Difference between revisions of "Ependymoma"

Jump to navigation Jump to search

Ependymoma (view source)

Revision as of 13:20, 19 September 2022

17,980 bytes added ,  13:20, 19 September 2022
→‎Microscopic: Spinal ependymoma
(redirect)
 
(→‎Microscopic: Spinal ependymoma)
 
(39 intermediate revisions by 2 users not shown)
Line 1: Line 1:
#redirect [[Neuropathology_tumours#Ependymoma]]
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Image      = Ependymoma_H%26E.jpg
| Width      =
| Caption    = Ependymoma grade II WHO. [[H&E stain]]
| Synonyms  =
| Micro      = Perivascular pseudorosettes, ependymal rosettes
| Subtypes  = Tanycytic, Clear cell, Papillary, Cellular
| LMDDx      = [[Subependymoma]], [[Glioblastoma]], [[Pilocytic astrocytoma]], [[Oligodendroglioma]]
| Stains    = 
| IHC        = GFAP +ve
| EM        =
| Molecular  =
| IF        =
| Gross      =
| Grossing  =
| Site      =
| Assdx      =
| Syndromes  =
| Clinicalhx =
| Signs      =
| Symptoms  =
| Prevalence =
| Bloodwork  =
| Rads      =
| Endoscopy  =
| Prognosis  = intermediate to poor (WHO Grades II & III)
| Other      =
| ClinDDx    =
| Tx        =
}}
 
'''Ependymoma''' is a [[neuropathology tumour]]. 
 
==General==
*Called the forgotten glial tumour.
*Anatomic location and molecular data is essential for tumor diagnosis.
 
 
Epidemiology:<ref name=Ref_PBoD8_1334>{{Ref PBoD8|1334}}</ref>
*Usual site:
**Adults: usually spinal cord.
**Children: usually posterior fossa.
*May be associated with [[neurofibromatosis type 2]].
 
 
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, YAP1-fusion positive
#Posterior fossa [[Subependymoma]]
#Posterior fossa ependymoma group A
#Posterior fossa ependymoma group B
#Spinal [[Subependymoma]]
#Spinal ependymoma
#Spinal ependymoma, MYCN-amplified
#[[Myxopapillary ependymoma]]
 
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:
**Papillary ependymoma.
**Clear cell ependymoma.
**Tanycytic 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.
**Anaplastic ependymoma. This is now called CNS grade 3 ependymoma.
 
==Gross==
*Usually discrete and enhancing.
*Ventricular location, but also within the spinal cord.
*Dissemination possible.
*[[Myxopapillary ependymoma]] classically at [[filum terminale]].
*[[Subependymoma]] typically seen in IVth ventricle.
<gallery>
File:AFIP405711R-EPENDYMOMA.jpg | Radiology (AFIP)
File:AFIP405713G-EPENDYMOMA.jpg | Ependymoma in the fourth ventricle (AFIP)
File:Ependymoma in the fourth ventricle.jpg | Gross (AFIP)
</gallery>
 
==Microscopic==
==="Classic" ependymoma===
*Come in two CNS WHO grades: 2 and 3.
*Usu. sharply demarcated from surrounding brain parenchyma.
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*'''Rosettes''' = circular nuclear free zones/cells arranged in a pseudoglandular fashion; comes in two flavours in ependymoma:
**''Perivascular pseudorosettes'' = (tumour) cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumour cells) surround blood vessel (nucleus-free zone); more common than ependymal rosette... but less specific.
**''Ependymal rosette'' ([[AKA]] ''true ependymal rosette'') = rosette has an empty space at the centre - '''key feature'''.
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**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>
*Branching capillaries usu. only in supratentorial ependymomas.
 
