Central Nervous System Solitary Fibrous Tumor Research Articles

Mutation of Tp53 in a Patient with Aggressive Central Nervous System Solitary Fibrous Tumor/Hemangiopericytoma

Introduction: Central Nervous System (CNS) Solitary Fibrous Tumor (SFT) / Hemangiopericytoma (HPC) is a fibroblastic mesenchymal tumor of the meninges that accounts for < 1% of intracranial tumours. The natural history of CNS SFT / HPC is characterized by a high rate of local (60%) and distant (20%) failure following gross total resection (GTR), and treatment options are limited. The identification of new genomic markers could be of interest to improve the understanding and management of CNS SFT / HPC. We present the results of a search for molecular alterations by next-generation sequencing (NGS) in a patient diagnosed with CNS SFT / HPC who experienced rapid distant failure. Case Description: A 64-year-old Caucasian man was diagnosed with a right hemisphere extra-axial frontal tumor after being referred for persistent headaches in October 2017. The patient underwent surgical resection followed by adjuvant radiation therapy of the operative cavity. A diagnosis of grade III HPC of the CNS was established. A diffuse metastatic recurrence with multiple bone lesions occurred rapidly after the initiation of radiation therapy. In July 2018, a CT-guided biopsy of the left iliac crest confirmed a highly proliferative metastatic recurrence and a FoundationOne CDx TM test was performed, which showed a somatic mutation of the tumor suppressor gene TP53 (Tumor Protein p53) (R175H). The microsatellite status was stable and the Tumor Mutational Burden (TMB) was low (1 Muts/Mb). A massive disease evolution of the disease occurred in September 2018. The patient died in November 2018 after neurological decline. Conclusion: This case report shows that an anatomopathological examination alone is insufficient to correctly classify these rare tumors and predict their aggressiveness. In this case report, the somatic mutation of TP53 (R175H) was associated with a very poor prognosis (survival of 13 months). Further studies including systematic NGS of CNS SFT / HPC are warranted to investigate the role of TP53 in prognostic assessment to adapt future treatment strategies.

Solitary fibrous tumor/hemangiopericytoma of central nervous system: a clinicopathologic analysis of 71 cases

Objective: As solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) share the same molecular genetics features, the 2016 WHO classification of central nervous system (CNS) tumors had created the combined term SFT/HPC and assigns three grades. This study aims to investigate the clinicopathologic characteristics, diagnosis, differential diagnosis and prognosis of CNS SFT/HPC. Methods: Seventy-one cases of CNS SFT and HPC were retrospectively reclassified and studied. Histopathological, immunohistochemical and imaging features were analyzed. The follow-up data were analyzed. Results: There were 37 male and 34 female patients. The median age was 48 years (range, 3-77 years). Twelve cases (17%) were WHO grade Ⅰ, 26 (37%) were WHO grade Ⅱ and 33 (46%) were WHO grade Ⅲ. Microscopically the tumor could show traditional SFT phenotype, HPC phenotype or mixed phenotype. Immunochemically, 97%(69/71) were positive for STAT6, with 96%(66/69)showing diffuse strong staining. Approximately 90% were diffusely positive for bcl-2, CD99 and vimentin. The expression rate of CD34 decreased with increasing tumor grade, and the mean expression rate was 78%. SSTR2a was variably expressed in 10% (7/71) of cases including one case showing strong cytoplasmic staining. A few cases expressed EMA, CD57 and S-100 focally. The Ki-67 index ranged from 1% to 50%. Thirty four patients were followed up for 8-130 months; 12 patients(35%)had recurrences, and two (6%) had liver metastases. Conclusions: CNS SFT/HPC is relatively uncommon. There was significant morphological overlap or transition between different grades. STAT6 is a specific marker for the diagnosis of this tumor. Surgical resection is the preferred treatment. WHO grade Ⅱ and Ⅲ SFT/HPC show rates of local recurrence and systemic metastasis, with liver being the most common site of extracranial metastasis.

Solitary Fibrous Tumor of Central Nervous System: Clinical and Prognostic Study of 24 Cases.

