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.

[A Case of Meningeal Solitary Fibrous Tumour/Haemangiopericytoma WHO Grade III Metastasized to the Spleen Shortly After Tumor Resection].

Revision of WHO guidelines in 2016 led to the classification of solitary fibrous tumours(SFTs)and haemangiopericytomas(HPCs)as a single tumor entity characterized by NAB2-STAT6 fusion. Standard-of-care treatment involves surgery, but local recurrence and distant metastasis sometimes occur. The average latency to metastasis after surgery is 99 months. A 38-year-old female patient presented with a complaint of headache. An 8×5×2cm lesion showing Gd-T1 enhancement was detected near the superior sagittal sinus. Pathological assessment following resection revealed proliferating, polymorphic, atypical tumor cells with distinct nucleoli in a "patternless pattern." Cellularity was moderate to high, and mitotic figures were observed in 15/10 high power fields. Immunohistochemically, tumor cells tested positive for STAT6, and RT-PCR revealed a NAB2-STAT6 fusion gene(exons 6 and 17, respectively), supporting a diagnosis of SFT/HPC WHO grade III. Despite postoperative radiotherapy, multiple metastases to the spleen were detected 8 months after surgery, and distal pancreatectomy with splenectomy was performed. The pathology of the splenic tumor was similar to that of the intracranial tumor. Recurrent disease in a lymph node was detected 1 month later, and local radiation therapy was administered. The patient died of cancerous peritonitis 5 months later. In this case, exceedingly rapid metastasis to the spleen occurred, despite the administration of vigorous treatment. Here, we review SFT/HPC incidence, treatment, and outcomes to better understand this rare malignancy.

Invasiveness is associated with metastasis and decreased survival in hemangiopericytoma of the central nervous system.

Meningeal hemangiopericytoma (m-HPC) is a rare tumor of the central nervous system (CNS), which is distinguished clinically from meningioma by its tendency to recur and metastasize. The histological classification and grading scheme for m-HPC is still evolving and few studies have identified tumor features that are associated with metastasis. All patients at our institution with m-HPC were assessed for patient, tumor, and treatment characteristics associated with survival, recurrence, and metastasis. New findings were validated using the SEER database. Twenty-seven patients were identified in our institutional records with m-HPC with a median follow-up time of 85 months. Invasiveness was the strongest predictor of decreased overall survival (OS) and decreased metastasis-free survival (MFS) (p = 0.004 and 0.001). On subgroup analysis, bone invasion trended towards decreased OS (p = 0.056). Bone invasion and soft tissue invasion were significantly associated with decreased MFS (p = 0.001 and 0.012). An additional 315 patients with m-HPC were identified in the SEER database that had information on tumor invasion and 263 with information on distant metastasis. Invasion was significantly associated with decreased survival (HR = 5.769, p = 0.007) and metastasis (OR 134, p = 0.000) in the SEER data. In this study, the authors identified a previously unreported tumor characteristic, invasiveness, as the strongest factor associated with decreased survival and metastasis. The association of invasion with decreased survival and metastasis was confirmed in a separate, larger, publicly available database. Invasion may be a useful parameter in the histological grading and clinical management of hemangiopericytoma of the CNS.

Surgical resection of sinonasal hemangiopericytoma involving anterior skull base: Case reports and literature review.

Hemangiopericytomas are soft tissue tumors composed of pericytic cells that are characterized by their "staghorn" vascular branching and their variable clinical presentation. Fifteen to 25% of all HPC occur in the head and neck, with only 5% found in the nose or paranasal sinuses. Sinonasal hemangiopericytoma (SNHPC) is considered distinct from its soft tissue counterpart - the former showing a more uniform cellular organization, has convincing pericytic differentiation and is associated with a far better prognosis. With less than 200 cases of SNHPC reported in the literature, only limited assumptions can be made about this rare tumor. The purpose of this article is to add to the growing body of literature on this disease. We report two new cases of SNHCP - both in female patients who presented with epistaxis and anosmia. Pulsatile vascular masses were visualized with nasal endoscopy - one in the left middle meatus and the second one near the cribriform plate. CT and MRI studies show enhancing masses in the left nasal cavities with thinning and erosion of the skull base. Diagnoses were confirmed by pathology which reported spindle cell neoplasm staining positively for VEGF, NSE, factor XIIIa, S-100 protein, and CD34, and negative for actin, desmin, CD31, and pankeratin, consistent with hemangiopericytoma. In one patient, embolization of the sphenopalatine and labial artery as well as pre-operative radiation therapy was performed before complete endoscopic resection was undertaken. The second patient had a tumor invading the skull base, so a craniofacial resection was performed. Both patients remained free of disease two years after surgery. Review of the literature and treatment options are discussed.

