Schwannoma Research Articles

TGF-β superfamily-induced transcriptional activation pathways establish the RAD52-dependent ALT machinery during malignant transformation of MPNSTs

To study telomere maintenance mechanism (TMM) activation during malignant transformation, we compared neurofibroma (NF) and malignant peripheral nerve sheath tumor (MPNST) in the same patient with type-1 neurofibromatosis (NF1), a total of 20 NF-MPNST pairs in 20 NF1 patients. These comparisons minimized genetic bias and contrasted only changes associated with malignant transformation, while subtracting changes that developed upon the transformation of normal cells to the benign tumor. TGF-β superfamily genes were found to activate the PAX and SOX transcription factors, leading to TMM activation. BMPER activates PAX6 through BMP2 and PAX7 through BMP4; BMP15 activates SOX14; and INHBC activates PAX9 and SOX14. The activated PAX and SOX genes sequentially establish the core architecture of the RAD52-dependent alternative lengthening of telomeres (ALT). Specifically, PAX7 activates the recombinase (RAD52) and a negative regulator (SLX4IP). PAX6 and SOX14 activate positive regulators (BLM and BRCA2, respectively). PAX9 and SOX14 activate RAD9B and FEN1, which are responsible for the stability of homologous recombination intermediates and increase, together with RAD52, the telomere length. Telomere elongation achieved by the activation of PAX7 and PAX9 is associated with a poor prognosis. We demonstrated that TGF-β superfamily-induced transcriptional activation pathways activated the RAD52-dependent ALT during malignant transformation of MPNSTs.

Targeting MERTK on tumour cells and macrophages: a potential intervention for sporadic and NF2-related meningioma and schwannoma tumours

Meningioma and schwannoma are common tumours of the nervous system. They occur sporadically or as part of the hereditary NF2-related schwannomatosis syndrome. There is an unmet need for new effective drug treatments for both tumour types. In this paper, we demonstrate overexpression/activation of TAM (TYRO3/AXL/MERTK) receptors (TAMs) and overexpression/release of ligand GAS6 in patient-derived meningioma tumour cells and tissue. For the first time, we reveal the formation of MERTK/TYRO3 heterocomplexes in meningioma and schwannoma tissue. We demonstrate the dependence of AXL and TYRO3 expression on MERTK in both tumour types, as well as interdependency of MERTK and AXL expression in meningioma. We show that MERTK and AXL contribute to increased proliferation and survival of meningioma and schwannoma cells, which we inhibited in vitro using the MERTK/FLT3 inhibitor UNC2025 and the AXL inhibitor BGB324. UNC2025 was effective in both tumour types with superior efficacy over BGB324. Finally, we found that TAMs are expressed by tumour-associated macrophages in meningioma and schwannoma tumours and that UNC2025 strongly depleted macrophages in both tumour types.

G6PD and ACSL3 are synthetic lethal partners of NF2 in Schwann cells

Neurofibromatosis Type II (NFII) is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent Schwann cell tumors, as well as meningiomas and ependymomas. Unfortunately, few pharmacological options are available for NFII. Here, we undertake a genome-wide CRISPR/Cas9 screen to search for synthetic-lethal genes that, when inhibited, cause death of NF2 mutant Schwann cells but not NF2 wildtype cells. We identify ACSL3 and G6PD as two synthetic-lethal partners for NF2, both involved in lipid biogenesis and cellular redox. We find that NF2 mutant Schwann cells are more oxidized than control cells, in part due to reduced expression of genes involved in NADPH generation such as ME1. Since G6PD and ME1 redundantly generate cytosolic NADPH, lack of either one is compatible with cell viability, but not down-regulation of both. Since genetic deficiency for G6PD is tolerated in the human population, G6PD could be a good pharmacological target for NFII.

Small RNA Deep Sequencing Uncovers microRNAs Associated with Hearing Loss in Vestibular Schwannoma.

