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→Microscopic: Spinal ependymoma
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==General== | ==General== | ||
*Called the forgotten glial tumour. | *Called the forgotten glial tumour. | ||
*Anatomic location is essential for tumor diagnosis. | *Anatomic location and molecular data is essential for tumor diagnosis. | ||
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There are currently | There are currently ten main ependymal tumors:<ref name=Ref_WHOCNS_74>{{Ref WHOCNS|74}}</ref> | ||
#Supratentorial [[Subependymoma]] | |||
#Supratentorial ependymoma, ZFTA-fusion positive | #Supratentorial ependymoma, ZFTA-fusion positive | ||
#Supratentorial ependymoma, YAP1-fusion positive | #Supratentorial ependymoma, YAP1-fusion positive | ||
#Posterior fossa [[Subependymoma]] | |||
#Posterior fossa ependymoma group A | #Posterior fossa ependymoma group A | ||
#Posterior fossa ependymoma group B | #Posterior fossa ependymoma group B | ||
#Spinal [[Subependymoma]] | |||
#Spinal ependymoma | #Spinal ependymoma | ||
#Spinal ependymoma, MYCN-amplified | #Spinal ependymoma, MYCN-amplified | ||
#[[Myxopapillary ependymoma]] | #[[Myxopapillary ependymoma]] | ||
Ependymoma (not otherwise specified). | Ependymoma, NOS (not otherwise specified): Molecular analysis still missing. | ||
Ependymoma, NEC (not elsewhere classfied): Tumor cannot assigned to any of the defined entities. | |||
Note: Molecularly defined ependymomas can be still graded as CNS grade 2 or 3 depending on histological features. | |||
*Depreceated terminologies: | *Depreceated terminologies: | ||
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**Cellular ependymoma. | **Cellular ependymoma. | ||
**Ependymoma, RELA fusion-positive.<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref><ref>{{Cite journal | last1 = Pietsch | first1 = T. | last2 = Wohlers | first2 = I. | last3 = Goschzik | first3 = T. | last4 = Dreschmann | first4 = V. | last5 = Denkhaus | first5 = D. | last6 = Dörner | first6 = E. | last7 = Rahmann | first7 = S. | last8 = Klein-Hitpass | first8 = L. | title = Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to pathological activation of the NF-κB signaling pathway. | journal = Acta Neuropathol | volume = 127 | issue = 4 | pages = 609-11 | month = Apr | year = 2014 | doi = 10.1007/s00401-014-1264-4 | PMID = 24562983 }}</ref> This is now called Supratentorial ependymoma, ZFTA-fusion positive. | **Ependymoma, RELA fusion-positive.<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref><ref>{{Cite journal | last1 = Pietsch | first1 = T. | last2 = Wohlers | first2 = I. | last3 = Goschzik | first3 = T. | last4 = Dreschmann | first4 = V. | last5 = Denkhaus | first5 = D. | last6 = Dörner | first6 = E. | last7 = Rahmann | first7 = S. | last8 = Klein-Hitpass | first8 = L. | title = Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to pathological activation of the NF-κB signaling pathway. | journal = Acta Neuropathol | volume = 127 | issue = 4 | pages = 609-11 | month = Apr | year = 2014 | doi = 10.1007/s00401-014-1264-4 | PMID = 24562983 }}</ref> This is now called Supratentorial ependymoma, ZFTA-fusion positive. | ||
**Anaplastic ependymoma. | **Anaplastic ependymoma. This is now called CNS grade 3 ependymoma. | ||
==Gross== | ==Gross== | ||
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==Microscopic== | ==Microscopic== | ||
===Classic ependymoma=== | ==="Classic" ependymoma=== | ||
*Come in two CNS WHO grades: 2 and 3. | |||
*Usu. sharply demarcated from surrounding brain parenchyma. | |||
Features: | Features: | ||
*Cells have a "tadpole-like" morphology. | *Cells have a "tadpole-like" morphology. | ||
| Line 87: | Line 94: | ||
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref> | *Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref> | ||
