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Child's Nervous System

, Volume 35, Issue 11, pp 2047–2054 | Cite as

The molecular oncology of bilateral high-grade thalamic astrocytomas in children

  • Amir GoodarziEmail author
  • Nicholas Garza
  • Mirna Lechpammer
  • Reuben Anthony
  • Marike Zwienenberg
Case-Based Update

Abstract

Background

Bilateral thalamic astrocytomas in children are exceedingly rare. These highly malignant tumors seldom respond to conventional treatment strategies and carry a grim prognosis for patients. However, recent advances in molecular oncology have had a positive impact on prognostication and treatment strategies of these tumors.

Case-based review

We present a new case of WHO grade III bilateral thalamic astrocytoma in a child and review the pathophysiology, molecular oncogenesis, and relevant treatment strategies for this rare disease.

Conclusions

High-grade thalamic astrocytomas affecting both thalami pose a challenge to pediatric neurosurgeons, neuro-oncologists, and neuropathologists given the lack of effective treatment strategies. Understanding recent revelations in the field of molecular oncology can assist clinicians in adequately formulating a treatment plan in this patient population.

Keywords

Molecular Oncology Histones Glioma 

Notes

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

References

  1. 1.
    Di Rocco C, Iannelli A (2002) Bilateral thalamic tumors in children. Childs Nerv Syst 18:440–444.  https://doi.org/10.1007/s00381-002-0609-9 CrossRefPubMedGoogle Scholar
  2. 2.
    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820.  https://doi.org/10.1007/s00401-016-1545-1 CrossRefGoogle Scholar
  3. 3.
    Cheng Y, Ng HK, Zhang SF, Ding M, Pang JCS, Zheng J, Poon WS (1999) Genetic alterations in pediatric high-grade astrocytomas. Hum Pathol 30:1284–1290CrossRefGoogle Scholar
  4. 4.
    Gielen GH, Gessi M, Hammes J, Kramm CM, Waha A, Pietsch T (2013) H3F3A K27M mutation in pediatric CNS tumors: a marker for diffuse high-grade astrocytomas. Am J Clin Pathol 139:345–349.  https://doi.org/10.1309/AJCPABOHBC33FVMO CrossRefPubMedGoogle Scholar
  5. 5.
    Rizzo D, Ruggiero A, Martini M, Rizzo V, Maurizi P, Riccardi R (2015) Molecular biology in pediatric high-grade glioma: impact on prognosis and treatment. Biomed Res Int 2015:215135–215110.  https://doi.org/10.1155/2015/215135 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Cinalli G, Aguirre DT, Mirone G, Ruggiero C, Cascone D, Quaglietta L, Aliberti F, Santi S’, Buonocore MC, Nastro A, Spennato P (2018) Surgical treatment of thalamic tumors in children. J Neurosurg Pediatr 21:247–257.  https://doi.org/10.3171/2017.7.Peds16463 CrossRefPubMedGoogle Scholar
  7. 7.
    Esteve F et al (1999) MR spectroscopy of bilateral thalamic gliomas. AJNR Am J Neuroradiol 20:876–881PubMedGoogle Scholar
  8. 8.
    Gupta A, Shaller N, McFadden KA (2017) Pediatric thalamic gliomas: an updated review. Arch Pathol Lab Med 141:1316–1323.  https://doi.org/10.5858/arpa.2017-0249-RA CrossRefPubMedGoogle Scholar
  9. 9.
    Schwartzentruber J, Korshunov A, Liu XY, Jones DTW, Pfaff E, Jacob K, Sturm D, Fontebasso AM, Quang DAK, Tönjes M, Hovestadt V, Albrecht S, Kool M, Nantel A, Konermann C, Lindroth A, Jäger N, Rausch T, Ryzhova M, Korbel JO, Hielscher T, Hauser P, Garami M, Klekner A, Bognar L, Ebinger M, Schuhmann MU, Scheurlen W, Pekrun A, Frühwald MC, Roggendorf W, Kramm C, Dürken M, Atkinson J, Lepage P, Montpetit A, Zakrzewska M, Zakrzewski K, Liberski PP, Dong Z, Siegel P, Kulozik AE, Zapatka M, Guha A, Malkin D, Felsberg J, Reifenberger G, von Deimling A, Ichimura K, Collins VP, Witt H, Milde T, Witt O, Zhang C, Castelo-Branco P, Lichter P, Faury D, Tabori U, Plass C, Majewski J, Pfister SM, Jabado N (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482:226–231.  https://doi.org/10.1038/nature10833 CrossRefPubMedGoogle Scholar
