Nerve Sheath Tumors Research Articles

Proof of Concept for Genome Profiling of the Neurofibroma/Sarcoma Sequence in Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by the predisposition to develop tumors such as malignant peripheral nerve sheath tumors (MPNSTs) which represents the primary cause of death for NF1-affected patients. Regardless of the high incidence and mortality, the molecular mechanisms underneath MPNST growth and metastatic progression remain poorly understood. In this proof-of-concept study, we performed somatic whole-exome sequencing (WES) to profile the genomic alterations in four samples from a patient with NF1-associated MPNST, consisting of a benign plexiform neurofibroma, a primary MPNST, and metastases from lung and skin tissues. By comparing genomic patterns, we identified a high level of variability across samples with distinctive genetic changes which allow for the definition of profiles of the early phase with respect to the late metastatic stages. Pathogenic and likely pathogenic variants were abundant in the primary tumor, whereas the metastatic samples exhibited a high level of copy-number variations (CNVs), highlighting a possible genomic instability in the late phases. The most known MPNST-related genes, such as TP53 and SUZ12, were identified in CNVs observed within the primary tumor. Pathway analysis of altered early genes in MPNST pointed to a potential role in cell motility, division and metabolism. Moreover, we employed survival analysis with the TCGA sarcoma genomic dataset on 262 affected patients, in order to corroborate the predictive significance of the identified early and metastatic MPNST driver genes. Specifically, the expression changes related to the mutated genes, such as in RBMX, PNPLA6 and AGAP2, were associated with reduced patient survival, distinguishing them as potential prognostic biomarkers. This study underlines the relevance of integrating genomic results with clinical information for early diagnosis and prognostic understanding of tumor aggressiveness.

FDG-PET/CT Avid Uptake of a Biopsy-Proven Aggressive Melanotic Schwannoma of the S2 Spinal Nerve Root

Abstract Background Malignant melanotic nerve sheath tumors (MMNSTs), also known as a melanocytic schwannoma (MS), are a rare type of peripheral nerve sheath tumors including Schwann cells with melanocytic differentiation. Only a few cases of spinal MMNST have been reported in literature. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) could be used to detect these lesions. Case Description A 70-year-old man with a 6-month history of backache was admitted to our hospital. PET/CT showed a paravertebral soft tissue mass along the spinal nerve at the S2 level with strong FDG uptake, and a nodule with increased FDG uptake in the right lobe of the left liver. A CT-guided biopsy of the S2 lesion was performed. The final diagnosis was spinal MS with hepatic metastasis. The patient received stereotactic body radiation therapy. Conclusion Herein, we report the PET/CT findings of a case of MS with hepatic metastasis. FDG-PET/CT is helpful in the differential diagnosis of benign and malignant lesions although nonspecific.

Radiation-Induced Intraosseous Malignant Peripheral Nerve Sheath Tumor: A Case Report.

The significance of radiation therapy in cancer treatment comes with associated complications, including fibrosis, osteonecrosis, and the development of secondary malignancies, such as malignant peripheral nerve sheath tumors (MPNSTs). We emphasize the importance of understanding these complications for an effective patient management. We report a 47-year-old man with a history of squamous cell carcinoma of the tongue, treated with surgery, chemotherapy, and radiation therapy. The patient later presented with symptoms that led to the discovery of an intraosseous MPNST. Histopathological examination revealed characteristic features of MPNST, including spindle cells arranged is sweeping fascicles with contrasting hypercellular and hypocellular areas, producing a marble-like pattern, with atypical wavy, buckled, hyperchromatic nuclei, and brisk mitotic activity. Immunohistochemical analysis showed patchy positive staining for S100 and SOX10, and a complete loss of H3K27me3 expression. This report underscores the challenge of diagnosing secondary malignancies post-radiation therapy and the importance of careful histological examination to differentiate them from other conditions. In conclusion, radiation-induced secondary malignancies are a significant late side effect of radiation therapy that can profoundly impact treatment decision-making and requires a high index of suspicion during post radiation surveillance. Malignant peripheral nerve sheath tumor serves as a pertinent example, highlighting the importance of considering long-term risks when developing optimal management plans for cancer patients.

Early Detection of Malignant and Premalignant Peripheral Nerve Tumors Using Cell-Free DNA Fragmentomics.

