Difference between revisions of "Glioblastoma"

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Glioblastoma (view source)

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| Prognosis  = very poor
| Prognosis  = very poor
| Other      =
| Other      =
| ClinDDx    = [[metastatic]] carcinoma
| ClinDDx    = [[Metastatic_brain_tumours|metastatic brain tumours]]
}}
}}
'''Glioblastoma''' a very common malignant primary [[brain tumour]] in adults. It has a very poor prognosis.  
'''Glioblastoma''' a very common malignant primary [[brain tumour]] in adults. It has a very poor prognosis.  
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*Median survival is measured in months.<ref>{{Cite journal  | last1 = Jubelirer | first1 = SJ. | title = A review of the treatment and survival rates of 138 patients with glioblastoma multiforme. | journal = W V Med J | volume = 92 | issue = 4 | pages = 186-90 | month =  | year =  | doi =  | PMID = 8772403 }}</ref>
*Median survival is measured in months.<ref>{{Cite journal  | last1 = Jubelirer | first1 = SJ. | title = A review of the treatment and survival rates of 138 patients with glioblastoma multiforme. | journal = W V Med J | volume = 92 | issue = 4 | pages = 186-90 | month =  | year =  | doi =  | PMID = 8772403 }}</ref>
*Only about 5% can expect to survive more than three years.<ref name=pmid17785346>{{Cite journal  | last1 = Krex | first1 = D. | last2 = Klink | first2 = B. | last3 = Hartmann | first3 = C. | last4 = von Deimling | first4 = A. | last5 = Pietsch | first5 = T. | last6 = Simon | first6 = M. | last7 = Sabel | first7 = M. | last8 = Steinbach | first8 = JP. | last9 = Heese | first9 = O. | title = Long-term survival with glioblastoma multiforme. | journal = Brain | volume = 130 | issue = Pt 10 | pages = 2596-606 | month = Oct | year = 2007 | doi = 10.1093/brain/awm204 | PMID = 17785346 }}</ref>
*Only about 5% can expect to survive more than three years.<ref name=pmid17785346>{{Cite journal  | last1 = Krex | first1 = D. | last2 = Klink | first2 = B. | last3 = Hartmann | first3 = C. | last4 = von Deimling | first4 = A. | last5 = Pietsch | first5 = T. | last6 = Simon | first6 = M. | last7 = Sabel | first7 = M. | last8 = Steinbach | first8 = JP. | last9 = Heese | first9 = O. | title = Long-term survival with glioblastoma multiforme. | journal = Brain | volume = 130 | issue = Pt 10 | pages = 2596-606 | month = Oct | year = 2007 | doi = 10.1093/brain/awm204 | PMID = 17785346 }}</ref>
*Current classification recognizes three types:
** Glioblastoma, IDH-wildtype (aka primary GBM, ICD-O: 9440/3).
** Glioblastoma, IDH-mutant (aka secondary GBM, ICD-O: 9445/3).
** Glioblastoma, NOS (lack of molecular data).
==Macroscopy==
Features:
* Usu. in white matter.
** central necrotic core.
** ill-defined borders.
** yellowish to dark-brown changes.
** midline shift due to tumor mass.
* In the corpus callosum as bihemispheric "butterfly glioma"
<gallery>
File:Glioblastoma multiforme - MRT T1KM ax.jpg | Ring-enhancement in GBM (WC/Hellerhoff)
File:Glioblastoma macro.jpg | Left insular GBM macroscopy (WC/Sbrandner)
File:Glioblastoma multiforme.jpg | "Butterfly glioma" (WC/AFIP)
</gallery>


