14
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Surgical management of peripheral nerve sheath tumours in children, with special consideration of neurofibromatoses

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          Peripheral nerve sheath tumours in children are a rare and heterogeneous group, consisting mostly of benign tumours as well as malignant neoplasms. Especially in the paediatric population, diagnostics and indication for therapy pose relevant challenges for neurosurgeons and paediatric neurologists alike. Most paediatric cases that need surgical intervention are associated to neurofibromatosis type 1 (NF1).

          Methods

          We retrospectively reviewed all paediatric cases treated at the Department of Neurosurgery in Tübingen between 2006 and 2017 for peripheral nerve sheath tumours. We analysed clinical signs, symptoms, histology, association to an underlying phacomatosis and sensory/motor function.

          Results

          Of the 82 identified patients, the majority had NF1 (76.8%). Nine children bore a sporadic tumour without underlying phacomatosis (11%), 8 had NF2 (9.8%) and 2 schwannomatosis (2.4%), A total of 168 surgical interventions were performed, and 206 tumours were removed. Indication for surgery was in most instances significant tumour growth (45.2%) followed by pain (33.9%). New deficits led to surgery in 12.5% of interventions; malignancy was suspected in 8.3%. Histopathology revealed mostly neurofibromas (82.5%), divided into cutaneous neurofibromas (10.7%), infiltrating plexiform neurofibromas (25.7%) and peripheral nerve-born neurofibromas (46.1%). 12.1% of tumours were schwannomas, 2.9% MPNST, 1.5% ganglioneuroma ( n = 3) and 1 hybrid-neurofibroma and perineurinoma each. Leading symptoms, such as pain and motor and sensory deficits, improved after 125/166 interventions (74.4%), remained unchanged following 39 interventions (23.2%) and worsened in 4 occasions (2.4%).

          Conclusion

          Surgery is safe and effective for (neurofibromatosis associated) peripheral nerve sheath tumours in the paediatric population; however, management needs a multidisciplinary setting. We propose early surgical resection in paediatric patients with peripheral nerve sheath tumours with significant growth, or pain, or motor deficit, or suspected malignancy.

          Related collections

          Most cited references30

          • Record: found
          • Abstract: found
          • Article: not found

          Selumetinib in Children with Inoperable Plexiform Neurofibromas

          No approved therapies exist for inoperable plexiform neurofibromas in patients with neurofibromatosis type 1. We conducted an open-label, phase 2 trial of selumetinib to determine the objective response rate among patients with plexiform neurofibromas and to assess clinical benefit. Children with neurofibromatosis type 1 and symptomatic inoperable plexiform neurofibromas received oral selumetinib twice daily at a dose of 25 mg per square meter of body-surface area on a continuous dosing schedule (28-day cycles). Volumetric magnetic resonance imaging and clinical outcome assessments (pain, quality of life, disfigurement, and function) were performed at least every four cycles. Children rated tumor pain intensity on a scale from 0 (no pain) to 10 (worst pain imaginable). A total of 50 children (median age, 10.2 years; range, 3.5 to 17.4) were enrolled from August 2015 through August 2016. The most frequent neurofibroma-related symptoms were disfigurement (44 patients), motor dysfunction (33), and pain (26). A total of 35 patients (70%) had a confirmed partial response as of March 29, 2019, and 28 of these patients had a durable response (lasting ≥1 year). After 1 year of treatment, the mean decrease in child-reported tumor pain-intensity scores was 2 points, considered a clinically meaningful improvement. In addition, clinically meaningful improvements were seen in child-reported and parent-reported interference of pain in daily functioning (38% and 50%, respectively) and overall health-related quality of life (48% and 58%, respectively) as well as in functional outcomes of strength (56% of patients) and range of motion (38% of patients). Five patients discontinued treatment because of toxic effects possibly related to selumetinib, and 6 patients had disease progression. The most frequent toxic effects were nausea, vomiting, or diarrhea; an asymptomatic increase in the creatine phosphokinase level; acneiform rash; and paronychia. In this phase 2 trial, most children with neurofibromatosis type 1 and inoperable plexiform neurofibromas had durable tumor shrinkage and clinical benefit from selumetinib. (Funded by the Intramural Research Program of the National Institutes of Health and others; ClinicalTrials.gov number, NCT01362803 .)
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems.

