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Background

The ependymoma is the least common gliomatous neoplasms of the brain. However, it is one of the more common spinal cord tumors.

OUTLINE

Epidemiology  
Pathogenesis  
Laboratory/Radiologic/Other Diagnostic Testing  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/Immunohistochemistry/Electron Microscopy  
Differential Diagnosis  
Prognosis and Treatment  
Commonly Used Terms  
Internet Links  


EPIDEMIOLOGY CHARACTERIZATION
GEOGRAPHY  


An infectious aetiology for childhood brain tumours? Evidence from space-time clustering and seasonality analyses.

McNally RJ, Cairns DP, Eden OB, Alexander FE, Taylor GM, Kelsey AM, Birch JM.

Cancer Research UK Paediatric & Familial Cancer Research Group, Central Manchester and Manchester Children's University Hospitals NHS Trust, Manchester M27 4HA, UK.

Br J Cancer 2002 Apr 8;86(7):1070-7 Abstract quote

To investigate whether infections or other environmental exposures may be involved in the aetiology of childhood central nervous system tumours, we have analysed for space-time clustering and seasonality using population-based data from the North West of England for the period 1954 to 1998.

Knox tests for space-time interactions between cases were applied with fixed thresholds of close in space, <5 km, and close in time, <1 year apart. Addresses at birth and diagnosis were used. Tests were repeated replacing geographical distance with distance to the Nth nearest neighbour. N was chosen such that the mean distance was 5 km. Data were also examined by a second order procedure based on K-functions. Tests for heterogeneity and Edwards' test for sinusoidal variation were applied to examine changes of incidence with month of birth or diagnosis.

There was strong evidence of space-time clustering, particularly involving cases of astrocytoma and ependymoma. Analyses of seasonal variation showed excesses of cases born in the late Autumn or Winter. Results are consistent with a role for infections in a proportion of cases from these diagnostic groups. Further studies are needed to identify putative infectious agents.

 

PATHOGENESIS CHARACTERIZATION
LOSS OF HETEROZYGOSITY  


CDKN2A/p16 in ependymomas.

Bortolotto S, Chiado-Piat L, Cavalla P, Bosone I, Mauro A, Schiffer D.

Department of Neuroscience, University of Turin, Italy.

J Neurooncol 2001 Aug;54(1):9-13 Abstract quote

Sixteen cases of ependymoma were studied for CDKN2A/p16 inactivation by immunohistochemistry using a p16 monoclonal antibody, by homozygous deletion (HD) assay and 5'CpG promoter methylation assay (methylation-specific PCR).

Three out of 16 cases were p16 immuno-negative: two corresponded to grade II ependymomas and one to grade III. The latter ependymoma, characterized by a high Ki-67/MIB-1 LI, was the only one of the whole series to show CDKN2A HD. No promoter methylation was found in the two immuno-negative cases without CDKN2A HD. Alternative mechanisms, such as point mutations or alterations in p16 post-translational regulation, may be responsible for p16 inactivation.

Since in our series just one out of eight anaplastic cases showed negative immunostaining and CDKN2A HD, p16/CDKN2A inactivation may not play an important role in the malignant transformation of ependymomas. Amplification of CCNDI and CDK4, p27/Kipl degradation and TP53 mutations were previously studied by other authors and were demonstrated not to correlate with anaplasia.

Up to date, molecular genetic studies have not been useful in recognizing the anaplastic variant in ependymomas.


Genetic abnormalities detected in ependymomas by comparative genomic hybridisation.

Carter M, Nicholson J, Ross F, Crolla J, Allibone R, Balaji V, Perry R, Walker D, Gilbertson R, Ellison DW.

Department of Neurosurgery, Southampton General Hospital, Southampton, UK.

Br J Cancer 2002 Mar 18;86(6):929-39 Abstract quote

Using comparative genomic hybridisation, we have analysed genetic imbalance in a series of 86 ependymomas from children and adults. Tumours were derived from intracranial and spinal sites, and classified histologically as classic, anaplastic or myxopapillary. Ependymomas showing a balanced profile were significantly (P<0.0005) more frequent in children than adults. Profiles suggesting intermediate ploidy were common (44% of all tumours), and found more often (P<0.0005) in tumours from adults and the spinal region.

Loss of 22q was the most common specific abnormality, occurring in 50% of spinal (medullary) ependymomas and 26% of tumours overall. Genetic profiles combining loss of 22q with other specific abnormalities--gain of 1q, loss of 6q, loss of 10q/10, loss of 13, loss of 14q/14--varied according to site and histology. In particular, we showed that classic ependymomas from within the cranium and spine have distinct genetic profiles. Classic and anaplastic ependymomas with gain of 1q tended to occur in the posterior fossa of children and to behave aggressively.