==Microscopic==
==Microscopic==
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**Endothelial proliferation ([[AKA]] microvascular proliferation).
**Endothelial proliferation ([[AKA]] microvascular proliferation).
**+/-"Pseudopalisading necrosis" - tumour cells lined-up like a picket fence around necrotic areas.
**+/-"Pseudopalisading necrosis" - tumour cells lined-up like a picket fence around necrotic areas.
Glioblastoma variants:
*Giant cell glioblastoma (ICD-O: 9441/3)
** Bizarre multinucleated giant cells.
** Reticulin may be abundant.
** Mean age 44 years, outcome somewhat better than conventional GBM.
** IDH-wildtype, but frequent p53 mutations.
*Epitheloid glioblastoma (ICD-O: 9440/3) <ref>te journal  | last1 = Kleinschmidt-DeMasters | first1 = BK. | last2 = Aisner | first2 = DL. | last3 = Birks | first3 = DK. | last4 = Foreman | first4 = NK. | title = Epithelioid GBMs show a high percentage of BRAF V600E mutation. | journal = Am J Surg Pathol | volume = 37 | issue = 5 | pages = 685-98 | month = May | year = 2013 | doi = 10.1097/PAS.0b013e31827f9c5e | PMID = 23552385 }}</ref>
** Closely packed epithelioid to rhabdoid cells, often dicohesive.
** Xanthomaous changes less common than in PXA.
** Children and young adults, outcome particularly poor.
** Up to 50% BRAF V600E mutations.
*[[Gliosarcoma]] (ICD-O: 9442/3)
Morphological patterns in Glioblastoma:
* Lipidized (foamy)cells <ref>{{Cite journal  | last1 = Kepes | first1 = JJ. | last2 = Rubinstein | first2 = LJ. | title = Malignant gliomas with heavily lipidized (foamy) tumor cells: a report of three cases with immunoperoxidase study. | journal = Cancer | volume = 47 | issue = 10 | pages = 2451-9 | month = May | year = 1981 | doi =  | PMID = 7023643 }}</ref>
* Adipocyte-like maturation <ref>{{Cite journal  | last1 = Rickert | first1 = CH. | last2 = Riemenschneider | first2 = MJ. | last3 = Schachenmayr | first3 = W. | last4 = Richter | first4 = HP. | last5 = Bockhorn | first5 = J. | last6 = Reifenberger | first6 = G. | last7 = Paulus | first7 = W. | title = Glioblastoma with adipocyte-like tumor cell differentiation--histological and molecular features of a rare differentiation pattern. | journal = Brain Pathol | volume = 19 | issue = 3 | pages = 431-8 | month = Jul | year = 2009 | doi = 10.1111/j.1750-3639.2008.00199.x | PMID = 18691268 }}</ref>
* Rhabdoid glioblastoma (focal loss of [[INI-1]]) <ref>{{Cite journal  | last1 = Hiroyuki | first1 = M. | last2 = Ogino | first2 = J. | last3 = Takahashi | first3 = A. | last4 = Hasegawa | first4 = T. | last5 = Wakabayashi | first5 = T. | title = Rhabdoid glioblastoma: an aggressive variaty of astrocytic tumor. | journal = Nagoya J Med Sci | volume = 77 | issue = 1-2 | pages = 321-8 | month = Feb | year = 2015 | doi =  | PMID = 25797998 }}</ref>
* Melanotic glioblastoma <ref>{{Cite journal  | last1 = Jaiswal | first1 = S. | last2 = Agrawal | first2 = V. | last3 = Vij | first3 = M. | last4 = Sahu | first4 = RN. | last5 = Jaiswal | first5 = AK. | last6 = Behari | first6 = S. | title = Glioblastoma with melanotic differentiation. | journal = Clin Neuropathol | volume = 29 | issue = 5 | pages = 330-3 | month =  | year =  | doi =  | PMID = 20860897 }}</ref>