To analyze the correlation between the miRNA expression profile in vestibular schwannoma (VS) tumor tissue and preoperative patient's hearing status, using the RNA-seq technique. Nineteen tumor samples were collected from patients operated for VS in a Tertiary Academic Center. Samples were classified into "good hearing" and "poor hearing" study group based on the results of audiometric studies. Tumor miRNA expression was analyzed using high-throughput RNA sequencing (RNA-seq) technique, using NovaSeq 6000 Illumina system. Functional analysis was performed with the use of DIANA miRpath v. 4.0 online tool. The most overexpressed miRNAs in VS samples derived from poor hearing patients belonged to miR 449a/b, miR 15/16-1, and hypoxamiR families. Functional analysis showed that the differentially expressed miRNAs regulate cellular pathways associated with hypoxia, adherence junction functions, and signaling pathways such as Hippo, FOXO, MAPK, and Wnt signaling pathway. Our study identified a specific miRNA expression profile in VS tumor tissues that correlates with hearing impairment. These results suggest potential new molecular mechanisms related to hearing loss in the course of VS. 3 (cohort study) Laryngoscope, 134:3778-3785, 2024.

Development of a vestibular schwannoma tumor slice model for pharmacological testing

BackgroundOur goal was to develop a 3D tumor slice model, replicating the individual tumor microenvironment and for individual pharmaceutical testing in vestibular schwannomas with and without relation to NF2. MethodsTissue samples from 16 VS patients (14 sporadic, 2 NF2-related) were prospectively analyzed. Slices of 350 µm thickness were cultured in vitro, and the 3D tumor slice model underwent thorough evaluation for culturing time, microenvironment characteristics, morphology, apoptosis, and proliferation rates. Common drugs - Lapatinib (10 µM), Nilotinib (20 µM), and Bevacizumab (10 µg/ml) - known for their responses in VS were used for treatment. Treatment responses were assessed using CC3 as an apoptosis marker and Ki67 as a proliferation marker. Standard 2D cell culture models of the same tumors served as controls. ResultsThe 3D tumor slice model accurately mimicked VS ex vivo, maintaining stability for three months. Cell count within the model was approximately tenfold higher than in standard cell culture, and the tumor microenvironment remained stable for 46 days. Pharmacological testing was feasible for up to three weeks, revealing interindividual differences in treatment response to Lapatinib and intraindividual variability in response to Lapatinib and Nilotinib. The observed effects were less pronounced in tumor slices than in standard cell culture, indicating the model's proximity to in vivo tumor biology and enhanced realism. Bevacizumab had limited impact in both models. ConclusionThis study introduces a 3D tumor slice model for sporadic and NF2-related VS, demonstrating stability for up to 3 months, replication of the schwannoma microenvironment, and utility for individualized pharmacological testing.

Plexiform schwannoma: A rare histological entity at a rare site

Plexiform schwannoma is an uncommon Schwann cell tumor, characterized by its multinodular growth with a plexiform histological pattern. Plexiform schwannoma arises from the soft tissues around the head and neck region. Few cases are associated with neurofibromatosis type 2 or schwannomatosis. We present a rare case of this tumor in a 25-year-old man, who presented with a discrete movable, deep seated nodule, associated with pain and tenderness over the spinal region, across the seventh cervical vertebrae with chief complaints of dizziness and vertigo for the last one year.

High-throughput RNA sequencing identifies the miRNA expression profile, target genes, and molecular pathways contributing to growth of sporadic vestibular schwannomas.

To assess the differences in the miRNA expression profile between small (stage I Koos classification) and large solid vestibular schwannoma (VS) tumors, using the RNA-seq technique. Twenty tumor samples (10 small and 10 large tumors) were collected from patients operated for VS in a Tertiary Academic Center. Tumor miRNA expression was analyzed using high-throughput RNA sequencing (RNA-seq) technique, with NovaSeq 6000 Illumina system. Bioinformatics analysis was done using statistical software R. Gene enrichment and functional analysis was performed using miRTargetLink 2.0 and DIANA miRpath 3.0 online tools. We identified 9 differentially expressed miRNAs in large VS samples: miR-7, miR-142 (-3p and -5p), miR-155, miR-342, miR-1269, miR-4664, and miR-6503 were upregulated, whereas miR-204 was significantly down-regulated in comparison to small VS samples. Gene enrichment analysis showed that the most enriched target genes were SCD, TMEM43, LMNB2, JARID2, and CCND1. The most enriched functional pathways were associated with lipid metabolism, along with signaling pathways such as Hippo and FOXO signaling pathway. We identified a set of 9 miRNAs that are significantly deregulated in large VS in comparison to small, intracanalicular tumors. The functional enrichment analysis of these miRNAs suggests novel mechanisms, such as that lipid metabolism, as well as Hippo and FOxO signaling pathways that may play an important role in VS growth regulation.

