The many faces of solitary fibrous tumor; diversity of histological features, differential diagnosis and role of molecular studies and surrogate markers in avoiding misdiagnosis and predicting the behavior.

BACKGROUND: Solitary Fibrous Tumor (SFT) is a distinct soft tissue neoplasm associated with NAB2-STAT6 gene fusion. It can involve a number of anatomic sites and exhibits a wide spectrum of histological features. MAIN BODY: Apart from diversity in morphological features seen even in conventional SFT, two histologic variants (fat-forming and giant cell-rich) are also recognized. In addition, a malignant form and dedifferentiation are well recognized. Owing to diverse histological features and involvement of diverse anatomic locations, SFT can mimic other soft tissue neoplasms of different lineages including schwannoma, spindle cell lipoma, dermatofibrosarcoma protuberans, liposarcoma, gastrointestinal stromal tumor (GIST), malignant peripheral nerve sheath tumor (MPNST), and synovial sarcoma. SFT is classified as an intermediate (rarely metastasizing) tumor according to World Health Organization Classification of Tumors of Soft tissue and Bone, 5th edition. The management and prognosis of SFT differs from its malignant mimics and correct diagnosis is therefore important. Although SFT expresses a distinct immunohistochemical (IHC) profile, the classic histomorphological and IHC profile is not seen in all cases and diagnosis can be challenging. NAB2-STAT6 gene fusion has recently emerged as a sensitive and specific molecular marker and its IHC surrogate marker signal transducer and activator of transcription 6 (STAT6) has also shown significant sensitivity and specificity. However, few recent studies have reported STAT6 expression in other soft tissue neoplasms. CONCLUSION: This review will focus on describing the diversity of histological features of SFT, differential diagnoses and discussing the features helpful in distinguishing SFT from its histological mimics.

[A Case of Anaplastic Carcinoma with Osteoclastlike Giant Cells of the Pancreas Concomitant with Lung Recurrence of Solitary Fibrous Tumor].

A 32-year-old woman presented with epigastric pain and an abdominal mass. Abdominal CT showed a 130mm pancreatic tail mass with an enhanced rim, central necrosis, and small calcification. A 6mm lung tumor was also found via chest CT. Her medical history included surgical resection of cerebral solitary fibrous tumor when she was 24 years old. When she was 31 years old, it had recurred but was cured by gamma knife radiosurgery. We performed distal pancreatectomy and splenectomy with lymph node dissection. According to pathological and immunohistochemical findings, it was diagnosed as an anaplastic carcinoma with osteoclast-like giant cells. She underwent surgical resection of the lung tumor 2 months after pancreatic resection and was diagnosed with metastasis from the solitary fibrous tumor. Fourteen months since undergoing pancreatectomy, the patient experienced no recurrence from both diseases. We report a rare resected case of anaplastic carcinoma of pancreas concomitant with recurrent solitary fibrous tumor.

Solitary fibrous tumor involving the pancreas: report of the cytologic features and first report of a primary pancreatic solitary fibrous tumor diagnosed by fine-needle aspiration biopsy.

INTRODUCTION: Solitary fibrous tumor (SFT) of the pancreas is rare, with only 16 reported cases in English studies. The cytologic features of pancreatic SFT have not been well described. We report 2 cases of SFT (1 primary and 1 metastatic) involving the pancreas and discuss the cytomorphologic findings, including the first primary SFT of the pancreas specifically diagnosed using cytology. MATERIALS AND METHODS: The cases of 2 patients with a diagnosis of SFT of the pancreas from material obtained via fine needle aspiration (FNA) are reported. Clinical information was retrieved from the patients' medical records. The FNA cytology slides, previous relevant surgical pathologic findings, and findings from subsequent pancreatic resections were reviewed. RESULTS: Of the 2 patients, 1 had had secondary involvement of the pancreas from a primary central nervous system SFT, and 1 had had a primary pancreatic SFT diagnosed by FNA. Immunohistochemistry for STAT6 was crucial for establishing the diagnosis using FNA. CONCLUSIONS: We have reported 2 cases of SFT involving the pancreas, including the first reported case of primary pancreatic SFT diagnosed preoperatively using FNA. Metastatic SFT from central nervous system primaries should be considered when diagnosing SFT of the pancreas.

Solitary fibrous tumors of the head and neck region revisited: a single-institution study of 20 cases and review of the literature.

