Giant cell glioblastoma

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Primary Author(s)*

Jay Alden, DO

Cancer Category/Type

  • Diffuse astrocytic and olidodendroglial tumors

Cancer Sub-Classification / Subtype

Glioblastoma, IDH-wildtype (IDH-wt)

Definition / Description of Disease

  • Rare histologic variant of IDH-wt glioblastoma [1]
  • Large, multinucleate giant cells with occasional abundant reticuln network [1]

Synonyms / Terminology

Epidemiology / Prevalence

  • Constitute <1% of glioblastomas [2]
  • May be more common in pediatric population [3]
  • Mean age 51 years [3]

Clinical Features

  • No evidence of a precursor lesion [1]
  • Presenting symptoms similar to IDH-wt glioblastoma
  • Radiographically and grossly circumscribed borders, may be mistaken for other neoplastic or non-neoplastic lesions [4]

Sites of Involvement

  • Localization similar to IDH-wt glioblastoma [3][2]

Morphologic Features

  • Bizarre, multi-nucleate giant cells with atypical mitotic figures [5]
  • Cells may contain numerous nuclei [1]
  • Palisading and ischemic necrosis [1]
  • Pseudo-rosette like perivascular tumor cell concentration [1]
Hematoxylin and Eosin stained section of giant cell glioblastoma showing bizarre multinucleate cells

Immunophenotype

Finding Marker
Positive (by definition) IDH-1
Positive (variable level) GFAP [6]
Positive (Majority) P53 [7] [6]
Negative (nearly universal) Neuronal Antigens [8]

Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence
EXAMPLE t(9;22)(q34;q11.2) EXAMPLE 3'ABL1 / 5'BCR EXAMPLE der(22) EXAMPLE 5%
EXAMPLE t(8;21)(q22;q22) EXAMPLE 5'RUNX1 / 3'RUNXT1 EXAMPLE der(8) EXAMPLE 5%

Characteristic Chromosomal Aberrations / Patterns

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Genomic Gain/Loss/LOH

  • Near haploidization may be a primary oncogenic event underlying a subset of GCG's [9]
    • Recurrent loss of chromosomes 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 13, 14, 15, 17, 18, 19, 22
    • Typically have gains or retain heterozygosity of chromosome 7
  • Similar genomic findings have been described in other oncocytic tumors [10] [11] [12] [13]
  • Oncogenenesis in such cases may be related to widespread loss of tumor suppressors in a catastrophic reduplication event early in tumorigenesis [10]

Gene Mutations (SNV/INDEL)

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Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)
TP53 Tumor Suppressor 75-90% [14]
PTEN Tumor Suppressor 33% [15]
ATRX Tumor Suppressor Expression loss 19% [15]
TERT Telomerase 25% [15]
EGFR Oncogene Amplification 6% [15]

Other Mutations

Type Gene/Region/Other
Concomitant Mutations EXAMPLE IDH1 R123H
Secondary Mutations EXAMPLE Trisomy 7
Mutually Exclusive EXAMPLE EGFR Amplification

Epigenomics (Methylation)

  • MGMT promoter methylation may help predict response to alkylating chemotherapy [16]

Genes and Main Pathways Involved

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Diagnostic Testing Methods

  • Diagnosis typically made based on morphology with immunohistochemical staining
    • GCG are typically distinguished from pleomorphic xanthastrocytoma by their lack of neuronal immunoreactivity [8]
  • Genomic testing for 1p/19q codeletion may help distinguish from oligodendroma

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

  • GCG's have a poor prognosis, but may have better outcome than conventional IDH-wt GB [17] [18] [3] [19] [2]
  • Median survival 13.5 months vs 9.8 for conventional IDH-wt GB [2]
  • May be better circumscribed than conventional IDH-wt GB, making these lesions risky for radiographic misdiagnosis and delayed therapy [4]

Familial Forms

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Other Information

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Links

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Notes

References

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  2. 2.0 2.1 2.2 2.3 Ortega, Alicia; et al. (2014). "Treatment and survival of patients harboring histological variants of glioblastoma". Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia. 21 (10): 1709–1713. doi:10.1016/j.jocn.2014.05.003. ISSN 1532-2653. PMID 24980627.
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