* Glioblastoma with oligodendroglial component (no improved survival) <ref>{{Cite journal  | last1 = Hegi | first1 = ME. | last2 = Janzer | first2 = RC. | last3 = Lambiv | first3 = WL. | last4 = Gorlia | first4 = T. | last5 = Kouwenhoven | first5 = MC. | last6 = Hartmann | first6 = C. | last7 = von Deimling | first7 = A. | last8 = Martinet | first8 = D. | last9 = Besuchet Schmutz | first9 = N. | title = Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial. | journal = Acta Neuropathol | volume = 123 | issue = 6 | pages = 841-52 | month = Jun | year = 2012 | doi = 10.1007/s00401-011-0938-4 | PMID = 22249618 }}</ref>
*Granular cell Glioblastoma <ref>{{Cite journal  | last1 = Schittenhelm | first1 = J. | last2 = Psaras | first2 = T. | title = Glioblastoma with granular cell astrocytoma features: a case report and literature review. | journal = Clin Neuropathol | volume = 29 | issue = 5 | pages = 323-9 | month =  | year =  | doi =  | PMID = 20860896 }}</ref>
*Glioblastoma with primitive neuronal component.<ref>{{Cite journal  | last1 = Louis | first1 = DN. | last2 = Perry | first2 = A. | last3 = Reifenberger | first3 = G. | last4 = von Deimling | first4 = A. | last5 = Figarella-Branger | first5 = D. | last6 = Cavenee | first6 = WK. | last7 = Ohgaki | first7 = H. | last8 = Wiestler | first8 = OD. | last9 = Kleihues | first9 = P. | title = The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. | journal = Acta Neuropathol | volume = 131 | issue = 6 | pages = 803-20 | month = Jun | year = 2016 | doi = 10.1007/s00401-016-1545-1 | PMID = 27157931 }}</ref>
**formerly known as: PNET-like component.
**have a tendency to CSF dissemination.<ref>{{Cite journal  | last1 = Perry | first1 = A. | last2 = Miller | first2 = CR. | last3 = Gujrati | first3 = M. | last4 = Scheithauer | first4 = BW. | last5 = Zambrano | first5 = SC. | last6 = Jost | first6 = SC. | last7 = Raghavan | first7 = R. | last8 = Qian | first8 = J. | last9 = Cochran | first9 = EJ. | title = Malignant gliomas with primitive neuroectodermal tumor-like components: a clinicopathologic and genetic study of 53 cases. | journal = Brain Pathol | volume = 19 | issue = 1 | pages = 81-90 | month = Jan | year = 2009 | doi = 10.1111/j.1750-3639.2008.00167.x | PMID = 18452568 }}</ref>
*Small cell glioblastoma.
*Ependymal-like growth patterns.
*Glioneuronal tumor with neuropil-like islands.<ref>{{Cite journal  | last1 = Ishizawa | first1 = K. | last2 = Hirose | first2 = T. | last3 = Sugiyama | first3 = K. | last4 = Kageji | first4 = T. | last5 = Nobusawa | first5 = S. | last6 = Homma | first6 = T. | last7 = Komori | first7 = T. | last8 = Sasaki | first8 = A. | title = Pathologic diversity of glioneuronal tumor with neuropil-like islands: a histological and immunohistochemical study with a special reference to isocitrate dehydrogenase 1 (IDH1) in 5 cases. | journal = Clin Neuropathol | volume = 31 | issue = 2 | pages = 67-76 | month =  | year =  | doi =  | PMID = 22385787 }}</ref>