**There is little variation in size, shape and staining. | **There is little variation in size, shape and staining. | ||
*Hyalinized vessels. | |||
*Calcification. | |||
*Rare cases with cartilagineous metaplasia.<ref>{{Cite journal | last1 = Wang | first1 = X. | last2 = Zhang | first2 = S. | last3 = Ye | first3 = Y. | last4 = Chen | first4 = Y. | last5 = Liu | first5 = X. | title = Ependymoma with cartilaginous metaplasia might have more aggressive behavior: a case report and literature review. | journal = Brain Tumor Pathol | volume = 29 | issue = 3 | pages = 172-6 | month = Jul | year = 2012 | doi = 10.1007/s10014-011-0079-4 | PMID = 22228122 }}</ref> | *Rare cases with cartilagineous metaplasia.<ref>{{Cite journal | last1 = Wang | first1 = X. | last2 = Zhang | first2 = S. | last3 = Ye | first3 = Y. | last4 = Chen | first4 = Y. | last5 = Liu | first5 = X. | title = Ependymoma with cartilaginous metaplasia might have more aggressive behavior: a case report and literature review. | journal = Brain Tumor Pathol | volume = 29 | issue = 3 | pages = 172-6 | month = Jul | year = 2012 | doi = 10.1007/s10014-011-0079-4 | PMID = 22228122 }}</ref> | ||
*Branching capillaries usu. only in supratentorial ependymomas. | |||
DDx ( | ===Supratentorial ependymoma=== | ||
*Usu. connected to the ventricles. | |||
*Mostly frontal or temporal lobe. | |||
*Approx. 1/3 of all ependymal tumours (41% in children). | |||
*Irregular CM enhancement. | |||
*YAP1-fused tumors in children oft large at time of diagnosis. | |||
*Cysts and/or calcification possible. | |||
*Sharply demarcated from adjacent brain parenchyma. | |||
*True ependymal rosettes are rare. | |||
*Occasionally branching capillary vessels. | |||
*Clear cell phenotypes more common than in other locations. | |||
*Complete surgical resection is the best predictor. | |||
*CSF spread in up to 15% of tumours. | |||
===Posterior fossa ependymoma=== | |||
*Usu. 4th ventricle, less common in CPA. | |||
*Most frequent in children. | |||
*May contain tumour nodules with increased cell density. | |||
*Micocysts, vascular hyalinization and calcification can be present. | |||
*No morphologic differences between Group A and B tumours. | |||
*Perivascular pseudorosettes almost always present. | |||
*Rare papillary or tanicytic patterns. | |||
DDx (supratentorial and posterior fossa ependymoma): | |||
*[[Subependymoma]]. | *[[Subependymoma]]. | ||
*[[Glioblastoma]] (GBM). | *[[Glioblastoma]] (GBM). | ||
*Gliomas with BCOR internal tandem duplication. | |||
*[[Astroblastoma]], MN1-altered. | |||
**Invasive border = GBM; circumscribed border of lesion = ependymoma. | **Invasive border = GBM; circumscribed border of lesion = ependymoma. | ||
*[[Oligodendroglioma]] (Clear cell ependymoma)) | |||
*CNS embryonal tumour with BCOR internal tandem duplication. | |||
===Spinal ependymoma=== | |||
*Isomorphic nuclei. | |||
*Mitotic activity usu. very low. | |||
*Calcification, hemorrhage, cystic and/or metaplastic changes may be seen. | |||
*Most tumours show CNS grade 2 histology. | |||
**CNS grade 3 tumours should be examined for MYCN amplification. | |||
*Outcome usu. good, extent of resection is prognostic. | |||
DDx (spinal ependymoma): | |||
*[[Pilocytic astrocytoma]] (Tanycytic ependymoma) | *[[Pilocytic astrocytoma]] (Tanycytic ependymoma) | ||
* | *Diffuse midline glioma, H3 K27-altered | ||
*Small cell glioblastoma (MYCN-amplified spinal ependymoma) | |||
===Images=== | |||
www: | www: | ||
*[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)]. | *[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)]. | ||
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File:EMA_ependymoma_periluminal.jpg | Periluminal EMA positivity in a ependymoma. (WC/jensflorian) | File:EMA_ependymoma_periluminal.jpg | Periluminal EMA positivity in a ependymoma. (WC/jensflorian) | ||