Our extensive data on ependymomas demonstrate significant associations between genetic aberrations and clinicopathological variables, and represent a starting point for further biological and clinical studies.


Analysis of the NF2 gene in oligodendrogliomas and ependymomas.

Alonso ME, Bello MJ, Arjona D, Gonzalez-Gomez P, Lomas J, de Campos JM, Kusak ME, Isla A, Rey JA.

Laboratorio de Oncogenetica Molecular, Dept. C. Experimental, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.

Cancer Genet Cytogenet 2002 Apr 1;134(1):1-5 Abstract quote

Allelic losses of chromosome 22 are commonly found in ependymomas and oligodendrogliomas, suggesting that at least one tumor suppressor gene on chromosome 22 must be inactivated during the multistep process of tumorigenesis in these glial tumors. The neurofibromatosis 2 gene (NF2) located at 22q12, is a candidate tumor suppressor gene potentially involved in the pathogenesis of gliomas.

Because there have been only a few studies of the NF2 gene in glial tumors other than astrocytoma, we screened the entire 17 NF2 exons for mutations in a series of 47 nonastrocytic tumors, including 40 oligodendrogliomas and 7 ependymomas. Only one mutation was detected, a 59-base pair insertion in exon 3 from a spinal anaplastic ependymoma.

These results concur with previous findings proposing preferential inactivation of the NF2 gene in a subgroup of ependymomas, and suggest that the NF2 gene is not the target of chromosome 22 aberrations in oligodendrogliomas.


Differential Involvement of Protein 4.1 Family Members DAL-1 and NF2 in Intracranial and Intraspinal Ependymomas.

Singh PK, Gutmann DH, Fuller CE, Newsham IF, Perry A.

Departments of Pathology (PKS, CEF, AP) and Neurology (DHG), Washington University School of Medicine, St. Louis, Missouri.

Mod Pathol 2002 May;15(5):526-31 Abstract quote

Ependymomas are malignant CNS neoplasms with highly variable biologic behavior, including a generally better prognosis for intraspinal tumors. Inactivation of the NF2 gene on 22q12 and loss of its protein product, merlin, have been well documented in subsets of meningiomas and ependymomas. DAL-1, a related tumor suppressor and protein 4.1 family member on 18p11.3, has also been recently implicated in meningioma pathogenesis, though its role in ependymoma remains unknown.

Therefore, we evaluated 27 ependymomas (12 intracranial and 15 spinal) using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to determine NF2/merlin and DAL-1/DAL-1 status at the DNA and protein levels. Demonstrable NF2 and DAL-1 gene deletions were each detected in 6 (22%) ependymomas. All 5 merlin losses by IHC occurred in spinal ependymomas (P =.047), whereas 5 (71%) DAL-1-negative cases were intracranial (P =.185). The former result is consistent with prior observations that NF2 mutations are generally limited to spinal ependymomas. In contrast to meningiomas, simultaneous merlin and DAL-1 losses were not encountered.

Our findings suggest that (1) NF2 and DAL-1 losses are involved in the pathogenesis of spinal and intracranial ependymoma subsets, respectively and (2) given the number of cases with no demonstrable losses, other cellular perturbations must also be critical for tumori-genesis.

 

LABORATORY/RADIOLOGIC/
OTHER TESTS

CHARACTERIZATION
RADIOLOGIC  


Differential expression of somatostatin receptors in ependymoma: implications for diagnosis.

Guyotat J, Champier J, Jouvet A, Signorelli F, Houzard C, Bret P, Saint Pierre G, Fevre Montange M.

Service de Neurochirurgie B, Hopital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon, France.

Int J Cancer 2001 May 20;95(3):144-51 Abstract quote

Somatostatin receptors (SSts) have been found in a variety of brain tumors, e.g., meningiomas, medulloblastomas and astrocytomas. Our aim was to investigate their expression in ependymomas.

Using RT-PCR, expression of mRNA for the different SSt subtypes was analyzed and quantified in 28 ependymomas and correlated with different variables (age, tumor location, histological grade, recurrence and survival). In addition, in 8 cases, protein expression was studied in vitro, using immunohistochemistry, and in vivo, by somatostatin scintigraphy. mRNAs for all 5 subtypes were variably expressed in each ependymoma. The Southern blotting signal obtained after SSt(1) and SSt(2) amplification was higher than that for the other receptor subtypes.