===Images===
===Images===
<gallery>
<gallery>
File:Gbm all in one.jpg | Core features of GBM: Necrosis, MVP and mitoses (WC/jensflorian)
File:Glioblastoma anaplastic cells HE.jpg | Anaplastic cells in GBM (WC/jensflorian)
File:Glioblastoma endothelial proliferations.jpg | Endothelial proliferations in GBM (WC/jensflorian)
File:Glioblastoma mitotic activity.jpg | Mitotic activity in GBM (WC/jensflorian)
File:GBM pseudopalisading necrosis.jpg | Pseudopalisading necrosis in GBM (WC/jensflorian)
File:Glioblastoma brain infiltration zone.jpg | Diffuse brain infiltration in GBM (WC/jensflorian)
File:Glioma vessels.jpg | MVP adjacent to tumor infiltration border in GBM (WC/jensflorian)
Image:Glioblastoma - low mag.jpg | GBM - low mag. (WC)
Image:Glioblastoma - low mag.jpg | GBM - low mag. (WC)
Image:Glioblastoma - intermed mag.jpg | GBM juxtaposed with near normal white matter - intermed. mag. (WC)
Image:Glioblastoma - intermed mag.jpg | GBM juxtaposed with near normal white matter - intermed. mag. (WC)
Image:Glioblastoma - high mag.jpg | GBM juxtaposed with near normal white matter - high mag. (WC)
Image:Glioblastoma - high mag.jpg | GBM juxtaposed with near normal white matter - high mag. (WC)
Image:Glioblastoma - very high mag.jpg | GBM - very high mag. (WC)
Image:Glioblastoma - very high mag.jpg | GBM - very high mag. (WC)
</gallery>
<gallery>
Image:Glioblastoma with extreme nuclear enlargement - high mag.jpg | GBM - high mag. (WC)
Image:Glioblastoma with extreme nuclear enlargement - high mag.jpg | GBM - high mag. (WC)
Image:Glioblastoma_with_extreme_nuclear_enlargement_-_very_high_mag.jpg | Extreme nuclear enlargement in a GBM - very high mag. (WC)
Image:Glioblastoma_with_extreme_nuclear_enlargement_-_very_high_mag.jpg | Extreme nuclear enlargement in a GBM - very high mag. (WC)
File:Giant cell glioblastoma HE X200.jpg | Giant cell glioblastoma (WC/jensflorian)
File:Adenoid glioblastoma HE.jpg | Adenoid growth pattern in GBM (WC/jensflorian)
File:AFIP-00405573-Glioblastoma-Micro.jpg | Adenoid growth pattern in GBM (AFIP)
File:Epitheloid glioblastoma HE.jpg | Epitheloid glioblastoma (WC/jensflorian)
File:GBM PNET HE x10.jpg | GBM with PNET component (WC/jensflorian)
File:Glioblastoma PNET component.jpg | GBM with PNET component (WC/jensflorian)
File:Glioblastoma oligodendroglial features.jpg | GBM with oligodendroglial component (WC/jensflorian)
File:Glioblastoma pleomoprhism HE.jpg | Nuclear pleomorphism in with oligodendroglial component (WC/jensflorian)
File:Glioblastoma granular cell astrocytoma component.jpg | GBM with granular cell component (WC/jensflorian)
File:Glioblastoma ependymal features.jpg | Glioblastoma with ependymal-like growth pattern (WC/jensflorian)
File:GBM_with_Neuropil_island_HE.jpg | GBM with neuropil-like islands (WC/jensflorian)
File:AFIP00405522M-GLIOBLASTOMA ARISING IN ASTROCYTOMA.jpg | Spinal cord GBM (AFIP)
File:GBM mimicking melanoma.jpg | Glioblastoma mimicking a (amelanotic) melanoma (WC/jensflorian)
File:GBM layers.jpg | Resection borders in a recurrent GBM (WC/jensflorian)
File:Glioblastoma-radiation_changes_HE.jpg | Radiation changes in a recurrent GBM (WC/jensflorian)
File:GBM_nested_epithelial.jpg | Nested epitheloid appearance in a GBM specimen (WC/jensflorian)
Image:Glioblastoma_%281%29.jpg | Glioblastoma - pseudopalisading of tumour cells (WC)
Image:Glioblastoma_-_high_mag.jpg | Glioblastoma with fragment of near-normal white matter - high mag. (WC)
Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | Anaplastic astrocytoma - very high mag. (WC)
</gallery>
</gallery>
www:
www:
*[http://moon.ouhsc.edu/kfung/jty1/OPAQ/PathQuiz/PQ-Images/N0A002-1.gif Microvascular proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/OPAQ/PathQuiz/PQ-Images/N0A002-1.gif Microvascular proliferation in a GBM (ouhsc.edu)].
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==IHC==
==IHC==
*GFAP +ve (cytoplasm).
*GFAP +ve (cytoplasm).
*IDH-1 -ve.
*[[MAP2]] +ve.
**+ve if developed from lower grade astrocytoma. (???)
*[[IDH-1]] -ve (95%).
**+ve if developed from lower grade astrocytoma (secondary GBM) -> classify tumor as Glioblastoma, IDH-mutant.
*[[WT-1]] +ve (cytoplasm).
*p53 +ve (70%).
*Neurofilament -ve.
*Synaptophysin -ve (residual Cortex may be +ve).
*panCK -ve (except for GBM with epithelial component).
*[[ATRX]]: +ve (no loss, nuclei)
**-ve if developed from lower grade astrocytoma (secondary GBM).
*EMA: Dot-like expression less common than in [[ependymoma]]s.
*MIB-1 usu. 15-30%, but varies greatly.
 
