The PDQ childhood brain tumor treatment summaries are organized primarily according to the World Health Organization (WHO) classification of nervous system tumors. For a full description of the classification of nervous system tumors and a link to the corresponding treatment summary for each type of brain tumor, refer to the PDQ summary on Childhood Brain and Spinal Cord Tumors Treatment Overview.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%. Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis.
Ependymomas arise from ependymal cells that line the ventricles and passageways in the brain and the center of the spinal cord. Ependymal cells produce cerebrospinal fluid (CSF). These tumors are classified as supratentorial or infratentorial. In children, most ependymomas are infratentorial tumors that arise in or around the fourth ventricle. According to the 2016 revision to the WHO classification of tumors of the central nervous system, ependymal tumors are classified into the following five main subtypes:
Subependymoma (WHO Grade I).
Myxopapillary ependymoma (WHO Grade I).
Ependymoma (WHO Grade II).
Ependymoma, RELA fusion–positive (WHO Grade II or Grade III).
Anaplastic ependymoma (WHO Grade III).
The location of the tumor determines the clinical presentation. Treatment begins with surgery. The type of adjuvant therapy given, such as a second surgery, chemotherapy, or radiation therapy, depends on the following:
Subtype of ependymoma.
Whether the tumor was completely removed during the initial surgery.
Whether the tumor has disseminated throughout the central nervous system.
Childhood ependymoma comprises approximately 9% of all childhood brain tumors, representing about 200 cases per year in the United States.[3,4]
Molecular characterization studies have identified several biological subtypes of ependymoma based on their distinctive DNA methylation and gene expression profiles and on their distinctive spectrum of genomic alterations.[5-7]
Posterior fossa A, CpG island methylator phenotype (CIMP)-positive ependymoma, termed EPN-PFA.
C11orf95-RELA–negative and YAP1 fusion–positive ependymoma.
Approximately two-thirds of childhood ependymomas arise in the posterior fossa, and two major genomically defined subtypes of posterior fossa tumors are recognized. Similarly, most pediatric supratentorial tumors can be categorized into one of two genomic subtypes. These subtypes and their associated clinical characteristics are described below.
The most common posterior fossa ependymoma subtype is EPN-PFA and is characterized by the following:
Presentation in young children (median age, 3 years).
Low rates of mutations that affect protein structure (approximately five per genome), with no recurring mutations.
A balanced chromosomal profile (refer to Figure 3) with few chromosomal gains or losses.[5,6]
Gain of chromosome 1q, a known poor prognostic factor for ependymomas, in approximately 25% of cases.[5,7]
Favorable outcome in comparison to EPN-PFA, with 5-year PFS of 73% and overall survival (OS) of 100%.
The largest subset of pediatric supratentorial (ST) ependymomas are characterized by gene fusions involving RELA,[9,10] a transcriptional factor important in NF-κB pathway activity. This subtype is termed ST-EPN-RELA and is characterized by the following:
Represents approximately 70% of supratentorial ependymomas in children,[9,10] and presents at a median age of 8 years.
Presence of C11orf95-RELA fusions resulting from chromothripsis involving chromosome 11q13.1.
Evidence of NF-κB pathway activation at the protein and RNA level.
Low rates of mutations that affect protein structure and absence of recurring mutations outside of C11orf95-RELA fusions.
Presence of homozygous deletions of CDKN2A, a known poor prognostic factor for ependymomas, in approximately 15% of cases.
Gain of chromosome 1q, a known poor prognostic factor for ependymomas, in approximately one-quarter of cases.
Unfavorable outcome in comparison to other ependymoma subtypes, with 5-year PFS of 29% and OS of 75%.
Supratentorial clear cell ependymomas with branching capillaries commonly show theC11orf95-RELA fusion, and one series of 20 patients with a median age of 10.4 years showed a relatively favorable prognosis (5-year PFS of 68% and OS of 72%).
