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Child's Nervous System

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01-10-2012 | Case-Based Update

Malignant transformation in pediatric spinal intramedullary tumors: case-based update

Authors: E. Winograd, N. Pencovich, M. Yalon, D. Soffer, L. Beni-Adani, S. Constantini

Published in: Child's Nervous System | Issue 10/2012

Abstract

Background

In children, intramedullary spinal cord neoplasms are rare. These are typically low-grade neuroepithelial tumors, most commonly astrocytomas, ependymomas, and gangliogliomas. Malignant transformation, while common in recurrent adult low-grade gliomas, is an unusual event in pediatric low-grade neoplasms, specifically in intramedullary spinal cord tumors.

Illustrative cases

We report two cases of malignant transformation in low-grade neuroepithelial tumors of the pediatric intramedullary spinal cord. Two children with intramedullary tumors, one with a WHO grade I ganglioglioma and one with a low-grade astrocytoma, were treated surgically, diagnosed histologically, and followed through the course of their disease. Both patients’ tumors transformed to higher grades without prior irradiation or chemotherapy, and without a genetic predisposition to tumorigenesis.

Discussion

Malignant transformation can occur in low-grade intramedullary neoplasms in children. This is a novel documented event for pediatric intramedullary spinal cord tumors and a rare event for all pediatric low-grade neuroepithelial tumors without induction by irradiation. A survey of the relevant literature reveals an underwhelming number of studies focusing on malignant transformation in children’s CNS tumors relative to adults. Further investigation into molecular mechanisms of pediatric low-grade neoplasms may reveal more aggressive tumor sub-variants predisposed to malignant degeneration.

Amini A, Chin SS, Schmidt MH (2007) Malignant transformation of conus medullaris ganglioglioma: case report. J Neurooncol 82(3):313–315PubMedCrossRef

Broniscer A, Baker SJ, West AN, Fraser MM, Proko E, Kocak M, Dalton J, Zambetti GP, Ellison DW, Kun LE, Gajjar A, Gilbertson RJ, Fuller CE (2007) Clinical and molecular characteristics of malignant transformation of low-grade glioma in children. J Clin Oncol 25(6):682–689PubMedCrossRef

Christensen BC, Smith AA, Zheng S, Koestler DC, Houseman EA, Marsit CJ, Wiemels JL, Nelson HH, Karagas MR, Wrensch MR, Kelsey KT, Wiencke JK (2011) DNA methylation, isocitrate dehydrogenase mutation, and survival in glioma. J Natl Cancer Inst 103:143–153PubMedCrossRef

Civitello LA, Packer RJ, Rorke LB, Siegel K, Sutton LN, Schut L (1988) Leptomeningeal dissemination of low-grade gliomas in childhood. Neurology 38(4):562–566PubMedCrossRef

Constantini S, Houten J, Miller DC, Freed D, Ozek MM, Rorke LB, Allen JC, Epstein FJ (1996) Intramedullary spinal cord tumors in children under the age of 3 years. J Neurosurg 85(6):1036–1043PubMedCrossRef

Constantini S, Miller DC, Allen JC, Rorke LB, Freed D, Epstein FJ (2000) Radical excision of intramedullary spinal cord tumors: surgical morbidity and long-term follow-up evaluation in 164 children and young adults. J Neurosurg 93(2 Suppl):183–193PubMed

Dirks PB, Jay V, Becker LE, Drake JM, Humphreys RP, Hoffman HJ, Rutka JT (1994) Development of anaplastic changes in low-grade astrocytomas of childhood. Neurosurgery 34(1):68–78PubMedCrossRef

Dutta D, Chendil V, Munshi A, Gupta T, Jalali R (2010) Spontaneous regression of optic chiasmatic glioma in pediatric patients: when to intervene? J Cancer Res Ther 6(4):591–593PubMedCrossRef

Houillier C, Wang X, Kaloshi G, Mokhtari K, Guillevin R, Laffaire J, Paris S, Boisselier B, Idbaih A, Laigle-Donadey F, Hoang-Xuan K, Sanson M, Delattre JY (2010) IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology 75:1560–1566PubMedCrossRef

10.