Early detection of neurofibromatosis type 1 (NF1)-associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1. cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: bin-wise fragment size ratios, end motifs, and fragment non-negative matrix factorization signatures. The novel cohort of patients with NF1 validated that our previous cfDNA copy-number alteration-based approach identifies malignant PNST (MPNST) but cannot distinguish between benign and premalignant states. Fragmentomic methods were able to differentiate premalignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. Novel cfDNA fragmentomic signatures distinguish AN from benign plexiform neurofibromas and MPNST, enabling more precise clinical diagnosis and management. This study pioneers the early detection of malignant and premalignant PNST in NF1 and provides a blueprint for decentralizing noninvasive cancer surveillance in hereditary cancer predisposition syndromes.

Epidemiology, tumour characteristics, treatment and outcomes associated with spinal nerve sheath tumours: a systematic review protocol

IntroductionNerve sheath tumours arise from both the central and peripheral nervous systems. In particular, cases of spinal or paraspinal origins are scarce and poorly covered in the literature. This systematic...

Linking FOXM1 and PD-L1 to CDK4/6-MEK targeted therapy resistance in malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, Ras-driven sarcomas characterized by loss of the NF1 tumor suppressor gene and hyperactivation of MEK and CDK4/6 kinases. MPNSTs lack effective therapies. We recently demonstrated remarkable efficacy of dual CDK4/6-MEK inhibition in mice with de novo MPNSTs, which was heightened by combined targeting of the immune checkpoint protein, PD-L1. The triple combination therapy targeting CDK4/6, MEK, and PD-L1 led to extended MPNST regression and improved survival, although most tumors eventually acquired drug resistance. Here, we consider the immune activation phenotype caused by CDK4/6-MEK inhibition in MPNSTs that uniquely involved intratumoral plasma cell accumulation. We discuss how PD-L1 and FOXM1, a tumor-promoting transcription factor, are functionally linked and may be key mediators of resistance to CDK4/6-MEK targeted therapies. Finally, the role of FOXM1 in suppressing anti-tumor immunity and potentially thwarting immune-based therapies is considered. We suggest that future therapeutic strategies targeting the oncogenic network of CDK4/6, MEK, PD-L1, and FOXM1 represent exciting future treatment options for MPNST patients.

Primary Aortic Malignant Peripheral Nerve Sheath Tumor.

A 74year-old woman suffering 1month persisting lumbago was referred with diagnosis of thoracic aortic aneurysm. Blood examinations indicated slightly or moderately elevated noradrenaline, dopamine, and homovanillic acid with normal-range vanillylmandelic acid. Contrast-enhanced CT scans revealed a tumor, protruding both intra- and extra-luminally, in the wall of the distal descending thoracic aorta without any primary focuses in the whole body. Primary aortic sarcoma or periaortic catecholamine-producing paraganglioma infiltrating the aorta was suspected. The tumor with the normal proximal and distal aorta 2-3cm apart from it was completely resected under femoro-femoral partial cardiopulmonary bypass. Macroscopically, the tumor was originated from the aortic wall and protruded both intra- and extra-luminally. Immunohistochemically, positive S-100 and vimentin; Ki67 levels of 40%; and negative CD34, CK AE1/AE3, and SMA were identified. The aforementioned findings definitively diagnosed primary aortic malignant peripheral nerve sheath tumor, which has been never reported in the literature.

Marginal Excision as a Surgical Treatment for The Schwannoma of Posterior Aspect of Femur: A Case Report

Introduction: Schwannoma is a benign nerve sheath neoplasm attached to a peripheral nerve that often develops in the middle-aged population. It usually presents as an asymptomatic mass at first but can be transformed into a pain, swelling, neurologic, or mechanical symptom in several patients. In this study, we are reporting a case of a schwannoma of the posterior aspect of the thigh, in a young adult male. Case Presentation: We reported a 31-year-old male complained of sharp pain, tingling sensation, and mechanical block in the posterior aspect of the right thigh. Radiological imaging showed the tumor of the posterior aspect of the right thigh, with associated soft tissue edema, the cortex is not invaded. Surgical resection was performed on the patient and the tumor was excised with marginal excision surgery technique. Conclusions: The schwannomas of the femur can successfully be excised with no postoperative complications. There is no sign of a recurrent tumor in six months after the procedure.

The Multimodality Management of Malignant Peripheral Nerve Sheath Tumours.

