Malignant transformation of a gangliocytoma/ganglioglioma into a glioblastoma multiforme: a molecular genetic analysis

Case report

Yutaka Hayashi Department of Neurosurgery, Kanazawa University School of Medicine, Kanazawa, Japan; and Department of Neuropathology, Charité, Humboldt University, Berlin, Germany

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Masayuki Iwato Department of Neurosurgery, Kanazawa University School of Medicine, Kanazawa, Japan; and Department of Neuropathology, Charité, Humboldt University, Berlin, Germany

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Mitsuhiro Hasegawa Department of Neurosurgery, Kanazawa University School of Medicine, Kanazawa, Japan; and Department of Neuropathology, Charité, Humboldt University, Berlin, Germany

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Osamu Tachibana Department of Neurosurgery, Kanazawa University School of Medicine, Kanazawa, Japan; and Department of Neuropathology, Charité, Humboldt University, Berlin, Germany

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Andreas von Deimling Department of Neurosurgery, Kanazawa University School of Medicine, Kanazawa, Japan; and Department of Neuropathology, Charité, Humboldt University, Berlin, Germany

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Junkoh Yamashita Department of Neurosurgery, Kanazawa University School of Medicine, Kanazawa, Japan; and Department of Neuropathology, Charité, Humboldt University, Berlin, Germany

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✓ A gangliocytoma/ganglioglioma with no atypical or malignant features was subtotally resected from the right temporal lobe of a 16-year-old woman. A second resection was performed 8 years later to treat a locally recurrent lesion with increased cellularity that was diagnosed as a World Health Organization Grade II ganglioglioma on the basis of neuropathological examination. Molecular analysis of the recurrent tumor revealed a TP53 gene mutation, but no amplification of the epidermal growth factor receptor (EGFR) gene. Radiotherapy (60 Gy) was administered after the second resection. The patient returned 1 year later with a second focal recurrence. The specimen obtained during the third resection of tumor exhibited exclusively astrocytic differentiation, cellular pleomorphism with multinucleated cells, high mitotic activity, and endothelial proliferation. Therefore, the tumor was diagnosed to be a glioblastoma multiforme (GBM). Molecular analysis of tumor DNA from the second recurrent tumor demonstrated the presence of the TP53 mutation, which previously had been observed in the first recurrent tumor, but again no evidence of EGFR amplification. Findings demonstrate that the presence of TP53 mutation in progressed gangliogliomas should be interpreted as a progression-associated mutation rather than a consequence of treatment. This is the first report to indicate that the molecular pathways of gangliocytomas/gangliogliomas progressing to become GBMs may parallel those of diffuse astrocytomas progressing to become GBMs.

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  • 1.

    Araujo JF, , Souza MR, & Sperlescu A, et al: Evolução maligna de um ganglioglioma. Arq Neuropsiquiatr 56:486490, 1998 Araujo JF, Souza MR, Sperlescu A, et al: Evolução maligna de um ganglioglioma. Arq Neuropsiquiatr 56:486–490, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Brat DJ, , James CD, & Jedlicka AE, et al: Molecular genetic alterations in radiation-induced astrocytomas. Am J Pathol 154:14311438, 1999 Brat DJ, James CD, Jedlicka AE, et al: Molecular genetic alterations in radiation-induced astrocytomas. Am J Pathol 154:1431–1438, 1999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Hayashi Y, , Ueki K, & Waha A, et al: Association of EGFR gene amplification and CDKN2 (p16/MTS1) gene deletion in glioblastoma multiforme. Brain Pathol 7:871875, 1997 Hayashi Y, Ueki K, Waha A, et al: Association of EGFR gene amplification and CDKN2 (p16/MTS1) gene deletion in glioblastoma multiforme. Brain Pathol 7:871–875, 1997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Hirose T, , Scheithauer BW, & Lopes MBS, et al: Ganglioglioma. An ultrastructural and immunohistochemical study. Cancer 79:9891003, 1997 Hirose T, Scheithauer BW, Lopes MBS, et al: Ganglioglioma. An ultrastructural and immunohistochemical study. Cancer 79:989–1003, 1997

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Ichimura K, , Bolin MB, & Goike HM, et al: Deregulation of the p14ARF/MDM2/p53 pathway is a prerequisite for human astrocytic gliomas with G1-S transition control gene abnormalities. Cancer Res 60:417424, 2000 Ichimura K, Bolin MB, Goike HM, et al: Deregulation of the p14ARF/MDM2/p53 pathway is a prerequisite for human astrocytic gliomas with G1-S transition control gene abnormalities. Cancer Res 60:417–424, 2000

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Jay V, , Squire J, & Becker LE, et al: Malignant transformation in a ganglioglioma with anaplastic neuronal and astrocytic components. Report of a case with flow cytometric and cytogenetic analysis. Cancer 73:28622868, 1994 Jay V, Squire J, Becker LE, et al: Malignant transformation in a ganglioglioma with anaplastic neuronal and astrocytic components. Report of a case with flow cytometric and cytogenetic analysis. Cancer 73:2862–2868, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Kalyan-Raman UP, & Olivero WC: Ganglioglioma: a correlative clinicopathological and radiological study of ten surgically treated cases with follow-up. Neurosurgery 20:428433, 1987 Kalyan-Raman UP, Olivero WC: Ganglioglioma: a correlative clinicopathological and radiological study of ten surgically treated cases with follow-up. Neurosurgery 20:428–433, 1987