Whole-Body Positron Emission Tomography with 18F-Fluorodeoxyglucose/Magnetic Resonance Imaging as a Screening Tool for the Detection of Malignant Transformation in Individuals with Neurofibromatosis Type 1

Malignant peripheral nerve sheath tumors (MPNST) are the leading cause of death in Neurofibromatosis type 1 (NF1). They can result from premalignant neurofibromas (NF) including NF with atypia and atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP). Some phenotypic characteristics have been described as associated with their development. The aim was to outline our use of whole-body 18F-FDG-PET/MRI in adults with NF1, especially in the screening of asymptomatic individuals with a higher risk of developing a MPNST, and to study its impact on NF classification (malignant vs premalignant) and MPNST staging over time. Individuals with NF1 who underwent a 18F-FDG-PET/MRI between 2017 to 2021 were included, analyzing separately the screened population. Maximum standard uptake value and diffusion-weighed imaging were assessed. Biopsy/surgery confirmed the diagnosis. In all, 345 18F-FDG-PET/MRI were performed in 241 patients including 149 asymptomatic (62%), but at risk. Eight MPNST in 8 screened individuals (5%), 6 NF with atypia in 4 (3%) and 29 ANNUBP in 23 (15%) were diagnosed. Over time, the proportion of grade 3 MPNST and the malignant/premalignant ratio in screened individuals significantly decreased (p=0.03 and p<0.001, respectively). This study emphasizes the diagnostic and screening performances of whole-body 18F-FDG-PET/MRI in adults with NF1.

Functional interactions between neurofibromatosis tumor suppressors underlie Schwann cell tumor de-differentiation and treatment resistance

Schwann cell tumors are the most common cancers of the peripheral nervous system and can arise in patients with neurofibromatosis type-1 (NF-1) or neurofibromatosis type-2 (NF-2). Functional interactions between NF1 and NF2 and broader mechanisms underlying malignant transformation of the Schwann lineage are unclear. Here we integrate bulk and single-cell genomics, biochemistry, and pharmacology across human samples, cell lines, and mouse allografts to identify cellular de-differentiation mechanisms driving malignant transformation and treatment resistance. We find DNA methylation groups of Schwann cell tumors can be distinguished by differentiation programs that correlate with response to the MEK inhibitor selumetinib. Functional genomic screening in NF1-mutant tumor cells reveals NF2 loss and PAK activation underlie selumetinib resistance, and we find that concurrent MEK and PAK inhibition is effective in vivo. These data support a de-differentiation paradigm underlying malignant transformation and treatment resistance of Schwann cell tumors and elucidate a functional link between NF1 and NF2.

Unbalancing cAMP and Ras/MAPK pathways as a therapeutic strategy for cutaneous neurofibromas.

Cutaneous neurofibromas (cNFs) are benign Schwann cell (SC) tumors arising from subepidermal glia. Individuals with neurofibromatosis type 1 (NF1) may develop thousands of cNFs, which greatly affect their quality of life. cNF growth is driven by the proliferation of NF1-/- SCs and their interaction with the NF1+/- microenvironment. We analyzed the crosstalk between human cNF-derived SCs and fibroblasts (FBs), identifying an expression signature specific to the SC-FB interaction. We validated the secretion of proteins involved in immune cell migration, suggesting a role of SC-FB crosstalk in immune cell recruitment. The signature also captured components of developmental signaling pathways, including the cAMP elevator G protein-coupled receptor 68 (GPR68). Activation of Gpr68 by ogerin in combination with the MEK inhibitor (MEKi) selumetinib reduced viability and induced differentiation and death of human cNF-derived primary SCs, a result corroborated using an induced pluripotent stem cell-derived 3D neurofibromasphere model. Similar results were obtained using other Gpr68 activators or cAMP analogs/adenylyl cyclase activators in combination with selumetinib. Interestingly, whereas primary SC cultures restarted their proliferation after treatment with selumetinib alone was stopped, the combination of ogerin-selumetinib elicited a permanent halt on SC expansion that persisted after drug removal. These results indicate that unbalancing the Ras and cAMP pathways by combining MEKi and cAMP elevators could be used as a potential treatment for cNFs.

Increased CD16a (FcγRIIIA) Expression in The Tumor Microenvironment of Atypical Neurofibromatous Neoplasms of Uncertain Biologic Potential May Be Associated with Progression from Neurofibromas to Atypical Neurofibromas.