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that occasionally occur in the central nervous system (CNS). It is difficult to fully understand their clinical characteristics, partly due to a limited number of reported cases. We reviewed 24 patients admitted to our institution between 2009 and 2016 with CNS solitary fibrous tumors. We reviewed and analyzed patient profiles, such as demographics, presentations, imaging studies, extent of resection, and adjuvant treatment. Differences between malignant and benign SFTs were assessed using the χ2 test or Student's t-test. Kaplan-Meier analysis was used to estimate the disease-free survival (DFS) rate. The multivariate Cox regression analysis was performed to evaluate the possible predictive value of the DFS rate of the previously mentioned covariates. A total of 13 men and 11 women were enrolled in the study (the average age was 43). The median follow-up time was 58 months. Twenty-one patients underwent gross total resection (GTR), and 3 patients received a subtotal resection (STR). The tumors in 15 patients (62.5%) were atypical or malignant. One patient (4.2%) suffered SFT-related death (multiple organ failure by tumor metastasis), and 3 patients (12.5%) experienced tumor recurrence. We found that a large tumor size (≥10 cm, P < 0.001) and STR (P < 0.001) were negatively associated with the DFS rate. CNS SFTs are rare, slow-growing, less aggressive, and recrudescent tumors. Complete resection is the most effective therapy. Large tumor size and STRs might shorten DFS time.

Analyses of prognosis-related factors of intracranial solitary fibrous tumors and hemangiopericytomas help understand the relationship between the two sorts of tumors.

Increasing evidence has suggested a close relationship between solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) in the central nervous system (CNS). However, CNS SFTs differentiate from HPCs in their clinical behavior and patient prognoses. Analyses of prognosis-related factors can help clarify the relationship between SFT and HPC. The intracranial SFT and HPC cases treated in our departments from January 2002 to December 2012 were retrospectively reviewed. The SFT and HPC cases were also combined into an SFT/HPC group. The factors associated with patient progression-free survival (PFS) and overall survival (OS) were statistically analyzed using uni- and multivariate analyses. Fifty-eight intracranial SFT/HPC patients including 38 SFT patients and 20 HPC patients were treated during this period. The "Marseille grading" evaluated upon the histological aggressive phenotypes was applied in this study. The grading reflected a malignant progression ranging from "conventional" SFTs (grade I) to WHO III HPCs (grade III), and grade was negatively correlated with the PFS and OS of the SFT, HPC and SFT/HPC patients (P < 0.05).The multivariate analyses revealed that gross total resection (GTR) was significantly positively correlated with PFS and OS in the SFT, HPC and SFT/HPC patients and that radiotherapy was significantly positively correlated with PFS in the HPC and SFT/HPC patients (P < 0.05). In conclusion, the intracranial SFTs and HPCs share common prognostic factors including extent of surgery and pathology, moreover, the histological grading of the aggressive phenotypes supports the unifying of the CNS SFT and HPC into one tumor entity of SFT/HPC.

Solitary Fibrous Tumor/Hemangiopericytoma Dichotomy Revisited: A Restless Family of Neoplasms in the CNS.

Solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) both entered the literature as separate entities in the early to mid 1900s. In contrast to their central nervous system (CNS) counterparts, there has been a tendency to consider these 2 entities as 1 since the early 1990s, as soft tissue SFT gradually included the tumors previously diagnosed as HPC. The most recent World Health Organization (WHO) classification of the tumors of soft tissue considered the term HPC obsolete, and places all such tumors within the extrapleural SFT category. In contrast, CNS SFT and HPC continue to be regarded as different entities in the latest version of the WHO CNS tumor classification. A change in this approach is currently being considered for the upcoming revision of the WHO scheme, but it is not quite clear whether such a change will be as drastic as the one adopted by the soft tissue and bone tumor working group. This article focuses on the historical evolution of these 2 labels as primary CNS neoplasms, and reviews their differences and similarities in terms of clinical, pathologic, and molecular features.

Intracranial solitary fibrous tumors: A report of two cases and a review of the literature.

Solitary fibrous tumors (SFTs) are uncommon, with the pleura as a site of predilection. Central nervous system SFTs, particularly intracranial SFTs, are extremely rare. The lesions are generally benign and localized, and surgery is the main therapeutic solution. The current study reports the cases of a patient who presented with right haunch pain, right leg weakness and paresthesias for several months, and a patient with a history of unexpected loss of consciousness. Magnetic resonance imaging revealed the presence of lesions, with a spindle cell morphology evident on pathological examination. The immunohistochemical examination demonstrated a strong immunoreaction for cluster of differentiation 34, which supported the diagnosis of an SFT. Following a near-total resection, the patients had a good neural prognosis. The present study also provides a literature review, discussing the imageological and pathological characteristics of SFT, and the diagnostic methods that aid in distinguishing the entity from other spindle-cell central nervous system tumors.

