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Published in: Child's Nervous System 8/2020

01-08-2020 | Glioma | Review Article

Management of incidental brain tumors in children: a systematic review

Authors: Jehuda Soleman, Danil A. Kozyrev, Liat Ben-Sira, Shlomi Constantini, Jonathan Roth

Published in: Child's Nervous System | Issue 8/2020

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Abstract

Background

Due to technical advancements and availability of neuroimaging, detection of incidental pediatric brain tumors (IPBT) is growing rapidly. The management of these asymptomatic lesions remains unclear; radiological, pathological, and clinical risk factors for further growth and malignant transformation (MT) are not well defined.

Methods

We systematically reviewed the literature on the dilemmas and management of IPBT suggestive of a low-grade brain tumor (LGBT). Keyword searches of the PubMed and Medline (NCBI) databases identified studies on IPBT describing the prevalence, neuroimaging, management, or risk of MT through July 2019. References of the identified articles were also reviewed.

Results

A total of 2021 records were screened. Fifty-nine full-text articles were reviewed, and 34 published studies were included. IPBT are diagnosed in 0.2–5.7% of children undergoing brain imaging for various reasons. The accepted approach for management of lesions showing radiological characteristics suggestive of LGBT is radiological follow-up. The rate at which additional intervention is required during follow-up for these apparently low-grade lesions is 9.5%. Nevertheless, the dilemma of early surgical resection or biopsy vs. clinical and radiological follow-up of IPBT is still unresolved. The risk in these cases is missing a transformation to a higher grade tumor. However, MT of pediatric LGBT is very rare, occurring in less than 3% of the cases of proven low-grade gliomas in children. The risk of future MT in pediatric low-grade gliomas seems to be greater in the presence of specific molecular markers such as BRAF V-600E, CDKN2A, and H3F3A K27M.