No significant correlation was seen between the level of SSt(1) and SSt(2) mRNA expression and age, location, histological grading, recurrence or survival. In the 8 cases, SSt(1) staining was negative in 3 and low in 5. Staining for SSt(2A) was positive but low in every specimen analyzed. SSt(1) and SSt(2) immunoreactivity was seen only in the cytoplasm of tumoral cells. Somatostatin scintigraphy showed clear uptake, which agreed with MRI data in the majority of cases. However, no correlation was seen between tracer uptake intensity and histological grade, SSt(1) and SSt(2) mRNA expression or immunostaining intensity.

This evidence for the expression of SSt(2) receptors in ependymomas opens interesting prospects for their follow-up.


Surveillance neuroimaging in childhood intracranial ependymoma: how effective, how often, and for how long?

Good CD, Wade AM, Hayward RD, Phipps KP, Michalski AJ, Harkness WF, Chong WK.

Department of Neuroradiology, Great Ormond Street Hospital for Sick Children, London, United Kingdom.

J Neurosurg 2001 Jan;94(1):27-32 Abstract quote

OBJECT: The authors examined images obtained in 52 children with intracranial ependymomas to determine risk factors for tumor recurrence and to assess the impact of surveillance imaging on patient outcome.

METHODS: Data obtained in all children with intracranial ependymomas were prospectively entered into a database from January 1987 to June 2000. The imaging and clinical details in all patients were reviewed. Fifty-two children with histologically proven intracranial ependymomas were treated at the authors' institution; recurrences developed in 28 (54%) of them, with a median time from surgery to first recurrence of 14.5 months (range 3-65 months). Of these tumor recurrences, 43% were asymptomatic and were noted on surveillance imaging. Seventeen children died, all of whom had recurrences. Incomplete excision of the primary tumor was significantly associated with reduced time to recurrence (p = 0.0144) and time to death (p = 0.0472). The age of the patient, location of the primary tumor, histological findings, and the presence or absence of spinal metastases on preoperative imaging were not significantly associated with outcome. The risk of death at any given time was 12-fold greater in patients in whom a recurrence was identified due to symptoms rather than on surveillance images (p = 0.016).

CONCLUSIONS: Recurrent childhood ependymoma has a poor prognosis. The extent of the initial local tumor resection is the factor most closely associated with outcome. Surveillance imaging reveals a substantial number of asymptomatic recurrences, and survival appears to be improved in these patients compared with those identified by symptoms. The improvement in survival is thought to be greater than that expected just from earlier diagnosis.

LABORATORY MARKERS  

 

GROSS APPEARANCE/
CLINICAL VARIANTS
CHARACTERIZATION
GENERAL  
VARIANTS  
OVARY  


Primary ependymoma of the ovary, in which long-term oral etoposide (VP-16) was effective in prolonging disease-free survival.

Mikami M, Komuro Y, Sakaiya N, Tei C, Kurahashi T, Komiyama S, Hirose T.

Department of Obstetrics and Gynecology, National Saitama Hospital, Suwa 2-1, Wako, Saitama 351-0102, Japan.

Gynecol Oncol 2001 Oct;83(1):149-52 Abstract quote

BACKGROUND: Ovarian ependymoma is an extremely unusual teratoma of the ovary with only eight cases previously reported in the literature worldwide.

CASE: A 26-year-old woman presented in 1992 with a sensation of abdominal fullness. The laparotomy revealed ovarian cancer (stage III), which proved to be an ependymoma pathologically. Three courses of the PVP regimen (cisplatin, vinblastine, peplomycin) and pelvic irradiation were administered postoperatively. Oral administration of etoposide (VP-16) was initiated after the residual tumor began to proliferate, and the tumor decreased in size and never regrew during etoposide administration for a total of 5 years and 8 months. The recurrent tumor was observed soon after the drug was discontinued.

CONCLUSION: Oral administration of etoposide was effective in prolonging disease-free survival.

 

HISTOLOGICAL TYPES CHARACTERIZATION
GENERAL  
VARIANTS  
ANAPLASTIC  


Low frequency of chromosomal imbalances in anaplastic ependymomas as detected by comparative genomic hybridization.

Scheil S, Bruderlein S, Eicker M, Herms J, Herold-Mende C, Steiner HH, Barth TF, Moller P.

Institute of Pathology, University of Ulm, Germany.

Brain Pathol 2001 Apr;11(2):133-43 Abstract quote

We screened 26 ependymomas in 22 patients (7 WHO grade I, myxopapillary, myE; 6 WHO grade II, E; 13 WHO grade III, anaplastic, aE) using comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). 25 out of 26 tumors showed chromosomal imbalances on CGH analysis.