A solitary fibrous tumor (SFT) is a rare, NAB2-STAT6 fusion gene-associated mesenchymal neoplasm. It most commonly arises in the pleural site, but it can occur at many other sites, and rarely also in the head and neck (H&N) region. STFs may show many growth patterns and therefore can be easily mistaken for other more common H&N spindle cell or epithelial lesions. In this study, we present our experience in the diagnosis of 20 cases of SFT in the H&N region and discuss their most notable mimickers. In all cases, STAT6 expression was found positive by immunohistochemistry, and the NAB2-STAT6 fusion was confirmed by next-generation sequencing. Three major fusion variants were detected: NAB2ex2-STAT6int1 (5/20, 25%), NAB2ex6-STAT6ex16 (4/20, 20%), and NAB2ex4-STAT6ex2 (3/20, 15%). Clinical follow-up was available for 16 patients (median follow-up time: 84 months). One patient with a morphologically malignant SFT experienced multiple local recurrences, followed by dissemination into the lungs and meninges. This malignant SFT also displayed an aberrant FLI1 expression, which was not previously reported in SFT cases. We also summarize findings from 200 cases of SFT of the H&N region, which included cases from our study, and from previous studies that reported on the fusion status of the STAT6 gene. The results suggest that metastatic disease developed only in cases with STAT6 variants that included the DNA-binding domain (STAT6-full variants), which contradicts expectations from previous reports and deserves further investigation.

Metastatic Solitary Fibrous Tumour of the Kidney Presenting more than a Decade Later with Pulmonary Disease

Introduction Solitary fibrous tumours are rare mesenchymal tumours that most commonly originate from the visceral pleura. Extra-thoracic primary sites including; head and neck, soft tissue, retroperitoneum and the urological tract, are associated with late recurrence. Case We present a case of metastatic pulmonary Solitary Fibrous Tumour presenting 11 years post resection of renal primary Solitary Fibrous Tumour. The patient underwent apical segmentectomy of the right lower lobe extending to wedge excision of right upper lobe due to fissure involvement with lymphadenectomy. The patient was discharged day 12 post surgery. Discussion Robust guidance regarding long-term management of solitary fibrous tumours is lacking. Salvage resection offers favourable long-term prognosis. This case demonstrates the importance of long-term surveillance.

Tumor-to-Tumor Metastasis: Pulmonary Carcinoid Metastasizing to Solitary Fibrous Tumor.

BACKGROUND Tumor-to-tumor metastasis is an uncommon phenomenon in which a primary tumor metastasizes into another tumor. CASE REPORT An 81-year-old Asian woman was referred to our hospital for evaluation and treatment of a solid mass in the right middle lung lobe that had rapidly enlarged for 1.5 years compared to that observed over the last 5 years. On computed tomography (CT), the mass was 68×60 mm, and 2 different tumors appeared to exist in the upper portion of the mass. Blood examination findings revealed high serum levels of progastrin-releasing peptide and neuron-specific enolase. Based on the radiographic course of the tumor and elevated levels of tumor markers, we suspected that a new malignant tumor, such as a neuroendocrine tumor, had developed dorsally adjacent to the benign tumor. CT-guided percutaneous needle biopsy of the lung indicated a solitary fibrous tumor (SFT), which did not lead to the diagnosis of another tumor adjacent to the original tumor. Therefore, a right middle lobectomy was performed. The resected specimen contained 2 different tumors: an SFT and a typical carcinoid without mitosis or necrosis. On microscopic examination, they were separated from each other by normal alveolar tissue. In addition, a typical carcinoid was also observed inside the SFT lesion, completely enclosed by the SFT tissue. These findings suggested that the carcinoid metastasized to the SFT in the same lung lobe. CONCLUSIONS To the best of our knowledge, this is the first case of a pulmonary typical carcinoid metastasizing to an intraparenchymal SFT.

A DSTYK mutation activates ERK1/2 signaling to promote intraspinal dissemination in a case of solitary fibrous tumor/hemangiopericytoma.

