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2,599 bytes added , 11:58, 13 April 2020

→‎Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

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*No evidence of a precursor lesion <ref name=":0" />

*Presenting symptoms similar to IDH-wt glioblastoma

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*Radiographically and grossly circumscribed borders, may be mistaken for other neoplastic or non-neoplastic lesions <ref>{{Cite journal|last=Turner|first=Ryan|last2=Matthys|first2=Samuel|last3=Heymann|first3=John|last4=Gelman|first4=Benjamin|date=2018|title=Imaging findings in the progression of a giant cell glioblastoma|url=https://www.ncbi.nlm.nih.gov/pubmed/30128062|journal=Radiology Case Reports|volume=13|issue=5|pages=1007–1011|doi=10.1016/j.radcr.2018.07.010|issn=1930-0433|pmc=6097408|pmid=30128062}}</ref>

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*Radiographically and grossly circumscribed borders, may be mistaken for other neoplastic or non-neoplastic lesions <ref name=":6">{{Cite journal|last=Turner|first=Ryan|last2=Matthys|first2=Samuel|last3=Heymann|first3=John|last4=Gelman|first4=Benjamin|date=2018|title=Imaging findings in the progression of a giant cell glioblastoma|url=https://www.ncbi.nlm.nih.gov/pubmed/30128062|journal=Radiology Case Reports|volume=13|issue=5|pages=1007–1011|doi=10.1016/j.radcr.2018.07.010|issn=1930-0433|pmc=6097408|pmid=30128062}}</ref>

==Sites of Involvement==

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!Finding!!Marker

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|Positive (by definition)

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|IDH-1

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|Positive (variable level)||GFAP <ref name=":3">{{Cite journal|last=Katoh|first=M.|last2=Aida|first2=T.|last3=Sugimoto|first3=S.|last4=Suwamura|first4=Y.|last5=Abe|first5=H.|last6=Isu|first6=T.|last7=Kaneko|first7=S.|last8=Mitsumori|first8=K.|last9=Kojima|first9=H.|date=1995|title=Immunohistochemical analysis of giant cell glioblastoma|url=https://www.ncbi.nlm.nih.gov/pubmed/7550996|journal=Pathology International|volume=45|issue=4|pages=275–282|doi=10.1111/j.1440-1827.1995.tb03456.x|issn=1320-5463|pmid=7550996}}</ref>

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|Positive (Majority)||P53 <ref>{{Cite journal|last=Peraud|first=A.|last2=Watanabe|first2=K.|last3=Plate|first3=K. H.|last4=Yonekawa|first4=Y.|last5=Kleihues|first5=P.|last6=Ohgaki|first6=H.|date=1997|title=p53 mutations versus EGF receptor expression in giant cell glioblastomas|url=https://www.ncbi.nlm.nih.gov/pubmed/9370234|journal=Journal of Neuropathology and Experimental Neurology|volume=56|issue=11|pages=1236–1241|doi=10.1097/00005072-199711000-00008|issn=0022-3069|pmid=9370234}}</ref> <ref name=":3" />

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|Negative (nearly universal)||Neuronal Antigens <ref>{{Cite journal|last=Martinez-Diaz|first=Hilda|last2=Kleinschmidt-DeMasters|first2=B. K.|last3=Powell|first3=Suzanne Z.|last4=Yachnis|first4=Anthony T.|date=2003|title=Giant cell glioblastoma and pleomorphic xanthoastrocytoma show different immunohistochemical profiles for neuronal antigens and p53 but share reactivity for class III beta-tubulin|url=https://www.ncbi.nlm.nih.gov/pubmed/12946225|journal=Archives of Pathology & Laboratory Medicine|volume=127|issue=9|pages=1187–1191|doi=10.1043/1543-2165(2003)1272.0.CO;2|issn=1543-2165|pmid=12946225}}</ref>

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|Negative (nearly universal)||Neuronal Antigens <ref name=":7">{{Cite journal|last=Martinez-Diaz|first=Hilda|last2=Kleinschmidt-DeMasters|first2=B. K.|last3=Powell|first3=Suzanne Z.|last4=Yachnis|first4=Anthony T.|date=2003|title=Giant cell glioblastoma and pleomorphic xanthoastrocytoma show different immunohistochemical profiles for neuronal antigens and p53 but share reactivity for class III beta-tubulin|url=https://www.ncbi.nlm.nih.gov/pubmed/12946225|journal=Archives of Pathology & Laboratory Medicine|volume=127|issue=9|pages=1187–1191|doi=10.1043/1543-2165(2003)1272.0.CO;2|issn=1543-2165|pmid=12946225}}</ref>