Neurofibroma (NF) is a benign tumor in the peripheral nervous system, but it can infiltrate around structures and cause functional impairment and disfigurement. We incidentally found that the expression of CD16a (Fc gamma receptor IIIA) was increased in NFs compared to in non-neoplastic nerves and hypothesized that CD16 could be relevant to NF progression. We evaluated the expressions of CD16a, CD16b, CD68, TREM2, Galectin-3, S-100, and SOX10 in 38 cases of neurogenic tumors (NF, n = 18; atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP), n = 14; and malignant peripheral nerve sheath tumor (MPNST), n = 6) by immunohistochemical staining. In the tumor microenvironment (TME) of the ANNUBPs, CD16a and CD16b expression levels had increased more than in the NFs or MPNSTs. CD68 and Galectin-3 expression levels in the ANNUBPs were higher than in the MPNSTs. Dual immunohistochemical staining showed an overlapping pattern for CD16a and CD68 in TME immune cells. Increased CD16a expression was detected in the ANNUBPs compared to the NFs but decreased with malignant progression. The CD16a overexpression with CD68 positivity in the ANNUBPs potentially reflects that the TME immune modulation could be associated with NF progression to an ANNUBP. Further studies should explore the role of CD16a in immunomodulation for accelerating NF growth.

The frequency of various spinal cord tumors (SCTs) in surgically treated patients at Shiraz Shahid Chamran Hospital from 2012 to 2022

Abstract Aim The incidence of spinal cord tumors (SCTs) in a population considering sex, age, histopathology, and emplacement position of tumors is different between various regions. Therefore, the present study aimed to evaluate the frequency of various SCTs in surgically treated patients in a reference spinal surgery center in Shiraz, Iran. Method Documented information related to 109 SCT patients surgically treated was collected from the archive of Shahid Chamran Hospital (the reference center of spinal cord surgery in the south of Iran) in Shiraz from 2012 to 2022. This information includes demographics, medical history, histology, and position of SCTs within the spinal cord. Result The population of patients included 65 men and 44 women, with a mean age of 44.7 years old. Most patients (26 cases) were in the age group of 50–59 years. Neurological function in most patients (51 cases) was equivalent to level D of the ASIA impairment scale (AIS), and the most common complaints of patients (83 cases) were related to pain. Finally, anatomic and histologic evaluations indicated that intradural and schwannoma tumors were the most common types of tumors, with 64 and 25 cases, respectively. Conclusions In the present study, most of the findings are consistent with the previous reports. Schwannoma and ependymoma tumors were the most common types of SCTs and the most common types of intramedullary tumors, respectively. The sixth decade of life was the most common age of incidence. Neurological function in most patients with SCT was equivalent to levels of D and E of AIS. However, regarding the factor of gender, our results are similar to those of the Asian population. More comprehensive studies in the future likely reveal the probable role of environmental, genetic, and hormonal factors in the etiology of SCTs.

Primary lipoblastic nerve sheath tumor in an inguinal lymph node mimicking metastatic tumor: a case report and literature review

Lipoblastic nerve sheath tumors of soft tissue are characterized as schwannoma tumors that exhibit adipose tissue and lipoblast-like cells with signet-ring morphology. They have been documented to arise in various anatomic locations, including the thigh, groin, shoulder, and retroperitoneum. However, to our knowledge, this tumor has not been previously reported as a lymph node primary. We present herein the first case of a benign primary lipoblastic nerve sheath tumor arising in an inguinal lymph node in a 69-year-old man. Microscopic examination revealed a multinodular tumor comprising fascicles of spindle cells, as well as adipocytic and lipoblast-like signet-ring cell component in the context of schwannoma. Despite the presence of some bizarre cells with nuclear atypia, no obvious mitotic activity or necrosis was observed. Immunohistochemical analysis showed strong and diffuse expression of S-100, SOX10, CD56, and NSE in the spindle cells as well as in the signet-ring lipoblast-like cells and the mature adipocytes. Sequencing analysis of the neoplasm identified six non-synonymous single nucleotide variant genes, specifically NF1, BRAF, ECE1, AMPD3, CRYAB, and NPHS1, as well as four nonsense mutation genes including MRE11A, CEP290, OTOA, and ALOXE3. The patient remained alive and well with no evidence of recurrence over a period of ten-year follow-up.

