title: Pediatric thalamic glioma with H3F3A K27M mutation, which was detected before and after malignant transformation: a case report.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurosurgery, Osaka City General Hospital, 2-13-22 Miyakojima hondori, Miyakojima-ku, Osaka, 534-0021, Japan. ishibashi@med.osaka-cu.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Department of Pathology, Osaka City General Hospital, 2-13-22 Miyakojima hondori, Miyakojima-ku, Osaka, 534-0021, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Pathology, Osaka City General Hospital, 2-13-22 Miyakojima hondori, Miyakojima-ku, Osaka, 534-0021, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fukushima
authors.affiliation: Department of Neurosurgery, Osaka City General Hospital, 2-13-22 Miyakojima hondori, Miyakojima-ku, Osaka, 534-0021, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Neurosurgery, Osaka City General Hospital, 2-13-22 Miyakojima hondori, Miyakojima-ku, Osaka, 534-0021, Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Iwai
authors.affiliation: Department of Pediatric Neurosurgery, Osaka City General Hospital, 2-13-22 Miyakojima hondori, Miyakojima-ku, Osaka, 534-0021, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Department of Pediatric Hematology/Oncology, Osaka City General Hospital, 2-13-22 Miyakojima hondori, Miyakojima-ku, Osaka, 534-0021, Japan.
authors.forename: Kai
authors.initials: K
authors.lastname: Yamasaki
authors.affiliation: Department of Pediatric Hematology/Oncology, Osaka City General Hospital, 2-13-22 Miyakojima hondori, Miyakojima-ku, Osaka, 534-0021, Japan.
authors.forename: Jyunichi
authors.initials: J
authors.lastname: Hara
authors.affiliation: Division of Stem Cell Research, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Shofuda
authors.affiliation: Division of Regenerative Medicine, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan.
authors.forename: Daiksuke
authors.initials: D
authors.lastname: Kanematsu
authors.affiliation: Division of Stem Cell Research, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan.
authors.forename: Ema
authors.initials: E
authors.lastname: Yoshioka
authors.affiliation: Division of Regenerative Medicine, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan.|Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan.
authors.forename: Yonehiro
authors.initials: Y
authors.lastname: Kanemura
mesh_terms: D000293:Adolescent; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005260:Female; D006657:Histones / Q000235:genetics*; D006801:Humans; D009154:Mutation; D013788:Thalamus / Q000473:pathology*
chemical_list: C000609950:H3-3A protein, human; D006657:Histones
keywords: H3F3A K27M mutation; Malignant transformation; Thalamic gliomas