Myxoid Solitary Fibrous Tumor of the Central Nervous System

Solitary fibrous tumors (SFTs) most commonly occur in the pleura, but may also occur in the central nervous system (CNS). Among the numerous cases of CNS SFT that have been reported, totaling to more than 220 cases, the myxoid SFT of the CNS has been the least recognized and most misleading subtype.1 Differential diagnosis from chordoid or myxo-chordoid meningioma, myxoid peripheral nerve sheath tumor, metastatic or primary low-grade fibromyxoid sarcoma, primary intracranial myxoma, and metastatic tumor from a cardiac primary tumor is therefore necessary. Here, we present a case of a myxoid SFT located in the tentorium cerebelli. A 45-year-old woman presented with headache, general weakness, and impaired vision. A magnetic resonance imaging scan revealed a lunulating, contoured, enhancing mass measuring 7.0×6.0×2.0 cm with hemorrhagic foci, located in the right posterior parietal and temporooccipital convexities. Under the diagnosis of meningioma, open craniotomy, right parietotemporooccipital, and subtotal tumor removal was performed. Upon observation, many firm, rubbery, and bosselated tumor fragments, tan-white in color, were identified. The cut surface was relatively homogeneous, with a whitish fibrotic appearance and softer areas of gelatinous myxoid change, approximately 50%. Necrotic areas were not observed. Microscopic examination revealed a predominantly hypocellular area in the myxoid stroma, intervening with foci of a morphologically typical, densely cellular SFT with spindle cells and collagenous stroma (Fig. 1). In the hypocellular and myxoid areas, a proliferation of cytologically bland spindled cells was randomly arranged in a loose myxoid matrix, forming interconnecting strands, and resulting in degeneration. The neoplastic cells had oval to elongated nuclei, with evenly distributed chromatin, inconspicuous nucleoli, and scant pale cytoplasm. Immunohistochemically, the tumor cells showed a strong expression of CD34, vimentin, Bcl2 and CD99, but were negative for epithelial membrane antigen (EMA), pan-cytokeratin, and glial fibrillary acidic protein (GFAP). The Ki-67 labeling index was lower than 4%. On the basis of these findings, the final diagnosis was myxoid SFT. Fig. 1 Histologic findings. Myxoid stroma with focal ropy collagen in a rich vascularized tumor (A), moderately cellular area exhibiting spindle cells and collagenous stroma (B), and strong immunoreactivity for CD34 (C). Myxoid SFT of the CNS is an extremely rare tumor and differential diagnosis may be difficult to achieve owing to confusion with several other myxoid spindle cell neoplasms. Indeed, myxoid SFT of the CNS must be differentiated from chordoid or myxo-chordoid meningioma, myxoid peripheral nerve sheath tumor, metastatic or primary low-grade fibromyxoid sarcoma, primary intracranial myxoma, meningeal hemangiopericytoma and metastatic tumor from a cardiac primary. Immunohistochemistry has proven to be a useful tool in attaining an accurate diagnosis. SFT of the CNS commonly shows strong positivity for CD34, Bcl2, and vimentin, but is negative for S-100 protein, GFAP, and EMA. Negativity for S-100 rules out chordoid or myxo-chordoid meningioma (vimentin+/EMA+/CD34+/S-100-), myxoid peripheral nerve sheath tumor (vimentin+/S-100+/EMA-/CD34-), metastatic or primary low-grade fibromyxoid sarcoma, and primary intracranial myxoma. Positivity for CD34 and Bcl2 may rule out the meningeal hemangiopericytoma (vimentin+/EMA-/CD34-/Bcl2-).2 Through clinical correlation, metastatic cardiac myxoma may be easily suspected. The histogenesis of SFT is still unclear; however, tumor cells were shown to share similar histological features with fibroblasts. Microscopically, there are 3 common elements that appear in SFTs: spindle cells, a dense collagenous matrix, and prominent blood vessels.1 Spindle cells have oval nuclei with scant cytoplasm, and the cell borders are unclear. They may arrange into fascicles with no specific direction, creating a swirling pattern. The collagenous area is variable in size, and takes the form of ropy collagen. Cell density also varies, with hypercellular and hypocellular areas.3 Our case also shows a predominantly hypocellular area with myxoid stroma, and a hypercellular area with collagenous stroma. When fibrous tumors with myxoid nature involve the CNS, proper immunostaining and histologic differentiation should be done for differential diagnosis.

