Difference between revisions of "Ependymoma"

From Libre Pathology
Jump to navigation Jump to search
(→‎Grading: update)
Line 133: Line 133:
===Grading===
===Grading===
Easy:
Easy:
*Subependymoma = WHO grade I.
*Subependymoma = CNS WHO grade 1.
*Myxopapillary ependymoma = WHO grade I.
*Myxopapillary ependymoma = CNS WHO grade 2.
Not-so-easy:
*Classic ependymoma = WHO grade II.
*Anaplastic ependymoma = WHO grade III.


Grade II vs. Grade III:
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>
Line 148: Line 146:


Notes:
Notes:
*Many tumours fall between grade II and grade III.  These are called "indeterminate" by many.
*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>


Revision as of 12:46, 12 April 2022

Ependymoma
Diagnosis in short

Ependymoma grade II WHO. H&E stain
LM Perivascular pseudorosettes, ependymal rosettes
Subtypes Tanycytic, Clear cell, Papillary, Cellular
LM DDx Subependymoma, Glioblastoma, Pilocytic astrocytoma, Oligodendroglioma
IHC GFAP +ve
Prognosis intermediate to poor (WHO Grades II & III)


Ependymoma is a neuropathology tumour.

General

  • Called the forgotten glial tumour.
  • Anatomic location is essential for tumor diagnosis.


Epidemiology:[1]

  • Usual site:
    • Adults: usually spinal cord.
    • Children: usually posterior fossa.
  • May be associated with neurofibromatosis type 2.


There are currently eight main ependymal tumors:[2]

  1. Supratentorial ependymoma, ZFTA-fusion positive
  2. Supratentorial ependymoma, YAP1-fusion positive
  3. Posterior fossa ependymoma group A
  4. Posterior fossa ependymoma group B
  5. Spinal ependymoma
  6. Spinal ependymoma, MYCN-amplified
  7. Myxopapillary ependymoma
  8. Subependymoma

Ependymoma (not otherwise specified).

  • Depreceated terminologies:
    • Papillary ependymoma.
    • Clear cell ependymoma.
    • Tanycytic ependymoma.
    • Cellular ependymoma.
    • Ependymoma, RELA fusion-positive.[3][4] This is now called Supratentorial ependymoma, ZFTA-fusion positive.
    • Anaplastic ependymoma.

Gross

  • Radiology (AFIP)

  • Ependymoma in the fourth ventricle (AFIP)

  • Gross (AFIP)

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.[5]
  • 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".[6]
    • There is little variation in size, shape and staining.
  • Hyalinized vessels.
  • Calcification.
  • Rare cases with cartilagineous metaplasia.[7]
  • Branching capillaries usu. only in supratentorial ependymomas.

DDx (classic ependymoma):

Images

www:

  • Ependymoma smear. (AFIP)

  • Perivascular pseudorosettes in a ependymoma. (AFIP)

  • Ependymoma - intermed. mag. (WC)

  • Ependymoma - low mag. (WC)

  • Ependymoma - high mag. (WC/Sbrandner)

  • True ependymal and pseudorosettes in a ependymoma. (WC/jensflorian)

  • Ependymal linings in a ependymoma. (WC/jensflorian)

  • GFAP IHC in a ependymoma. (WC/Sbrandner)

  • Periluminal EMA positivity in a ependymoma. (WC/jensflorian)

  • Dot-like EMA immunreactivity n a ependymoma. (WC/Marvin101)

  • Tanycytic morphology in ependymoma must not confused with pilocytic astrocytoma. (WC/jensflorian)

  • Tanycytic morphology in ependymoma - low mag. (WC/jensflorian)

  • Papillary morphology in ependymoma - low mag. (WC/jensflorian)

  • Papillary morphology in ependymoma - intermed. mag. (WC/jensflorian)

  • Clear cell morphology in ependymoma may mimic oligodendroglioma. (WC/jensflorian)

  • Brisk mitotic activity in a anaplastic ependymoma. (WC/jensflorian)

  • Metaplastic transformation in an anaplastic ependymoma. (WC/jensflorian)

  • L1CAM immunohistochemistry indicates presence of ZFTA-fusion.

  • Nuclear NFkappaB IHC indicates presence of ZFTA-fusion.

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[8]


Notes:

  • Many tumours fall between grade 2 and grade 3.
  • Rare cases with sarcomatous or cartilaginous components.[9][10]

IHC

  • Reticulin-ve.
  • GFAP+ve.
  • MIB1 (usu low).
  • IDH-1-ve.
  • EMA (dots and rings).[11]
  • Olig2-ve.[12]
  • H3K27me in posterior fossa (loss indicates group A).[13]
  • L1CAM in supratentorial tumors (expression indicates RELA fusion).[14]

Molecular

Two distinct molecular subgroups exist in the posterior fossa:[15]

  • Group A ependymomas:
    • typically found in children.
    • laterally.
    • relatively unfavorable clinical outcome.
    • CpG island methylator phenotype.[16]
    • Loss of H3K27me.[17]
  • Group B ependymomas:
    • typically adults.
    • midline.
    • relatively favorable clinical outcomes.
    • gene expression profiles similar to that of spinal cord ependymomas.
    • increased Chromosomal 1q gains. [18]

Supratentorial ependymomas have also a distinct profile:

  • 70 % of these ependymomas have recurrent gene fusions involving RELA and C11orf95[19]
  • EPHB2 amplifications and CDKN2A deletions in a subset of these tumors[20]

Note: Molecular subgroups have no treatment implications (at the moment).