The chromosomal region most frequently affected by losses of genomic material clustered on 13q (9/26). 6/7 myE showed a loss on 13q14-q31. Other chromosomes affected by genomic losses were 6q (5/26), 4q (5/26), 10 (5/26), and 2q (4/26). The most consistent chromosomal abnormality in ependymomas so far reported, is monosomy 22 or structural abnormality 22q, identified in approximately one third of Giemsa-banded cases with abnormal karyotypes. Using FISH, loss or monosomy 22q was detected in small subpopulations of tumor cells in 36% of cases. The most frequent gains involved chromosome arms 17 (8/26), 9q (7/26), 20q (7/26), and 22q (6/26). Gains on 1q were found exclusively in pediatric ependymomas (5/10). Using FISH, MYCN proto-oncogene DNA amplifications mapped to 2p23-p24 were found in 2 spinal ependymomas of adults. On average, myE demonstrated 9.14, E 5.33, and aE 1.77 gains and/or losses on different chromosomes per tumor using CGH.

Thus, and quite paradoxically, in ependymomas, a high frequency of imbalanced chromosomal regions as revealed by CGH does not indicate a high WHO grade of the tumor but is more frequent in grade I tumors.


A clinicopathologic study of 81 patients with ependymomas and proposal of diagnostic criteria for anaplastic ependymoma.

Ming-Tak DH, Hs CY, Wong TT, Chian H.

Department of Pathology and Laboratory Medicine, Neurological Institute, Veterans General Hospital-Taipei, Taiwan, ROC.

J Neurooncol 2001 Aug;54(1):77-85 Abstract quote

Optimal histologic criteria for the classification of and grading of ependymomas, including their anaplastic forms, remain elusive. This is especially true because of the poor correlation of these criteria with clinical outcome.

The aim of this study was to identify the histopathologic parameters that could distinguish different prognostic groups of patients with ependymomas. Eighty-one patients with ependymal tumors, including those originally diagnosed ependymomas, anaplastic ependymomas and myxopapillary ependymomas, were enrolled in this study.

Thirteen histologic parameters, including hypercellularity, nuclear pleomorphism, mitoses, endothelial proliferation, necrosis, clear cell, thrombi, dystrophic calcification, psammoma bodies, bone, cartilage, Rosenthal fibers and MIB-1 labeling index (LI), were evaluated in each patient and correlated with clinical outcome. We assigned one score for each histopathologic parameter evaluated and used a stepwise selection method with entry model based on the significance of the log-rank statistic to formulate a scoring model. Four parameters were chosen in this process, including mitoses > or = 4/10 hpf (1.7/mm2), hypercellularity, endothelial proliferation and necrosis. The sum of these four parameters (scores) was the histopathologic score of the tumor. The progression-free survival (PFS) and overall survival (OS) of patients with histopathologic scores 0 and 1 were significantly better than those with histopathologic scores 2, 3 and 4 (p < 0.001 and p = 0.005, respectively).

Because of the latter finding, we proposed that anaplastic ependymoma could be diagnosed by the presence of any two of the aforementioned four parameters. Multivariate analyses including clinical and histopathologic variables showed that histopathologic score > or = 2 and subtotal resection were the factors related to increased risk of recurrence, while histopathologic score > or = 2 was the only factor related to overall survival. Based on the above findings, we concluded that histopathology is an important prognostic indicator for patients with ependymomas.

CLEAR CELL  


Intramedullary clear cell ependymoma in the cervical spinal cord: case report.

Akutsu H, Shibata Y, Okazaki M, Hyodo A, Matsumura A.

Department of Neurosurgery, Kitaibaraki City General Hospital, Kitaibaraki, Japan.

Neurosurgery 2000 Dec;47(6):1434-7; discussion 1437-8 Abstract quote

OBJECTIVE AND IMPORTANCE: Clear cell ependymoma of the spinal cord has not been reported in the literature, although ependymoma in the cerebral and cerebellar hemispheres has been described. We present the first case report of this rare histological type of ependymoma arising in the cervical spinal cord and emphasize the importance of recognizing this histological entity.

CLINICAL PRESENTATION: A 42-year-old woman presented with numbness in both upper limbs and spastic gait. Magnetic resonance imaging revealed an intramedullary tumor at the C6-T1 level with syringomyelia.

INTERVENTION: The tumor was totally removed. Histological analysis revealed that the tumor was composed of round cells with perinuclear halos similar to those observed in oligodendroglioma. However, we diagnosed clear cell ependymoma because these tumor cells exhibited epithelial features and ependymal rosettes under light microscopic examination.