CNS Hemangiopericytoma: A Systematic Review of 523 Patients.

BACKGROUND: Central nervous system (CNS) hemangiopericytomas are rare mesenchymal tumors of the brain. In the absence of randomized clinical trials or large studies, the only information we have about the natural history and the management is from isolated clinical case series. They have suggested that surgery is beneficial, with conflicting results on the role of complete resection and adjuvant radiation. We have conducted a systematic review of clinical case series of CNS hemangiopericytoma analyzing the biology of the tumor and the best follow-up and management strategy. METHODS: Fifteen pertinent clinical case series on newly diagnosed CNS hemangiopericytoma were selected by a review of literature. A total of 523 patients were analyzed for age, sex, mode of recurrence and metastases, and survival after complete/incomplete resection with or without radiation. RESULTS: The mean age was found to be 44.17 (±3.59) years. The incidence was higher in male individuals younger than 45 years and in older female individuals. Complete resection and adjuvant radiation significantly improved survival in comparison with incomplete resection and no radiation, respectively (P<0.0001). Furthermore, a significant trend of the tumor to recur locally compared with extraneural and neural axis metastases was noted (P<0.0001). The mean time for distant metastases was seen to be 91.33 (±12.66) months. CONCLUSIONS: Complete resection followed by adjuvant radiation improves survival. Extraneural metastases, especially to lung, bone, and liver, are not uncommon and can occur late in the disease course for which continued follow-up is required. There is also a need to establish a systemic treatment regimen to control the distant metastases.

Hemangiopericytomas in the Central Nervous System: A Multicenter Study of Korean Cases with Validation of the Usage of STAT6 Immunohistochemistry for Diagnosis of Disease.

BACKGROUND: Hemangiopericytoma (HPC) in the central nervous system (CNS) is a rare disease with distinctive biological/clinical characteristics compared with meningioma. METHODS: Cases of HPCs of the CNS were collected, and clinicopathological records were retrospectively reviewed and analyzed. Immunohistochemistry (IHC) for proliferative markers (Ki-67, PHH3) and STAT6 were performed. RESULTS: A total of 140 cases were collected, with mean follow-up of 77 months (median 58.8 months; range 0.53-540.5 months). 1-, 5-, 10-, and 20-year survival rates were 99.1, 94.0, 74.4, and 61.9 %, respectively. Thirty-nine patients (27.9 %) had recurrent disease. Mean and median times to recurrence were 62.9 and 47.3 months with 1-, 5-, 10-, and 20-year recurrence-free survival rates of 98.3, 78.3, 50.1, and 11.0 %, respectively. Thirteen patients (9.3 %) developed extracranial metastases. No adjuvant radiation therapy, higher histologic grades, failure of gross-total resection, and cases with gamma-knife surgery (GKS) were factors associated with shorter disease-free survival (log-rank test, p = 0.02, 0.00, 0.02, 0.00), among which high histologic grade and cases with GKS were significant in multivariable analysis. Strong nuclear STAT6 expression was noted in HPCs in 62 cases of HPCs (60/62, 96.8 %), whereas diffuse weak positivity was demonstrated in all meningioma cases. CONCLUSIONS: The survival rate in patients with HPC of the CNS is comparable to that of previously reported series. Recurrence remains a critical clinical issue of the disease. Identification of NAB2-STAT6 fusion transcript with surrogate IHC marker is a valuable diagnostic tool in the differential diagnosis of the disease.

[Rib Metastasis from Intracranial Hemangiopericytoma: Report of a Case].

