Recurrent schwannomatosis with mosaic SMARCB1 loss: A case report

Lakhina,Yuliya; Lim,Megan A.; Yonk,Marybeth G.; Campbell,Melissa; Tora,Muhibullah S.; Du,Yuhong; Koshkin,Sergei; Lei,Kecheng; Boulis,Nicholas M.

doi:10.3892/etm.2025.12897

July-2025 Volume 30 Issue 1

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July-2025 Volume 30 Issue 1

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Case Report Open Access

Recurrent schwannomatosis with mosaic SMARCB1 loss: A case report

Authors:
- Yuliya Lakhina
- Megan A. Lim
- Marybeth G. Yonk
- Melissa Campbell
- Muhibullah S. Tora
- Yuhong Du
- Sergei Koshkin
- Kecheng Lei
- Nicholas M. Boulis
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Affiliations: Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA, Carle Illinois College of Medicine, University of Illinois Urbana Champaign, Champaign, IL 61801, USA, Department of Pharmacology and Chemical Biology Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, GA 30322, USA, Department of Medical Oncology, Thomas Jefferson University, PA 19144, USA

Copyright: © Lakhina et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 147
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Published online on: May 27, 2025

https://doi.org/10.3892/etm.2025.12897
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Abstract

Schwannomatosis is a non‑cancerous disorder causing peripheral nerve sheath tumors (schwannomas), often leading to chronic pain. It is linked to loss of SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily B member 1 (SMARCB1) or leucine zipper‑transcription regulator 1 (LTZR1) gene function, though some patients may initially show minor mutations or no clinical signs, resulting in misdiagnosis, missed assessments, increased recurrence risk, unawareness of malignancy and overlooked genetic counseling during pregnancy. The present study reports a patient with a sporadic synonymous mutation in the SMARCB1 gene [SNP c.1032 C>T (p.Gly344Gly {GGC>GGT}) in exon 8]. This patient, a 53‑year‑old female with an 8‑year history of schwannomatosis, presented to the neurosurgical department for recurrent tumor removal. Tumor tissue was analyzed using immunohistochemistry, hematoxylin and eosin staining, and enzyme‑linked immunosorbent assay. Initially, the clinical impact of the SMARCB1 mutation on schwannomatosis was unclear. However, resected schwannomas showed 10‑60% mosaic loss of nuclear SMARCB1 protein, with protein assays confirming low SMARCB1 levels, particularly in the distal thigh schwannoma. This case highlights the tumorigenic potential of SMARCB1 single nucleotide polymorphisms, emphasizing the need for multimodal diagnosis, long‑term follow‑up, awareness of recurrence and malignancy, and timely surgical planning in schwannomatosis patients.

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1	MacCollin M, Chiocca EA, Evans DG, Friedman JM, Horvitz R, Jaramillo D, Lev M, Mautner VF, Niimura M, Plotkin SR, et al: Diagnostic criteria for schwannomatosis. Neurology. 64:1838–1845. 2005.PubMed/NCBI View Article : Google Scholar
2	Tamura R, Yo M and Toda M: Historical development of diagnostic criteria for NF2-related schwannomatosis. Neurol Med Chir (Tokyo). 64:299–308. 2024.PubMed/NCBI View Article : Google Scholar
3	Kresak JL and Walsh M: Neurofibromatosis: A review of NF1, NF2, and schwannomatosis. J Pediatr Genet. 5:98–104. 2016.PubMed/NCBI View Article : Google Scholar
4	Merker VL, Esparza S, Smith MJ, Stemmer-Rachamimov A and Plotkin SR: Clinical features of schwannomatosis: A retrospective analysis of 87 patients. Oncologist. 17:1317–1322. 2012.PubMed/NCBI View Article : Google Scholar
5	Min BJ, Kang YK, Chung YG, Seo ME, Chang KB and Joo MW: Germline mutations for novel candidate predisposition genes in sporadic schwannomatosis. Clin Orthop Relat Res. 478:2442–2450. 2020.PubMed/NCBI View Article : Google Scholar
6	Kohashi K and Oda Y: Oncogenic roles of SMARCB1/INI1 and its deficient tumors. Cancer Sci. 108:547–552. 2017.PubMed/NCBI View Article : Google Scholar
7	Dhamija R, Plotkin S, Gomes A and Babovic-Vuksanovic D: LZTR1- and SMARCB1-Related Schwannomatosis. In: GeneReviews^® [Internet]. Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and Amemiya A (eds). Seattle (WA): University of Washington, Seattle, 1993.
8	Smith MJ, Wallace AJ, Bowers NL, Eaton H and Evans DG: SMARCB1 mutations in schwannomatosis and genotype correlations with rhabdoid tumors. Cancer Genet. 207:373–378. 2014.PubMed/NCBI View Article : Google Scholar
9	Cooper GW and Hong AL: SMARCB1-deficient cancers: Novel molecular insights and therapeutic vulnerabilities. Cancers (Basel). 14(3645)2022.PubMed/NCBI View Article : Google Scholar
10	Loh J, Ong PY, Goh DLM, Puhaindran ME, Vellayappan BA, Ow SGW, Chan G and Lee SC: Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore. Hered Cancer Clin Pract. 20(23)2022.PubMed/NCBI View Article : Google Scholar
11	Koeller KK and Shih RY: Intradural extramedullary spinal neoplasms: Radiologic-pathologic correlation. Radiographics. 39:468–490. 2019.PubMed/NCBI View Article : Google Scholar
12	National Library of Medicine: ClinVar. https://www.ncbi.nlm.nih.gov/clinvar/.
13	Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al: Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med. 17:405–424. 2015.PubMed/NCBI View Article : Google Scholar
14	Takahashi T, Hirai T, Yoshii T, Inose H, Yuasa M, Matsukura Y, Morishita S, Kobayashi Y, Utagawa K, Kawabata A, et al: Risk factors for recurrence and regrowth of spinal schwannoma. J Orthop Sci. 28:554–559. 2023.PubMed/NCBI View Article : Google Scholar
15	Fehlings MG, Nater A, Zamorano JJ, Tetreault LA, Varga PP, Gokaslan ZL, Boriani S, Fisher CG, Rhines L, Bettegowda C, et al: Risk factors for recurrence of surgically treated conventional spinal schwannomas: Analysis of 169 patients from a multicenter international database. Spine (Phila Pa 1976). 41:390–398. 2016.PubMed/NCBI View Article : Google Scholar
16	Jo VY and Fletcher CDM: SMARCB1/INI1 loss in epithelioid schwannoma: A clinicopathologic and immunohistochemical study of 65 cases. Am J Surg Pathol. 41:1013–1022. 2017.PubMed/NCBI View Article : Google Scholar
17	Schaefer IM, Dong F, Garcia EP, Fletcher CDM and Jo VY: Recurrent SMARCB1 inactivation in epithelioid malignant peripheral nerve sheath tumors. Am J Surg Pathol. 43:835–843. 2019.PubMed/NCBI View Article : Google Scholar

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Recurrent schwannomatosis with mosaic SMARCB1 loss: A case report

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