Huang H, Hara A, Homma T, Yonekawa Y, Ohgaki H (2005) Altered expression of immune defense genes in pilocytic astrocytomas. J Neuropathol Exp Neurol 64(10):891–901PubMedCrossRef

11.

Jay V, Squire J, Blaser S, Hoffman HJ, Hwang P (1997) Intracranial and spinal metastases from a ganglioglioma with unusual cytogenetic abnormalities in a patient with complex partial seizures. Childs Nerv Syst 13(10):550–555PubMedCrossRef

12.

Kothbauer KF (2007) Neurosurgical management of intramedullary spinal cord tumors in children. Pediatr Neurosurg 43(3):222–235PubMedCrossRef

13.

Laffaire J, Everhard S, Idbaih A, Criniere E, Marie Y, de Reynies A, Schiappa R, Mokhtari K, Hoang-Xuan K, Sanson M, Delattre JY, Thillet J, Ducray F (2011) Methylation profiling identifies 2 groups of gliomas according to their tumorigenesis. Neuro Oncol 13:84–98PubMedCrossRef

14.

McCormack BM, Miller DC, Budzilovich GN, Voorhees GJ, Ransohoff J (1992) Treatment and survival of low-grade astrocytoma in adults—1977–1988. Neurosurgery 31(4):636–642, discussion 642PubMedCrossRef

15.

Paraskevopoulos D, Patsalas I, Karkavelas G, Foroglou N, Magras I, Selviaridis P (2011) Pilomyxoid astrocytoma of the cervical spinal cord in a child with rapid progression into glioblastoma: case report and literature review. Childs Nerv Syst 27:313–321PubMedCrossRef

16.

Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812PubMedCrossRef

17.

Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M, Zhang J, Bax DA, Coyle B, Barrow J, Hargrave D, Lowe J, Gajjar A, Zhao W, Broniscer A, Ellison DW, Grundy RG, Baker SJ (2010) Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol 28(18):3061–3068PubMedCrossRef

18.

Perilongo G, Moras P, Carollo C, Battistella A, Clementi M, Laverda A, Murgia A (1999) Spontaneous partial regression of low-grade glioma in children with neurofibromatosis-1: a real possibility. J Child Neurol 14(6):352–356PubMedCrossRef

19.

Perrini P, Caniglia M, Pieroni M, Castagna M, Parenti GF (2010) Malignant transformation of intramedullary melanocytoma: case report. Neurosurgery 67(3):E867–E869, discussion E869PubMedCrossRef

20.

Pfister S, Janzarik WG, Remke M, Ernst A, Werft W, Becker N, Toedt G, Wittmann A, Kratz C, Olbrich H, Ahmadi R, Thieme B, Joos S, Radlwimmer B, Kulozik A, Pietsch T, Herold-Mende C, Gnekow A, Reifenberger G, Korshunov A, Scheurlen W, Omran H, Lichter P (2008) BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J Clin Invest 118(5):1739–1749PubMedCrossRef

21.

Qaddoumi I, Sultan I, Gajjar A (2009) Outcome and prognostic features in pediatric gliomas: a review of 6212 cases from the Surveillance, Epidemiology, and End Results database. Cancer 115(24):5761–5770PubMedCrossRef

22.

Rodriguez FJ, Scheithauer BW, Burger PC, Jenkins S, Giannini C (2010) Anaplasia in pilocytic astrocytoma predicts aggressive behavior. Am J Surg Pathol 34:147–160PubMedCrossRef

23.

Rodriguez EF, Scheithauer BW, Giannini C, Rynearson A, Cen L, Hoesley B, Gilmer-Flynn H, Sarkaria JN, Jenkins S, Long J, Rodriguez FJ (2011) PI3K/AKT pathway alterations are associated with clinically aggressive and histologically anaplastic subsets of pilocytic astrocytoma. Acta Neuropathol 121(3):407–420PubMedCrossRef

24.

Rozen WM, Joseph S, Lo PA (2008) Spontaneous regression of low-grade gliomas in pediatric patients without neurofibromatosis. Pediatr Neurosurg 44(4):324–328PubMedCrossRef

25.

