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Systematic review and cumulative analysis of clinical properties of BRAF V600E mutations in PLNTY histological samples

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Abstract

Purpose

Polymorphous low-grade neuroepithelial tumors of the young (PLNTY) represent a rare pediatric-type tumor that most commonly presents as medically refractory epilepsy. PLNTY has only recently been recognized as a distinct clinical entity, having been first described in 2016 and added to the World Health Organization classification of CNS tumors in 2021. Molecular studies have determined that PLNTY is uniformly driven by aberrant MAPK pathway activation, with most tumors carrying either a BRAF V600E mutation or activating FGFR2 or FGFR3 fusion protein. Although it is known that these driver mutations are mutually exclusive, little is known about differences in clinical presentation or treatment outcomes between PLNTY cases driven by these distinct mutations.

Methods

We performed a systematic review and cumulative analysis of PLNTY cases to assess whether or not PLNTY tumors carrying the BRAF V600E mutation exhibit different clinical behaviors. By searching the literature for all cases of PLNTY wherein BRAF V600E status was characterized, we compiled a dataset of 62 unique patient instances. Using a logistic regression-based approach, we assessed a primary outcome of what factors of a clinical presentation were associated with BRAF V600E mutations and a secondary outcome of what factors predicted total seizure freedom post-surgical resection.

Results

PLNTY cases carrying BRAF V600E mutations in the literature were strongly positively associated with adult patients (p = 0.0055, OR = 6.556; 95% Conf. Int. = 1.737–24.742). BRAF V600E status was also positively associated with tumor involvement of the temporal lobe (p = 0.0046, OR = 11.036; 95% Conf. Int. = 2.100–58.006). Male sex was also positively associated with BRAF V600E status, but the result did not quite achieve statistical significance (p = 0.0731). BRAF V600E status was not found to be associated with post-operative seizure freedom.

Conclusions

These findings indicate that BRAF V600E-positive PLNTY exhibit characteristic clinical presentations but are not necessarily different in treatment responsiveness. Non-BRAF V600E tumors are more commonly associated with young patients.

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References

  1. Huse JT, Snuderl M, Jones DTW et al (2017) Polymorphous low-grade neuroepithelial Tumor of the young (PLNTY): an epileptogenic Neoplasm with oligodendroglioma-like components, aberrant CD34 expression, and genetic alterations involving the MAP kinase pathway. Acta Neuropathol (Berl) 133:417–429. https://doi.org/10.1007/s00401-016-1639-9

    Article  CAS  PubMed  Google Scholar 

  2. Ida CM, Johnson DR, Nair AA et al (2021) Polymorphous low-Grade Neuroepithelial Tumor of the Young (PLNTY): molecular profiling confirms frequent MAPK pathway activation. J Neuropathol Exp Neurol 80:821–829. https://doi.org/10.1093/jnen/nlab075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Furuta T, Moritsubo M, Muta H et al Pediatric and elderly polymorphous low-grade neuroepithelial Tumor of the young: typical and unusual case reports and literature review. Neuropathology. https://doi.org/10.1111/neup.12889

  4. Riva G, Cima L, Villanova M et al (2018) Low-grade neuroepithelial Tumor: unusual presentation in an adult without history of seizures. Neuropathol off J Jpn Soc Neuropathol 38:557–560. https://doi.org/10.1111/neup.12504

    Article  CAS  Google Scholar 

  5. Benson JC, Summerfield D, Carr C et al (2020) Polymorphous low-Grade Neuroepithelial Tumor of the Young as a partially calcified Intra-axial Mass in an adult. AJNR Am J Neuroradiol 41:573–578. https://doi.org/10.3174/ajnr.A6500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bitar M, Danish SF, Rosenblum MK (2018) A newly diagnosed case of polymorphous low-grade neuroepithelial Tumor of the young. Clin Neuropathol 37:178–181. https://doi.org/10.5414/NP301081

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bale TA, Sait SF, Benhamida J et al (2021) Malignant transformation of a polymorphous low grade neuroepithelial Tumor of the young (PLNTY). Acta Neuropathol (Berl) 141:123–125. https://doi.org/10.1007/s00401-020-02245-4