Solitary fibrous tumors of the central nervous system: report of five cases with unusual clinicopathological and outcome patterns

This is a retrospective study of 11 patients harboring a solitary fibrous tumor (SFT) of the central nervous system (CNS), with special emphasis on unusual clinicopathological and outcomes patterns. Between 2000 and 2008, 11 patients harboring CNS SFTs were treated at our institution. Patient charts were retrospectively reviewed and tumor location, clinical presentation, imaging characteristics, extent of resection, dural origin, pathological features, adjuvant treatment, and follow-up data were collected, focusing on five atypical cases (four intracranial and one within the spine). One intracranial SFT arose from the sella turcica and relapsed threefold during the 6 years following partial removal. Disease progressed as successive isolated local recurrences treated by subsequent surgical interventions and gamma-knife radiosurgery. The MiB-1 labeling index analysis showed a steady increase in these sequential recurrences (ranging from less than 3% up to 6%) without obvious malignant transformation. The second SFT occurred in the cerebellopontine angle and exhibited a high MiB-1 index (10%) without noticeable features of malignancy. It relapsed twice during the 5 years following gross total resection without demonstrating a more aggressive histological pattern. The third SFT arose from the cerebellar tentorium, widely invaded the lateral sinus and adjacent bone, had a low MiB-1 index, and has not recurred within the 2 years after incomplete resection. The two remaining SFTs presented with unusual clinicoradiological features. We described a extremely rare case of intraventricular SFT, and a case of extradural SFT of the thoracic spine (T8-T9) radiologically consistent with a schwannoma. Immunohistochemistry confirmed that all tumors were SFTs. These atypical presentations gave us the opportunity to provide further information about the variability of the clinicoradiological patterns and natural histological course of CNS SFTs.

Solitary Fibrous Tumor Arising from Cranial Nerve VI in the Prepontine Cistern: Case Report and Review of a Tumor Subpopulation Mimicking Schwannoma

The authors present a report of a solitary fibrous tumor (SFT) arising from the intradural component of the VIth cranial nerve as it travels through the prepontine cistern. SFTs of the central nervous system are extremely rare entities that clinically masquerade as dural-based lesions, such as meningiomas or hemangiopericytomas. Because of their infrequency and clinical similarity to other central nervous system (CNS) lesions, diagnosis is largely dependent on pathological features. In this study, the authors define a subpopulation of SFTs that seem to arise directly from nerve, rather than meninges, and clinically mimic the appearance of a schwannoma. The patient was a 29-year-old woman with a several-month history of progressive right arm and leg numbness and mild hemiparesis, with the development of diplopia 2 weeks before admission. Outside imaging revealed a 3.9-cm mass in the prepontine cistern with extension into Meckel's cave and the cavernous sinus, resulting in significant brainstem compression. The patient underwent preoperative angiography with embolization of feeding vessels off of the left meningohypophyseal trunk. The patient was then taken to the operating room by a combined neurosurgical and ear, nose, and throat team, where the patient underwent a retrolabyrinthine/subtemporal craniotomy for tumor resection. During resection of the prepontine component, the tumor was identified as originating from the left Cranial Nerve VI as it traversed through the prepontine cistern. Resection of the tumor component involving the cavernous sinus and Meckel's cave was deferred for follow-up treatment with intensity-modulated radiation therapy. Pathological examination revealed tissue consistent with the diagnosis of SFT. SFTs involving the CNS are rare entities that are almost always diagnosed after tissue is obtained because of their clinical and radiographic similarity to meningiomas. This patient had an SFT masquerading as a VIth cranial nerve schwannoma. Although the natural history of SFTs in the CNS is not completely understood, correct diagnosis is important, given the rate of recurrence found in the more common pleural-based SFT and examples of CNS SFTs with malignant features.

Atypical presentations of solitary fibrous tumors of the central nervous system: an analysis of unusual clinicopathological and outcome patterns in three new cases with a review of the literature

Central nervous system (CNS) solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms recognized less than a decade ago. Approximately 60 cases of SFT have been reported in the central nervous system. We describe three atypical SFTs of the CNS, two intracranial and one within the spine. One intracranial SFT arose from the sella turcica and expanded into the suprasellar areas. It relapsed twice during the 3 years following partial resection, and the MiB 1 labeling index steadily increased without obvious malignant transformation. The second SFT arose from the confluence of the sinuses, widely invaded the lateral sinus and adjacent bones, had a low MiB 1 index and has not recurred after 5 years. The intraspinal tumor occurred at T5-T7 in a patient with multiple café-au-lait spots, was predominantly myxoid and developed a second similar lesion at S3-S5 14 years later. The MiB 1 index was lower in the second tumor. Immunohistochemistry confirmed that all were SFTs. These atypical presentations gave us an opportunity to provide further information about the natural histological course of CNS SFTs.