Rumana CS, Valadka AB (1998) Radiation therapy and malignant degeneration of benign supratentorial gangliogliomas. Neurosurgery 42(5):1038–1043PubMedCrossRef

26.

Scheithauer BW HC, Tihan T et al (2007) Pilocytic astrocytoma. In: Louis D, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system, 4th edn. International Agency for Research on Cancer, Lyon, pp 14–21

27.

Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold-Mende C, Schmieder K, Wesseling P, Mawrin C, Hasselblatt M, Louis D, Korshunov A, Pfister S, Hartmann C, Paulus W, Reifenberger G, von Deimling A (2011) Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathologica 121:397–405PubMedCrossRef

28.

Schmidt MH, Berger MS, Lamborn KR, Aldape K, McDermott MW, Prados MD, Chang SM (2003) Repeated operations for infiltrative low-grade gliomas without intervening therapy. J Neurosurg 98(6):1165–1169PubMedCrossRef

29.

Stokland T, Liu JF, Ironside JW, Ellison DW, Taylor R, Robinson KJ, Picton SV, Walker DA (2010) A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population-based cohort study (CCLG CNS9702). Neuro Oncol 12(12):1257–1268PubMed

30.

Stuer C, Vilz B, Majores M, Becker A, Schramm J, Simon M (2007) Frequent recurrence and progression in pilocytic astrocytoma in adults. Cancer 110(12):2799–2808PubMedCrossRef

31.

Tabori U, Vukovic B, Zielenska M, Hawkins C, Braude I, Rutka J, Bouffet E, Squire J, Malkin D (2006) The role of telomere maintenance in the spontaneous growth arrest of pediatric low-grade gliomas. Neoplasia 8(2):136–142PubMedCrossRef

32.

Thompson WD Jr, Kosnik EJ (2005) Spontaneous regression of a diffuse brainstem lesion in the neonate. Report of two cases and review of the literature. J Neurosurg 102(1 Suppl):65–71PubMed

33.

Tien RD, Tuori SL, Pulkingham N, Burger PC (1992) Ganglioglioma with leptomeningeal and subarachnoid spread: results of CT, MR, and PET imaging. AJR Am J Roentgenol 159(2):391–393PubMed

34.

Tihan T, Fisher PG, Kepner JL, Godfraind C, McComb RD, Goldthwaite PT, Burger PC (1999) Pediatric astrocytomas with monomorphous pilomyxoid features and a less favorable outcome. J Neuropathol Exp Neurol 58(10):1061–1068PubMedCrossRef

35.

Vertosick FT Jr, Selker RG, Arena VC (1991) Survival of patients with well-differentiated astrocytomas diagnosed in the era of computed tomography. Neurosurgery 28(4):496–501PubMedCrossRef

36.

Von Deimling A, Korshunov A, Hartmann C (2010) The next generation of glioma biomarkers: MGMT methylation, BRAF fusions and IDH1 mutations. Brain Pathol 21(1):74–87CrossRef

37.

Wacker MR, Cogen PH, Etzell JE, Daneshvar L, Davis RL, Prados MD (1992) Diffuse leptomeningeal involvement by a ganglioglioma in a child. Case report. J Neurosurg 77(2):302–306PubMedCrossRef

38.

Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773PubMedCrossRef

39.

Yang S, Yang X, Hong G (2009) Surgical treatment of one hundred seventy-four intramedullary spinal cord tumors. Spine (Phila Pa 1976) 34(24):2705–2710CrossRef

Title: Malignant transformation in pediatric spinal intramedullary tumors: case-based update
Authors: E. Winograd
N. Pencovich
M. Yalon
D. Soffer
L. Beni-Adani
S. Constantini
Publication date: 01-10-2012
Publisher: Springer-Verlag
Published in: Child's Nervous System / Issue 10/2012
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI: https://doi.org/10.1007/s00381-012-1851-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Malignant transformation in pediatric spinal intramedullary tumors: case-based update

Abstract

Background

Illustrative cases

Discussion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Illustrative cases

Discussion

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