File:Ependymoma_EMA.jpg | Dot-like EMA immunreactivity n a ependymoma. (WC/Marvin101) | File:Ependymoma_EMA.jpg | Dot-like EMA immunreactivity n a ependymoma. (WC/Marvin101) | ||
File:Tanycytic ependymoma HE.jpg | Tanycytic ependymoma must not confused with [[pilocytic astrocytoma]]. (WC/jensflorian) | File:Tanycytic ependymoma HE.jpg | Tanycytic morphology in ependymoma must not confused with [[pilocytic astrocytoma]]. (WC/jensflorian) | ||
File:Tanicytic_ependymoma_x10.jpg | Tanycytic ependymoma - low mag. (WC/jensflorian) | File:Tanicytic_ependymoma_x10.jpg | Tanycytic morphology in ependymoma - low mag. (WC/jensflorian) | ||
File:Papillary_Ependymoma.jpg | Papillary ependymoma - low mag. (WC/jensflorian) | File:Papillary_Ependymoma.jpg | Papillary morphology in ependymoma - low mag. (WC/jensflorian) | ||
File:Papillary_ependymoma_HE_x40.jpg | Papillary ependymoma - intermed. mag. (WC/jensflorian) | File:Papillary_ependymoma_HE_x40.jpg | Papillary morphology in ependymoma - intermed. mag. (WC/jensflorian) | ||
File:Clear_cell_ependymoma_HE.jpg | Clear cell ependymoma may mimic [[oligodendroglioma]]. (WC/jensflorian) | File:Clear_cell_ependymoma_HE.jpg | Clear cell morphology in ependymoma may mimic [[oligodendroglioma]]. (WC/jensflorian) | ||
File:HE_anaplastic_epedymomas_mitoses_pleomorphism.jpg | Brisk mitotic activity in a anaplastic ependymoma. (WC/jensflorian) | File:HE_anaplastic_epedymomas_mitoses_pleomorphism.jpg | Brisk mitotic activity in a anaplastic ependymoma. (WC/jensflorian) | ||
File:Cartilaginous metaplasia ependymoma.jpg|Metaplastic transformation in an anaplastic ependymoma. (WC/jensflorian) | File:Cartilaginous metaplasia ependymoma.jpg|Metaplastic transformation in an anaplastic ependymoma. (WC/jensflorian) | ||
File:Ependymoma_L1CAM_IHC.jpg | L1CAM immunohistochemistry indicates presence of | File:Ependymoma_L1CAM_IHC.jpg | L1CAM immunohistochemistry indicates presence of ZFTA-fusion. | ||
File:Ependymoma_NFkappaB_IHC.jpg | Nuclear NFkappaB IHC indicates presence of | File:Ependymoma_NFkappaB_IHC.jpg | Nuclear NFkappaB IHC indicates presence of ZFTA-fusion. | ||
</gallery> | </gallery> | ||
===Grading=== | ===Grading=== | ||
Easy: | Easy: | ||
*Subependymoma = WHO grade | *Subependymoma = CNS WHO grade 1. | ||
*Myxopapillary ependymoma = WHO grade | *Myxopapillary ependymoma = CNS WHO grade 2. | ||
Grade | Not so easy: | ||
All other ependymomas: WHO CNS Grade 2 vs. Grade 3 depends on: | |||
*Cellular density. | *Cellular density. | ||
*Mitoses. | *Mitoses (no clear cut-off). | ||
*Necrosis. | *Necrosis (not prognostic). | ||
*Microvascular proliferation. | *Microvascular proliferation. | ||
*Poor interobserver reliability<ref>{{Cite journal | last1 = Ellison | first1 = DW. | last2 = Kocak | first2 = M. | last3 = Figarella-Branger | first3 = D. | last4 = Felice | first4 = G. | last5 = Catherine | first5 = G. | last6 = Pietsch | first6 = T. | last7 = Frappaz | first7 = D. | last8 = Massimino | first8 = M. | last9 = Grill | first9 = J. | title = Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. | journal = J Negat Results Biomed | volume = 10 | issue = | pages = 7 | month = May | year = 2011 | doi = 10.1186/1477-5751-10-7 | PMID = 21627842 }}</ref> | *Poor interobserver reliability<ref>{{Cite journal | last1 = Ellison | first1 = DW. | last2 = Kocak | first2 = M. | last3 = Figarella-Branger | first3 = D. | last4 = Felice | first4 = G. | last5 = Catherine | first5 = G. | last6 = Pietsch | first6 = T. | last7 = Frappaz | first7 = D. | last8 = Massimino | first8 = M. | last9 = Grill | first9 = J. | title = Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. | journal = J Negat Results Biomed | volume = 10 | issue = | pages = 7 | month = May | year = 2011 | doi = 10.1186/1477-5751-10-7 | PMID = 21627842 }}</ref> | ||
