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Central nervous system neuroepithelial tumors with MN1-alteration: an individual patient data meta-analysis of 73 cases

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Abstract

MN1 alteration characterizes a recently described group of neuroepithelial tumors with varied morphological features. In cIMPACT-NOW update 6, only those with astroblastoma morphology has been accepted as a newly recognized tumor type, whereas the rest of morphological variants are considered lesions sub-judice. We perform an individual patient data meta-analysis of MN1-altered neuroepithelial tumors comprising a total of 73 cases, in order to study the survival data and predictive markers for better diagnosis and management of this rare molecular entity. The 5- and 10-year progression-free survival are 38% and 0%, whereas the 5- and 10-year overall survival are 89% and 55%, respectively. Among all the morphological variants of MN1-altered tumor, astroblastoma morphology is significantly associated with an improved overall survival, emphasizing the importance of providing an integrated histologic and molecular diagnosis. Histological grading within the molecularly-defined MN1-altered astroblastoma remains controversial. In tumors with astroblastoma morphology, the odds of MN1-altered status among patients less than 15-year-old is 10.5 times that of those 15-year-old and older, and female of 9.4 times that of the male gender. Gross tumor resection appears as main treatment modality for better disease control based on observational data.

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References

  1. Boisseau W, Euskirchen P, Mokhtari K, Dehais C, Touat M, Hoang-Xuan K et al (2019) Molecular profiling reclassifies adult astroblastoma into known and clinically distinct tumor entities with frequent mitogen-activated protein kinase pathway alterations. Oncologist 24:1584–1592. https://doi.org/10.1634/theoncologist.2019-0223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Brat D, Perry A (2018) Other glial neoplasms. In: Brat D, Perry A (eds) Practical surgical neuropathology a diagnostic approach, 2nd edn. Elsevier, Philadelphia, pp 175–178

    Google Scholar 

  3. Burford A, Mackay A, Popov S, Vinci M, Carvalho D, Clarke M et al (2018) The ten-year evolutionary trajectory of a highly recurrent paediatric high grade neuroepithelial tumour with MN1:BEND2 fusion. Neuro-Oncology 20:i40. https://doi.org/10.1093/neuonc/noy059

    Article  PubMed Central  Google Scholar 

  4. Hirose T, Nobusawa S, Sugiyama K, Amatya VJ, Fujimoto N, Sasaki A et al (2018) Astroblastoma: a distinct tumor entity characterized by alterations of the X chromosome and MN1 rearrangement. Brain Pathol 28:684–694. https://doi.org/10.1111/bpa.12565

    Article  CAS  PubMed  Google Scholar 

  5. Korshunov A, McLendon R, Judkins A, Pfister S, Eberhart C, Fuller G et al (2016) Embryonal tumour with multilayered rosettes, C19MC-altered In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system revised, 4th edn. International Agency for Research on Cancer, Lyon, pp 201–205

  6. Lehman NL, Hattab EM, Mobley BC, Usubalieva A, Schniederjan MJ, McLendon RE et al (2017) Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults. Neuro Oncol 19:31–42. https://doi.org/10.1093/neuonc/now118

    Article  CAS  PubMed  Google Scholar 

  7. Lehman NL, Usubalieva A, Lin T, Allen SJ, Tran QT, Mobley BC et al (2019) Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis. Acta Neuropathol Commun 7:42. https://doi.org/10.1186/s40478-019-0689-3

    Article  PubMed  PubMed Central  Google Scholar 

  8. Louis DN, Perry A, Burger P, Ellison DW, Reifenberger G, von Deimling A et al (2014) International Society of Neuropathology-Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol 24:429–435. https://doi.org/10.1111/bpa.12171

    Article  PubMed  Google Scholar 

  9. Louis DN, Wesseling P, Aldape K, Brat DJ, Capper D, Cree IA et al (2020) cIMPACT-NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT-Utrecht meeting on future CNS tumor classification and grading. Brain Pathol. https://doi.org/10.1111/bpa.12832

    Article  PubMed  Google Scholar 

  10. McLendon R, Judkins A, Eberhart C, Fuller G, Sarkar C, Ng H et al (2016) Other CNS embryonal tumours. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system revised, 4th edn. International Agency for Research on Cancer, Lyon, pp 206–208

