Abstract
Purpose
Bailey and Cushing established ependymoma as a brain tumour entity in the first brain tumour classification (1926). Diagnosis of ependymomas is not subject to controversy as long as other tumours presenting ependymoma-like features have been ruled out. Grading conversely is a source of debate. Description of histological features establishing diagnosis and grading of ependymomas may help to better understand this controversy.
Methods
Literature has been reviewed using PubMed with the following key words: ependymoma, +/− prognosis, +/− biomaker, +/− grading, +/− immunohistochemistry, +/− proliferative index.
Results
Grading controversy arises from elusive WHO features and individual characteristics of ependymomas including tumour location, tumour pattern/variant and variable expression of biomarkers.
Conclusion
There is a need for a grading scheme with a proven general ability to dissociate grades, and to predict individual clinical evolution. Only then will stratified and targeted therapeutics for ependymal tumours be possible.
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References
Agaoglu FY, Ayan I, Dizdar Y, Kebudi R, Gorgun O, Darendeliler E (2005) Ependymal tumors in childhood. Pediatr Blood Cancer 45:298–303
Bennetto L, Foreman N, Harding B, Hayward R, Ironside J, Love S, Ellison D (1998) Ki-67 immunolabelling index is a prognostic indicator in childhood posterior fossa ependymomas. Neuropathol Appl Neurobiol 24:434–440
Burger PC, Scheithauer BW (2007) Tumors of the central nervous system. ARP, Washington DC
Carter M, Nicholson J, Ross F, Crolla J, Allibone R, Balaji V, Perry R, Walker D, Gilbertson R, Ellison DW (2002) Genetic abnormalities detected in ependymomas by comparative genomic hybridisation. Br J Cancer 86:929–939
Ernestus RI, Wilcke O, Schroder R (1989) Intracranial ependymomas: prognostic aspects. Neurosurg Rev 12:157–163
Ernestus RI, Wilcke O, Schroder R (1991) Supratentorial ependymomas in childhood: clinicopathological findings and prognosis. Acta Neurochir (Wien) 111:96–102
Ernestus RI, Schroder R, Stutzer H, Klug N (1996) Prognostic relevance of localization and grading in intracranial ependymomas of childhood. Childs Nerv Syst 12:522–526
Ernestus RI, Schroder R, Stutzer H, Klug N (1997) The clinical and prognostic relevance of grading in intracranial ependymomas. Br J Neurosurg 11:421–428
Fassett DR, Pingree J, Kestle JR (2005) The high incidence of tumor dissemination in myxopapillary ependymoma in pediatric patients. Report of five cases and review of the literature. J Neurosurg 102:59–64
Figarella-Branger D, Civatte M, Bouvier-Labit C, Gouvernet J, Gambarelli D, Gentet JC, Lena G, Choux M, Pellissier JF (2000) Prognostic factors in intracranial ependymomas in children. J Neurosurg 93:605–613
Friede RL, Pollak A (1978) The cytogenetic basis for classifying ependymomas. J Neuropathol Exp Neurol 37:103–118
Hirose Y, Aldape K, Bollen A, James CD, Brat D, Lamborn K, Berger M, Feuerstein BG (2001) Chromosomal abnormalities subdivide ependymal tumors into clinically relevant groups. Am J Pathol 158:1137–1143
Horn B, Heideman R, Geyer R, Pollack I, Packer R, Goldwein J, Tomita T, Schomberg P, Ater J, Luchtman-Jones L, Rivlin K, Lamborn K, Prados M, Bollen A, Berger M, Dahl G, McNeil E, Patterson K, Shaw D, Kubalik M, Russo C (1999) A multi-institutional retrospective study of intracranial ependymoma in children: identification of risk factors. J Pediatr Hematol Oncol 21:203–211
Ishizawa K, Komori T, Shimada S, Hirose T (2008) Olig2 and CD99 are useful negative markers for the diagnosis of brain tumors. Clin Neuropathol 27:118–128
Jaing TH, Wang HS, Tsay PK, Tseng CK, Jung SM, Lin KL, Lui TN (2004) Multivariate analysis of clinical prognostic factors in children with intracranial ependymomas. J Neurooncol 68:255–261
Jouvet A, Fauchon F, Liberski P, Saint-Pierre G, Didier-Bazes M, Heitzmann A, Delisle MB, Biassette HA, Vincent S, Mikol J, Streichenberger N, Ahboucha S, Brisson C, Belin MF, Fevre-Montange M (2003) Papillary tumor of the pineal region. Am J Surg Pathol 27:505–512
Kawano N, Yada K, Yagishita S (1989) Clear cell ependymoma. A histological variant with diagnostic implications. Virchows Arch A Pathol Anat Histopathol 415:467–472