            Peripheral nerve sheath tumors are common neoplasms, with classic identifiable features, but on occasion, they are diagnostically challenging. Although well-defined subtypes of peripheral nerve sheath tumors were described early in the history of surgical pathology, controversies regarding the classification and grading of these tumors persist. Advances in molecular biology have provided new insights into the nature of the various peripheral nerve sheath tumors, and have begun to suggest novel targeted therapeutic approaches. In this review, we discuss current concepts and problematic areas in the pathology of peripheral nerve sheath tumors. Diagnostic criteria and differential diagnosis for the major categories of nerve sheath tumors are proposed, including neurofibroma, schwannoma, and perineurioma. Diagnostically challenging variants, including plexiform, cellular and melanotic schwannomas are highlighted. A subset of these affects the childhood population, and has historically been interpreted as malignant, although current evidence and outcome data suggest they represent benign entities. The growing current literature and the author's experience with difficult to classify borderline or "hybrid tumors" are discussed and illustrated. Some of these classification gray zones occur with frequency in the gastrointestinal tract, an anatomical compartment that must always be entertained when examining these neoplasms. Other growing recent areas of interest include the heterogeneous group of pseudoneoplastic lesions involving peripheral nerve composed of mature adipose tissue and/or skeletal muscle, such as the enigmatic neuromuscular choristoma. Malignant peripheral nerve sheath tumors (MPNST) represent a diagnostically controversial group; difficulties in grading and guidelines to separate "atypical neurofibroma" from MPNST are provided. There is an increasing literature of MPNST mimics which neuropathologists must be aware of, including synovial sarcoma and ossifying fibromyxoid tumor. Finally, we discuss entities that are lacking from the section on cranial and paraspinal nerves in the current WHO classification, and that may warrant inclusion in future classifications. In summary, although the diagnosis and classification of most conventional peripheral nerve sheath tumors are relatively straightforward for the experienced observer, yet borderline and difficult-to-classify neoplasms continue to be problematic. In the current review, we attempt to provide some useful guidelines for the surgical neuropathologist to help navigate these persistent, challenging problems.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Malignant peripheral nerve sheath tumors.

              Malignant peripheral nerve sheath tumors (MPNST) are uncommon, biologically aggressive soft tissue sarcomas of neural origin that pose tremendous challenges to effective therapy. In 50% of cases, they occur in the context of neurofibromatosis type I, characterized by loss of function mutations to the tumor suppressor neurofibromin; the remainder arise sporadically or following radiation therapy. Prognosis is generally poor, with high rates of relapse following multimodality therapy in early disease, low response rates to cytotoxic chemotherapy in advanced disease, and propensity for rapid disease progression and high mortality. The last few years have seen an explosion in data surrounding the potential molecular drivers and targets for therapy above and beyond neurofibromin loss. These data span multiple nodes at various levels of cellular control, including major signal transduction pathways, angiogenesis, apoptosis, mitosis, and epigenetics. These include classical cancer-driving genetic aberrations such as TP53 and phosphatase and tensin homolog (PTEN) loss of function, and upregulation of mitogen-activated protein kinase (MAPK) and (mechanistic) target of rapamycin (TOR) pathways, as well as less ubiquitous molecular abnormalities involving inhibitors of apoptosis proteins, aurora kinases, and the Wingless/int (Wnt) signaling pathway. We review the current understanding of MPNST biology, current best practices of management, and recent research developments in this disease, with a view to informing future advancements in patient care.
                Bookmark

                Author and article information

                Contributors
                julian.zipfel@med.uni-tuebingen.de
                Journal
                Childs Nerv Syst
                Childs Nerv Syst
                Child's Nervous System
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0256-7040
                1433-0350
                6 June 2020
                6 June 2020
                2020
                : 36
                : 10
                : 2433-2442
                Affiliations
                [1 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Division of Paediatric Neurosurgery, Department of Neurosurgery, , University Hospital of Tübingen, ; Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany
                [2 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Department of Neurosurgery, , University Hospital Tübingen, ; Tübingen, Germany
                [3 ]GRID grid.10392.39, ISNI 0000 0001 2190 1447, Centre for Neurofibromatosis at the Centre of Rare Diseases, , University Hospital and University of Tübingen, ; Tübingen, Germany
                [4 ]GRID grid.488549.c, Department of Paediatric Neurology, , University Children’s Hospital Tübingen, ; Tübingen, Germany
                [5 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Department of Neurology, , University Hospital Tübingen, ; Tübingen, Germany
                [6 ]GRID grid.488549.c, Department of Paediatric Surgery, , University Children’s Hospital Tübingen, ; Tübingen, Germany
                [7 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Department of Maxillofacial Surgery, , University Hospital Tübingen, ; Tübingen, Germany
                [8 ]GRID grid.13648.38, ISNI 0000 0001 2180 3484, Neurofibromatosis Centre Hamburg, Department of Neurology, , University Medical Center Hamburg-Eppendorf, ; Hamburg, Germany
                Author information
                http://orcid.org/0000-0003-4725-713X
                Article
                4703
                10.1007/s00381-020-04703-6
                8272701
                32506255
                64da5f81-eb65-4df4-a572-6bd18e7bcb40
                © The Author(s) 2020, corrected publication 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 May 2020
                : 25 May 2020
                Categories
                Annual Issue Paper
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Neurology
                malignant peripheral nerve sheath tumour,neurofibromatosis type 1,perineurinomas
                Neurology
                malignant peripheral nerve sheath tumour, neurofibromatosis type 1, perineurinomas

                Comments

                Comment on this article