A second, less common subset of supratentorial ependymomas, termed ST-EPN-YAP1, has fusions involving YAP1 and are characterized by the following:
Presence of a gene fusion involving YAP1, with MAMLD1 being the most common fusion partner.[5,9]
A relatively stable genome with few chromosomal changes other than the YAP1 fusion.
Relatively favorable prognosis (although based on small numbers), with a 5-year PFS of 66% and OS of 100%.
Clinical implications of genomic alterations
The absence of recurring mutations in the EPN-PFA and EPN-PFB subtypes at diagnosis precludes using their genomic profiles to guide therapy. The RELA and YAP1 fusion genes present in supratentorial ependymomas are not directly targetable with agents in the clinic, but can provide leads for future research.
The clinical presentation of ependymoma is dependent on tumor location.
Infratentorial (posterior fossa) ependymoma: In children, approximately 65% to 75% of ependymomas arise in the posterior fossa. Children with posterior fossa ependymoma may present with signs and symptoms of obstructive hydrocephalus due to obstruction at the level of the fourth ventricle. They may also present with ataxia, neck pain, or cranial nerve palsies.
Supratentorial ependymoma: Supratentorial ependymoma may result in headache, seizures, or location-dependent focal neurologic deficits.
Spinal cord ependymoma: Spinal cord ependymomas, which are often the myxopapillary variant, tend to cause back pain, lower extremity weakness, and/or bowel and bladder dysfunction.
Every patient suspected of having ependymoma is evaluated with diagnostic imaging of the whole brain and spinal cord. The most sensitive method available for evaluating spinal cord subarachnoid metastasis is spinal magnetic resonance imaging (MRI) performed with gadolinium. This is ideally done before surgery to avoid confusion with postoperative blood. If MRI is used, the entire spine is generally imaged in at least two planes with contiguous MRI slices performed after gadolinium enhancement. If feasible, CSF cytological evaluation is conducted.
Unfavorable factors affecting outcome (except as noted) include the following:
Gene expression profile.
Posterior fossa ependymoma can be divided into the following two groups based on distinctive patterns of gene expression.[5,6,14,15]
EPN-PFA occurs primarily in young children and is characterized by a largely balanced genomic profile with an increased occurrence of chromosome 1q gain [8,16-18] and expression of genes and proteins previously shown to be associated with poor prognosis, such as tenascin C and epidermal growth factor receptor.[16,19]
In contrast, EPN-PFB occurs primarily in older children and adults and is characterized by a more favorable prognosis and by numerous cytogenetic abnormalities involving whole chromosomes or chromosomal arms.
Other factors that have been reported to be associated with poor prognosis for pediatric ependymoma include expression of the enzymatic subunit of telomerase (hTERT) [20-22] and expression of the neural stem cell marker Nestin.[Level of evidence: 3iiiA]
Tumor location. Cranial variants of ependymoma have a less favorable outcome than primary spinal cord ependymomas.[24,25] Location within the spinal cord may also affect outcome, with tumors in the lower portion of the spinal cord having a worse prognosis.[Level of evidence: 3iiiA]
Immunohistochemical testing has identified increased expression of markers of proliferation (e.g., Ki-67 and MIB-1) [33,34] and increased expression of EZH2, a polycomb complex protein involved in epigenetic regulation of gene expression, as prognostic factors for greater risk of treatment failure.
Follow-up After Treatment
Surveillance neuroimaging, coupled with clinical assessments, are generally recommended after treatment for ependymoma. The frequency and duration have been arbitrarily determined and the utility is uncertain. Most practitioners obtain MRI imaging of the brain and/or spinal cord every 3 months for the first 1 to 2 years after treatment. After 2 years, imaging every 6 months for the next 3 years is often undertaken.
Louis DN, Ohgaki H, Wiestler OD: WHO Classification of Tumours of the Central Nervous System. 4th rev.ed. Lyon, France: IARC Press, 2016.
Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
Gurney JG, Smith MA, Bunin GR: CNS and miscellaneous intracranial and intraspinal neoplasms. In: Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649, Chapter 3, pp 51-63. Also available online. Last accessed August 12, 2016.