A 65-year-old man had undergone the surgical treatment for intracranial hemangiopericytoma(HPC) in 2011. In June 2013, the X-ray abnormality in health examination was pointed out. Chest Computed tomography shows a 30 mm-sized tumor lesion with bone destruction in the 6th left rib bone. Fluorodeoxyglucose-positron emission tomography revealed no lesion except for the tumor. Surgical resection of the rib tumor was performed in July 2013. Pathologically it was diagnosed as bone metastasis of HPC. The postoperative course was uneventful, but multiple bone metastases were found 6 months after surgery.

Early magnetic resonance imaging biomarkers to predict local control after high dose stereotactic body radiotherapy for patients with sarcoma spine metastases.

BACKGROUND CONTEXT: Recent advances in image guidance and stereotactic body radiotherapy (SBRT) have resulted in unprecedented local control for spinal metastases of all histologies. However, little is known about early imaging biomarkers of local control. PURPOSE: This study aimed to identify early magnetic resonance imaging (MRI) biomarkers to predict local control after SBRT for patients with sarcoma spine metastases. STUDY DESIGN/SETTING: This study used a retrospective case series at a large tertiary cancer center. PATIENT SAMPLE: From 2011 to 2014, 9 consecutive patients with 12 metastatic sarcoma lesions to the spine were treated with SBRT and underwent evaluation with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) both pre- and post-SBRT. OUTCOME MEASURE: Changes in perfusion metrics, including the wash-in rate constant (Ktrans), plasma volume (Vp), composite multiparametric magnetic resonance imaging (mpMRI) score, bi-dimensional tumor size, and a graded response assessment were performed and correlated to local control. METHODS: All measurements were independent and blinded by two neuroradiologists. R2 statistics were performed to document correlation, and two-tailed t tests were used to compare groups. p<.05 was deemed statistically significant. RESULTS: The median time from SBRT until posttreatment MRI was 57 days. Local failure developed in one lesion (8.3%) 10 months after SBRT. The Vp mean, Ktrans mean, Vp max, and Ktrans max were significantly decreased post-SBRT as compared with pre-SBRT (58.7%, 63.2%, 59.0%, and 55.2%; all p-values <.05). Bi-dimensional tumor measurements demonstrated an average increase in size across the cohort, and 50%, 25%, and 25% of the treated lesions demonstrated features of "worsening," "no change," or "improvement," respectively, by both radiologists' graded impressions. There was good inter-reader reliability for both size and subjective disease response scores (R2=0.84). The mpMRI score had 100% accuracy in predicting local control at time of last follow-up. There was no apparent correlation with size changes compared with the mpMRI score change post-SBRT (R2=0.026). CONCLUSIONS: We report the first analysis on the utility of DCE-MRI for metastatic sarcoma spine metastases treated with SBRT. We demonstrate that early assessment at 2 months post-SBRT using size and subjective neuroradiology impressions is insufficient to judge ultimate disease progression, and that a combination of perfusion parameters provides excellent correlation to local control.

Living-Donor Liver Transplantation for Hepatic Metastasis From Meningeal Hemangiopericytoma: A Case Report.

We report the case of a 58-year-old man referred to our hospital for liver tumor treatment. The patient had a history of neurosurgery for a meningeal hemangiopericytoma 16 years previously. Pre-operative imaging revealed a hypervascular tumor extending from Couinaud segment 4 to segment 8 of the liver, measuring 95 mm in diameter, indicating an atypical hepatocellular carcinoma. Because right trisectionectomy of the liver was considered to be high risk, living-donor liver transplantation (LDLT) was indicated. After transcatheter arterial embolization, LDLT was performed with the use of a left-lobe liver graft from the patient's son. Post-operative histological findings of the liver tumor were identical to those for meningeal hemangiopericytoma, therefore the patient was diagnosed with meningeal hemangiopericytoma that had metastasized to the liver. After LDLT, the patient had a healthy, active life for 2 years; then, a subcutaneous relapse was discovered in the left chest. The patient did not undergo any systemic chemotherapy in response to the relapse. After thoracic and orthopedic surgeries and radiotherapy for multiple metastases, the patient died 5 years and 5 months after LDLT. LDLT could be an effective treatment for localized metastatic hemangiopericytoma in the liver, but it should be indicated only for carefully selected patients.

