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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  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 WHO Classification of Tumours of the Central Nervous System, 4th ed, Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (Eds), IARC, Lyon 2016. Pg 46-47
  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.
  3. ↑ 3.0 3.1 3.2 3.3 Kozak, Kevin R.; et al. (2009). "Giant cell glioblastoma: a glioblastoma subtype with distinct epidemiology and superior prognosis". Neuro-Oncology. 11 (6): 833–841. doi:10.1215/15228517-2008-123. ISSN 1523-5866. PMC 2802403. PMID 19332771.
  4. ↑ 4.0 4.1 Turner, Ryan; et al. (2018). "Imaging findings in the progression of a giant cell glioblastoma". Radiology Case Reports. 13 (5): 1007–1011. doi:10.1016/j.radcr.2018.07.010. ISSN 1930-0433. PMC 6097408. PMID 30128062.
  5. ↑ Margetts, J. C.; et al. (1989). "Giant-celled glioblastoma of brain. A clinico-pathological and radiological study of ten cases (including immunohistochemistry and ultrastructure)". Cancer. 63 (3): 524–531. doi:10.1002/1097-0142(19890201)63:33.0.co;2-d. ISSN 0008-543X. PMID 2912529.
  6. ↑ 6.0 6.1 Katoh, M.; et al. (1995). "Immunohistochemical analysis of giant cell glioblastoma". Pathology International. 45 (4): 275–282. doi:10.1111/j.1440-1827.1995.tb03456.x. ISSN 1320-5463. PMID 7550996.
  7. ↑ Peraud, A.; et al. (1997). "p53 mutations versus EGF receptor expression in giant cell glioblastomas". Journal of Neuropathology and Experimental Neurology. 56 (11): 1236–1241. doi:10.1097/00005072-199711000-00008. ISSN 0022-3069. PMID 9370234.
  8. ↑ 8.0 8.1 Martinez-Diaz, Hilda; et al. (2003). "Giant cell glioblastoma and pleomorphic xanthoastrocytoma show different immunohistochemical profiles for neuronal antigens and p53 but share reactivity for class III beta-tubulin". Archives of Pathology & Laboratory Medicine. 127 (9): 1187–1191. doi:10.1043/1543-2165(2003)1272.0.CO;2. ISSN 1543-2165. PMID 12946225.
  9. ↑ Bigner, S. H.; et al. (1985). "A serially transplantable human giant cell glioblastoma that maintains a near-haploid stem line". Cancer Genetics and Cytogenetics. 18 (2): 141–153. doi:10.1016/0165-4608(85)90064-0. ISSN 0165-4608. PMID 3840409.
  10. ↑ 10.0 10.1 Ganly, Ian; et al. (2018). "Integrated Genomic Analysis of Hürthle Cell Cancer Reveals Oncogenic Drivers, Recurrent Mitochondrial Mutations, and Unique Chromosomal Landscapes". Cancer Cell. 34 (2): 256–270.e5. doi:10.1016/j.ccell.2018.07.002. ISSN 1878-3686. PMC 6247912. PMID 30107176.
  11. ↑ Corver, Willem E.; et al. (2012). "Genome haploidisation with chromosome 7 retention in oncocytic follicular thyroid carcinoma". PloS One. 7 (6): e38287. doi:10.1371/journal.pone.0038287. ISSN 1932-6203. PMC 3365880. PMID 22675538.
  12. ↑ Corver, Willem E.; et al. (2014). "Near-haploidization significantly associates with oncocytic adrenocortical, thyroid, and parathyroid tumors but not with mitochondrial DNA mutations". Genes, Chromosomes & Cancer. 53 (10): 833–844. doi:10.1002/gcc.22194. ISSN 1098-2264. PMID 24909752.
  13. ↑ Gopal, Raj K.; et al. (2018). "Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hürthle Cell Carcinoma". Cancer Cell. 34 (2): 242–255.e5. doi:10.1016/j.ccell.2018.06.013. ISSN 1878-3686. PMC 6121811. PMID 30107175.
  14. ↑ Martinez, Ramon; et al. (2007). "Cytogenetic and molecular genetic analyses of giant cell glioblastoma multiforme reveal distinct profiles in giant cell and non-giant cell subpopulations". Cancer Genetics and Cytogenetics. 175 (1): 26–34. doi:10.1016/j.cancergencyto.2007.01.006. ISSN 0165-4608. PMID 17498554.
  15. ↑ 15.0 15.1 15.2 15.3 Oh, Ji Eun; et al. (2016). "Genetic Alterations in Gliosarcoma and Giant Cell Glioblastoma". Brain Pathology (Zurich, Switzerland). 26 (4): 517–522. doi:10.1111/bpa.12328. ISSN 1750-3639. PMID 26443480.
  16. ↑ Hegi, Monika E.; et al. (2005). "MGMT gene silencing and benefit from temozolomide in glioblastoma". The New England Journal of Medicine. 352 (10): 997–1003. doi:10.1056/NEJMoa043331. ISSN 1533-4406. PMID 15758010.
  17. ↑ Burger, P. C.; et al. (1980). "Histologic factors of prognostic significance in the glioblastoma multiforme". Cancer. 46 (5): 1179–1186. doi:10.1002/1097-0142(19800901)46:53.0.co;2-0. ISSN 0008-543X. PMID 6260329.
  18. ↑ Huang, M. C.; et al. (1996). "A clinico-immunohistochemical study of giant cell glioblastoma". Noshuyo Byori = Brain Tumor Pathology. 13 (1): 11–16. ISSN 0914-8108. PMID 8916121.
  19. ↑ Oh, Taemin; et al. (2014). "Survival outcomes of giant cell glioblastoma: institutional experience in the management of 20 patients". Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia. 21 (12): 2129–2134. doi:10.1016/j.jocn.2014.04.011. ISSN 1532-2653. PMID 25037316.
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