Top

Published in:

01-12-2016 | Case Report

Pediatric thalamic glioma with H3F3A K27M mutation, which was detected before and after malignant transformation: a case report

Authors: Kenichi Ishibashi, Takeshi Inoue, Hiroko Fukushima, Yusuke Watanabe, Yoshiyasu Iwai, Hiroaki Sakamoto, Kai Yamasaki, Jyunichi Hara, Tomoko Shofuda, Daiksuke Kanematsu, Ema Yoshioka, Yonehiro Kanemura

Published in: Child's Nervous System | Issue 12/2016

Abstract

Purpose

Histone H3.3 (H3F3A) mutation in the codon for lysine 27 (K27M) has been found as driver mutations in pediatric glioblastoma and has been suggested to play critical roles in the pathogenesis of thalamic gliomas and diffuse intrinsic pontine gliomas. We report a case of thalamic glioma with H3F3A K27M mutation, which was detected in both the primary tumor diagnosed as diffuse astrocytoma obtained during the first surgery and also in the tumor diagnosed as anaplastic astrocytoma obtained at the second surgery.

Case presentation

A 14-year-old girl presented with mild headache. Magnetic resonance imaging (MRI) showed a small intraaxial lesion in the left thalamus, which increased in size. Stereotactic tumor biopsy was performed 2 years after the initial diagnosis, and a pathological diagnosis of diffuse astrocytoma (WHO grade 2) was made. The tumor grew further and showed contrast enhancement on MRI despite 16 months of chemotherapy. Surgical removal via the transcallosal approach was then performed, and postoperative pathological diagnosis was anaplastic astrocytoma (WHO grade 3), indicating malignant transformation of the tumor. Molecular diagnosis of tumor tissue obtained at first and second surgeries revealed H3F3A K27M mutation in both primary and secondary specimens.

Conclusion

This report demonstrates minute neuroradiological and pathological features of malignant transformation from thalamic low grade glioma with H3F3A K27M mutation. It is noteworthy that this mutation was found in this case when the tumor was still a low-grade glioma. Tissue sampling for genetic analysis is useful in patients with thalamic gliomas to predict the clinical course and efficacy of treatments.

Aihara K, Mukasa A, Gotoh K, Saito K, Nagae G, Tsuji S, Tatsuno K, Yamamoto S, Takayanagi S, Narita Y et al (2014) H3F3A K27M mutations in thalamic gliomas from young adult patients. Neuro Oncol 16:140–146. doi:10.1093/neuonc/not144 CrossRefPubMed

Albright AL (2004) Feasibility and advisability of resections of thalamic tumors in pediatric patients. J Neurosurg 100:468–472. doi:10.3171/ped.2004.100.5.0468 PubMed

Baroncini M, Vinchon M, Mineo JF, Pichon F, Francke JP, Dhellemmes P (2007) Surgical resection of thalamic tumors in children: approaches and clinical results. Childs Nerv Syst 23:753–760. doi:10.1007/s00381-007-0299-4 CrossRefPubMed

Bender S, Tang Y, Lindroth AM, Hovestadt V, Jones DT, Kool M, Zapatka M, Northcott PA, Sturm D, Wang W et al (2013) Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24:660–672. doi:10.1016/j.ccr.2013.10.006 CrossRefPubMed

Castel D, Philippe C, Calmon R, Le Dret L, Truffaux N, Boddaert N, Pages M, Taylor KR, Saulnier P, Lacroix L et al (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. doi:10.1007/s00401-015-1478-0 CrossRefPubMedPubMedCentral

Cuccia V, Monges J (1997) Thalamic tumors in children. Childs Nerv Syst 13:514–520. doi:10.1007/s003810050128, discussion 521CrossRefPubMed

Fernandez C, Maues de Paula A, Colin C, Quilichini B, Bouvier-Labit C, Girard N, Scavarda D, Lena G, Figarella-Branger D (2006) Thalamic gliomas in children: an extensive clinical, neuroradiological and pathological study of 14 cases. Childs Nerv Syst 22:1603–1610. doi:10.1007/s00381-006-0184-6 CrossRefPubMed

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. doi:10.1309/AJCPABOHBC33FVMO CrossRefPubMed

Grasso CS, Tang YJ, Truffaux N, Berlow NE, Liu LN, Debily MA, Quist MJ, Davis LE, Huang EC, Woo PJ et al (2015) Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat Med 21:555–559. doi:10.1038/nm.3855 CrossRefPubMedPubMedCentral

10.

Hashizume R, Andor N, Ihara Y, Lerner R, Gan H, Chen X, Fang D, Huang X, Tom MW, Ngo V et al (2014) Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat Med 20:1394–1396. doi:10.1038/nm.3716 CrossRefPubMedPubMedCentral

11.

Hoffman LM, DeWire M, Ryall S, Buczkowicz P, Leach J, Miles L, Ramani A, Brudno M, Kumar SS, Drissi R et al (2016) Spatial genomic heterogeneity in diffuse intrinsic pontine and midline high-grade glioma: implications for diagnostic biopsy and targeted therapeutics. Acta Neuropathol Commun 4:1. doi:10.1186/s40478-015-0269-0 CrossRefPubMedPubMedCentral

12.

Kis D, Mate A, Kincses ZT, Voros E, Barzo P (2014) The role of probabilistic tractography in the surgical treatment of thalamic gliomas. Neurosurgery. doi:10.1227/NEU.0000000000000333 PubMed

13.