CONCLUSION: Histological diagnosis was crucial to our determining whether to perform postoperative adjuvant therapy in this patient. Neurosurgeons should be aware of the possibility of this histological entity among intramedullary spinal cord tumors.

MYXOPAPILLARY EPENDYMOMA  


Antineuronal nuclei immunohistochemical staining patterns in childhood ependymomas.

Parker JR, Armstrong DL, Strother D, Rudman DM, Dauser RC, Laurent JP, Deyd J, Rouah PE.

Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.

J Child Neurol 2001 Aug;16(8):548-52 Abstract quote

NeuN, the mouse-derived monoclonal antibody to the reportedly neuron-specific nuclear protein, has been observed to react with many different types of normal, postmitotic neurons throughout the central and peripheral nervous systems.

We retrospectively examined 23 surgical specimens (collected from 20 patients) originally diagnosed at our institution between 1983 and 1999 as ependymoma (9), myxopapillary ependymoma (1), anaplastic/malignant ependymoma (10), and primitive neuroectodermal tumor with ependymal differentiation (3). The ependymomas included lesions from the spine (3), cerebrum (5), and posterior fossa (15). Representative formalin-fixed, paraffin-embedded sections from each tumor were subjected to immunohistochemical staining with antibody against NeuN (Chemicon International, Inc, Temecula, CA).

Five astrocytomas, four primitive neuroectodermal tumors, and normal cerebral cortex and ependyma from autopsy brains of premature newborns, term infants, and older children served as controls. Thirteen ependymal tumors had positive nuclear staining ranging from rare tumor cells to numerous groups of cells; of these, 9 were anaplastic ependymomas and had the most staining. These studies suggest that some ependymomas arise from a pluripotential neuroglial cell.

SUBEPENDYMOMA  


Pedunculated subependymomas of lateral ventricle.

Marchel A, Kroh H, Bojarski P.

Department of Neurosurgery, Medical University of Warsaw, Poland.

Folia Neuropathol 2001;39(1):33-6 Abstract quote

The authors describe two cases of extremely rare, pedunculated subependymomas of lateral ventricle.

One patient presented with symptoms of intracranial hypertension (case 2); CT scan revealed evidence of intraventricular mass, but in second patient (case 1) coexisting symptomatic anaplastic astrocytoma masked on CT-scan the presence of asymptomatic intraventricular tumour, which was found no earlier than at autopsy.

The cellular origin of this rare intracranial neoplasm is discussed.

 

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER
CHARACTERIZATION
SPECIAL STAINS  
IMMUNOPEROXIDASE  
CD99  


CD99 immunoreactivity in ependymoma.

Choi YL, Chi JG, Suh YL.

Department of Diagnostic Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Appl Immunohistochem Mol Morphol 2001 Jun;9(2):125-9 Abstract quote

The expression of CD99 in normal ependymal cells and ependymoma has been reported. However, only limited numbers of tumors have been studied, and the pattern of CD99 expression has not been described.

The authors' purpose was to investigate CD99 immunoreactivity in ependymoma and its use for differential diagnosis. Twenty-five ependymomas were immunostained with antibody directed at CD99. The result of immunostaining of ependymomas was compared with 63 nonependymal tumors that histologically resemble ependymal neoplasms. The nonependymal tumors included 19 astrocytic tumors, 6 oligodendroglial tumors, 8 choroid plexus neoplasms, 2 central neurocytomas, 5 medulloblastomas, 10 primitive neuroectodermal tumors (PNET), and 13 pituitary adenomas. All ependymomas showed strong expression of CD99 in membranous pattern with intracytoplasmic or intercellular dots (ICDs). The expression pattern of CD99 was not correlated with histologic type or grade of ependymomas. Among 63 nonependymal tumors, 11 (17.5%) showed incomplete membrane staining for CD99; diffuse in 4 PNETs and focal in 5 choroid plexus neoplasms (3 papillomas and 2 carcinomas) and one each of pituitary adenoma and oligodendroglioma. The ICD was not found in nonependymal tumors except a case of choroid plexus papilloma. However, membrane staining or ICD for CD99 was not distinctive in nonependymal tumors.

In conclusion, the characteristic pattern of anti-CD99 antibody, i.e., diffuse strong membranous immunostaining with ICDs, is useful in distinguishing ependymomas from the central nervous system tumors that histologically mimic ependymoma.

NeuN  


Antineuronal nuclei immunohistochemical staining patterns in childhood ependymomas.