Conclusions

The natural history, management, and prognosis of IPBT remain ambiguous. It seems that lesions suggestive of LGBT can initially be followed, since many of these lesions remain stable over time and MT is rare. However, controversy among centers concerning the ideal approach still exists. Further observational and prospective cohort studies, focusing on potential clinical and radiological characteristics or risk factors suggestive of high-grade tumors, tumor progress, or MT of IPBT, are needed.
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Literature
10.
go back to reference Jansen PR, Dremmen M, van den Berg A, Dekkers IA, Blanken LME, Muetzel RL, Bolhuis K, Mulder RM, Kocevska D, Jansen TA, de Wit MCY, Neuteboom RF, Polderman TJC, Posthuma D, Jaddoe VWV, Verhulst FC, Tiemeier H, van der Lugt A, White TJH (2017) Incidental findings on brain imaging in the general pediatric population. N Engl J Med 377:1593–1595. https://doi.org/10.1056/NEJMc1710724CrossRefPubMed Jansen PR, Dremmen M, van den Berg A, Dekkers IA, Blanken LME, Muetzel RL, Bolhuis K, Mulder RM, Kocevska D, Jansen TA, de Wit MCY, Neuteboom RF, Polderman TJC, Posthuma D, Jaddoe VWV, Verhulst FC, Tiemeier H, van der Lugt A, White TJH (2017) Incidental findings on brain imaging in the general pediatric population. N Engl J Med 377:1593–1595. https://​doi.​org/​10.​1056/​NEJMc1710724CrossRefPubMed
22.
go back to reference 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 34:68–78PubMed 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 34:68–78PubMed
23.
go back to reference Ishibashi K, Inoue T, Fukushima H, Watanabe Y, Iwai Y, Sakamoto H, Yamasaki K, Hara J, Shofuda T, Kanematsu D, Yoshioka E, Kanemura Y (2016) Pediatric thalamic glioma with H3F3A K27M mutation, which was detected before and after malignant transformation: a case report. Childs Nerv Syst 32:2433–2438. https://doi.org/10.1007/s00381-016-3161-8CrossRefPubMed Ishibashi K, Inoue T, Fukushima H, Watanabe Y, Iwai Y, Sakamoto H, Yamasaki K, Hara J, Shofuda T, Kanematsu D, Yoshioka E, Kanemura Y (2016) Pediatric thalamic glioma with H3F3A K27M mutation, which was detected before and after malignant transformation: a case report. Childs Nerv Syst 32:2433–2438. https://​doi.​org/​10.​1007/​s00381-016-3161-8CrossRefPubMed
25.
go back to reference Kim NR, Wang K-C, Bang J-S, Choe G, Park Y, Kim SK, Cho BK, Chi JG (2003) Glioblastomatous transformation of ganglioglioma: case report with reference to molecular genetic and flow cytometric analysis. Pathol Int 53:874–882CrossRefPubMed Kim NR, Wang K-C, Bang J-S, Choe G, Park Y, Kim SK, Cho BK, Chi JG (2003) Glioblastomatous transformation of ganglioglioma: case report with reference to molecular genetic and flow cytometric analysis. Pathol Int 53:874–882CrossRefPubMed
36.
go back to reference Castelo-Branco P, Choufani S, Mack S, Gallagher D, Zhang C, Lipman T, Zhukova N, Walker EJ, Martin D, Merino D, Wasserman JD, Elizabeth C, Alon N, Zhang L, Hovestadt V, Kool M, Jones DTW, Zadeh G, Croul S, Hawkins C, Hitzler J, Wang JCY, Baruchel S, Dirks PB, Malkin D, Pfister S, Taylor MD, Weksberg R, Tabori U (2013) Methylation of the TERT promoter and risk stratification of childhood brain tumours: an integrative genomic and molecular study. Lancet Oncol 14:534–542. https://doi.org/10.1016/S1470-2045(13)70110-4CrossRefPubMed Castelo-Branco P, Choufani S, Mack S, Gallagher D, Zhang C, Lipman T, Zhukova N, Walker EJ, Martin D, Merino D, Wasserman JD, Elizabeth C, Alon N, Zhang L, Hovestadt V, Kool M, Jones DTW, Zadeh G, Croul S, Hawkins C, Hitzler J, Wang JCY, Baruchel S, Dirks PB, Malkin D, Pfister S, Taylor MD, Weksberg R, Tabori U (2013) Methylation of the TERT promoter and risk stratification of childhood brain tumours: an integrative genomic and molecular study. Lancet Oncol 14:534–542. https://​doi.​org/​10.​1016/​S1470-2045(13)70110-4CrossRefPubMed
38.
go back to reference Mistry M, Zhukova N, Merico D, Rakopoulos P, Krishnatry R, Shago M, Stavropoulos J, Alon N, Pole JD, Ray PN, Navickiene V, Mangerel J, Remke M, Buczkowicz P, Ramaswamy V, Guerreiro Stucklin A, Li M, Young EJ, Zhang C, Castelo-Branco P, Bakry D, Laughlin S, Shlien A, Chan J, Ligon KL, Rutka JT, Dirks PB, Taylor MD, Greenberg M, Malkin D, Huang A, Bouffet E, Hawkins CE, Tabori U (2015) BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high-grade glioma. J Clin Oncol 33:1015–1022. https://doi.org/10.1200/JCO.2014.58.3922CrossRefPubMedPubMedCentral Mistry M, Zhukova N, Merico D, Rakopoulos P, Krishnatry R, Shago M, Stavropoulos J, Alon N, Pole JD, Ray PN, Navickiene V, Mangerel J, Remke M, Buczkowicz P, Ramaswamy V, Guerreiro Stucklin A, Li M, Young EJ, Zhang C, Castelo-Branco P, Bakry D, Laughlin S, Shlien A, Chan J, Ligon KL, Rutka JT, Dirks PB, Taylor MD, Greenberg M, Malkin D, Huang A, Bouffet E, Hawkins CE, Tabori U (2015) BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high-grade glioma. J Clin Oncol 33:1015–1022. https://​doi.​org/​10.​1200/​JCO.​2014.​58.​3922CrossRefPubMedPubMedCentral
42.