Central Brain Tumor Registry of the United States: Statistical Report: Primary Brain Tumors in the United States, 1997-2001. Hinsdale, Ill: Central Brain Tumor Registry of the United States, 2004. Also available onlineExit Disclaimer. Last accessed August 12, 2016.
Pajtler KW, Witt H, Sill M, et al.: Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups. Cancer Cell 27 (5): 728-43, 2015. [PUBMED Abstract]
Witt H, Mack SC, Ryzhova M, et al.: Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20 (2): 143-57, 2011. [PUBMED Abstract]
Korshunov A, Witt H, Hielscher T, et al.: Molecular staging of intracranial ependymoma in children and adults. J Clin Oncol 28 (19): 3182-90, 2010. [PUBMED Abstract]
Parker M, Mohankumar KM, Punchihewa C, et al.: C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. Nature 506 (7489): 451-5, 2014. [PUBMED Abstract]
Pietsch T, Wohlers I, Goschzik T, et al.: Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to pathological activation of the NF-κB signaling pathway. Acta Neuropathol 127 (4): 609-11, 2014. [PUBMED Abstract]
Figarella-Branger D, Lechapt-Zalcman E, Tabouret E, et al.: Supratentorial clear cell ependymomas with branching capillaries demonstrate characteristic clinicopathological features and pathological activation of nuclear factor-kappaB signaling. Neuro Oncol 18 (7): 919-27, 2016. [PUBMED Abstract]
Andreiuolo F, Puget S, Peyre M, et al.: Neuronal differentiation distinguishes supratentorial and infratentorial childhood ependymomas. Neuro Oncol 12 (11): 1126-34, 2010. [PUBMED Abstract]
Moreno L, Pollack IF, Duffner PK, et al.: Utility of cerebrospinal fluid cytology in newly diagnosed childhood ependymoma. J Pediatr Hematol Oncol 32 (6): 515-8, 2010. [PUBMED Abstract]
Wani K, Armstrong TS, Vera-Bolanos E, et al.: A prognostic gene expression signature in infratentorial ependymoma. Acta Neuropathol 123 (5): 727-38, 2012. [PUBMED Abstract]
Ramaswamy V, Hielscher T, Mack SC, et al.: Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis. J Clin Oncol 34 (21): 2468-77, 2016. [PUBMED Abstract]
Mendrzyk F, Korshunov A, Benner A, et al.: Identification of gains on 1q and epidermal growth factor receptor overexpression as independent prognostic markers in intracranial ependymoma. Clin Cancer Res 12 (7 Pt 1): 2070-9, 2006. [PUBMED Abstract]
Kilday JP, Mitra B, Domerg C, et al.: Copy number gain of 1q25 predicts poor progression-free survival for pediatric intracranial ependymomas and enables patient risk stratification: a prospective European clinical trial cohort analysis on behalf of the Children's Cancer Leukaemia Group (CCLG), Societe Francaise d'Oncologie Pediatrique (SFOP), and International Society for Pediatric Oncology (SIOP). Clin Cancer Res 18 (7): 2001-11, 2012. [PUBMED Abstract]
Godfraind C, Kaczmarska JM, Kocak M, et al.: Distinct disease-risk groups in pediatric supratentorial and posterior fossa ependymomas. Acta Neuropathol 124 (2): 247-57, 2012. [PUBMED Abstract]
Korshunov A, Golanov A, Timirgaz V: Immunohistochemical markers for intracranial ependymoma recurrence. An analysis of 88 cases. J Neurol Sci 177 (1): 72-82, 2000. [PUBMED Abstract]
Tabori U, Ma J, Carter M, et al.: Human telomere reverse transcriptase expression predicts progression and survival in pediatric intracranial ependymoma. J Clin Oncol 24 (10): 1522-8, 2006. [PUBMED Abstract]
