Management of neurofibromatosis type 2 and schwannomatosis associated peripheral and intraspinal schwannomas: influence of surgery, genetics, and localization

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Abstract

Introduction

Peripheral and intraspinal schwannomas are common and clinically complex pathologies in patients with Neurofibromatosis Type 2 (NF2) and Schwannomatosis (SWNT). Functional preservation and pain relief are the major goals in treating these tumors.

Methods

This retrospective observational study investigates the clinical and functional outcome of 205 operated peripheral (n = 148, 72%) and intraspinal (n = 57, 28%) schwannomas in 85 patients (53 NF2, 32 SWNT) treated at our department between 2006 and 2017. Associated factors such as genetics, age, and location were evaluated.

Results

Persisting drug-resistant pain was the most common symptom (84%, n = 173) and indication for surgery (54%, n = 110). Improvement in pain intensity was postoperatively seen in 81%. Peripheral nerve schwannomas exhibited worse pain intensity preoperatively compared to intraspinal lesions ( p = 0.017 NF2, p = 0.029 SWNT). More total resections could be achieved in 93% of SWNT vs. 82% of NF2-associated tumors, p = 0.030). NF2 patients with intraspinal lesions were more neurologically affected ( p < 0.05). Perioperative comparison of both tumor syndromes showed more neurological deficits ( p = 0.027), and less pain ( p = 0.024) in NF2-associated tumors. Mosaic NF2 patients had worse pain levels before surgery, and SWNT patients had a worse neurological function and more pain compared to non-mosaic or non-mutated cases.

Conclusions

Resection of peripheral and intraspinal schwannomas is an effective and low-risk treatment in both NF2 and SWNT. Patients with severe pain have a particular benefit from surgical treatment. Intraspinal lesions are associated with worse neurological function whereas peripheral lesions showed a higher pain intensity. The influence of mutations needs to be further investigated in larger cohorts.

Supplementary Information

The online version contains supplementary material available at 10.1007/s11060-022-04061-0.

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Most cited references 20

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Clinical features of schwannomatosis: a retrospective analysis of 87 patients.

Vanessa L Merker, Sonia Esparza, Miriam J Law Smith … (2012)

Schwannomatosis is a recently recognized form of neurofibromatosis characterized by multiple noncutaneous schwannomas, a histologically benign nerve sheath tumor. As more cases are identified, the reported phenotype continues to expand and evolve. We describe the spectrum of clinical findings in a cohort of patients meeting established criteria for schwannomatosis.

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Is Open Access

The molecular pathogenesis of schwannomatosis, a paradigm for the co-involvement of multiple tumour suppressor genes in tumorigenesis

Hildegard Kehrer-Sawatzki, Said Farschtschi, Victor-Felix Mautner … (2016)

Schwannomatosis is characterized by the predisposition to develop multiple schwannomas and, less commonly, meningiomas. Despite the clinical overlap with neurofibromatosis type 2 (NF2), schwannomatosis is not caused by germline NF2 gene mutations. Instead, germline mutations of either the SMARCB1 or LZTR1 tumour suppressor genes have been identified in 86% of familial and 40% of sporadic schwannomatosis patients. In contrast to patients with rhabdoid tumours, which are due to complete loss-of-function SMARCB1 mutations, individuals with schwannomatosis harbour predominantly hypomorphic SMARCB1 mutations which give rise to the synthesis of mutant proteins with residual function that do not cause rhabdoid tumours. Although biallelic mutations of SMARCB1 or LZTR1 have been detected in the tumours of patients with schwannomatosis, the classical two-hit model of tumorigenesis is insufficient to account for schwannoma growth, since NF2 is also frequently inactivated in these tumours. Consequently, tumorigenesis in schwannomatosis must involve the mutation of at least two different tumour suppressor genes, an occurrence frequently mediated by loss of heterozygosity of large parts of chromosome 22q harbouring not only SMARCB1 and LZTR1 but also NF2. Thus, schwannomatosis is paradigmatic for a tumour predisposition syndrome caused by the concomitant mutational inactivation of two or more tumour suppressor genes. This review provides an overview of current models of tumorigenesis and mutational patterns underlying schwannomatosis that will ultimately help to explain the complex clinical presentation of this rare disease. Electronic supplementary material The online version of this article (doi:10.1007/s00439-016-1753-8) contains supplementary material, which is available to authorized users.

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Author and article information

Contributors

Isabel Gugel: isabel.gugel@med.uni-tuebingen.de

Florian Grimm: florian.grimm@med.uni-tuebingen.de

Marcos Tatagiba: marcos.tatagiba@med.uni-tuebingen.de

Martin U. Schuhmann: martin.schuhmann@med.uni-tuebingen.de

Julian Zipfel: julian.zipfel@med.uni-tuebingen.de

Journal

Journal ID (nlm-ta): J Neurooncol

Journal ID (iso-abbrev): J Neurooncol

Title: Journal of Neuro-Oncology

Publisher: Springer US (New York )

ISSN (Print): 0167-594X

ISSN (Electronic): 1573-7373

Publication date (Electronic): 30 June 2022

Publication date PMC-release: 30 June 2022

Publication date (Print): 2022

Volume: 159

Issue: 2

Pages: 271-279

Affiliations

[1 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Department of Neurosurgery, , University Hospital Tübingen, ; 72076 Tübingen, BW Germany

[2 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Centre of Neurofibromatosis and Rare Diseases, , University Hospital Tübingen, ; 72076 Tübingen, BW Germany

[3 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Section of Pediatric Neurosurgery, , University Hospital Tübingen, ; 72076 Tübingen, BW Germany

Article

Publisher ID: 4061

DOI: 10.1007/s11060-022-04061-0

PMC ID: 9424169

PubMed ID: 35771312

SO-VID: a9dc09c4-5629-41a2-a90b-9c8bd40403c0

License:

Open AccessThis 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

Date received : 27 April 2022

Date accepted : 7 June 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100003542, Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg;

Award ID: 31-7635.41/215/2

Award Recipient : Isabel Gugel

Funded by: Universitätsklinikum Tübingen (8868)

Open Access :

Open Access funding enabled and organized by Projekt DEAL.

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: schwannoma,neurofibromatosis type 2,schwannomatosis,surgery,peripheral nerve sheath tumor,spinal schwannoma

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: schwannoma, neurofibromatosis type 2, schwannomatosis, surgery, peripheral nerve sheath tumor, spinal schwannoma

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Management of neurofibromatosis type 2 and schwannomatosis associated peripheral and intraspinal schwannomas: influence of surgery, genetics, and localization

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Abstract

Introduction

Methods

Results

Conclusions

Supplementary Information

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Karger: Oncology

Most cited references 20

Clinical features of schwannomatosis: a retrospective analysis of 87 patients.

The molecular pathogenesis of schwannomatosis, a paradigm for the co-involvement of multiple tumour suppressor genes in tumorigenesis

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