In Silico Identification of Therapeutic Targets and Novel Drug Candidates for Malignant Peripheral Nerve Sheath Tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive form of sarcomas with a poor prognosis and limited treatment options. Therefore, new therapeutic targets are urgently needed to identify novel drugs. Based on the Gene Expression Omnibus database, an integrated analysis was performed to identify differentially expressed genes (DEGs) in MPNSTs compared to neurofibromas (NFs). Then functional enrichment analyses, protein-protein interaction (PPI) network construction, and hub gene selection were conducted. We explored DEG-guided repurposable drugs to treat MPNST based on the Library of Integrated Network-Based Cellular Signatures (LINCS) database. Furthermore, the binding affinity between predicted drug candidates and the MPNST-associated hub gene was calculated using molecular docking. We identified 89 DEGs in common with all three MPNSTs datasets. In the PPI networks, twist family bHLH transcription factor 1 (Twist1) with higher node degrees was further evaluated as a therapeutic target. Cytochalasin-d, cabozantinib, everolimus, refametinib, and BGT-226 were extracted from the LINCS database, which showed lower normalized connectivity scores (-1.88, -1.81, -1.78, -1.76, and -1.72, respectively) and was considered as drug candidates. In addition, the results of molecular docking between the five drugs and Twist1 showed a binding affinity of -6.61, -7.03, -7.73, -3.94, and -7.07 kcal/mol, respectively. Overall, our results describe the importance of Twist1 in MPNST pathogenesis. Everolimus was also found to be a potential therapeutic drug for MPNSTs.

Spinal intradural extramedullary tumors: microscopic keyhole resection with the focus on intraoperative neurophysiological monitoring and long-term outcome

ObjectiveSpinal schwannomas (SS) and spinal meningiomas (SM) account for most intradural extramedullary (IDEM) tumors. These tumors are usually benign lesions, which generally respond favorably to surgical excision. Few studies up to now tried to determine the long-term outcome after minimally invasive surgery (MIS) with multimodal intraoperative neurophysiological monitoring (IONM) for IDEM tumors. The aim of this study was to present one of the largest case series with special regard to IONM findings and long-term outcome after MIS-keyhole surgery with a tubular retractor system.MethodsBetween January 2013 and August 2018, 87 patients with IDEM tumors who underwent tumor removal surgery via MIS-keyhole approach under multimodal IONM were retrospectively reviewed. The neurological status was assessed using a modified McCormick grading scale pre- and postoperatively. Multimodal IONM consisted of motor evoked potentials (MEP), somatosensory evoked potentials (SEP), and electromyography (EMG). Both short-term and long-term clinical evaluations as well as patients’ medical files were retrospectively analyzed.ResultsSurgeries were performed for resection of SS in 49 patients and SM in 38 patients. Tumor locations were cervical in 16.1%, thoracic in 48.3%, thoracolumbar in 4.6%, lumbar 31%. Critical IONM changes were detected in 9 operations (10.3%) in which there were 2 SEPs, 5 MEPs, and 2 EMG events. Three IONM changes (2 MEPs, 1 EMG) were turned out to be transient change in nature since they were resolved in a short time when immediate corrective actions were initiated. Six patients with permanent IONM changes (2SEPs, 3MEPs, 1EMG event), all deficits had resolved during hospitalization or on short -term follow-up evaluation. Sensitivity, specificity, and positive and negative predicted values of IONM were 100, 96, 67, and 100%, respectively. Gross total resection rate was 100%, and a stable or improved McCormick grade exhibited in all patients. No tumor recurrence and no spinal instability were found in the long-term follow-up evaluation (mean 5.2 ± 2.9 years postoperatively). Overall, 94% of patients were either satisfied or very satisfied with their operation, and 93% patients reported excellent or good general clinical outcome according to Odom’s criteria.ConclusionMIS-keyhole surgery with multimodal IONM for IDEM tumors enables a high level of satisfaction and a satisfying long-term clinical and surgical outcome.

Adrenal and periadrenal schwannoma: histological, molecular and clinical characterization of an institutional case series.