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Kleihues P, , Berger PC, & Scheithauer BW: The new WHO classification of brain tumours. Brain Pathol 3:255268, 1993 Kleihues P, Berger PC, Scheithauer BW: The new WHO classification of brain tumours. Brain Pathol 3:255–268, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Kleihues P, & Cavenee WK: Pathology and Genetics of Tumours of the Nervous System. Lyon: IARC Press, 2000 Kleihues P, Cavenee WK: Pathology and Genetics of Tumours of the Nervous System. Lyon: IARC Press, 2000

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Miller DC, , Lang FF, & Epstein FJ: Central nervous system gangliogliomas. Part 1: Pathology. J Neurosurg 79:859866, 1993 Miller DC, Lang FF, Epstein FJ: Central nervous system gangliogliomas. Part 1: Pathology. J Neurosurg 79:859–866, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Prayson RA, , Khajavi K, & Comair YG: Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors. J Neuropathol Exp Neurol 54:513520, 1995 Prayson RA, Khajavi K, Comair YG: Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors. J Neuropathol Exp Neurol 54:513–520, 1995

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Ron E, , Modan B, & Boice JD Jr, et al: Tumors of the brain and nervous system after radiotherapy in childhood. N Engl J Med 319:10331039, 1988 Ron E, Modan B, Boice JD Jr, et al: Tumors of the brain and nervous system after radiotherapy in childhood. N Engl J Med 319:1033–1039, 1988

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Rubinstein AB, , Shalit MN, & Cohen ML, et al: Radiation-induced cerebral meningioma: a recognizable entity. J Neurosurg 61:966971, 1984 Rubinstein AB, Shalit MN, Cohen ML, et al: Radiation-induced cerebral meningioma: a recognizable entity. J Neurosurg 61:966–971, 1984

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Rumana CS, & Valadka AB: Radiation therapy and malignant degeneration of benign supratentorial gangliogliomas. Neurosurgery 42:10381043, 1998 Rumana CS, Valadka AB: Radiation therapy and malignant degeneration of benign supratentorial gangliogliomas. Neurosurgery 42:1038–1043, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Russell DS, & Rubinstein LJ: Pathology of Tumours of the Nervous system, ed 5. Baltimore: Williams & Wilkins, 1989 Russell DS, Rubinstein LJ: Pathology of Tumours of the Nervous system, ed 5. Baltimore: Williams & Wilkins, 1989

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Sambrook J, , Fritsch EF, & Maniatis T: Molecular Cloning: A Laboratory Manual, ed 2. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1989 Sambrook J, Fritsch EF, Maniatis T: Molecular Cloning: A Laboratory Manual, ed 2. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1989

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Selch MT, , Goy BW, & Lee SP, et al: Gangliogliomas: experience with 34 patients and review of the literature. Am J Clin Oncol 21:557564, 1998 Selch MT, Goy BW, Lee SP, et al: Gangliogliomas: experience with 34 patients and review of the literature. Am J Clin Oncol 21:557–564, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Soffer D, , Pittaluga S, & Feiner M, et al: Intracranial meningiomas following low-dose irradiation to the head. J Neurosurg 59:10481053, 1983 Soffer D, Pittaluga S, Feiner M, et al: Intracranial meningiomas following low-dose irradiation to the head. J Neurosurg 59:1048–1053, 1983

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Tada M, , Sawamura Y, & Abe H, et al: Homozygous p53 gene mutation in a radiation-induced glioblastoma 10 years after treatment for an intracranial germ cell tumor: case report. Neurosurgery 40:393396, 1997 Tada M, Sawamura Y, Abe H, et al: Homozygous p53 gene mutation in a radiation-induced glioblastoma 10 years after treatment for an intracranial germ cell tumor: case report. Neurosurgery 40:393–396, 1997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    von Deimling A, , Eibl RH, & Ohgaki H, et al: p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma. Cancer Res 52:29872990, 1992 von Deimling A, Eibl RH, Ohgaki H, et al: p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma. Cancer Res 52:2987–2990, 1992

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    von Deimling A, , Fimmers R, & Schmidt MC, et al: Comprehensive allelotype and genetic analysis of 466 human nervous system tumors. J Neuropathol Exp Neurol 59:544558, 2000 von Deimling A, Fimmers R, Schmidt MC, et al: Comprehensive allelotype and genetic analysis of 466 human nervous system tumors. J Neuropathol Exp Neurol 59:544–558, 2000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    von Deimling A, , von Ammon K, & Schoenfeld D, et al: Subsets of glioblastoma multiforme defined by molecular genetic analysis. Brain Pathol 3:1926, 1993 von Deimling A, von Ammon K, Schoenfeld D, et al: Subsets of glioblastoma multiforme defined by molecular genetic analysis. Brain Pathol 3:19–26, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Watanabe K, , Tachibana O, & Sato K, et al: Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol 6:217224, 1996 Watanabe K, Tachibana O, Sato K, et al: Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol 6:217–224, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Wolf HK, , Müller MB, & Spänle M, et al: Ganglioglioma: a detailed histopathological and immunohistochemical analysis of 61 cases. Acta Neuropathol 88:166173, 1994 Wolf HK, Müller MB, Spänle M, et al: Ganglioglioma: a detailed histopathological and immunohistochemical analysis of 61 cases. Acta Neuropathol 88:166–173, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Zentner J, , Wolf HK, & Ostertun B, et al: Gangliogliomas: clinical, radiological, and histopathological findings in 51 patients. J Neurol Neurosurg Psychiatry 57:14971502, 1994 Zentner J, Wolf HK, Ostertun B, et al: Gangliogliomas: clinical, radiological, and histopathological findings in 51 patients. J Neurol Neurosurg Psychiatry 57:1497–1502, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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