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Notes: | Notes: | ||
*Many tumours fall between grade | *Many tumours fall between grade 2 and grade 3. | ||
*Rare cases with sarcomatous or cartilaginous components.<ref>{{Cite journal | last1 = Vajtai | first1 = I. | last2 = Kuhlen | first2 = D. | last3 = Kappeler | first3 = A. | last4 = Mariani | first4 = L. | last5 = Zimmermann | first5 = A. | last6 = Paulus | first6 = W. | title = Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma". | journal = Pathol Res Pract | volume = 206 | issue = 7 | pages = 493-8 | month = Jul | year = 2010 | doi = 10.1016/j.prp.2009.07.013 | PMID = 19853384 }}</ref><ref>{{Cite journal | last1 = Boukas | first1 = A. | last2 = Joshi | first2 = A. | last3 = Jenkins | first3 = A. | last4 = Holliman | first4 = D. | title = Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature. | journal = Pediatr Neurosurg | volume = 49 | issue = 2 | pages = 93-8 | month = | year = 2013 | doi = 10.1159/000356931 | PMID = 24401698 }}</ref> | *Rare cases with sarcomatous or cartilaginous components.<ref>{{Cite journal | last1 = Vajtai | first1 = I. | last2 = Kuhlen | first2 = D. | last3 = Kappeler | first3 = A. | last4 = Mariani | first4 = L. | last5 = Zimmermann | first5 = A. | last6 = Paulus | first6 = W. | title = Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma". | journal = Pathol Res Pract | volume = 206 | issue = 7 | pages = 493-8 | month = Jul | year = 2010 | doi = 10.1016/j.prp.2009.07.013 | PMID = 19853384 }}</ref><ref>{{Cite journal | last1 = Boukas | first1 = A. | last2 = Joshi | first2 = A. | last3 = Jenkins | first3 = A. | last4 = Holliman | first4 = D. | title = Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature. | journal = Pediatr Neurosurg | volume = 49 | issue = 2 | pages = 93-8 | month = | year = 2013 | doi = 10.1159/000356931 | PMID = 24401698 }}</ref> | ||
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*[[IDH-1]]-ve. | *[[IDH-1]]-ve. | ||
*EMA (dots and rings).<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Paulus | first2 = W. | title = Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. | journal = Acta Neuropathol | volume = 106 | issue = 4 | pages = 385-8 | month = Oct | year = 2003 | doi = 10.1007/s00401-003-0752-8 | PMID = 12898159 }}</ref> | *EMA (dots and rings).<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Paulus | first2 = W. | title = Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. | journal = Acta Neuropathol | volume = 106 | issue = 4 | pages = 385-8 | month = Oct | year = 2003 | doi = 10.1007/s00401-003-0752-8 | PMID = 12898159 }}</ref> | ||
**Widespread and strong EMA expression is indicative of YAP1-fused ependymoma. | |||
*Olig2-ve.<ref>{{Cite journal | last1 = Švajdler | first1 = M. | last2 = Rychlý | first2 = B. | last3 = Mezencev | first3 = R. | last4 = Fröhlichová | first4 = L. | last5 = Bednárová | first5 = A. | last6 = Pataky | first6 = F. | last7 = Daum | first7 = O. | title = SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors. | journal = Histol Histopathol | volume = 31 | issue = 1 | pages = 95-102 | month = Jan | year = 2016 | doi = 10.14670/HH-11-654 | PMID = 26287936 }}</ref> | *Olig2-ve.<ref>{{Cite journal | last1 = Švajdler | first1 = M. | last2 = Rychlý | first2 = B. | last3 = Mezencev | first3 = R. | last4 = Fröhlichová | first4 = L. | last5 = Bednárová | first5 = A. | last6 = Pataky | first6 = F. | last7 = Daum | first7 = O. | title = SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors. | journal = Histol Histopathol | volume = 31 | issue = 1 | pages = 95-102 | month = Jan | year = 2016 | doi = 10.14670/HH-11-654 | PMID = 26287936 }}</ref> | ||
* | *H3K27me3 nuclear loss in Posterior fossa group A ependymoma (nuclear loss is diagnostic).<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref> | ||