<gallery>
File:Glioblastoma GFAP.jpg | GFAP immunostaining in GBM (WC/Marvin 101)
File:Wilms tumor protein wt1 immunohistocehmistry glioblastoma.JPG | WT1 immunostaining in GBM (WC/jensflorian)
File:Glioblastoma P53.jpg | GBM with strong p53 immunreactivity (WC/jensflorian)
File:Glioblastoma Ck7.jpg|CK7 staining in glioblastoma with epithelial component (WC/jensflorian)
File:GBM_with_Neuropil_island_MIB1.jpg|Reduced proliferation in neuropil-like islands (MIB1).
File:GBM_with_Neuropil_island_Syn.jpg |Synaptophysin immunoreactivity in neuropil-like islands (WC/jensflorian).
Image:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg | Anaplastic astrocytic tumor cells - GFAP - very high mag. (WC)
</gallery>
 
==Molecular==
*IDH1/2 sequencing in cases below 55 years is mandatory to separate between Glioblastoma, IDH-wildtype and Glioblastoma IDH-mutant.
** In cases above 55 years, negative IDH1 R132H immunohistochemistry may be sufficient.
 
* 70% of IDH-wildtype glioblastoma show chr.7 gain and chr.10 loss.<ref>{{Cite journal  | last1 = Ceccarelli | first1 = M. | last2 = Barthel | first2 = FP. | last3 = Malta | first3 = TM. | last4 = Sabedot | first4 = TS. | last5 = Salama | first5 = SR. | last6 = Murray | first6 = BA. | last7 = Morozova | first7 = O. | last8 = Newton | first8 = Y. | last9 = Radenbaugh | first9 = A. | title = Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. | journal = Cell | volume = 164 | issue = 3 | pages = 550-63 | month = Jan | year = 2016 | doi = 10.1016/j.cell.2015.12.028 | PMID = 26824661 }}</ref>
*Seen in inherited tumor syndromes:
**[[Lynch syndrome]]
**[[Neurofibromatosis 1]]
**[[Li-Fraumeni syndrome]]
**Turcot-Syndrome
 
*Most common alterations (TCGA<ref>{{Cite journal  | last1 = Verhaak | first1 = RG. | last2 = Hoadley | first2 = KA. | last3 = Purdom | first3 = E. | last4 = Wang | first4 = V. | last5 = Qi | first5 = Y. | last6 = Wilkerson | first6 = MD. | last7 = Miller | first7 = CR. | last8 = Ding | first8 = L. | last9 = Golub | first9 = T. | title = Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. | journal = Cancer Cell | volume = 17 | issue = 1 | pages = 98-110 | month = Jan | year = 2010 | doi = 10.1016/j.ccr.2009.12.020 | PMID = 20129251 }}</ref>)
**Tp53 (42% of the tumors mutated)
**PTEN (33%).
**NF1 (21%).
**EGFR (18%).
**RB1 (11%).
**PI3K-pathway genes (7-10%).
 
*Pediatric glioblastoma
**are morphologically indistinct from adult GBM.
**show frequent H3F3A mutations  and PDGFRA mutations (Note: H3F3A K27M mutations are classified as [[Astrocytoma#H3.3_K27M_mutated_glioma_of_the_midline|K27 mutated midline glioma]]).
**Consider Epithelioid GBM, when BRAF V600E mutated.
 
*Diagnostic/therapeutic relevant markers:
**[[MGMT]] promoter methylation status<ref>{{Cite journal  | last1 = Quillien | first1 = V. | last2 = Lavenu | first2 = A. | last3 = Karayan-Tapon | first3 = L. | last4 = Carpentier | first4 = C. | last5 = Labussière | first5 = M. | last6 = Lesimple | first6 = T. | last7 = Chinot | first7 = O. | last8 = Wager | first8 = M. | last9 = Honnorat | first9 = J. | title = Comparative assessment of 5 methods (methylation-specific polymerase chain reaction, MethyLight, pyrosequencing, methylation-sensitive high-resolution melting, and immunohistochemistry) to analyze O6-methylguanine-DNA-methyltranferase in a series of 100 glioblastoma patients. | journal = Cancer | volume = 118 | issue = 17 | pages = 4201-11 | month = Sep | year = 2012 | doi = 10.1002/cncr.27392 | PMID = 22294349 }}</ref>
**Absence of LOH 1p/19q (otherwise classify tumor as [[oligodendroglioma]]).<ref>{{Cite journal  | last1 = Masui | first1 = K. | last2 = Mischel | first2 = PS. | last3 = Reifenberger | first3 = G. | title = Molecular classification of gliomas. | journal = Handb Clin Neurol | volume = 134 | issue =  | pages = 97-120 | month =  | year = 2016 | doi = 10.1016/B978-0-12-802997-8.00006-2 | PMID = 26948350 }}</ref>


==See also==
==See also==
Jensflorian
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