  10. 10.
    Wu G, Broniscer A, McEachron T, Lu C, Paugh BS, Becksfort J, Qu C, Ding L, Huether R, Parker M, Zhang J, Gajjar A, Dyer MA, Mullighan CG, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Ellison DW, Zhang J, Baker SJ, St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251–253.  https://doi.org/10.1038/ng.1102 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Mackay A et al (2017) Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma. Cancer Cell 32:520–537 e525.  https://doi.org/10.1016/j.ccell.2017.08.017 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Broniscer A, Hwang SN, Chamdine O, Lin T, Pounds S, Onar-Thomas A, Chi L, Shurtleff S, Allen S, Gajjar A, Northcott P, Orr BA (2018) Bithalamic gliomas may be molecularly distinct from their unilateral high-grade counterparts. Brain Pathol 28:112–120.  https://doi.org/10.1111/bpa.12484 CrossRefPubMedGoogle Scholar
  13. 13.
    Korshunov A, Schrimpf D, Ryzhova M, Sturm D, Chavez L, Hovestadt V, Sharma T, Habel A, Burford A, Jones C, Zheludkova O, Kumirova E, Kramm CM, Golanov A, Capper D, von Deimling A, Pfister SM, Jones DTW (2017) H3-/IDH-wild type pediatric glioblastoma is comprised of molecularly and prognostically distinct subtypes with associated oncogenic drivers. Acta Neuropathol 134:507–516.  https://doi.org/10.1007/s00401-017-1710-1 CrossRefPubMedGoogle Scholar
  14. 14.
    Castel D, Philippe C, Calmon R, le Dret L, Truffaux N, Boddaert N, Pagès M, Taylor KR, Saulnier P, Lacroix L, Mackay A, Jones C, Sainte-Rose C, Blauwblomme T, Andreiuolo F, Puget S, Grill J, Varlet P, Debily MA (2015) Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol 130:815–827.  https://doi.org/10.1007/s00401-015-1478-0 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Abedalthagafi M, Phillips JJ, Kim GE, Mueller S, Haas-Kogen DA, Marshall RE, Croul SE, Santi MR, Cheng J, Zhou S, Sullivan LM, Martinez-Lage M, Judkins AR, Perry A (2013) The alternative lengthening of telomere phenotype is significantly associated with loss of ATRX expression in high-grade pediatric and adult astrocytomas: a multi-institutional study of 214 astrocytomas. Mod Pathol 26:1425–1432.  https://doi.org/10.1038/modpathol.2013.90 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Wiestler B, Capper D, Holland-Letz T, Korshunov A, von Deimling A, Pfister SM, Platten M, Weller M, Wick W (2013) ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. Acta Neuropathol 126:443–451.  https://doi.org/10.1007/s00401-013-1156-z CrossRefPubMedGoogle Scholar
  17. 17.
    Durant ST (2012) Telomerase-independent paths to immortality in predictable cancer subtypes. J Cancer 3:67–82.  https://doi.org/10.7150/jca.3965 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Nguyen DN, Heaphy CM, de Wilde RF, Orr BA, Odia Y, Eberhart CG, Meeker AK, Rodriguez FJ (2013) Molecular and morphologic correlates of the alternative lengthening of telomeres phenotype in high-grade astrocytomas. Brain Pathol 23:237–243.  https://doi.org/10.1111/j.1750-3639.2012.00630.x CrossRefPubMedGoogle Scholar
  19. 19.