Parker JR, Armstrong DL, Strother D, Rudman DM, Dauser RC, Laurent JP, Deyd J, Rouah PE.

Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.

J Child Neurol 2001 Aug;16(8):548-52 Abstract quote

NeuN, the mouse-derived monoclonal antibody to the reportedly neuron-specific nuclear protein, has been observed to react with many different types of normal, postmitotic neurons throughout the central and peripheral nervous systems.

We retrospectively examined 23 surgical specimens (collected from 20 patients) originally diagnosed at our institution between 1983 and 1999 as ependymoma (9), myxopapillary ependymoma (1), anaplastic/malignant ependymoma (10), and primitive neuroectodermal tumor with ependymal differentiation (3). The ependymomas included lesions from the spine (3), cerebrum (5), and posterior fossa (15). Representative formalin-fixed, paraffin-embedded sections from each tumor were subjected to immunohistochemical staining with antibody against NeuN (Chemicon International, Inc, Temecula, CA).

Five astrocytomas, four primitive neuroectodermal tumors, and normal cerebral cortex and ependyma from autopsy brains of premature newborns, term infants, and older children served as controls. Thirteen ependymal tumors had positive nuclear staining ranging from rare tumor cells to numerous groups of cells; of these, 9 were anaplastic ependymomas and had the most staining. These studies suggest that some ependymomas arise from a pluripotential neuroglial cell.

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
ASTROBLASTOMA  


Astroblastoma: radiologic-pathologic correlation and distinction from ependymoma.

Port JD, Brat DJ, Burger PC, Pomper MG.

Neuroradiology Division, Johns Hopkins Hospital, Baltimore, MD, USA.

AJNR Am J Neuroradiol 2002 Feb;23(2):243-7 Abstract quote

Summary: Astroblastoma is a rare primary glial tumor with a characteristic appearance on neuroradiologic images.

Typically, astroblastomas are large, lobulated, peripheral, supratentorial, solid, and cystic masses with relatively little associated vasogenic edema and tumor infiltration for their large size.

The solid component of the mass has a bubbly appearance and a T2 signal that is isointense to gray matter. Punctate calcifications are often present. Neuroradiologists should be familiar with the characteristic appearance of this tumor.

CAUDA EQUINA TUMORS  


Cauda equina tumors: a French multicenter retrospective review of 231 adult cases and review of the literature.

Wager M, Lapierre F, Blanc JL, Listrat A, Bataille B.

Service de Neurochirurgie, C.H.U., La Miletrie, Poitiers, France.

Neurosurg Rev 2000 Sep;23(3):119-29; discussion 130-1 Abstract quote

Large series of cauda equina tumors in adults are seldom reported. This French series retrospectively reviews 231 cases collected for the congress of the Societe Francaise de Neurochirurgie in 1996. The authors first analyze this series and then discuss the pertinent literature.

Schwannoma was the most frequent benign tumor in this series, followed by ependymoma. Very few malignant tumors were recorded; these were usually malignant neurinomas nearly always in neurofibromatosis patients. Some other rare tumors were also recorded, including paragangliomas. This series confirms the importance of the pretherapeutic neurological status in functional prognosis. All schwannomas can be cured, while ependymomas and paragangliomas may recur after a very long delay. Surgery must be as complete as possible, since adjuvant therapies are proven to have little efficacy. This type of tumor requires very long follow-up. Prognosis is good for hemangioblastomas.

Sphincter dysfunctions carries a poor prognosis and may appear after primary surgery, more often after treatment of recurrences.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
PROGNOSTIC FACTORS  
GENERAL  


Ependymomas: a clinicopathologic study.

Rawlings CE 3rd, Giangaspero F, Burger PC, Bullard DE.

Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.

Surg Neurol 1988 Apr;29(4):271-81 Abstract quote

Since 1924, when ependymomas were first classified as a distinctive glial neoplasm by Bailey, much has been published concerning these tumors, but there are important points of interest that are still not clear.

In order to study more fully the clinical and pathologic characteristics of the ependymoma, we identified 62 patients with histologically proven neoplasms. Twenty-two were supratentorial, 21 were infratentorial, and 19 were intramedullary spinal cord tumors. These groups had mean ages of 17, 7, and 41 years, respectively, at the time of first symptoms.

The presenting and accompanying symptoms were related to location and included headaches, nausea, visual changes, hemiparesis, and neck, back, and radicular pain. Neurological signs included papilledema, nystagmus, gait disturbance, cranial nerve palsies, altered mental status, paraparesis, and sensory dysfunction. Radiologic modalities of particular importance included computed tomography and myelography. Surgery and radiation therapy were the primary treatment modalities with median survival times from first symptoms being 92, 36, and 117 months for the above groups, respectively.