Adrenal schwannoma (AS) and periadrenal schwannoma (PAS) are exceedingly rare Schwann cell tumors that develop from the adrenal medulla and periadrenal peripheral nerves respectively. The underlying genetic events are elusive. We searched our institutional database for AS/PAS cases and reviewed the histology and clinical outcome. Comprehensive molecular work-up was performed. We found reports of 4 AS/PAS cases diagnosed between 1992 and 2022 among the 1248 adrenal lesions submitted for histopathology during the same time period (0.32%). Two patients were male, two were female, and the age span was 59-80 years. Median size was 70 mm (range 50-100 mm), and from a radiology perspective, the lesions were initially suspected of malignant lesions originating from either adrenals or kidneys. Hormonal analyses were normal in all cases. Histologically, three cases were annotated as cellular AS or PAS, and one case was annotated as microcystic AS. Molecular characterization using focused next-generation sequencing did not identify SMARCB1 or NF2 mutations, alterations previously associated to schwannoma at other anatomical sites. The postoperative period was without complications for all patients, and follow-up did not show any signs of relapse or metastatic disease. AS/PAS are rare neoplasms that are most often benign, and the molecular etiology is most likely not related to mutations in established schwannoma-related genes. Since these tumors may be misinterpreted as malignant, knowledge of this entity is essential for radiologists, endocrinologists, surgeons and pathologists.

The comparable tumour microenvironment in sporadic and NF2-related schwannomatosis vestibular schwannoma.

Bilateral vestibular schwannoma is the hallmark of NF2-related schwannomatosis, a rare tumour predisposition syndrome associated with a lifetime of surgical interventions, radiotherapy and off-label use of the anti-angiogenic drug bevacizumab. Unilateral vestibular schwannoma develops sporadically in non-NF2-related schwannomatosis patients for which there are no drug treatment options available. Tumour-infiltrating immune cells such as macrophages and T-cells correlate with increased vestibular schwannoma growth, which is suggested to be similar in sporadic and NF2-related schwannomatosis tumours. However, differences between NF2-related schwannomatosis and the more common sporadic disease include NF2-related schwannomatosis patients presenting an increased number of tumours, multiple tumour types and younger age at diagnosis. A comparison of the tumour microenvironment in sporadic and NF2-related schwannomatosis tumours is therefore required to underpin the development of immunotherapeutic targets, identify the possibility of extrapolating ex vivo data from sporadic vestibular schwannoma to NF2-related schwannomatosis and help inform clinical trial design with the feasibility of co-recruiting sporadic and NF2-related schwannomatosis patients. This study drew together bulk transcriptomic data from three published Affymetrix microarray datasets to compare the gene expression profiles of sporadic and NF2-related schwannomatosis vestibular schwannoma and subsequently deconvolved to predict the abundances of distinct tumour immune microenvironment populations. Data were validated using quantitative PCR and Hyperion imaging mass cytometry. Comparative bioinformatic analyses revealed close similarities in NF2-related schwannomatosis and sporadic vestibular schwannoma tumours across the three datasets. Significant inflammatory markers and signalling pathways were closely matched in NF2-related schwannomatosis and sporadic vestibular schwannoma, relating to the proliferation of macrophages, angiogenesis and inflammation. Bulk transcriptomic and imaging mass cytometry data identified macrophages as the most abundant immune population in vestibular schwannoma, comprising one-third of the cell mass in both NF2-related schwannomatosis and sporadic tumours. Importantly, there were no robust significant differences in signalling pathways, gene expression, cell type abundance or imaging mass cytometry staining between NF2-related schwannomatosis and sporadic vestibular schwannoma. These data indicate strong similarities in the tumour immune microenvironment of NF2-related schwannomatosis and sporadic vestibular schwannoma.

Patient-specific geometrical distortion corrections of MRI images improve dosimetric planning accuracy of vestibular schwannoma treated with gamma knife stereotactic radiosurgery.