go back to reference García-Gómez JM, Luts J, Julià-Sapé M, Krooshof P, Tortajada S, Robledo JV, Melssen W, Fuster-García E, Olier I, Postma G, Monleón D, Moreno-Torres À, Pujol J, Candiota AP, Martínez-Bisbal MC, Suykens J, Buydens L, Celda B, van Huffel S, Arús C, Robles M (2009) Multiproject-multicenter evaluation of automatic brain tumor classification by magnetic resonance spectroscopy. MAGMA 22:5–18. https://doi.org/10.1007/s10334-008-0146-yCrossRefPubMed García-Gómez JM, Luts J, Julià-Sapé M, Krooshof P, Tortajada S, Robledo JV, Melssen W, Fuster-García E, Olier I, Postma G, Monleón D, Moreno-Torres À, Pujol J, Candiota AP, Martínez-Bisbal MC, Suykens J, Buydens L, Celda B, van Huffel S, Arús C, Robles M (2009) Multiproject-multicenter evaluation of automatic brain tumor classification by magnetic resonance spectroscopy. MAGMA 22:5–18. https://​doi.​org/​10.​1007/​s10334-008-0146-yCrossRefPubMed
43.
go back to reference Tate AR, Underwood J, Acosta DM, Julià-Sapé M, Majós C, Moreno-Torres À, Howe FA, van der Graaf M, Lefournier V, Murphy MM, Loosemore A, Ladroue C, Wesseling P, Luc Bosson J, Cabañas ME, Simonetti AW, Gajewicz W, Calvar J, Capdevila A, Wilkins PR, Bell BA, Rémy C, Heerschap A, Watson D, Griffiths JR, Arús C (2006) Development of a decision support system for diagnosis and grading of brain tumours using in vivo magnetic resonance single voxel spectra. NMR Biomed 19:411–434. https://doi.org/10.1002/nbm.1016CrossRefPubMed Tate AR, Underwood J, Acosta DM, Julià-Sapé M, Majós C, Moreno-Torres À, Howe FA, van der Graaf M, Lefournier V, Murphy MM, Loosemore A, Ladroue C, Wesseling P, Luc Bosson J, Cabañas ME, Simonetti AW, Gajewicz W, Calvar J, Capdevila A, Wilkins PR, Bell BA, Rémy C, Heerschap A, Watson D, Griffiths JR, Arús C (2006) Development of a decision support system for diagnosis and grading of brain tumours using in vivo magnetic resonance single voxel spectra. NMR Biomed 19:411–434. https://​doi.​org/​10.​1002/​nbm.​1016CrossRefPubMed
45.
52.
go back to reference Pignatti F, van den Bent M, Curran D, Debruyne C, Sylvester R, Therasse P, Afra D, Cornu P, Bolla M, Vecht C, Karim AB, European Organization for Research and Treatment of Cancer Brain Tumor Cooperative Group, European Organization for Research and Treatment of Cancer Radiotherapy Cooperative Group (2002) Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 20:2076–2084. https://doi.org/10.1200/JCO.2002.08.121CrossRefPubMed Pignatti F, van den Bent M, Curran D, Debruyne C, Sylvester R, Therasse P, Afra D, Cornu P, Bolla M, Vecht C, Karim AB, European Organization for Research and Treatment of Cancer Brain Tumor Cooperative Group, European Organization for Research and Treatment of Cancer Radiotherapy Cooperative Group (2002) Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 20:2076–2084. https://​doi.​org/​10.​1200/​JCO.​2002.​08.​121CrossRefPubMed
56.
go back to reference Brown PD, Wald JT, McDermott MW et al (2003) Oncodiagnosis panel: 2002. Patient’s symptoms not related to the lesion seen in the MR images. Radiographics 23:1591–1611CrossRefPubMed Brown PD, Wald JT, McDermott MW et al (2003) Oncodiagnosis panel: 2002. Patient’s symptoms not related to the lesion seen in the MR images. Radiographics 23:1591–1611CrossRefPubMed
57.
go back to reference Fangusaro J, Onar-Thomas A, Young Poussaint T, Wu S, Ligon AH, Lindeman N, Banerjee A, Packer RJ, Kilburn LB, Goldman S, Pollack IF, Qaddoumi I, Jakacki RI, Fisher PG, Dhall G, Baxter P, Kreissman SG, Stewart CF, Jones DTW, Pfister SM, Vezina G, Stern JS, Panigrahy A, Patay Z, Tamrazi B, Jones JY, Haque SS, Enterline DS, Cha S, Fisher MJ, Doyle LA, Smith M, Dunkel IJ, Fouladi M (2019) Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol 20:1011–1022. https://doi.org/10.1016/S1470-2045(19)30277-3CrossRefPubMedPubMedCentral Fangusaro J, Onar-Thomas A, Young Poussaint T, Wu S, Ligon AH, Lindeman N, Banerjee A, Packer RJ, Kilburn LB, Goldman S, Pollack IF, Qaddoumi I, Jakacki RI, Fisher PG, Dhall G, Baxter P, Kreissman SG, Stewart CF, Jones DTW, Pfister SM, Vezina G, Stern JS, Panigrahy A, Patay Z, Tamrazi B, Jones JY, Haque SS, Enterline DS, Cha S, Fisher MJ, Doyle LA, Smith M, Dunkel IJ, Fouladi M (2019) Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol 20:1011–1022. https://​doi.​org/​10.​1016/​S1470-2045(19)30277-3CrossRefPubMedPubMedCentral
60.
go back to reference Patterson BC, Chen Y, Sklar CA, Neglia J, Yasui Y, Mertens A, Armstrong GT, Meadows A, Stovall M, Robison LL, Meacham LR (2014) Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the childhood cancer survivor study. J Clin Endocrinol Metab 99:2030–2037. https://doi.org/10.1210/jc.2013-4159CrossRefPubMedPubMedCentral Patterson BC, Chen Y, Sklar CA, Neglia J, Yasui Y, Mertens A, Armstrong GT, Meadows A, Stovall M, Robison LL, Meacham LR (2014) Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the childhood cancer survivor study. J Clin Endocrinol Metab 99:2030–2037. https://​doi.​org/​10.​1210/​jc.​2013-4159CrossRefPubMedPubMedCentral
Metadata
Title
Management of incidental brain tumors in children: a systematic review
Authors
Jehuda Soleman
Danil A. Kozyrev
Liat Ben-Sira
Shlomi Constantini
Jonathan Roth
Publication date
01-08-2020
Publisher
Springer Berlin Heidelberg
Published in
Child's Nervous System / Issue 8/2020
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-020-04658-8

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