    Article  PubMed  Google Scholar 

  8. Johnson DR, Giannini C, Jenkins RB et al (2019) Plenty of calcification: imaging characterization of polymorphous low-grade neuroepithelial Tumor of the young. Neuroradiology 61:1327–1332. https://doi.org/10.1007/s00234-019-02269-y

    Article  PubMed  Google Scholar 

  9. Armocida D, Berra LV, Frati A, Santoro A (2023) Radiological and surgical aspects of polymorphous low-grade neuroepithelial Tumor of the young (PLNTY). https://doi.org/10.1007/s13760-023-02231-z. Acta Neurol Belg

  10. Rizzi M, Castelli N, Di Giacomo R et al (2023) Left Mesial Temporooccipital PLNTY: Supracerebellar Transtentorial Approach in Epilepsy Surgery. World Neurosurg 171:136. https://doi.org/10.1016/j.wneu.2022.12.100

    Article  PubMed  Google Scholar 

  11. Zhao S, Wang J, Li MN et al (2022) [Clinicopathological features of polymorphous low-grade neuroepithelial Tumor of the young]. Zhonghua Bing Li Xue Za Zhi 51:640–646. https://doi.org/10.3760/cma.j.cn112151-20220315-00188

    Article  CAS  PubMed  Google Scholar 

  12. Kurokawa M, Kurokawa R, Capizzano AA et al (2022) Neuroradiological features of the polymorphous low-grade neuroepithelial Tumor of the young: five new cases with a systematic review of the literature. Neuroradiology 64:1255–1264. https://doi.org/10.1007/s00234-021-02879-5

    Article  PubMed  Google Scholar 

  13. Broggi G, Certo F, Altieri R et al (2021) A polymorphous low-grade neuroepithelial Tumor of the young (PLNTY) diagnosed in an adult. Report of a case and review of the literature. Surg Neurol Int 12:470. https://doi.org/10.25259/SNI_500_2021

    Article  PubMed  PubMed Central  Google Scholar 

  14. Fei X, Zhao J, Wei W et al (2022) Clinical, radiological, pathological features and seizure outcome with Surgical Management of Polymorphous Low-Grade Neuroepithelial Tumor of the Young Associated with Epilepsy. Front Oncol 12:863373. https://doi.org/10.3389/fonc.2022.863373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gupta R, Lucas C-HG, Wu J et al (2021) Low-grade glioneuronal tumors with FGFR2 fusion resolve into a single epigenetic group corresponding to ‘Polymorphous low-grade neuroepithelial Tumor of the young’. Acta Neuropathol (Berl) 142:595–599. https://doi.org/10.1007/s00401-021-02352-w

    Article  CAS  PubMed  Google Scholar 

  16. Hagiwara K, Kamada T, Suzuki SO et al (2022) Stereo-electroencephalography evidence of an eccentrically located seizure-onset zone around a polymorphous low-grade neuroepithelial Tumor of the young: illustrative case. J Neurosurg Case Lessons 3. https://doi.org/10.3171/CASE22106

  17. Lelotte J, Duprez Th, Raftopoulos C, Michotte A (2020) Polymorphous low-grade neuroepithelial Tumor of the young: case report of a newly described histopathological entity. Acta Neurol Belg 120:729–732. https://doi.org/10.1007/s13760-019-01241-0

    Article  CAS  PubMed  Google Scholar 

  18. Palejwala AH, O’Neal CM, Quinton MR et al (2022) Polymorphous low-grade neuroepithelial Tumor of the young: rare Tumor and review of the literature. Rare Tumors 14:20363613221083360. https://doi.org/10.1177/20363613221083360

    Article  PubMed  PubMed Central  Google Scholar 

  19. Sumdani H, Shahbuddin Z, Harper G, Hamilton L (2019) Case Report of rarely described polymorphous low-Grade Neuroepithelial Tumor of the Young and comparison with Oligodendroglioma. World Neurosurg 127:47–51. https://doi.org/10.1016/j.wneu.2019.03.181