Intracranial solitary fibrous tumors/hemangiopericytomas (SFT/HPCs) are vascular tumors that have a high rate of local recurrence and extracranial metastases. Intradural extramedullary spinal dissemination of intracranial SFT/HPC is extremely rare. There is a paucity of data available to elucidate the molecular mechanisms of intraspinal dissemination of intracranial SFT/HPC. Herein, we presented a case of intracranial SFT/HPC with intraspinal metastasis. The resected tumor specimens were enrolled in a clinical sequencing program, including whole-exome and transcriptome sequencing. By comparing genomic sequencing data of the intracranial tumors with intraspinal metastasis, we established the somatic mutational profiles of these tumors. Clonality analysis revealed a distinct subclonal structure in the intracranial tumor and its intraspinal metastasis, which might reflect the possibility of intratumoral clonal selection and evolution during the process of tumor dissemination. Through bioinformatics analysis and Sanger sequencing validation, a DSTYK mutation (Met296Ile) was identified as a candidate driver of intraspinal metastasis in this SFT/HPC case. Further, an intracranial tumor-derived SFT/HPC cell line, HPC3, was established to explore the mechanisms of the DSTYK mutation in promoting SFT/HPC metastasis. Based on the HPC3 cell model, we found that the DSTYK mutation promoted cell migration and invasion of HPC3 cells via activation of ERK1/2 signaling, which was inhibited by the MEK/ERK inhibitor AZD6244. The DSTYK mutation was also shown to upregulate the expression of two metastasis-related molecules: MMP2 and MMP9 in HPC3 cells; however, this effect was attenuated by AZD6244 treatment. Therefore, the DSTYK mutation may activate ERK1/2/MMP2/9 signaling to promote tumor cell metastasis in SFT/HPC. In conclusion, our study revealed the potential role of DSTYK mutation in the regulation of intraspinal metastasis of SFT/HPC, which might provide new biological insights into this rare disease.

Activity of axitinib in progressive advanced solitary fibrous tumour: Results from an exploratory, investigator-driven phase 2 clinical study.

BACKGROUND: To explore the activity of axitinib in advanced solitary fibrous tumour (SFT). PATIENTS AND METHODS: In this investigator-driven phase II study on axitinib in advanced and progressive SFT, patients received axitinib, 5 mg bis in day (BID), until progression or limiting toxicity. Pathologic diagnosis was centrally reviewed, distinguishing malignant SFT (M-SFT) and high-grade/dedifferentiated SFT (HG/D-SFT) subtypes. The primary end-point was the overall response rate (ORR) by Choi criteria (Choi). Secondary end-points were response by Response Evaluation Criteria in Solid Tumours (RECIST), progression-free survival (PFS) and overall survival (OS). RESULTS: From April 2015 and October 2017, 17 eligible patients entered the study (metastatic: 17; SFT subtype: 13 M-SFT, 4 HG/D-SFT; prior treatment: 9 antiangiogenics, 5 cytotoxics). All patients were evaluable for response. The best Choi response was seven partial response (PR) (ORR, 41.2%), six stable disease (SD) and four progressions. Choi-ORR was 54% (7/13) when only M-SFTs were considered. Four of seven responsive patients were pretreated with pazopanib. No responses were detected in HG/D-SFT. Best RECIST response was one PR (5.9%), 14 SD and two progressions. Toxicity was as expected. Median Choi-PFS was 5.1 (interquartile range [IQR]: 2.5-14.8) months. Median Choi-PFS was 14.8 (IQR: 5.1-18.0) and 2.8 (IQR: 2.0-5.9) months for patients responsive and non-responsive by Choi, respectively (p = 0.0416). At a 14.4-month median follow-up, median OS was 25.3 months. CONCLUSION: This study showed that axitinib is active in progressive advanced SFT. One-half of patients carrying the malignant variant of the disease responded, with a >12-month median progression arrest. Responses were better detected with Choi and seen even in patients resistant to other antiangiogenics. Tolerability was good.

Recurrence of multiple metastases after surgical removal of a primary malignant solitary fibrous tumor from the main bronchus: A case report.

RATIONALE: Limited knowledge is available regarding solitary fibrous tumors (SFTs), about 15% of which are malignant. In particular, the long-term survival of patients with malignant SFTs (mSFTs), the disease course, and the potential for recurrence of second primary tumors or distant metastases are largely undetermined. PATIENT CONCERNS: We report a rare case in which an mSFT was found at the main bronchus of the right lung of a 37-year-old man. DIAGNOSIS: The tumor cells of mSFT were spindle-shaped and expressed antigen Ki-67, B-cell lymphoma 2, cluster of differentiation 31, and vimentin. INTERVENTIONS: A total pneumonectomy was performed. OUTCOMES: The patient developed fibrosarcoma of the small intestine at 6 months, as well as extensive pleural and peritoneal metastases at 1 year, after removal of the primary mSFT from the right main bronchus. LESSONS: From these findings, we expect that patients with primary mSFT, especially of the lung, have a high potential to develop second tumors or distant metastases. Close monitoring after surgery is necessary to improve the outcomes of these patients.