To investigate the impact of MRI patient-specific geometrical distortion (PSD) on the quality of Gamma Knife stereotactic radiosurgery (GK-SRS) plans of the vestibular schwannoma (VS) tumors. Three open access datasets including the MPI-Leipzig Mind-Brain-Body (318 patients), the slow event-related fMRI designs dataset (62 patients), and the VS dataset (242 patients) were used. We used first two datasets to train a 3D convolution network to predict the distortion map of third dataset that were then used to calculate and correct the PSD. GK-SRS plans of VS dataset were used to evaluate dose distribution of PSD-corrected MRI images. GK-SRS prescription dose of VS cases was 12Gy. Geometric and dosimetric discrepancies were assessed between the dose distributions and contours before and after the PSD corrections. Geometry indices were center of the contours, Dice coefficient (DC), Hausdorff distance (HD), and dosimetric indices were , , , and doses, target coverage (TC), Paddick's conformity index (PCI), Paddick's gradient index (GI), and homogeneity index (HI). Geometric distortions of about 1.2mm were observed at the air-tissue interfaces at the air canal and nasal cavity borders. Average center of the targets was significantly distorted along the frequency encoding direction after the PSD-correction. Average DC and HD metrics were 0.90 and 2.13mm. Average , and in Gy significantly increased after PSD correction from 16.85 to 17.25, 12.30 to 12.77, and from 8.98 to 9.92. did not significantly change after the correction. Average TC and PCI significantly increased from 0.97 to 0.98, and 0.94 to 0.96. Average GI decreased significantly from 2.24 to 2.15 after PSD correction. However, HI did not significantly change after the correction. The proposed method could predict and correct the PSD that indicates the importance of PSD correction before GK-SRS plans of the VS patients.

SCHWANNOMA OF THE UPPER LIP IN A YOUNG PATIENT: AN UNUSUAL PRESENTATION

Schwannoma (SW), also known as neurilemmoma, is a slow-growing benign neoplasm that originates from Schwann cells. It usually appears as a solitary lesion in the 3rd and 5th decades of life, with no sex predilection. A 16-year-old girl presented an asymptomatic multilobular tumor, measuring 20 × 10 mm, covered by healthy mucosa, located on the right upper lip mucosa. Patient reported that lesion initiated after a trauma to the region causing tooth fracture four years ago. Medical history was not contributive. The possibilities of foreign body reaction and salivary gland tumors were raised. Occlusal and panoramic radiographs showed no alteration, and an incisional biopsy was performed. Histopathological analysis revealed an encapsulated lesion comprised of spindle-shaped cells arranged predominantly in a palisade, involving amorphous eosinophilic areas compatible with the diagnosis of SW. A complete surgical excision was performed, and the patient showed no recurrence after 10 months of follow-up. Support: CAPES. Schwannoma (SW), also known as neurilemmoma, is a slow-growing benign neoplasm that originates from Schwann cells. It usually appears as a solitary lesion in the 3rd and 5th decades of life, with no sex predilection. A 16-year-old girl presented an asymptomatic multilobular tumor, measuring 20 × 10 mm, covered by healthy mucosa, located on the right upper lip mucosa. Patient reported that lesion initiated after a trauma to the region causing tooth fracture four years ago. Medical history was not contributive. The possibilities of foreign body reaction and salivary gland tumors were raised. Occlusal and panoramic radiographs showed no alteration, and an incisional biopsy was performed. Histopathological analysis revealed an encapsulated lesion comprised of spindle-shaped cells arranged predominantly in a palisade, involving amorphous eosinophilic areas compatible with the diagnosis of SW. A complete surgical excision was performed, and the patient showed no recurrence after 10 months of follow-up. Support: CAPES.

Spinal Surgery in Patients with Type-1 Neurofibromatosis: A Comprehensive Review

AbstractType-1 neurofibromatosis (NF1) is a neurocutaneous syndrome classically known as peripheral NF to distinguish it from type-2 NF (central NF). Its main characteristic is the high predisposition to the growth of multiple tumors, which specially arouses the interest of spinal surgeons due to the presence of spinal cord compression and spinal deformities.Considering this, we have performed a comprehensive review, with illustrative cases of the main manifestations of NF1, focusing on the perspective of the spine surgeon. Articles were grouped according to the following subjects: diagnosis, skeletal complications, spinal deformity, and spinal tumors. For all of them, a detailed discussion on pearls for practice was presented.The diagnosis of NF1 is based on the presence of at least two out of seven criteria. Cutaneous findings are very common in NF1, and the most usual tumor is cutaneous neurofibroma (NFB). Plexiform neurofibromas are also found and present a high risk of becoming malignant peripheral nerve sheath tumors (MPNSTs), reducing life expectancy. Astrocytomas, especially pilocytic astrocytomas, are the most common central nervous system tumor, including in the spinal cord. Surgery is necessary to resect as much as possible without adding new neurological deficits. Spinal deformities are also commonly found (in 30–70% of the cases), potentially associated with dystrophic changes, which may result in acute and rapid progression.In the present review, we discuss specific characteristics found in this group of patients which are of paramount importance to properly manage this challenging disease.