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==Genomic Gain/Loss/LOH==

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* Near haploidization may be a primary oncogenic event underlying a subset of GCG's <ref>{{Cite journal|last=Bigner|first=S. H.|last2=Mark|first2=J.|last3=Schold|first3=S. C.|last4=Eng|first4=L. F.|last5=Bigner|first5=D. D.|date=1985|title=A serially transplantable human giant cell glioblastoma that maintains a near-haploid stem line|url=https://www.ncbi.nlm.nih.gov/pubmed/3840409|journal=Cancer Genetics and Cytogenetics|volume=18|issue=2|pages=141–153|doi=10.1016/0165-4608(85)90064-0|issn=0165-4608|pmid=3840409}}</ref>

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*Near haploidization may be a primary oncogenic event underlying a subset of GCG's <ref>{{Cite journal|last=Bigner|first=S. H.|last2=Mark|first2=J.|last3=Schold|first3=S. C.|last4=Eng|first4=L. F.|last5=Bigner|first5=D. D.|date=1985|title=A serially transplantable human giant cell glioblastoma that maintains a near-haploid stem line|url=https://www.ncbi.nlm.nih.gov/pubmed/3840409|journal=Cancer Genetics and Cytogenetics|volume=18|issue=2|pages=141–153|doi=10.1016/0165-4608(85)90064-0|issn=0165-4608|pmid=3840409}}</ref>

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** Recurrent loss of chromosomes 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 13, 14, 15, 17, 18, 19, 22

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**Recurrent loss of chromosomes 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 13, 14, 15, 17, 18, 19, 22

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** Typically have gains or retain heterozygosity of chromosome 7

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**Typically have gains or retain heterozygosity of chromosome 7

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* Similar genomic findings have been described in other oncocytic tumors <ref name=":4">{{Cite journal|last=Ganly|first=Ian|last2=Makarov|first2=Vladimir|last3=Deraje|first3=Shyamprasad|last4=Dong|first4=YiYu|last5=Reznik|first5=Ed|last6=Seshan|first6=Venkatraman|last7=Nanjangud|first7=Gouri|last8=Eng|first8=Stephanie|last9=Bose|first9=Promita|date=2018|title=Integrated Genomic Analysis of Hürthle Cell Cancer Reveals Oncogenic Drivers, Recurrent Mitochondrial Mutations, and Unique Chromosomal Landscapes|url=https://www.ncbi.nlm.nih.gov/pubmed/30107176|journal=Cancer Cell|volume=34|issue=2|pages=256–270.e5|doi=10.1016/j.ccell.2018.07.002|issn=1878-3686|pmc=6247912|pmid=30107176}}</ref> <ref>{{Cite journal|last=Corver|first=Willem E.|last2=Ruano|first2=Dina|last3=Weijers|first3=Karin|last4=den Hartog|first4=Wietske C. E.|last5=van Nieuwenhuizen|first5=Merlijn P.|last6=de Miranda|first6=Noel|last7=van Eijk|first7=Ronald|last8=Middeldorp|first8=Anneke|last9=Jordanova|first9=Ekaterina S.|date=2012|title=Genome haploidisation with chromosome 7 retention in oncocytic follicular thyroid carcinoma|url=https://www.ncbi.nlm.nih.gov/pubmed/22675538|journal=PloS One|volume=7|issue=6|pages=e38287|doi=10.1371/journal.pone.0038287|issn=1932-6203|pmc=3365880|pmid=22675538}}</ref> <ref>{{Cite journal|last=Corver|first=Willem E.|last2=van Wezel|first2=Tom|last3=Molenaar|first3=Kees|last4=Schrumpf|first4=Melanie|last5=van den Akker|first5=Brendy|last6=van Eijk|first6=Ronald|last7=Ruano Neto|first7=Dina|last8=Oosting|first8=Jan|last9=Morreau|first9=Hans|date=2014|title=Near-haploidization significantly associates with oncocytic adrenocortical, thyroid, and parathyroid tumors but not with mitochondrial DNA mutations|url=https://www.ncbi.nlm.nih.gov/pubmed/24909752|journal=Genes, Chromosomes & Cancer|volume=53|issue=10|pages=833–844|doi=10.1002/gcc.22194|issn=1098-2264|pmid=24909752}}</ref> <ref>{{Cite journal|last=Gopal|first=Raj K.|last2=Kübler|first2=Kirsten|last3=Calvo|first3=Sarah E.|last4=Polak|first4=Paz|last5=Livitz|first5=Dimitri|last6=Rosebrock|first6=Daniel|last7=Sadow|first7=Peter M.|last8=Campbell|first8=Braidie|last9=Donovan|first9=Samuel E.|date=2018|title=Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hürthle Cell Carcinoma|url=https://www.ncbi.nlm.nih.gov/pubmed/30107175|journal=Cancer Cell|volume=34|issue=2|pages=242–255.e5|doi=10.1016/j.ccell.2018.06.013|issn=1878-3686|pmc=6121811|pmid=30107175}}</ref>