Based on computer-generated survival curves, several characteristics significantly affected survival. These included tumor site, age, and neuraxis metastases. In patients with supratentorial tumors, cranial nerve palsies, microcystic changes, and mitotic figures were important, while in patients with infratentorial tumors, widened sutures, increased head circumference, age, epithelial features, and subependymal features significantly affected survival. Patients who had complete gross resection of a spinal cord tumor had no recurrences or mortality.


Clinical aspects and prognosis of ependymoma in infants and children. A single institution experience.

Humpl T, Neuser H, Bruhl K, Bartels U, Schwarz M, Gutjahr P.

Department of Pediatrics, University of Mainz, Germany.

Childs Nerv Syst 2001 Apr;17(4-5):246-51 Abstract quote

Thirty-two patients (22 boys and 10 girls) with a histologically confirmed diagnosis of ependymoma were treated between 1972 and 1999. A total macroscopic resection was achieved in 16 of these patients, whereas 15 resections were classified by the surgeon as subtotal. In 1 patient a ventriculostomy was created as part of a palliative strategy. All children over 3 years old were treated with postoperative radiotherapy.

Chemotherapy consisted of procarbazine, ifosfamide, etoposide, methotrexate, cisplatin and cytosine arabinoside. There was 1 perioperative death. Twenty children developed a relapse of disease within 2 months to 13 years and 1 month after the initial therapy. A maximal number of five recurrences were seen in 1 patient.

The value of adjuvant chemotherapy on the prognosis of children with ependymoma seems to be limited. With regard to the poor outcome, the advisability of further treatment after multiple recurrences is debatable.

GRADE  


Influence of tumor grade on time to progression after irradiation for localized ependymoma in children.

Merchant TE, Jenkins JJ, Burger PC, Sanford RA, Sherwood SH, Jones-Wallace D, Heideman RL, Thompson SJ, Helton KJ, Kun LE.

Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA

 

Int J Radiat Oncol Biol Phys 2002 May 1;53(1):52-7 Abstract quote

PURPOSE: To investigate the influence of histologic grade on progression-free survival (PFS) after irradiation (RT) for pediatric patients with localized ependymoma.

METHODS AND MATERIALS: Fifty patients with localized ependymoma (median age 3.6 years, range 1-18 years at the time of RT) were treated with RT between December 1982 and June 1999. Anaplastic features were identified in 14 of 50 patients. The extent of resection was characterized as gross-total in 36 patients, near-total in 5, and subtotal in 9. The median dose to the primary site was 54 Gy. Of the 50 patients, 23 received pre-RT chemotherapy.

RESULTS: Thirty-nine patients were alive at a median follow-up of 46 months (range 21-214) from diagnosis. Thirty-four patients remained progression free at a median follow-up of 35 months (range 13-183) after the initiation of RT. Progression occurred in 16 patients (12 local and 4 local and distant), with a median time to failure of 21.2 months (range 4.6-65.0). The tumor grade significantly influenced the PFS after RT (p < 0.0005). The estimated 3-year PFS rate was 28% +/- 14% for patients with anaplastic ependymoma compared with 84% +/- 8% for patients with differentiated ependymoma. These results remained significant when corrected for age at diagnosis (<3 years), pre-RT chemotherapy, and extent of resection. Patients who received pre-RT chemotherapy had an inferior 3-year PFS estimate after RT (49 +/- 12%) compared with those who did not (84% +/- 10%; p = 0.056). Anaplastic ependymoma was found more frequently in the supratentorial brain (p = 0.002). Six of 12 patients with supratentorial tumor developed recurrence; recurrence was restricted to patients with anaplastic ependymoma.

CONCLUSION: Tumor grade influences outcome for patients with ependymoma independent of other factors and should be considered in the design and analysis of prospective trials involving pediatric patients treated with RT. Chemotherapy before RT influences the PFS and overall survival after RT. The effect is more pronounced when progression occurs during chemotherapy.

MIB-1  


Prognostic value of Ki-67 (MIB-1) and p53 in ependymomas.

Suzuki S, Oka H, Kawano N, Tanaka S, Utsuki S, Fujii K.

Department of Neurosurgery, Kitasato University School of Medicine, Kanagawa, Japan.

 

Brain Tumor Pathol 2001;18(2):151-4 Abstract quote

To determine whether Ki-67 (MIB-1) and p53 have prognostic value in ependymomas, clinicopathologic study was undertaken in 29 patients with this tumor. The clinical course correlated well with the histological grade according to the World Health Organization (WHO) grading system, and it was the worst in patients with anaplastic ependymoma.