Malignant peripheral nerve sheath tumours (MPNST) are aggressive sarcomas that have nerve sheath differentiation and can present at any anatomical site. They can arise from precursor neurofibroma in the context of neurofibromatosis type 1 (NF1) or as de novo and sporadic tumours in the absence of an underlying genetic predisposition. The primary therapeutic approach is most often radical surgery, with non-surgical modalities playing an important role, especially in locally advanced or metastatic cases. The aim of multimodality approaches is to optimize both local and systemic control while keeping to a minimum acute and late treatment morbidity. Advances in the understanding of the underlying biology of MPNSTs in both sporadic and NF-1-related contexts are essential for the management and implementation of novel therapeutic approaches.

Multi-dimensional immunotyping of human NF1-associated peripheral nerve sheath tumors uncovers tumor-associated macrophages as key drivers of immune evasion in the tumor microenvironment.

Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas and the leading cause of mortality in individuals with neurofibromatosis type 1 (NF1). Despite many clinical trials, outcomes for patients with MPNST have remained stagnant and most succumb to their disease; thus, novel therapeutic approaches are needed. A better understanding of the MPNST immune ecosystem will aid in the development of strategies to activate the immune system against the tumor. Herein, we profile the tumor immune microenvironment (TIME) in NF1-associated peripheral nerve sheath tumors (PNST) to discover insights on the role that tumor-infiltrating immune cells play in malignant transformation. Utilizing fresh and formalin-fixed, paraffin-embedded tissue from patients diagnosed with NF1-PNST, we dissected the TIME by using immunohistochemistry, multiparameter flow cytometry, and comparative transcriptomic studies. Immunophenotyping confirmed increased immune cells infiltration during malignant progression, with a predominance of infiltrating myeloid cells, particularly CD163+ tumor-associated macrophages (TAM). The T cells within MPNST exhibited signs of tumor activation, characterized by high PD-1 expression. Additionally, MPNST specimens demonstrated elevated levels of immunosuppressive TAM, with heightened PD-L1 expression. The proportion of CD163+ myeloid cells within the TIME correlated with poorer progression free survival. Notably, loss of H3K27 trimethylation correlated with low immune cell infiltration in MPNST. Malignant transformation of NF1-PNST is characterized by an immunosuppressive microenvironment comprising of TAM with high expression of PD-L1, which are associated with inferior outcomes. These findings suggest a clinical potential of immune modulating therapeutics that can unleash an anti-tumor immune response.

Role of Fine Needle Aspiration Cytology in Paratesticular Neoplasms-A Case Reports-Based Systematic Review.

The cytology features of neoplastic paratesticular lesions are mostly documented as case reports. Thus, we conducted a case report-based literature review to identify the characteristics of paratesticular neoplasms and tried to determine the significance of FNAC in these tumors. The studies were searched using PubMed and Scopus. The quality assessment was done using the JBI critical appraisal checklist for case reports. The articles that received an overall rating of "Include" underwent data extraction. The data were extracted from the articles and analyzed. We included 34 case reports from 33 published articles. The mean age of patients was 44.74 (13-85) years, and the most common clinical manifestation was scrotal swelling (70.59%, 24/34). Lesions were commonly observed on the right side (65.63%, 21/32), and the most common tumor site was epididymis (35.29%, 12/34). A total of 38.24% (13/34) cases were nonmalignant, and 61.76% (21/34) were malignant on the cytological diagnosis. The adenomatoid tumor (53.85, 7/13) was the most common nonmalignant tumor. Other entities were schwannoma, benign spindle cell neoplasm with atypia, nerve sheath tumor, lipoma, undifferentiated pleomorphic sarcoma, rhabdomyosarcoma, epithelioid sarcoma, liposarcoma, malignant rhabdoid tumor, pigmented neuroectodermal tumor of infancy and mesothelioma. Considering the malignant and nonmalignant groups, the sensitivity, specificity, and diagnostic accuracy of cytology were 95.00%, 84.62%, and 90.91%, respectively. Cytopathologists should be familiar with the cytological features of various malignant and nonmalignant paratesticular tumors to prevent unnecessarily invasive surgical management. The current systematic review emphasizes usefulness of FNAC in the preoperative cytological identification of paratesticular tumors.