Malignant solitary fibrous tumor of the kidney with liver metastasis: A case report and literature review.

Solitary fibrous tumor (SFT) is a rare spindle cell soft tissue tumor which is rarely encountered in the clinical setting and imaging findings are nonspecific, mainly occurring in the tissue structure of the serosa. However, there is very little report on SFT originating in the kidney in the medical literature. We report a case of SFT with liver metastasis in an adult female and discuss the pathological features as it appears in our case.

Tumor-to-tumor metastasis of lung adenocarcinoma into a spinal intradural solitary fibrous tumor: a case report.

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms commonly involving visceral or parietal pleura. We present the first report of tumor-to-tumor metastasis involving a pulmonary adenocarcinoma donor and an intradural SFT recipient. The patient presented with a 1 year history of diffuse back pain. A spinal intradural contrast-enhancing mass at the T9/10 level and a tumor of the lung were diagnosed radiologically. Bronchoscopic biopsy confirmed pulmonary adenocarcinoma in the right upper lung lobe. Due to deteriorating neurological status with conus medullaris syndrome, we performed a neurosurgical excision of the lesion. Histological analysis of the tumor revealed tumor-to-tumor metastasis of the adenocarcinoma to the SFT.

Contrast enhanced imaging features of liver metastasis from a meningeal solitary fibrous tumor: a case report.

A solitary fibrous tumor seldom originates from the meninges, and the accuracy of imaging modalities in the diagnosis of meningeal SFT metastasisis is perlexing. Contrast enhanced imaging modalities, such as contrast enhanced ultrasound and contrast enhanced magnetic resonance imaging are valuable in the differential diagnosis of hepatic neoplasms. This case report demonstrated the contrast enhanced ultrasound and enhanced magnetic resonance imaging features of one case of liver metastasis from a menigeal solitary fibrous tumor.

Telomerase promoter mutations and copy number alterations in solitary fibrous tumours.

AIMS: Solitary 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 associate with adverse patient outcome in SFTs. METHODS: We analysed the hTERT gene for promoter mutations and copy number alterations in 43 primary extrameningeal SFTs (9 malignant and 34 benign tumours according to WHO 2013 criteria), six local recurrences and three metastatic lesions. RESULTS: Activating -124 C>T (n=12) or -148 C>T (n=2) mutations were found in 33% of the tumours and associated with older age (P=0.006), necrosis (P=0.009), higher mitotic rate (P=0.003), nuclear atypia (P=0.002), malignant histological diagnosis (P=0.04) and worse progression-free survival (P=0.023). We also observed frequent (24%) hTERT promoter mutations in histologically benign tumours without metastasis (mean follow-up >9 years), and in 14%-18% of low-risk SFTs as determined by three risk-stratification models. Mutations were seen in 2/6 metastatic tumours and metastatic lesions. hTERT copy number gain was seen in 11/28 hTERT promoter wild-type cases. CONCLUSIONS: Activating hTERT promoter mutations associate with aggressive histopathological features, indicating a role in tumour progression. Given the comparatively high prevalence of hTERT promoter mutations in low-risk and non-metastasising lesions, further studies are required to clarify the prognostic value of hTERT promoter analysis before implementing the analysis in clinical diagnostics.

Malignant Solitary Fibrous Tumor Metastatic to Widely Invasive Hurthle Cell Thyroid Carcinoma: A Distinct Tumor-to-Tumor Metastasis.

We illustrate a case of synchronous malignant solitary fibrous tumor of the thoracic cavity, and widely invasive thyroid Hurthle cell carcinoma. The Hurthle cell carcinoma was found to harbor distinct areas of malignant solitary fibrous tumor. This is a unique case of tumor-to-tumor metastasis that, to the best of our knowledge, has not been previously reported.

Solitary Fibrous Tumors of the Head and Neck: A Multi-Institutional Clinicopathologic Study.