*L1CAM in supratentorial tumors (expression indicates | *L1CAM in supratentorial tumors (expression indicates ZFTA fusion).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref> | ||
*p65 nuclear +ve in ZFTA-fused ependymoma. | |||
==Molecular== | ==Molecular== | ||
'''Supratentorial Ependymoma''' | |||
*SE, ZFTA-fusion positive: Adults and children (up to 80% of cases).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref> | |||
**ZFTA-RELA fusion most common alteration. | |||
**Chromothripsis. | |||
**EPHB2 amplifications and CDKN2A deletions in a subset of these tumors<ref>{{Cite journal | last1 = Philip-Hollingsworth | first1 = S. | last2 = Hollingsworth | first2 = RI. | last3 = Dazzo | first3 = FB. | title = Host-range related structural features of the acidic extracellular polysaccharides of Rhizobium trifolii and Rhizobium leguminosarum. | journal = J Biol Chem | volume = 264 | issue = 3 | pages = 1461-6 | month = Jan | year = 1989 | doi = | PMID = 2912966 }}</ref> | |||
*SE, YAP-fusion positive. | |||
**Restricted to children (6-7% of all supratentorial ependymomas). | |||
**YAP-MAMLD fusion most common alteration. | |||
'''Posterior fossa Ependymoma''' | |||
Two distinct molecular subgroups exist in the posterior fossa:<ref>{{Cite journal | last1 = Witt | first1 = H. | last2 = Mack | first2 = SC. | last3 = Ryzhova | first3 = M. | last4 = Bender | first4 = S. | last5 = Sill | first5 = M. | last6 = Isserlin | first6 = R. | last7 = Benner | first7 = A. | last8 = Hielscher | first8 = T. | last9 = Milde | first9 = T. | title = Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. | journal = Cancer Cell | volume = 20 | issue = 2 | pages = 143-57 | month = Aug | year = 2011 | doi = 10.1016/j.ccr.2011.07.007 | PMID = 21840481 }}</ref> | Two distinct molecular subgroups exist in the posterior fossa:<ref>{{Cite journal | last1 = Witt | first1 = H. | last2 = Mack | first2 = SC. | last3 = Ryzhova | first3 = M. | last4 = Bender | first4 = S. | last5 = Sill | first5 = M. | last6 = Isserlin | first6 = R. | last7 = Benner | first7 = A. | last8 = Hielscher | first8 = T. | last9 = Milde | first9 = T. | title = Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. | journal = Cancer Cell | volume = 20 | issue = 2 | pages = 143-57 | month = Aug | year = 2011 | doi = 10.1016/j.ccr.2011.07.007 | PMID = 21840481 }}</ref> | ||
* Group A ependymomas: | * Group A ependymomas: | ||
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**gene expression profiles similar to that of spinal cord ependymomas. | **gene expression profiles similar to that of spinal cord ependymomas. | ||
**increased Chromosomal 1q gains. <ref>{{Cite journal | last1 = Korshunov | first1 = A. | last2 = Witt | first2 = H. | last3 = Hielscher | first3 = T. | last4 = Benner | first4 = A. | last5 = Remke | first5 = M. | last6 = Ryzhova | first6 = M. | last7 = Milde | first7 = T. | last8 = Bender | first8 = S. | last9 = Wittmann | first9 = A. | title = Molecular staging of intracranial ependymoma in children and adults. | journal = J Clin Oncol | volume = 28 | issue = 19 | pages = 3182-90 | month = Jul | year = 2010 | doi = 10.1200/JCO.2009.27.3359 | PMID = 20516456 }}</ref> | **increased Chromosomal 1q gains. <ref>{{Cite journal | last1 = Korshunov | first1 = A. | last2 = Witt | first2 = H. | last3 = Hielscher | first3 = T. | last4 = Benner | first4 = A. | last5 = Remke | first5 = M. | last6 = Ryzhova | first6 = M. | last7 = Milde | first7 = T. | last8 = Bender | first8 = S. | last9 = Wittmann | first9 = A. | title = Molecular staging of intracranial ependymoma in children and adults. | journal = J Clin Oncol | volume = 28 | issue = 19 | pages = 3182-90 | month = Jul | year = 2010 | doi = 10.1200/JCO.2009.27.3359 | PMID = 20516456 }}</ref> | ||
==See also== | ==See also== | ||