Neurofibromatosis type 1: short review and clinical case

Neurofibromatosis type 1 (NF1) is acommon (1/3000) autosomal dominant disorder associated with amutation in the NF1 gene, located on the long arm of chromosome 17 (17q11.2). NF1 is diagnosed using well-known clinical criteria: café au lait spots, axillary and inguinal freckles, cutaneous and subcutaneous neurofibromas, optic pathway gliomas, and specific bone abnormalities. The pathognomonic feature of the disease is plexiform neurofibroma (PN), which is abenign peripheral nerve sheath tumor that occurs in 30-50% of patients with NF1. In addition to awide range of clinical manifestations, such as pain, motor, respiratory disorders, neurological deficits, cosmetic defects, etc., there is about a15% risk for the development of malignant peripheral nerve sheath tumors (MPNST). And it should be noted that the treatment of PN is acomplex task that does not have one standard solution. Thus, surgical treatment, which was the “gold standard” and remains one of the main methods of therapy, carries significant risks, such as postoperative neurological deficit, ahigh risk of intraoperative bleeding and is accompanied by ahigh percentage of relapses. Therefore, the emergence of targeted therapy and its use in the Russian Federation since 2021 has made asignificant contribution to the treatment of symptomatic inoperable plexiform neurofibromas.

MEK Inhibitors Lead to PDGFR Pathway Upregulation and Sensitize Tumors to RAF Dimer Inhibitors in NF1-Deficient Malignant Peripheral Nerve Sheath Tumor.

Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive subtype of soft-tissue sarcoma with a high propensity to metastasize and extremely limited treatment options. Loss of the RAS-GAP NF1 leads to sustained RAF/MEK/ERK signaling in MPNST. However, single-agent MEK inhibitors (MEKi) have failed to elicit a sustained inhibition of the MAPK signaling pathway in MPNST. We used pharmacological, biochemical, and genetic perturbations of the receptor tyrosine kinase and MAPK signaling pathway regulators to investigate the mechanisms of MEKi resistance and evaluated combination therapeutic strategies in various preclinical MPNST models in vitro and in vivo. Here, we report that MEKi treatment resistance in MPNST involves two adaptive pathways: direct transcriptional upregulation of the receptor tyrosine kinase PDGFRβ and MEKi-induced increase in RAF dimer formation and activation of downstream signaling. Although the pharmacologic combination of a MEKi with a PDGFRβ-specific inhibitor was more effective than treatment with the MEKi alone, the combination of the MEKi and RAF dimer inhibitors led to a robust inhibition of MAPK pathway signaling. This combination treatment was effective in vitro and in vivo, as demonstrated by the significant increase in drug synergism and its high effectiveness in decreasing MPNST viability. Our findings suggest that the combination of MEKis and PDGFR and/or RAF dimer inhibitors can overcome MEKi resistance and may serve as a novel targeted therapeutic strategy for patients with NF1-deficient MPNST, which in turn could impact future clinical investigations for this patient population.

Clinical Outcomes of Carbon Ion Radiation Therapy for Malignant Peripheral Nerve Sheath Tumors

Purposeto investigate outcome and toxicity of patients affected by malignant peripheral nerve sheath tumors (MPNSTs) treated with high-dose carbon ion radiotherapy (CIRT). Patients and methodswe retrospectively analyzed the outcome of 23 patients with MPNST treated between July 2013 and December 2020. Out of these, 13 patients (56.5%) had incompletely resected tumors, 8 patients (34.7%) experienced recurrence after surgery, and 2 patients (8.7%) had unresectable tumors. Before CIRT treatment, 4 patients underwent a second surgery after the first local recurrence (LR), and 1 patient underwent a third surgery for the second local relapse of disease. Six (26%) of patients received neoadjuvant chemotherapy. The most frequent tumor site was brachial plexus (N=9; 39.1%). In five patients (21.7%) neurofibromatosis type 1 (NF1) disorder was found, while 4 patients (17, 4%) had radiation-induced MPNST. The median CIRT prescribed total dose was 69.8 Gy [RBE] (range, 54-76.8) delivered in a median of 16 fractions (range, 15-22). Eleven patients (47.82%) were treated according to a sequential boost protocol with a median prescribed dose to CTV-LR of 45 Gy[RBE] (range, 41.4 – 54). ResultsAfter a median follow-up time of 23 months (range 3-100 months), the OS rates at 1-year and 2-year were respectively: 82.38%, 61.51%. The 1-year and 2-year LRFS rates were respectively: 65.07%, 48.80%; the 1-year and 2-year PFS rates were respectively: 56.37%, 40.99%. No patients showed acute or late Grade 4 toxicity or any treatment-related deaths. Ten patients (43.48%) reported acute toxicities of Grade ≥2: dermatitis in 6 patients, mucositis in 2 patients, peripheral neuropathy in 4 patients. Eight patients (34.78%) reported late toxicities of Grade ≥2, mainly due to loco-regional neuropathy. Conclusionshigh dose CIRT shows favorable local effect with acceptable toxicities in patients with gross residual and LR after surgery, or unresectable malignant peripheral nerve sheath tumors. Advanced treatment modalities such as particle therapy should be considered for MPNSTs.