  11. Mhatre R, Sugur HS, Nandeesh BN, Chickabasaviah Y, Saini J, Santosh V (2019) MN1 rearrangement in astroblastoma: study of eight cases and review of literature. Brain Tumor Pathol 36:112–120. https://doi.org/10.1007/s10014-019-00346-x

    Article  CAS  PubMed  Google Scholar 

  12. Neumann JE, Spohn M, Obrecht D, Mynarek M, Thomas C, Hasselblatt M et al (2019) Molecular characterization of histopathological ependymoma variants. Acta Neuropathol. https://doi.org/10.1007/s00401-019-02090-0

    Article  PubMed  PubMed Central  Google Scholar 

  13. Otero JJ, Rowitch D, Vandenberg S (2011) OLIG2 is differentially expressed in pediatric astrocytic and in ependymal neoplasms. J Neurooncol 104:423–438. https://doi.org/10.1007/s11060-010-0509-x

    Article  PubMed  Google Scholar 

  14. Petruzzellis G, Alessi I, Colafati GS, Diomedi-Camassei F, Ciolfi A, Pedace L et al (2019) Role of DNA methylation profile in diagnosing astroblastoma: a case report and literature review. Front Genet 10:391. https://doi.org/10.3389/fgene.2019.00391

    Article  PubMed  PubMed Central  Google Scholar 

  15. Shin SA, Ahn B, Kim SK, Kang HJ, Nobusawa S, Komori T et al (2018) Brainstem astroblastoma with MN1 translocation. Neuropathology 38:631–637. https://doi.org/10.1111/neup.12514

    Article  PubMed  Google Scholar 

  16. Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW, Capper D et al (2016) New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell 164:1060–1072. https://doi.org/10.1016/j.cell.2016.01.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Svajdler M, Rychly B, Mezencev R, Frohlichova L, Bednarova A, Pataky F et al (2016) SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: an immunohistochemical study of 98 glial tumors. Histol Histopathol 31:95–102. https://doi.org/10.14670/HH-11-654

    Article  CAS  PubMed  Google Scholar 

  18. Wood MD, Tihan T, Perry A, Chacko G, Turner C, Pu C et al (2018) Multimodal molecular analysis of astroblastoma enables reclassification of most cases into more specific molecular entities. Brain Pathol 28:192–202. https://doi.org/10.1111/bpa.12561

    Article  CAS  PubMed  Google Scholar 

  19. Yamada SM, Tomita Y, Shibui S, Takahashi M, Kawamoto M, Nobusawa S et al (2018) Primary spinal cord astroblastoma: case report. J Neurosurg Spine 28:642–646. https://doi.org/10.3171/2017.9.SPINE161302

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

    Wanwan Chen

  2. Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore

    Wanwan Chen, Chik Hong Kuick, Kenneth T. E. Chang & Char Loo Tan

  3. Department of Radiation Oncology, National University Health System, Singapore, Singapore

    Yu Yang Soon

  4. Department of Pathology, Siloam Hospital Lippo Village Karawaci, Tangerang, Indonesia

    Patricia Diana Pratiseyo

  5. Department of Radiology, Siloam Hospital Lippo Village Karawaci, Tangerang, Indonesia

    Ratna Sutanto

  6. Department of Neurosurgery, Siloam Hospital Lippo Village Karawaci, Tangerang, Indonesia

    Lutfi Hendriansyah

  7. Duke-NUS Medical School, Singapore, Singapore

    Kenneth T. E. Chang

  8. Department of Pathology, National University Health System, 5 Lower Kent Ridge Road, Main Building, Level 3, Singapore, 119074, Singapore

    Char Loo Tan

  9. Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Char Loo Tan

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  1. Wanwan Chen
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Correspondence to Char Loo Tan.

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Chen, W., Soon, Y.Y., Pratiseyo, P.D. et al. Central nervous system neuroepithelial tumors with MN1-alteration: an individual patient data meta-analysis of 73 cases. Brain Tumor Pathol 37, 145–153 (2020). https://doi.org/10.1007/s10014-020-00372-0

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  • DOI: https://doi.org/10.1007/s10014-020-00372-0

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