Tabori U, Wong V, Ma J, et al.: Telomere maintenance and dysfunction predict recurrence in paediatric ependymoma. Br J Cancer 99 (7): 1129-35, 2008. [PUBMED Abstract]
Modena P, Buttarelli FR, Miceli R, et al.: Predictors of outcome in an AIEOP series of childhood ependymomas: a multifactorial analysis. Neuro Oncol 14 (11): 1346-56, 2012. [PUBMED Abstract]
McGuire CS, Sainani KL, Fisher PG: Both location and age predict survival in ependymoma: a SEER study. Pediatr Blood Cancer 52 (1): 65-9, 2009. [PUBMED Abstract]
Benesch M, Frappaz D, Massimino M: Spinal cord ependymomas in children and adolescents. Childs Nerv Syst 28 (12): 2017-28, 2012. [PUBMED Abstract]
Oh MC, Sayegh ET, Safaee M, et al.: Prognosis by tumor location for pediatric spinal cord ependymomas. J Neurosurg Pediatr 11 (3): 282-8, 2013. [PUBMED Abstract]
Tamburrini G, D'Ercole M, Pettorini BL, et al.: Survival following treatment for intracranial ependymoma: a review. Childs Nerv Syst 25 (10): 1303-12, 2009. [PUBMED Abstract]
Merchant TE, Jenkins JJ, Burger PC, et al.: Influence of tumor grade on time to progression after irradiation for localized ependymoma in children. Int J Radiat Oncol Biol Phys 53 (1): 52-7, 2002. [PUBMED Abstract]
Korshunov A, Golanov A, Sycheva R, et al.: 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 (6): 1230-7, 2004. [PUBMED Abstract]
Amirian ES, Armstrong TS, Aldape KD, et al.: Predictors of survival among pediatric and adult ependymoma cases: a study using Surveillance, Epidemiology, and End Results data from 1973 to 2007. Neuroepidemiology 39 (2): 116-24, 2012. [PUBMED Abstract]
Tihan T, Zhou T, Holmes E, et al.: 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 (2): 165-77, 2008. [PUBMED Abstract]
Vaidya K, Smee R, Williams JR: Prognostic factors and treatment options for paediatric ependymomas. J Clin Neurosci 19 (9): 1228-35, 2012. [PUBMED Abstract]
Wolfsberger S, Fischer I, Höftberger R, et al.: Ki-67 immunolabeling index is an accurate predictor of outcome in patients with intracranial ependymoma. Am J Surg Pathol 28 (7): 914-20, 2004. [PUBMED Abstract]
Kurt E, Zheng PP, Hop WC, et al.: Identification of relevant prognostic histopathologic features in 69 intracranial ependymomas, excluding myxopapillary ependymomas and subependymomas. Cancer 106 (2): 388-95, 2006. [PUBMED Abstract]
Li AM, Dunham C, Tabori U, et al.: EZH2 expression is a prognostic factor in childhood intracranial ependymoma: a Canadian Pediatric Brain Tumor Consortium study. Cancer 121 (9): 1499-507, 2015. [PUBMED Abstract]
Good CD, Wade AM, Hayward RD, et al.: Surveillance neuroimaging in childhood intracranial ependymoma: how effective, how often, and for how long? J Neurosurg 94 (1): 27-32, 2001. [PUBMED Abstract]
Next section > Histopathologic Classification of Childhood Ependymal Tumors
ver historia personal en: www.cerasale.com.ar [dado de baja por la Cancillería Argentina por temas políticos, propio de la censura que rige en nuestro medio]//
weblog.maimonides.edu/farmacia/archives/UM_Informe_Autoevaluacion_FyB.pdf - //
weblog.maimonides.edu/farmacia/archives/0216_Admin_FarmEcon.pdf - //
www.proz.com/kudoz/english_to_spanish/art_literary/523942-key_factors.html - 65k - // www.llave.connmed.com.ar/portalnoticias_vernoticia.php?codigonoticia=17715 // www.frusculleda.com.ar/homepage/espanol/activities_teaching.htm // http://www.on24.com.ar/nota.aspx?idNot=36331 ||