A Rare Case of Malignant Peripheral Nerve Sheath Tumour of the Brachial Plexus with a Diagnostic Dilemma

Abstract The brachial plexus is usually involved by tumours of adjacent areas like the lungs, breast, and cervical spine. Primary tumour of the brachial plexus are rare. It constitutes less than 5% of upper extremity tumours. Still rare are malignant tumours. Once malignancy is diagnosed there should be no delay in surgery considering the aggressive nature. Here, we discuss the diagnostic dilemma in a case of a malignant peripheral nerve sheath tumour and its surgical approach. Surgical excision was challenging because of the complex anatomy, retroclavicular/infraclavicular extension and proximity tumour to adjacent vital structures.

Cold Atmospheric Plasma Induces Growth Arrest and Apoptosis in Neurofibromatosis Type 1-Associated Peripheral Nerve Sheath Tumor Cells.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder resulting from mutations in the NF1 gene. Patients harboring these mutations are predisposed to a spectrum of peripheral nerve sheath tumors (PNSTs) originating from Schwann cells, of which malignant peripheral nerve sheath tumors (MPNSTs) are the deadliest, with limited treatment options. Therefore, an unmet need still exists for more effective therapies directed at these aggressive malignancies. Cold atmospheric plasma (CAP) is a reactive oxygen species (ROS) and reactive nitrogen species (RNS) generating ionized gas that has been proposed to be a potential therapeutic modality for cancer. In this study, we sought to determine the effects of CAP on NF1-associated PNSTs. Utilizing established mouse and human cell lines to interrogate the effects of CAP in both in vitro and in vivo settings, we found that NF1-associated PNSTs were highly sensitive to CAP exposure, resulting in cell death. To our knowledge, this is the first application of CAP to NF1-associated PNSTs and provides a unique opportunity to study the complex biology of NF1-associated tumors.

Tuberculoma of deep peroneal nerve- a rare case report

Tuberculosis can mimick various diseases, causing a diagnostic dilemma.Tuberculomas of peripheral nerves arerare, only 9 cases were reported till date, we report a case of tuberculoma of deep peroneal nerve. A 29 year old subject, presented with complaints of painful swellings over right leg& foot since 2months. Patient developed diffuse swelling of right lower limb 5 years ago, for which he was treated with NSAIDs & serratiopeptidase by a local practitioner for 2 weeks after which he noticed tiny swellings on lower half of right shin & right foot which grew in size gradually &became painful since 2 months. Examination revealed tiny palpable mobile nodular soft swellings over lower aspect of right leg & over right foot. Ultrasonography of the swellings showed multiple ovale capsulated hypoechoic swellings largest measuring 18.9∗6.1 mm in the mid/lower leg subcutaneous plane anteriorly & similar lesions in the lower leg & dorsum of foot, suggesting benign neoplastic etiology of neural origin. Excision biopsy from deep peroneal nerve sheath tumour showed extensive areas of caseous necrosis with few epitheloid clusters with dense lymphocytic collections in the periphery, suggesting caseating granulomasof tubercular etiology. After making a diagnosis of tuberculoma of deep peroneal nerve, the patient has been initiated on Anti tubercular therapy & the patient respoded to ATT. Tuberculomas of peripheral nerves are rare. Final diagnosis comes from histopathology that reveals caseous necrosis surrounded by epitheloid histiocytes with or without granulomas Nerve exploration, lesion resection, and ATT results in good neurological recovery.

Interferon-Induced Transmembrane Protein 1 (IFITM1) Is Downregulated in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors.

Neurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder, is caused by mutations in the NF1 gene, which encodes the GTPase-activating protein neurofibromin. The pathogenesis of the tumor progression of benign plexiform neurofibromas (PNs) and malignant peripheral nerve sheath tumors (MPNSTs) remain unclear. Here, we found that interferon-induced transmembrane protein 1 (IFITM1) was downregulated in MPNST tissues compared to those in PN tissues from patients with NF1. Overexpression of IFITM1 in NF1-associated MPNST cells resulted in a significant decrease in Ras activation (GTP-Ras) and downstream extracellular regulatory kinase 1/2 (ERK1/2) phosphorylation, whereas downregulation of IFITM1 via treatment with small interfering RNA in normal Schwann cells had the opposite result, indicating that expression levels of IFITM1 are closely associated with tumor progression in NF1. Treatment of MPNST cells with interferon-gamma (IFN-γ) significantly augmented the expression of IFITM1, thereby leading to a decrease in Ras and ERK1/2 activation. Despite the small number of patient samples, these findings may potentially provide a new target for chemotherapy in patients with NF1-associated MPNSTs. In xenograft mice injected with MPNST cells, IFN-γ treatment successfully suppressed tumor progression with increased IFITM1 expression and decreased Ras and ERK1/2 activation in tumor tissues. Collectively, these results suggest that IFITM1 is closely involved in MPNST pathogenesis and that IFN-γ is a good candidate for the therapeutic treatment of MPNSTs in NF1.

Immunohistochemical Evaluation of Schlafen 11 (SLFN11) Expression in Cancer in the Search of Biomarker-Informed Treatment Targets: A Study of 127 Entities Represented by 6658 Tumors.

Schlafen 11 (SLFN11), a DNA/RNA helicase, acts as a regulator of cellular response to replicative stress and irreversibly triggers replication block and cell death. Several preclinical in vitro studies and clinical trials established that SLFN11 expression predicts outcomes in patients with advanced cancer treated with DNA-damaging chemotherapeutics and more recently with poly(ADP-ribose) polymerase inhibitors. SLFN11 expression status remains unknown in many cancer types, especially in mesenchymal tumors. This study evaluated a cohort of well characterized 3808 epithelial and 2850 mesenchymal and neuroectodermal tumors for SLFN11 expression using immunohistochemistry. Nuclear SLFN11 expression was rare in some of the most common carcinomas, for example, hepatocellular (1%), prostatic (2%), colorectal (5%), or breast (16%) cancers. In contrast, other epithelial tumors including mesotheliomas (92%), clear cell renal cell carcinomas (79%), small cell lung cancers (76%), squamous cell carcinomas of the tonsil (89%) and larynx (71%), or ovarian serous carcinomas (69%) were mostly SLFN11-positive. Compared with epithelial malignancies, SLFN11 expression was overall higher in neuroectodermal and mesenchymal tumors. Most positive entities included desmoplastic small round cell tumor (100%), Ewing sarcoma (92%), undifferentiated sarcoma (92%), solitary fibrous tumor (91%), dedifferentiated liposarcoma (89%), synovial sarcoma (86%), and malignant peripheral nerve sheath tumor (85%). Also, this study identifies tumors with potentially worse response to DNA-damaging drugs including antibody drug conjugates due to the absence of SLFN11 expression. Such entities may benefit from alternative treatments or strategies to overcome SLFN11 deficiency-related drug resistance. Our approach and results should serve as a foundation for future biomarker-associated clinical trials.

Robotic Resection of Spinal and Paraspinal Tumors.

Robotic arm surgical systems provide minimally invasive access and are commonly used in multiple surgical fields, with limited application in neurosurgery. Our institutional experience has led us to explore the benefits of a neurosurgeon trained to perform robotic surgery as part of a multidisciplinary team. The objective of this study is to evaluate the feasibility, safety, and outcomes of robotic resection for spinal nerve sheath tumors (NST). Retrospective case series of robotic-assisted intracavitary approaches and resection of NSTs including thoracic, retroperitoneal, and transperitoneal. Surgical outcomes are compared to a historical cohort of open surgical resection of NSTs. Nineteen cases presented, of which 2 were combined posterior spinal followed by robotic tumor resection. One of 19 cases was converted to an open surgery. Gross total resection was achieved in all cases. There were 2 cases of postoperative Horner's syndrome, and 1 case with an intraoperative durotomy that was repaired primarily with no postoperative sequelae. Median estimated blood loss was 50 cc (range: 5-650) and median length of stay was 1 day (range: 0-6), with 9 (47.4%) patients discharged on postoperative day 1 and 3 (15.8%) patients discharged on an outpatient basis. Compared with our previously reported institutional outcomes for open resection of 25 tumors, there was a significant increase in rates of gross total resection (100 vs 60%, P = .002) and decrease in length of stay (median 1 vs 5 days, P < .0001). Robotic resection of complex paraspinal tumors appears safe and effective including for preservation of neurological function and may reduce surgical morbidity. Integration of robotic surgical platforms holds the potential to significantly affect neurological surgery.