of the cases. Unfortunately, histological parameters are not always predictive of benign vs malignant solitary fibrous tumors. As solitary fibrous tumors are generally regarded as relatively chemoresistant tumors; treatment is often limited to localized treatment modalities. The optimal treatment of solitary fibrous tumors appears to be complete surgical resection for both primary and local recurrent disease. However, in cases of suboptimal resection, large disease burden, or advanced recurrence, a multidisciplinary approach may be preferable. Specifically, radiotherapy for inoperable local disease can provide palliation/shrinkage. Given their sometimes -unpredictable and often- protracted clinical course, long-term follow-up post-resection is recommended.

This report describes clinicopathological findings, including genetic data of STAT6, in a solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) of the central nervous system in an 83-year-old woman with a bulge in the left forehead. She noticed it about 5months before, and it had grown rapidly for the past 1month. Neuroradiological studies disclosed a well-demarcated tumor that accompanied the destruction of the skull. The excised tumor showed a prominent papillary structure, where atypical cells were compactly arranged along the fibrovascular core ('pseudopapillary'). There was rich vasculature, some of which resembled 'staghorn' vessels. Mitotic figures were occasionally found. Whorls, psammoma bodies, or intra-nuclear pseudoinclusions were not identified. By immunohistochemistry, CD34 was strongly positive in the tumor cells, and STAT6 was localized in their nuclei. By reverse transcription-polymerase chain reaction (RT-PCR), an NAB2-STAT6 fusion gene, NAB2 exon6-STAT6 exon17, was detected, establishing a definite diagnosis of SFT/HPC. 'Papillary' SFT/HPC needs to be recognized as a possible morphological variant of SFT/HPC, and should be borne in mind in its diagnostic practice.

The utility of STAT6 and ALDH1 expression in the differential diagnosis of solitary fibrous tumor versus prostate-specific stromal neoplasms

Introduction: Glomangiopericytoma (GPC) is a rare type of neoplasm with hemangiopericytoma-like vasculature and perivascular hyalinization of capillary-sized veins. CD34 and S100 protein staining might be positive in a small percentage of GPC. Solitary fibrous tumors (SFTs) present clinically like GPC. However, challenges remain when differentiating GPC from SFT. Case Presentation: A 37-year-old male, smoker, presented with 3 years history of right-sided epistaxis and nasal congestion. He was also complaining of hyposmia but no headaches or visual complaints. On nasal endoscopy, he was found to have a right-sided nasal mass occupying the ethmoid cavity. Computed tomography showed a right sinonasal mass abutting the anterior skull base and magnetic resonance imaging demonstrated a hyperintense, enhancing mass within the right ethmoid cavity, superior septum, and anterior skull base. The patient underwent endoscopic resection with gross total resection and skull base reconstruction. Postoperative pathology initially was thought to be an SFT; however, subsequent STAT6 expression was negative, and therefore GPC diagnosis was confirmed. At the most recent follow-up (6 months), the patient remained free of local disease. Discussion: SFT, unlike GPC, stains strongly for CD34, in this case, due to strong CD34, the diagnosis of SFT was initially made. Nuclear STAT6 expression is highly specific and sensitive for SFT. This later returned as negative; therefore, GPC was confirmed. Conclusion: We present a case of sinonasal GPC with skull base involvement that was treated with endoscopic resection. At the most recent follow-up (6 months), the patient remained free of local disease.

Solitary fibrous tumors (SFTs) are rare tumors of vascular origin, derived from pericytes surrounding blood vessels. Their frequency of presentation is mainly in adults, and they can be in various parts of the body, such as the extremities, head, neck, retroperitoneum, and abdomen. These tumors can be either benign or malignant, and their behavior and clinical course are variable, with a significant risk of recurrence and metastasis. We present a two-case report: the first involving a 25-year-old man with right hemiparesis and a history of two prior surgeries at another institution for a diagnosed SFT; the second involving a 48-year-old man with decreased visual acuity and personality changes, with a biopsy confirming SFT. Both cases were managed with embolization followed by resection, with no residual tumor remaining. Treatment of SFTs with embolization and complete surgical resection improves surgical outcomes and reduces the risk of recurrence.

Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation

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.