Komori T, Scheithauer BW, Anthony DC, Rosenblum MK, McLendon RE, Scott RM, Okazaki H, Kobayashi M (1998) Papillary glioneuronal tumor: a new variant of mixed neuronal-glial neoplasm. Am J Surg Pathol 22:1171–1183
Korshunov A, Golanov A, Timirgaz V (2000) Immunohistochemical markers for intracranial ependymoma recurrence. An analysis of 88 cases. J Neurol Sci 177:72–82
Korshunov A, Golanov A, Timirgaz V (2002) Immunohistochemical markers for prognosis of ependymal neoplasms. J Neurooncol 58:255–270
Korshunov A, Neben K, Wrobel G, Tews B, Benner A, Hahn M, Golanov A, Lichter P (2003) Gene expression patterns in ependymomas correlate with tumor location, grade, and patient age. Am J Pathol 163:1721–1727
Korshunov A, Golanov A, Sycheva R, Timirgaz V (2004) The histologic grade is a main prognostic factor for patients with intracranial ependymomas treated in the microneurosurgical era: an analysis of 258 patients. Cancer 100:1230–1237
Kurt E, Zheng PP, Hop WC, van der Weiden M, Bol M, van den Bent MJ, Avezaat CJ, Kros JM (2006) Identification of relevant prognostic histopathologic features in 69 intracranial ependymomas, excluding myxopapillary ependymomas and subependymomas. Cancer 106:388–395
Lehman NL (2008) Patterns of brain infiltration and secondary structure formation in supra-tentorial ependymal tumors. J Neuropathol Exp Neurol 67:900–910
Lehman NL (2008) Central nervous system tumors with ependymal features: a broadened spectrum of primarily ependymal differentiation? J Neuropathol Exp Neurol 67:177–188
Lellouch-Tubiana A, Boddaert N, Bourgeois M, Fohlen M, Jouvet A, Delalande O, Seidenwurm D, Brunelle F, Sainte-Rose C (2005) Angiocentric neuroepithelial tumor (ANET): a new epilepsy-related clinicopathological entity with distinctive MRI. Brain Pathol 15:281–286
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) WHO Classification of Tumours of the Central Nervous System. International Agency for Research on Cancer (IARC), Lyon
McGuire CS, Sainani KL, Fisher PG (2009) Both location and age predict survival in ependymoma: A SEER study. Pediatr Blood Cancer 52:65–69
Mendrzyk F, Korshunov A, Benner A, Toedt G, Pfister S, Radlwimmer B, Lichter P (2006) Identification of gains on 1q and epidermal growth factor receptor overexpression as independent prognostic markers in intracranial ependymoma. Clin Cancer Res 12:2070–2079
Merchant TE, Jenkins JJ, Burger PC, Sanford RA, Sherwood SH, Jones-Wallace D, Heideman RL, Thompson SJ, Helton KJ, Kun LE (2002) Influence of tumor grade on time to progression after irradiation for localized ependymoma in children. Int J Radiat Oncol Biol Phys 53:52–57
Modena P, Lualdi E, Facchinetti F, Veltman J, Reid JF, Minardi S, Janssen I, Giangaspero F, Forni M, Finocchiaro G, Genitori L, Giordano F, Riccardi R, Schoenmakers EF, Massimino M, Sozzi G (2006) Identification of tumor-specific molecular signatures in intracranial ependymoma and association with clinical characteristics. J Clin Oncol 24:5223–5233
Nazar GB, Hoffman HJ, Becker LE, Jenkin D, Humphreys RP, Hendrick EB (1990) Infratentorial ependymomas in childhood: prognostic factors and treatment. J Neurosurg 72:408–417
Perilongo G, Massimino M, Sotti G, Belfontali T, Masiero L, Rigobello L, Garre L, Carli M, Lombardi F, Solero C, Sainati L, Canale V, del Prever AB, Giangaspero F, Andreussi L, Mazza C, Madon E (1997) Analyses of prognostic factors in a retrospective review of 92 children with ependymoma: Italian Pediatric Neuro-oncology Group. Med Pediatr Oncol 29:79–85
Port JD, Brat DJ, Burger PC, Pomper MG (2002) Astroblastoma: radiologic-pathologic correlation and distinction from ependymoma. AJNR Am J Neuroradiol 23:243–247
Preusser M, Wolfsberger S, Czech T, Slavc I, Budka H, Hainfellner JA (2005) Surviving expression in intracranial ependymomas and its correlation with tumor cell proliferation and patient outcome. Am J Clin Pathol 124:543–549
Preusser M, Heinzl H, Gelpi E, Hoftberger R, Fischer I, Pipp I, Milenkovic I, Wohrer A, Popovici F, Wolfsberger S, Hainfellner JA (2008) Ki67 index in intracranial ependymoma: a promising histopathological candidate biomarker. Histopathology 53:39–47
