Ependymoma

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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.

Epidemiology:[1]

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

There are five main ependymal tumors:[2]

  1. Ependymoma (not otherwise specified).
    • Other flavours:[3]
      • Papillary ependymoma.
      • Clear cell ependymoma.
      • Tanycytic ependymoma.
  2. Ependymoma, RELA fusion-positive.[4]
    • L1CAM +ve / Nuclear NFkappaB +ve.[5]
    • Majority of supratentorial ependymoma in children.
  3. Anaplastic ependymoma.
  4. Myxopapillary ependymoma.
  5. Subependymoma.
    • Typically seen in IVth ventricle.

The designation Cellular ependymoma is depreceated.

Gross

  • Usually discrete and enhancing.
  • Ventricular location, but also within the spinal cord.
  • Dissemination possible.

  • Radiology (AFIP)

  • Ependymoma in the fourth ventricle (AFIP)

  • Gross (AFIP)

Microscopic

Classic ependymoma

Features:

  • Cells have a "tadpole-like" morphology.
    • May also be described as ice cream cone-shaped.[6]
  • 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".[7]
    • There is little variation in size, shape and staining.
  • Rare cases with cartilagineous metaplasia.[8]

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 ependymoma must not confused with pilocytic astrocytoma. (WC/jensflorian)

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

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

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

  • Clear cell 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 C11orf-RELA fusion.

  • Nuclear NFkappaB IHC indicates presence of C11orf-RELA fusion.

Grading

Easy:

  • Subependymoma = WHO grade I.
  • Myxopapillary ependymoma = WHO grade I.

Not-so-easy:

  • Classic ependymoma = WHO grade II.
  • Anaplastic ependymoma = WHO grade III.

Grade II vs. Grade III:

  • Cellular density.
  • Mitoses.
  • Necrosis.
  • Microvascular proliferation.
  • Poor interobserver reliability[9]


Notes:

  • Many tumours fall between grade II and grade III. These are called "indeterminate" by many.
  • Rare cases with sarcomatous or cartilaginous components.[10][11]

IHC

  • Reticulin+ve.
  • GFAP+ve.
  • MIB1 (usu low).
  • IDH-1-ve.
  • EMA (dots and rings).[12]
  • Olig2-ve.[13]
  • H3K27me in posterior fossa (loss indicates group A).[14]
  • L1CAM in supratentorial tumors (expression indicates RELA fusion).[15]

Molecular

Two distinct molecular subgroups exist in the posterior fossa:[16]

  • Group A ependymomas:
    • typically found in children.
    • laterally.
    • relatively unfavorable clinical outcome.
    • CpG island methylator phenotype.[17]
    • Loss of H3K27me.[18]
  • Group B ependymomas:
    • typically adults.
    • midline.
    • relatively favorable clinical outcomes.
    • gene expression profiles similar to that of spinal cord ependymomas.
    • increased Chromosomal 1q gains. [19]

Supratentorial ependymomas have also a distinct profile:

  • 70 % of these ependymomas have recurrent gene fusions involving RELA and C11orf95[20]
  • EPHB2 amplifications and CDKN2A deletions in a subset of these tumors[21]

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. ↑ URL: http://emedicine.medscape.com/article/1744030-overview. Accessed on: 17 January 2012.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html
  7. ↑ MUN. 6 Oct 2009.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
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