Kramm CM, Butenhoff S, Rausche U, Warmuth-Metz M, Kortmann RD, Pietsch T, Gnekow A, Jorch N, Janssen G, Berthold F et al (2011) Thalamic high-grade gliomas in children: a distinct clinical subset? Neuro Oncol 13:680–689. doi:10.1093/neuonc/nor045 CrossRefPubMedPubMedCentral

14.

Kurian KM, Zhang Y, Haynes HR, Macaskill NA, Bradley M (2013) Diagnostic challenges of primary thalamic gliomas-identification of a minimally enhancing neuroradiological subtype with aggressive neuropathology and poor clinical outcome. Clin Neuroradiol. doi:10.1007/s00062-013-0225-y PubMed

15.

Lewis PW, Muller MM, Koletsky MS, Cordero F, Lin S, Banaszynski LA, Garcia BA, Muir TW, Becher OJ, Allis CD (2013) Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science 340:857–861. doi:10.1126/science.1232245 CrossRefPubMedPubMedCentral

16.

Maes T, Carceller E, Salas J, Ortega A, Buesa C (2015) Advances in the development of histone lysine demethylase inhibitors. Curr Opin Pharmacol 23:52–60. doi:10.1016/j.coph.2015.05.009 CrossRefPubMed

17.

Nikbakht H, Panditharatna E, Mikael LG, Li R, Gayden T, Osmond M, Ho CY, Kambhampati M, Hwang EI, Faury D et al (2016) Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma. Nat Commun 7:11185. doi:10.1038/ncomms11185 CrossRefPubMedPubMedCentral

18.

Ntziachristos P, Tsirigos A, Welstead GG, Trimarchi T, Bakogianni S, Xu L, Loizou E, Holmfeldt L, Strikoudis A, King B et al (2014) Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia. Nature 514:513–517. doi:10.1038/nature13605 CrossRefPubMedPubMedCentral

19.

Okita Y, Nonaka M, Shofuda T, Kanematsu D, Yoshioka E, Kodama Y, Mano M, Nakajima S, Kanemura Y (2014) (11)C-methinine uptake correlates with MGMT promoter methylation in nonenhancing gliomas. Clin Neurol Neurosurg 125:212–216. doi:10.1016/j.clineuro.2014.08.004 CrossRefPubMed

20.

Packer RJ (2000) Chemotherapy: low-grade gliomas of the hypothalamus and thalamus. Pediatr Neurosurg 32:259–263, doi:28948CrossRefPubMed

21.

Prados MD, Wara WM, Edwards MS, Larson DA, Lamborn K, Levin VA (1995) The treatment of brain stem and thalamic gliomas with 78 Gy of hyperfractionated radiation therapy. Int J Radiat Oncol Biol Phys 32:85–91. doi:10.1016/0360-3016(95)00563-E CrossRefPubMed

22.

Puget S, Crimmins DW, Garnett MR, Grill J, Oliveira R, Boddaert N, Wray A, Lelouch-Tubiana A, Roujeau T, Di Rocco F et al (2007) Thalamic tumors in children: a reappraisal. J Neurosurg 106:354–362. doi:10.3171/ped.2007.106.5.354 PubMed

23.

Reardon DA, Gajjar A, Sanford RA, Heideman RL, Walter AW, Thompson SJ, Merchant TE, Li H, Jenkins JJ, Langston J et al (1998) Bithalamic involvement predicts poor outcome among children with thalamic glial tumors. Pediatr Neurosurg 29:29–35CrossRefPubMed

24.

Sai Kiran NA, Thakar S, Dadlani R, Mohan D, Furtado SV, Ghosal N, Aryan S, Hegde AS (2013) Surgical management of thalamic gliomas: case selection, technical considerations, and review of literature. Neurosurg Rev 36:383–393. doi:10.1007/s10143-013-0452-3 CrossRefPubMed

25.

Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K, Sturm D, Fontebasso AM, Quang DA, Tonjes M et al (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482:226–231. doi:10.1038/nature10833 CrossRefPubMed

26.

Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C, Pfaff E, Tonjes M, Sill M, Bender S et al (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22:425–437. doi:10.1016/j.ccr.2012.08.024 CrossRefPubMed

Title: Pediatric thalamic glioma with H3F3A K27M mutation, which was detected before and after malignant transformation: a case report
Authors: Kenichi Ishibashi
Takeshi Inoue
Hiroko Fukushima
Yusuke Watanabe
Yoshiyasu Iwai
Hiroaki Sakamoto
Kai Yamasaki
Jyunichi Hara
Tomoko Shofuda
Daiksuke Kanematsu
Ema Yoshioka
Yonehiro Kanemura
Publication date: 01-12-2016
Publisher: Springer Berlin Heidelberg
Published in: Child's Nervous System / Issue 12/2016
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI: https://doi.org/10.1007/s00381-016-3161-8

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Pediatric thalamic glioma with H3F3A K27M mutation, which was detected before and after malignant transformation: a case report

Abstract

Purpose

Case presentation

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Case presentation

Conclusion

Please log in to get access to this content

Other articles of this Issue 12/2016

Traumatic cervical internal carotid artery pseudoaneurysm in a child refractory to initial endovascular treatment: case report and technical considerations

Dorsal midbrain syndrome in two cases with two different presentations

Seizure control following treatment of brain arteriovenous malformations in pediatric patients

The incidence of severe intraventricular hemorrhage based on retrospective analysis of 35939 full-term newborns—report of two cases and review of literature

Neurofibroma of the cervical spine in infants

Evaluation of hypercoagulability state in perinatal arterial ischemic stroke with rotation thromboelastometry