    Andrae J, Gallini R, Betsholtz C (2008) Role of platelet-derived growth factors in physiology and medicine. Genes Dev 22:1276–1312.  https://doi.org/10.1101/gad.1653708 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Paugh BS, Zhu X, Qu C, Endersby R, Diaz AK, Zhang J, Bax DA, Carvalho D, Reis RM, Onar-Thomas A, Broniscer A, Wetmore C, Zhang J, Jones C, Ellison DW, Baker SJ (2013) Novel oncogenic PDGFRA mutations in pediatric high-grade gliomas. Cancer Res 73:6219–6229.  https://doi.org/10.1158/0008-5472.CAN-13-1491 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ (2014) The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 46:444–450.  https://doi.org/10.1038/ng.2938 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Koschmann C et al (2016) Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma. Oncotarget 7:65696–65706.  https://doi.org/10.18632/oncotarget.11602 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Parrales A, Iwakuma T (2015) Targeting oncogenic mutant p53 for cancer therapy. Front Oncol 5:288.  https://doi.org/10.3389/fonc.2015.00288 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Pollack IF, Finkelstein SD, Woods J, Burnham J, Holmes EJ, Hamilton RL, Yates AJ, Boyett JM, Finlay JL, Sposto R (2002) Expression of p53 and prognosis in children with malignant gliomas. N Engl J Med 346:420–427.  https://doi.org/10.1056/NEJMoa012224 CrossRefPubMedGoogle Scholar
  25. 25.
    Donson AM, Addo-Yobo SO, Handler MH, Gore L, Foreman NK (2007) MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma. Pediatr Blood Cancer 48:403–407.  https://doi.org/10.1002/pbc.20803 CrossRefPubMedGoogle Scholar
  26. 26.
    Srivastava A, Jain A, Jha P, Suri V, Sharma MC, Mallick S, Puri T, Gupta DK, Gupta A, Sarkar C (2010) MGMT gene promoter methylation in pediatric glioblastomas. Childs Nerv Syst 26:1613–1618.  https://doi.org/10.1007/s00381-010-1214-y CrossRefPubMedGoogle Scholar
  27. 27.
    Carter DJ, Wiedmeyer DA, Antuono PG, Ho KC (1989) Correlation of computed tomography and postmortem findings of a diffuse astrocytoma: a case report. Comput Med Imaging Graph 13:491–494CrossRefGoogle Scholar
  28. 28.
    Bilginer B, Narin F, Işıkay I, Oguz KK, Söylemezoglu F, Akalan N (2014) Thalamic tumors in children. Childs Nerv Syst 30:1493–1498.  https://doi.org/10.1007/s00381-014-2420-9 CrossRefPubMedGoogle Scholar
  29. 29.
    Kramm CM, Butenhoff S, Rausche U, Warmuth-Metz M, Kortmann RD, Pietsch T, Gnekow A, Jorch N, Janssen G, Berthold F, Wolff JE (2011) Thalamic high-grade gliomas in children: a distinct clinical subset? Neuro-Oncology 13:680–689.  https://doi.org/10.1093/neuonc/nor045 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Kann BH, Park HS, Lester-Coll NH, Yeboa DN, Benitez V, Khan AJ, Bindra RS, Marks AM, Roberts KB (2016) Postoperative radiotherapy patterns of care and survival implications for medulloblastoma in young children. JAMA Oncol 2:1574–1581.  https://doi.org/10.1001/jamaoncol.2016.2547 CrossRefPubMedGoogle Scholar
  31. 31.
    Grill J, Massimino M, Bouffet E, Azizi AA, McCowage G, Cañete A, Saran F, le Deley MC, Varlet P, Morgan PS, Jaspan T, Jones C, Giangaspero F, Smith H, Garcia J, Elze MC, Rousseau RF, Abrey L, Hargrave D, Vassal G (2018) Phase II, open-label, randomized, multicenter trial (HERBY) of bevacizumab in pediatric patients with newly diagnosed high-grade glioma. J Clin Oncol 36:951–958.  https://doi.org/10.1200/JCO.2017.76.0611 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Departments of Neurological SurgeryUniversity of California, DavisSacramentoUSA
  2. 2.School of MedicineUniversity of California, DavisSacramentoUSA
  3. 3.Department of PathologyUniversity of California, DavisSacramentoUSA
  4. 4.Department of Pediatric Hematology-OncologyUniversity of California, DavisSacramentoUSA

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