NAB2-STAT6 fusion gene analysis in two cases of meningeal solitary fibrous tumor/hemangiopericytoma with late distant metastases.

We present two cases of meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) with immunohistochemistry of STAT6 and analysis of NAB2-STAT6 fusion genes. Case 1 was a 37-year-old male with a left middle fossa tumor; case 2 was a 68-year-old female with a cerebellar tumor. They showed late metastasis to the lung or bone 8 or 13 years, respectively, after the first surgery. Histology of both primary and metastatic tumors showed a cellular hemangiopericytomatous pattern with nuclear atypia. The primary tumors showed nuclear staining of STAT6, but both metastatic tumors showed nuclear and cytoplasmic STAT6. DNA sequencing revealed two kinds of NAB2-STAT6 fusion genes. One consisted of exon 6 of NAB2, intron 6 of NAB2, and the middle of exon 17 of STAT6 (observed in the primary and metastatic tumors of case 1); the other consisted of exon 6 of NAB2 and the beginning of exon 17 of STAT6 (observed in the metastatic tumor of case 2). The primary tumor of case 2 had both fusion genes. To the best of our knowledge, we are the first to report NAB2-STAT6 fusion gene analysis in primary and metastatic meningeal SFT/HPCs and a case showed different fusion gene status in the metastatic tumor.

Haemangiopericytoma of the jaw.

Haemangiopericytoma (HPC) is a vascular tumour which originates in the pericytes of vessels and therefore it may occur at any site, but it is very uncommon in the jaw. From January 2000 to December 2011, a retrospective analysis of nine consecutive patients with HPCJ was performed. There were five patients with a primary tumour and four patients with a recurrent tumour. Of the nine patients, eight were male and one female. Their ages ranged from 23 years to 51 years, with a median age of 38 years. The tumours were located in the mandible in six patients and in maxilla in three cases. The median course of disease was 7.6 months (range 2-12 months). All patients underwent surgery. Two patients had postoperative adjuvant radiotherapy, and two cases were given postoperative adjuvant chemotherapy. The median follow-up period was 49 months (10-101 months). One patient suffered from lumbar metastasis, while another case had metastasis at local and multiple distant sites, and eventually died. There was no local recurrence or metastasis in other seven cases. HPCJ are rare and the clinical characteristics are not specific. The first choice of treatment is radical surgery. Adjuvant radiotherapy may be effective to improve the prognosis of HPCJ.

Pancreatic metastases of cerebellar hemangiopericytoma occurring 24 years after initial presentation: report of a case.

Hemangiopericytoma (HPC) preferentially developing in soft tissues and the meninges has been gradually recognized to be an aggressive, highly metastatic tumor. We herein report the case of a 65-year-old male with pancreatic metastases of cerebellar HPC that developed following two resections of intracranial local recurrent foci, 24 years after the initial craniotomy and 7 years after resection of metastases to the lungs and kidneys. Follow-up abdominal computed tomography scanning and magnetic resonance imaging revealed a solitary tumor in the pancreatic body. Since no other recurrent foci were detectable, distal pancreatectomy was performed. Another metastasis was incidentally found in the resected pancreas. Both foci were pathologically proven to be metastases of HPC. Among the 12 reported cases of pancreatic metastases of HPC, including ours, this case showed the longest duration between initial onset and the development of pancreatic metastases, suggesting that providing long-term follow-up is necessary for HPC patients.

Metastatic retroperitoneal hemangiopericytoma.

Hemangiopericytomas are rare mesenchymal lesions arising from pericytes within the walls of capillaries. They often have an unpredictable course. We present a case of a large retroperitoneal hemangiopericytoma in a 65-year-old woman who initially presented with upper gastrointestinal discomfort. Following exptirpative surgery, pathology was consistent with hemangiopericytoma of low malignant potential. Widespread metastasis was discovered on follow up imaging, 17 months following surgery. To our knowledge, this is the first case report demonstrating a primary retroperitoneal hemangioperictoma with confirmed metastases.