    Article  PubMed  Google Scholar 

  20. Surrey LF, Jain P, Zhang B et al (2019) Genomic Analysis of Dysembryoplastic Neuroepithelial Tumor Spectrum reveals a diversity of molecular alterations dysregulating the MAPK and PI3K/mTOR pathways. J Neuropathol Exp Neurol 78:1100–1111. https://doi.org/10.1093/jnen/nlz101

    Article  CAS  PubMed  Google Scholar 

  21. Tateishi K, Ikegaya N, Udaka N et al (2020) BRAF V600E mutation mediates FDG-methionine uptake mismatch in polymorphous low-grade neuroepithelial Tumor of the young. Acta Neuropathol Commun 8:139. https://doi.org/10.1186/s40478-020-01023-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gupta VR, Giller C, Kolhe R et al (2019) Polymorphous low-Grade Neuroepithelial Tumor of the Young: a Case Report with genomic findings. World Neurosurg 132:347–355. https://doi.org/10.1016/j.wneu.2019.08.221

    Article  PubMed  Google Scholar 

  23. Chen Y, Tian T, Guo X et al (2020) Polymorphous low-grade neuroepithelial Tumor of the young: case report and review focus on the radiological features and genetic alterations. BMC Neurol 20:123. https://doi.org/10.1186/s12883-020-01679-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Danyeli AE, Altinoz MA, Sari R, Elmaci I (2021) Polymorphous low-grade neuroepithelial Tumor of the young: a detailed pathomolecular analysis and discussion of a case. Clin Neuropathol 40:271–278. https://doi.org/10.5414/NP301370

    Article  PubMed  Google Scholar 

  25. Ge R, Fang HF, Chang YQ et al (2020) [Clinicopathological features of polymorphous low-grade neuroepithelial Tumor of the young]. Zhonghua Bing Li Xue Za Zhi 49:1131–1135. https://doi.org/10.3760/cma.j.cn112151-20200213-00086

    Article  CAS  PubMed  Google Scholar 

  26. Fabbri VP, Caporalini C, Asioli S, Buccoliero A (2022) Paediatric-type diffuse low-grade gliomas: a clinically and biologically distinct group of tumours with a favourable outcome. Pathologica 114:410–421. https://doi.org/10.32074/1591-951X-828

    Article  PubMed  PubMed Central  Google Scholar 

  27. Paredes-Aragón EM, AlKhaldi NA, Burneo JG et al (2023) Pearls & Oy-sters: Salt and Pepper sign, PLNTY for Drug-Resistant Epilepsy. Neurology 100:791–795. https://doi.org/10.1212/WNL.0000000000206782

    Article  PubMed  Google Scholar 

  28. Zhang K, Sassoon A (2018) Polymorphous low-Grade Neuroepithelial Tumor of the Young (PLNTY): two cases of the recently described Epileptogenic Neoplasm with Oligodendroglioma-Like Components and Heavy calcification. Am J Clin Pathol 150:S16–S17. https://doi.org/10.1093/ajcp/aqy090.040

    Article  Google Scholar 

  29. Hendrych M, Hemza J, Kočvarová J et al (2021) Polymorphous low-grade neuroepithelial Tumor of the young. Cesk Slov Neurol N 117:282–285

    Google Scholar 

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Author information

Authors and Affiliations

  1. The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michael E. Baumgartner

  2. Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA

    Shih-Shan Lang, Alexander M. Tucker, Peter J. Madsen & Benjamin C. Kennedy

  3. Division of Neurosurgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Shih-Shan Lang, Alexander M. Tucker, Peter J. Madsen, Phillip B. Storm & Benjamin C. Kennedy

  4. Division of Neurosurgery, Center for Data Driven Discovery in Biomedicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Phillip B. Storm

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  1. Michael E. Baumgartner
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Contributions

MEB and BCK devised the analysis strategy. MEB performed the search, statistical analysis, and initial manuscript preparation. SL, AMT, PJM, and PBS revised the manuscript and provided editorial support and feedback on analysis.

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Correspondence to Michael E. Baumgartner.

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Baumgartner, M.E., Lang, SS., Tucker, A.M. et al. Systematic review and cumulative analysis of clinical properties of BRAF V600E mutations in PLNTY histological samples. Childs Nerv Syst 40, 1361–1366 (2024). https://doi.org/10.1007/s00381-023-06256-w

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