===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]].
*[[Glioblastoma]] (GBM).
*Gliomas with BCOR internal tandem duplication.
*[[Astroblastoma]], MN1-altered.
**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)
*Diffuse midline glioma, H3 K27-altered
*Small cell glioblastoma (MYCN-amplified spinal ependymoma)
 
===Images===
www:
*[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)].
*[http://www.ajnr.org/cgi/content-nw/full/27/3/488/F10 Ependymoma - ependymal rosettes (ajnr.org)].
*[http://path.upmc.edu/cases/case95/micro.html Anaplastic ependymoma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case324.html Anaplastic ependymoma - case 2 (upmc.edu)].
<gallery>
File:AFIP405736M-EPENDYMOMA.jpg | Ependymoma smear. (AFIP)
File:AFIP405715M-EPENDYMOMA.jpg | Perivascular pseudorosettes in a ependymoma. (AFIP)
Image:Ependymoma_intermed_mag.jpg | Ependymoma - intermed. mag. (WC)
Image:Ependymoma_low_intermed_mag.jpg | Ependymoma - low mag. (WC)
File:Ependymoma_H%26E.jpg | Ependymoma - high mag. (WC/Sbrandner)
File:Ependymoma_true_ependymal_rosettes_and_pseudorosettes.jpg | True ependymal and pseudorosettes in a ependymoma. (WC/jensflorian)
File:Ependymal_linings_ependymoma_HE.jpg | Ependymal linings in a ependymoma. (WC/jensflorian)
File:Ependymoma_GFAP.jpg|  GFAP IHC in a ependymoma. (WC/Sbrandner)
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:Tanycytic ependymoma HE.jpg | Tanycytic morphology in ependymoma must not confused with [[pilocytic astrocytoma]]. (WC/jensflorian)
File:Tanicytic_ependymoma_x10.jpg | Tanycytic morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_Ependymoma.jpg | Papillary morphology in ependymoma - low 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 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:Cartilaginous metaplasia ependymoma.jpg|Metaplastic transformation in an anaplastic ependymoma. (WC/jensflorian)
File:Ependymoma_L1CAM_IHC.jpg | L1CAM immunohistochemistry indicates presence of ZFTA-fusion.
File:Ependymoma_NFkappaB_IHC.jpg | Nuclear NFkappaB IHC indicates presence of ZFTA-fusion.
</gallery>
 
===Grading===
Easy:
*Subependymoma = CNS WHO grade 1.
*Myxopapillary ependymoma = CNS WHO grade 2.
 
Not so easy:
All other ependymomas: WHO CNS Grade 2 vs. Grade 3 depends on:
*Cellular density.
*Mitoses (no clear cut-off).
*Necrosis (not prognostic).
*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>
 
 
Notes:
*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>
 
==IHC==
*Reticulin-ve.
*GFAP+ve.
*MIB1 (usu low).
*[[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>
**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>
*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 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==
'''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>
* Group A ependymomas:
**typically found in children.
**laterally.
**relatively unfavorable clinical outcome.
**CpG island methylator phenotype.<ref>{{Cite journal  | last1 = Mack | first1 = SC. | last2 = Witt | first2 = H. | last3 = Piro | first3 = RM. | last4 = Gu | first4 = L. | last5 = Zuyderduyn | first5 = S. | last6 = Stütz | first6 = AM. | last7 = Wang | first7 = X. | last8 = Gallo | first8 = M. | last9 = Garzia | first9 = L. | title = Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. | journal = Nature | volume = 506 | issue = 7489 | pages = 445-50 | month = Feb | year = 2014 | doi = 10.1038/nature13108 | PMID = 24553142 }}</ref>
**Loss of H3K27me.<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>
* Group B ependymomas:
**typically adults.
**midline.
**relatively favorable clinical outcomes.
**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>
 
==See also==
*[[Subependymoma]].
*[[Myxopapillary ependymoma]].
*[[Neuropathology tumours]].
 
==References==
{{Reflist|1}}
 
[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]
Jensflorian
Account-creators
1,040

edits

Retrieved from "https://librepathology.org/wiki/Special:MobileDiff/4253...52127"

Navigation menu