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*Similar genomic findings have been described in other oncocytic tumors <ref name=":4">{{Cite journal|last=Ganly|first=Ian|last2=Makarov|first2=Vladimir|last3=Deraje|first3=Shyamprasad|last4=Dong|first4=YiYu|last5=Reznik|first5=Ed|last6=Seshan|first6=Venkatraman|last7=Nanjangud|first7=Gouri|last8=Eng|first8=Stephanie|last9=Bose|first9=Promita|date=2018|title=Integrated Genomic Analysis of Hürthle Cell Cancer Reveals Oncogenic Drivers, Recurrent Mitochondrial Mutations, and Unique Chromosomal Landscapes|url=https://www.ncbi.nlm.nih.gov/pubmed/30107176|journal=Cancer Cell|volume=34|issue=2|pages=256–270.e5|doi=10.1016/j.ccell.2018.07.002|issn=1878-3686|pmc=6247912|pmid=30107176}}</ref> <ref>{{Cite journal|last=Corver|first=Willem E.|last2=Ruano|first2=Dina|last3=Weijers|first3=Karin|last4=den Hartog|first4=Wietske C. E.|last5=van Nieuwenhuizen|first5=Merlijn P.|last6=de Miranda|first6=Noel|last7=van Eijk|first7=Ronald|last8=Middeldorp|first8=Anneke|last9=Jordanova|first9=Ekaterina S.|date=2012|title=Genome haploidisation with chromosome 7 retention in oncocytic follicular thyroid carcinoma|url=https://www.ncbi.nlm.nih.gov/pubmed/22675538|journal=PloS One|volume=7|issue=6|pages=e38287|doi=10.1371/journal.pone.0038287|issn=1932-6203|pmc=3365880|pmid=22675538}}</ref> <ref>{{Cite journal|last=Corver|first=Willem E.|last2=van Wezel|first2=Tom|last3=Molenaar|first3=Kees|last4=Schrumpf|first4=Melanie|last5=van den Akker|first5=Brendy|last6=van Eijk|first6=Ronald|last7=Ruano Neto|first7=Dina|last8=Oosting|first8=Jan|last9=Morreau|first9=Hans|date=2014|title=Near-haploidization significantly associates with oncocytic adrenocortical, thyroid, and parathyroid tumors but not with mitochondrial DNA mutations|url=https://www.ncbi.nlm.nih.gov/pubmed/24909752|journal=Genes, Chromosomes & Cancer|volume=53|issue=10|pages=833–844|doi=10.1002/gcc.22194|issn=1098-2264|pmid=24909752}}</ref> <ref>{{Cite journal|last=Gopal|first=Raj K.|last2=Kübler|first2=Kirsten|last3=Calvo|first3=Sarah E.|last4=Polak|first4=Paz|last5=Livitz|first5=Dimitri|last6=Rosebrock|first6=Daniel|last7=Sadow|first7=Peter M.|last8=Campbell|first8=Braidie|last9=Donovan|first9=Samuel E.|date=2018|title=Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hürthle Cell Carcinoma|url=https://www.ncbi.nlm.nih.gov/pubmed/30107175|journal=Cancer Cell|volume=34|issue=2|pages=242–255.e5|doi=10.1016/j.ccell.2018.06.013|issn=1878-3686|pmc=6121811|pmid=30107175}}</ref>

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* Oncogenenesis in such cases may be related to widespread loss of tumor suppressors in a catastrophic reduplication event early in tumorigenesis <ref name=":4" />

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*Oncogenenesis in such cases may be related to widespread loss of tumor suppressors in a catastrophic reduplication event early in tumorigenesis <ref name=":4" />