[Primary left atrial hemangiopericytoma. Report of one case]. / Hemangiopericitoma de aurícula izquierda. Caso clínico.

We report a 41-year-old male presenting with progressive dyspnea lasting one month. A CAT scan disclosed a left atrial mass, that was surgically excised. The pathological study of the surgical piece showed a primary hemangiopericytoma. One month later, the patient consulted for cervical pain and a positron emission tomography showed multiple metastases. The patient died two months later.

Malignant fat-forming solitary fibrous tumor (so-called "lipomatous hemangiopericytoma"): clinicopathologic analysis of 14 cases.

Fat-forming solitary fibrous tumor is a rare variant of solitary fibrous tumor (SFT). Generally regarded as benign, very few fat-forming SFTs with malignant histologic features have been reported. Here, we report 14 histologically malignant fat-forming SFTs to better characterize this subset. Seven patients were female and 7 were male, with ages ranging 20 to 93 years (median, 57 y). Five tumors were located in the lower limb, 3 in the trunk, 3 in abdominopelvic locations, 2 in the head and neck region, and 1 in the upper limb. The tumor size ranged from 3.4 to 20 cm (median, 8.6 cm). Histologically, all exhibited at least focal hypercellularity; 12 tumors had mitoses >4/10 high-power fields (range, 2 to 37; median, 8), 12 showed at least moderate atypia, and 8 showed necrosis. It should be noted that 7 tumors contained only mature adipose tissue, whereas 5 contained multivacuolated lipoblasts and 2 had areas resembling atypical lipomatous tumor (ALT). Immunohistochemically, CD34 and CD99 were positive in most cases (11 of 14 and 8 of 10, respectively); MDM2 and CDK4 were both negative in all 4 cases tested (including both tumors with ALT-like areas). Follow-up data from 10 cases (median duration, 47.5 mo; range, 5 to 76) showed 2 patients with multiple metastases (both to lung and bones, and 1 each to breast and to soft tissue), both of whom died of disease. In conclusion, fat-forming SFTs exhibiting malignant histologic features have potential for aggressive behavior. The presence of lipoblasts and/or ALT-like areas, although described in some "benign" examples of fat-forming SFT, seems much more common in the malignant subset and may prompt a careful search for morphologic evidence of malignancy in any case of fat-forming SFT.

Primary malignant solitary fibrous tumor/hemangiopericytoma of the parotid gland / Tumor fibroso solitario maligno primario/hemangiopericitoma de la glándula parótida

Solitary fibrous tumor (SFT) was first described in the pleura by Lietaud in 1767; later in 1870, Wagner described the localized nature of this type of tumor and Klemperer and Rabin classified pleural tumors into two types: diffuse mesotheliomas and localized mesotheliomas. Recent years have seen the redefinition of this neoplasm, due to better technology; it is now proven that this neoplasm may have multiple different extrapleural origins including the head and neck regions. This diversity of locations is related to the particular mesenchymal histogenesis of SFT which allows its development from very unusual sites such as the salivary glands (SGs). In this particular site, this neoplasm is very infrequent and most of reported cases refer to benign disease, with just one case informed so far of primary malignant SFT (AU)

El tumor fibroso solitario (TFS) fue primeramente descrito en la pleura por Lietaud en 1767; posteriormente en 1870, Wagner describió la naturaleza localizada de este tipo de tumor y Klemperer y Rabin, en 1931, clasificaron los tumores pleurales en dos tipos: mesoteliomas difusos y mesoteliomas localizados. En los últimos años se ha redefinido esta neoplasia, debido a la mejora de las tecnologías; ahora se ha probado que puede tener múltiples y diferentes orígenes extra-pleurales, incluyendo la región de cabeza y cuello. Esta diversidad de localizaciones se relaciona con la histogénesis mesenquimal particular del TFS, que permite su desarrollo desde localizaciones muy inusuales tales como las glándulas salivares (GS). En esta localización particular este tumor es muy infrecuente, y muchos casos reportados se refieren a una enfermedad benigna, con un único caso informado hasta la fecha de TFS maligno primario (AU)