Ridley L, Rahman R, Brundler MA, Ellison D, Lowe J, Robson K, Prebble E, Luckett I, Gilbertson RJ, Parkes S, Rand V, Coyle B, Grundy RG (2008) Multifactorial analysis of predictors of outcome in pediatric intracranial ependymoma. Neuro Oncol 10:675–689
Rousseau E, Ruchoux MM, Scaravilli F, Chapon F, Vinchon M, De Smet C, Godfraind C, Vikkula M (2003) CDKN2A, CDKN2B and p14ARF are frequently and differentially methylated in ependymal tumours. Neuropathol Appl Neurobiol 29:574–583
Rousseau E, Palm T, Scaravilli F, Ruchoux MM, Figarella-Branger D, Salmon I, Ellison D, Lacroix C, Chapon F, Mikol J, Vikkula M, Godfraind C (2007) Trisomy 19 ependymoma, a newly recognized genetico-histological association, including clear cell ependymoma. Mol Cancer 6:47
Rubinstein LJ (1989) Pathology of tumours of the nervous system. Edward Arnold
Rushing EJ, Yashima K, Brown DF, White CL 3rd, Shay JW, Risser RC, Gazdar AF (1997) Expression of telomerase RNA component correlates with the MIB-1 proliferation index in ependymomas. J Neuropathol Exp Neurol 56:1142–1146
Rushing EJ, Brown DF, Hladik CL, Risser RC, Mickey BE, White CL 3rd (1998) Correlation of bcl-2, p53, and MIB-1 expression with ependymoma grade and subtype. Mod Pathol 11:464–470
Sala F, Talacchi A, Mazza C, Prisco R, Ghimenton C, Bricolo A (1998) Prognostic factors in childhood intracranial ependymomas: the role of age and tumor location. Pediatr Neurosurg 28:135–142
Singh PK, Gutmann DH, Fuller CE, Newsham IF, Perry A (2002) Differential involvement of protein 4.1 family members DAL-1 and NF2 in intracranial and intraspinal ependymomas. Mod Pathol 15:526–531
Snuderl M, Chi SN, De Santis SM, Stemmer-Rachamimov AO, Betensky RA, De Girolami U, Kieran MW (2008) Prognostic value of tumor microinvasion and metalloproteinases expression in intracranial pediatric ependymomas. J Neuropathol Exp Neurol 67:911–920
Taylor MD, Poppleton H, Fuller C, Su X, Liu Y, Jensen P, Magdaleno S, Dalton J, Calabrese C, Board J, Macdonald T, Rutka J, Guha A, Gajjar A, Curran T, Gilbertson RJ (2005) Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8:323–335
Tihan T, Zhou T, Holmes E, Burger PC, Ozuysal S, Rushing EJ (2008) The prognostic value of histological grading of posterior fossa ependymomas in children: a Children's Oncology Group study and a review of prognostic factors. Mod Pathol 21:165–177
Trembath D, Miller CR, Perry A (2008) Gray zones in brain tumor classification: evolving concepts. Adv Anat Pathol 15:287–297
Wang M, Tihan T, Rojiani AM, Bodhireddy SR, Prayson RA, Iacuone JJ, Alles AJ, Donahue DJ, Hessler RB, Kim JH, Haas M, Rosenblum MK, Burger PC (2005) Monomorphous angiocentric glioma: a distinctive epileptogenic neoplasm with features of infiltrating astrocytoma and ependymoma. J Neuropathol Exp Neurol 64:875–881
Wolfsberger S, Fischer I, Hoftberger R, Birner P, Slavc I, Dieckmann K, Czech T, Budka H, Hainfellner J (2004) Ki-67 immunolabeling index is an accurate predictor of outcome in patients with intracranial ependymoma. Am J Surg Pathol 28:914–920
Yan X, Cheng X, Liu J, Luo D, He X, Chen F, Qin C, Wang Y (2008) Clinicopathological evaluation of immunohistochemical Ki-67 and endothelial nitric oxide synthase expression in intracranial ependymoma. Clin Invest Med 31:E206–E211
Zamecnik J, Snuderl M, Eckschlager T, Chanova M, Hladikova M, Tichy M, Kodet R (2003) Pediatric intracranial ependymomas: prognostic relevance of histological, immunohistochemical, and flow cytometric factors. Mod Pathol 16:980–991
Zheng PP, Pang JC, Hui AB, Ng HK (2000) Comparative genomic hybridization detects losses of chromosomes 22 and 16 as the most common recurrent genetic alterations in primary ependymomas. Cancer Genet Cytogenet 122:18–25
Acknowledgements
The author wish to thank F. Scaravilli, M.D., Ph.D., D. Figarella-Branger, M.D., Ph.D., C. Galant, M.D., Ph.D., and N. Limaye, Ph.D. for their kind and critical review of the manuscript.
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Godfraind, C. Classification and controversies in pathology of ependymomas. Childs Nerv Syst 25, 1185–1193 (2009). https://doi.org/10.1007/s00381-008-0804-4
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DOI: https://doi.org/10.1007/s00381-008-0804-4