==Gene Mutations (SNV/INDEL)==

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|33% <ref name=":5">{{Cite journal|last=Oh|first=Ji Eun|last2=Ohta|first2=Takashi|last3=Nonoguchi|first3=Naosuke|last4=Satomi|first4=Kaishi|last5=Capper|first5=David|last6=Pierscianek|first6=Daniela|last7=Sure|first7=Ulrich|last8=Vital|first8=Anne|last9=Paulus|first9=Werner|date=2016|title=Genetic Alterations in Gliosarcoma and Giant Cell Glioblastoma|url=https://www.ncbi.nlm.nih.gov/pubmed/26443480|journal=Brain Pathology (Zurich, Switzerland)|volume=26|issue=4|pages=517–522|doi=10.1111/bpa.12328|issn=1750-3639|pmid=26443480}}</ref>

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|ATRX

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|ATRX

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|Tumor Suppressor

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==Epigenomics (Methylation)==

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~~Put your text here~~

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* MGMT promoter methylation may help predict response to alkylating chemotherapy <ref>{{Cite journal|last=Hegi|first=Monika E.|last2=Diserens|first2=Annie-Claire|last3=Gorlia|first3=Thierry|last4=Hamou|first4=Marie-France|last5=de Tribolet|first5=Nicolas|last6=Weller|first6=Michael|last7=Kros|first7=Johan M.|last8=Hainfellner|first8=Johannes A.|last9=Mason|first9=Warren|date=2005|title=MGMT gene silencing and benefit from temozolomide in glioblastoma|url=https://www.ncbi.nlm.nih.gov/pubmed/15758010|journal=The New England Journal of Medicine|volume=352|issue=10|pages=997–1003|doi=10.1056/NEJMoa043331|issn=1533-4406|pmid=15758010}}</ref>

==Genes and Main Pathways Involved==

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==Diagnostic Testing Methods==

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~~Put your text here~~

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* Diagnosis typically made based on morphology with immunohistochemical staining

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** GCG are typically distinguished from pleomorphic xanthastrocytoma by their lack of neuronal immunoreactivity <ref name=":7" />

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* Genomic testing for 1p/19q codeletion may help distinguish from oligodendroma

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

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~~Put your text here~~

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* GCG's have a poor prognosis, but may have better outcome than conventional IDH-wt GB <ref>{{Cite journal|last=Burger|first=P. C.|last2=Vollmer|first2=R. T.|date=1980|title=Histologic factors of prognostic significance in the glioblastoma multiforme|url=https://www.ncbi.nlm.nih.gov/pubmed/6260329|journal=Cancer|volume=46|issue=5|pages=1179–1186|doi=10.1002/1097-0142(19800901)46:53.0.co;2-0|issn=0008-543X|pmid=6260329}}</ref> <ref>{{Cite journal|last=Huang|first=M. C.|last2=Kubo|first2=O.|last3=Tajika|first3=Y.|last4=Takakura|first4=K.|date=1996|title=A clinico-immunohistochemical study of giant cell glioblastoma|url=https://www.ncbi.nlm.nih.gov/pubmed/8916121|journal=Noshuyo Byori = Brain Tumor Pathology|volume=13|issue=1|pages=11–16|issn=0914-8108|pmid=8916121}}</ref> <ref name=":2" /> <ref>{{Cite journal|last=Oh|first=Taemin|last2=Rutkowski|first2=Martin J.|last3=Safaee|first3=Michael|last4=Sun|first4=Matthew Z.|last5=Sayegh|first5=Eli T.|last6=Bloch|first6=Orin|last7=Tihan|first7=Tarik|last8=Parsa|first8=Andrew T.|date=2014|title=Survival outcomes of giant cell glioblastoma: institutional experience in the management of 20 patients|url=https://www.ncbi.nlm.nih.gov/pubmed/25037316|journal=Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia|volume=21|issue=12|pages=2129–2134|doi=10.1016/j.jocn.2014.04.011|issn=1532-2653|pmid=25037316}}</ref> <ref name=":1" />

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* Median survival 13.5 months vs 9.8 for conventional IDH-wt GB <ref name=":1" />

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* May be better circumscribed than conventional IDH-wt GB, making these lesions risky for radiographic misdiagnosis and delayed therapy <ref name=":6" />

==Familial Forms==

Jay.Alden

13

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Changes

Giant cell glioblastoma (view source)

Revision as of 11:58, 13 April 2020