See also

References

  1. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1334. ISBN 978-1416031215.
  2. ↑ The International Agency for Research on Cancer (Editors: Louis, D.N.; Ohgaki, H.; Wiestler, O.D.; Cavenee, W.K.) (2007). Pathology and Genetics of Tumours of Tumors of the Central Nervous System (IARC WHO Classification of Tumours) (4th ed.). Lyon: World Health Organization. pp. 74. doi:10.1007/s00401-007-0243-4. ISBN 978-9283224303.
  3. ↑ Parker, M.; Mohankumar, KM.; Punchihewa, C.; Weinlich, R.; Dalton, JD.; Li, Y.; Lee, R.; Tatevossian, RG. et al. (Feb 2014). "C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma.". Nature 506 (7489): 451-5. doi:10.1038/nature13109. PMID 24553141.
  4. ↑ Pietsch, T.; Wohlers, I.; Goschzik, T.; Dreschmann, V.; Denkhaus, D.; Dörner, E.; Rahmann, S.; Klein-Hitpass, L. (Apr 2014). "Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to pathological activation of the NF-κB signaling pathway.". Acta Neuropathol 127 (4): 609-11. doi:10.1007/s00401-014-1264-4. PMID 24562983.
  5. ↑ http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html
  6. ↑ MUN. 6 Oct 2009.
  7. ↑ Wang, X.; Zhang, S.; Ye, Y.; Chen, Y.; Liu, X. (Jul 2012). "Ependymoma with cartilaginous metaplasia might have more aggressive behavior: a case report and literature review.". Brain Tumor Pathol 29 (3): 172-6. doi:10.1007/s10014-011-0079-4. PMID 22228122.
  8. ↑ Ellison, DW.; Kocak, M.; Figarella-Branger, D.; Felice, G.; Catherine, G.; Pietsch, T.; Frappaz, D.; Massimino, M. et al. (May 2011). "Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts.". J Negat Results Biomed 10: 7. doi:10.1186/1477-5751-10-7. PMID 21627842.
  9. ↑ Vajtai, I.; Kuhlen, D.; Kappeler, A.; Mariani, L.; Zimmermann, A.; Paulus, W. (Jul 2010). "Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma".". Pathol Res Pract 206 (7): 493-8. doi:10.1016/j.prp.2009.07.013. PMID 19853384.
  10. ↑ Boukas, A.; Joshi, A.; Jenkins, A.; Holliman, D. (2013). "Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature.". Pediatr Neurosurg 49 (2): 93-8. doi:10.1159/000356931. PMID 24401698.
  11. ↑ Hasselblatt, M.; Paulus, W. (Oct 2003). "Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas.". Acta Neuropathol 106 (4): 385-8. doi:10.1007/s00401-003-0752-8. PMID 12898159.
  12. ↑ Švajdler, M.; Rychlý, B.; Mezencev, R.; Fröhlichová, L.; Bednárová, A.; Pataky, F.; Daum, O. (Jan 2016). "SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors.". Histol Histopathol 31 (1): 95-102. doi:10.14670/HH-11-654. PMID 26287936.
  13. ↑ Panwalkar, P.; Clark, J.; Ramaswamy, V.; Hawes, D.; Yang, F.; Dunham, C.; Yip, S.; Hukin, J. et al. (Jul 2017). "Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome.". Acta Neuropathol. doi:10.1007/s00401-017-1752-4. PMID 28733933.
  14. ↑ Parker, M.; Mohankumar, KM.; Punchihewa, C.; Weinlich, R.; Dalton, JD.; Li, Y.; Lee, R.; Tatevossian, RG. et al. (Feb 2014). "C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma.". Nature 506 (7489): 451-5. doi:10.1038/nature13109. PMID 24553141.
  15. ↑ Witt, H.; Mack, SC.; Ryzhova, M.; Bender, S.; Sill, M.; Isserlin, R.; Benner, A.; Hielscher, T. et al. (Aug 2011). "Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma.". Cancer Cell 20 (2): 143-57. doi:10.1016/j.ccr.2011.07.007. PMID 21840481.
  16. ↑ Mack, SC.; Witt, H.; Piro, RM.; Gu, L.; Zuyderduyn, S.; Stütz, AM.; Wang, X.; Gallo, M. et al. (Feb 2014). "Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.". Nature 506 (7489): 445-50. doi:10.1038/nature13108. PMID 24553142.
  17. ↑ Panwalkar, P.; Clark, J.; Ramaswamy, V.; Hawes, D.; Yang, F.; Dunham, C.; Yip, S.; Hukin, J. et al. (Jul 2017). "Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome.". Acta Neuropathol. doi:10.1007/s00401-017-1752-4. PMID 28733933.
  18. ↑ Korshunov, A.; Witt, H.; Hielscher, T.; Benner, A.; Remke, M.; Ryzhova, M.; Milde, T.; Bender, S. et al. (Jul 2010). "Molecular staging of intracranial ependymoma in children and adults.". J Clin Oncol 28 (19): 3182-90. doi:10.1200/JCO.2009.27.3359. PMID 20516456.
  19. ↑ Parker, M.; Mohankumar, KM.; Punchihewa, C.; Weinlich, R.; Dalton, JD.; Li, Y.; Lee, R.; Tatevossian, RG. et al. (Feb 2014). "C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma.". Nature 506 (7489): 451-5. doi:10.1038/nature13109. PMID 24553141.
  20. ↑ Philip-Hollingsworth, S.; Hollingsworth, RI.; Dazzo, FB. (Jan 1989). "Host-range related structural features of the acidic extracellular polysaccharides of Rhizobium trifolii and Rhizobium leguminosarum.". J Biol Chem 264 (3): 1461-6. PMID 2912966.
Retrieved from "https://librepathology.org/w/index.php?title=Ependymoma&oldid=51986"