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. 2025 Apr 14;31(8):1400-1406.
doi: 10.1158/1078-0432.CCR-24-3278.

Update on Cancer and Central Nervous System Tumor Surveillance in Pediatric NF2-, SMARCB1-, and LZTR1-Related Schwannomatosis

Melissa R Perrino  1 , Marjolijn C J Jongmans  2   3 , Gail E Tomlinson  4 , Mary-Louise C Greer  5   6 , Sarah R Scollon  7 , Sarah G Mitchell  8 , Jordan R Hansford  9 , Kris Ann P Schultz  10 , Wendy K Kohlmann  11   12 , Jennifer M Kalish  13   14   15   16 , Suzanne P MacFarland  17 , Anirban Das  18 , Kara N Maxwell  17   19 , Stefan M Pfister  20 , Rosanna Weksberg  21 , Orli Michaeli  22 , Uri Tabori  18 , Gina M Ney  23 , Philip J Lupo  24 , Jack J Brzezinski  18 , Douglas R Stewart  23 , Emma R Woodward  25   26 , Christian P Kratz  27
Affiliations

Update on Cancer and Central Nervous System Tumor Surveillance in Pediatric NF2-, SMARCB1-, and LZTR1-Related Schwannomatosis

Melissa R Perrino et al. Clin Cancer Res. .

Abstract

Schwannomatosis (SWN) is a distinct cancer predisposition syndrome caused by germline pathogenic variants in the genes NF2, SMARCB1, or LZTR1. There is a significant clinical overlap between these syndromes with the hallmark of increased risk for cranial, spinal, and peripheral schwannomas. Neurofibromatosis type 2 was recently renamed as NF2-related SWN and is the most common SWN syndrome, with increased risk for bilateral vestibular schwannomas, intradermal schwannomas, meningiomas, and less commonly, ependymoma. SMARCB1-related SWN is a familial SWN syndrome associated with peripheral and spinal schwannomas and an increased risk for meningiomas and malignant peripheral nerve sheath tumors, even in the absence of radiation. These individuals do not develop bilateral vestibular schwannomas. Finally, patients with LZTR1-related SWN typically present with peripheral schwannomas, and unilateral vestibular schwannomas have been reported. The following perspective is intended to highlight the clinical presentation and international tumor surveillance recommendations across these SWN syndromes.

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Conflict of interest statement

Conflicts of interest: MRP has received honoraria from Alexion unrelated to this work. JRH has received honoraria from Alexion and Bayer Pharmaceuticals, unrelated to this work, and is a member of the Servier International scientific advisory board. MCG serves as a research consultant for Alimentiv and holds an investigator-initiated grant from AbbVie unrelated to this work. The remaining authors have no disclosures or conflicts of interest to report.

References

    1. Plotkin SR, Messiaen L, Legius E, Pancza P, Avery RA, Blakeley JO, et al. Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation. Genetics in Medicine 2022;24(9):1967–77 doi 10.1016/j.gim.2022.05.007. - DOI - PubMed
    1. Evans DG, Hartley CL, Smith PT, King AT, Bowers NL, Tobi S, et al. Incidence of mosaicism in 1055 de novo NF2 cases: much higher than previous estimates with high utility of next-generation sequencing. Genetics in Medicine 2020;22(1):53–9 doi 10.1038/s41436-019-0598-7. - DOI - PubMed
    1. Hadfield KD, Newman WG, Bowers NL, Wallace A, Bolger C, Colley A, et al. Molecular characterisation of SMARCB1 and NF2 in familial and sporadic schwannomatosis. J Med Genet 2008;45(6):332–9 doi 10.1136/jmg.2007.056499. - DOI - PubMed
    1. Hulsebos TJ, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P. Germline mutation of INI1/SMARCB1 in familial schwannomatosis. Am J Hum Genet 2007;80(4):805–10 doi 10.1086/513207. - DOI - PMC - PubMed
    1. Carter JM, O’Hara C, Dundas G, Gilchrist D, Collins MS, Eaton K, et al. Epithelioid malignant peripheral nerve sheath tumor arising in a schwannoma, in a patient with “neuroblastoma-like” schwannomatosis and a novel germline SMARCB1 mutation. Am J Surg Pathol 2012;36(1):154–60 doi 10.1097/PAS.0b013e3182380802. - DOI - PMC - PubMed

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Supplementary concepts