Solitary fibrous tumors (SFTs) of the head and neck are uncommon. Lesions previously diagnosed in the head and neck as hemangiopericytomas (HPCs), giant cell angiofibromas (GCAs), and orbital fibrous histiocytomas (OFHs) are now recognized as within the expanded spectrum of SFTs. To better understand the clinicopathologic profile of head and neck SFTs, we performed a multi-institutional study of 88 examples. There was no sex predilection (F:M ratio 1.2), and the median patient age was 52 years (range: 15 to above 89 y). The sinonasal tract and orbit were the most common sites involved (30% and 25%), followed by the oral cavity and salivary glands (15% and 14%). Original diagnoses included HPC (25%), SFT (67%), and OFH (6%), with 1 SFT and 1 OFH noted as showing GCA-like morphology. On review, the predominant histologic pattern was classic SFT-like in 53% and cellular (former HPC-like) in 47%; lipomatous differentiation (8%) and GCA-like pattern (7%) were less prevalent. Subsets demonstrated nuclear atypia (23%), epithelioid morphology (15%), or coagulative necrosis (6%). Infiltrative growth (49%) and osseous invasion (82%) were prevalent among evaluable cases. Of the 48 SFTs with follow-up (median: 43 mo), 19 showed recurrence (40%). Of these, 4 patients were alive with disease and 4 dead of disease. Size and mitotic rate were negative prognosticators using a joint prognostic proportional hazards regression model. Three patients experienced metastasis, to lungs, parotid, bone, and skull base, including one case showing overtly sarcomatous "dedifferentiation." As a group, SFTs present in a wide anatomic and morphologic spectrum in the head and neck. Only rare examples metastasize or cause death from disease. However, the fairly high local recurrence rate underscores their aggressive potential and highlights the importance of prospective recognition.

Pancreatic metastasis from an osseous solitary fibrous tumour.

A 73-year-old man presented with a right-sided chest wall mass that showed an epitheloid neoplasm with mild cytologic atypia on core needle biopsy. He underwent surgical resection, and final pathology revealed solitary fibrous tumour/hemangiopericytoma with negative margins. Three years after surgical resection, the patient presented with fatigue, abdominal pain, weight loss and mildly elevated liver function tests. Further workup revealed a 1.2 cm hypervascular mass in the neck of the pancreas. This case report summarises the surgical treatment and outcomes for a patient who presented with this rare tumour.

Solitary fibrous tumour of the liver-report on metastasis and local recurrence of a malignant case and review of literature.

BACKGROUND: Solitary fibrous tumours (SFT) are neoplasms of mesenchymal origin that predominantly arise from the pleura. SFT of the liver (SFTL) are a rare occurrence with little number of cases reported in English literature. Malignant cases of hepatic SFT are an even rarer occurrence. For this reason, the prognostic evaluation of SFTLs is unknown and difficult to measure. METHODS: A search on English literature on "Solitary Fibrous Tumour of the Liver" was conducted on common search engines (PubMed, Google). All published articles, case reports and literature reviews and their reference lists were reviewed. CASE REPORT: This paper presents a 61-year-old male who was referred to a tertiary hospital in April 2010 with marked hepatomegaly. USS, CT and MRI scans were suggestive of a neoplasm, and the patient underwent a subsegmental IVb resection in June 2010. The specimen demonstrated histological and immunohistochemical features of malignant SFTL with clear resection margins. The patient was followed up regularly for 3 years with imaging and no suggestion of recurrence. Six years after the initial surgery, the patient represented with worsening right upper quadrant pain and dyspnoea secondary to extensive tumour recurrence adjacent to the resection site and metastatic deposits in the pleura. The patient was managed symptomatically and discharged for community follow-up after palliative involvement. CONCLUSIONS: SFTL are rare with only 84 cases reported in the English Literature including the present case. The average age of patients is 57.1 and occurs in females more than males (1.4:1). Most SFTLs follow a benign course, however, 17.9% of cases displayed malignant histological features. Only three cases including the current case are reported to have both local recurrence and metastasis. Surgical resection remains the mainstay of treatment and appears to be curative of most cases. The rarity of this tumour makes it difficult to evaluate its prognosis and natural course.

[Malignant solitary fibrous tumor of the lung metastatic to the thyroid gland:a case report].

Solitary fibrous tumors(SFT) of the thyroid gland are rarely reported，especially metastases from a malignant solitary fibrous tumor(MSFT) of lung. We herein present a 35 year old man with history of SFT of lung and a 6 month history of rapidly enlarging thyroid masses. The CT showed masses in the left thyroid lobe. We performed thyroid lobectomy plus central compartment neck dissection. Immunohistochemically,Bcl2,Vim and CD99 were positive,while CK,CD34,EMA,TG,P53 and S100 were negative. Combined with patient medical history and pathological diagnosis,it confirmed that MSFT of the lung metastatic to the thyroid gland. within a period of 7 months of follow up,no reoccurrence was found so far.