The percent expression of MIB-1 and p53 correlated with the histological grade of malignancy. With regard to the subtypes of benign ependymoma, the clinical course was the worst in clear-cell ependymoma, which had a significantly higher expression of MIB-1 and p53 than the other subtypes. Tanycytic ependymoma showed the most benign clinical course and the lowest expression of MIB-1 and p53.

Although the WHO grading generally tended to correlate with the clinical course of ependymomas, these two subtypes--clear-cell ependymoma and tanycytic ependymoma--exhibited biological properties different from those of other grade II ependymomas.

TREATMENT  
CHEMOTHERAPY  


Postoperative chemotherapy without irradiation for ependymoma in children under 5 years of age: a multicenter trial of the French Society of Pediatric Oncology.

Grill J, Le Deley MC, Gambarelli D, Raquin MA, Couanet D, Pierre-Kahn A, Habrand JL, Doz F, Frappaz D, Gentet JC, Edan C, Chastagner P, Kalifa C; French Society of Pediatric Oncology.

Department of Pediatrics, Institut Gustave Roussy, Villejuif, France.


J Clin Oncol 2001 Mar 1;19(5):1288-96 Abstract quote

PURPOSE: To evaluate a strategy that avoids radiotherapy in first-line treatment in children under 5 years of age with brain or posterior fossa ependymoma, by exclusively administering 16 months of adjuvant multiagent chemotherapy after surgery.

PATIENTS AND METHODS: Between June 1990 and October 1998, 73 children with ependymoma (82% with high-grade tumors) were enrolled onto this multicenter trial. Children received adjuvant conventional chemotherapy after surgery consisting of seven cycles of three courses alternating two drugs at each course (procarbazine and carboplatin, etoposide and cisplatin, vincristine and cyclophosphamide) over a year and a half. Systematic irradiation was not envisaged at the end of chemotherapy. In the event of relapse or progression, salvage treatment consisted of a second surgical procedure followed by local irradiation with or without second-line chemotherapy.

RESULTS: Conventional chemotherapy was well tolerated and could be administered in outpatient clinics. No radiologically documented response to chemotherapy more than 50% was observed. With a median follow-up of 4.7 years (range, 5 months to 8 years), the 4-year progression-free survival rate in this series was 22% (95% confidence interval [CI], 13% to 43%) and the overall survival rate was 59% (95% CI, 47% to 71%). Overall, 40% (95% CI, 29% to 51%) of the patients were alive having never received radiotherapy 2 years after the initiation of chemotherapy and 23% (95% CI, 14% to 35%) were still alive at 4 years without recourse to this modality. In the multivariate analysis, the two factors associated with a favorable outcome were a supratentorial tumor location (P =.0004) and complete surgery (P =.0009). Overall survival at 4 years was 74% (95% CI, 59% to 86%) for the patients in whom resection was radiologically complete and 35% (95% CI, 18% to 56%) for the patients with incomplete resection.

CONCLUSION: A significant proportion of children with ependymoma can avoid radiotherapy with prolonged adjuvant chemotherapy. Deferring irradiation at the time of relapse did not compromise overall survival of the entire patient population.

RADIATION  
INTRACRANIAL
 


Postoperative radiotherapy for intracranial ependymoma: analysis of prognostic factors and patterns of failure.

Oya N, Shibamoto Y, Nagata Y, Negoro Y, Hiraoka M.

Department of Radiology, Faculty of Medicine, Kyoto University, Japan.

J Neurooncol 2002 Jan;56(1):87-94 Abstract quote

The long-term results of external beam radiotherapy following surgical resection in patients with intracranial ependymomas were evaluated to identify the prognostic factors and the pattern of recurrence.

Between June 1961 and January 1999, 48 patients with intracranial ependymoma were treated with external beam irradiation with >40 Gy following surgery. Total doses of 40.5-63.4Gy were delivered to the tumor site in 22-46 fractions over 33-101 days. Six patients with spinal deposit or positive cerebrospinal fluid cytology received whole spinal axis irradiation, and 4 patients received prophylactic spinal irradiation. The median follow-up of surviving patients was 110 months. The 10-year overall and relapse-free survival rates were 47% and 42%, respectively. In multivariate analysis, female gender, lower tumor grade and total resection were found to be associated with better relapse-free survival. Twenty of 26 recurrences developed at the primary tumor site (inside the irradiation field), two at the unirradiated cerebellum and spinal cord, and four at the spinal cord without intracranial failure. Only one of 34 patients with supratentorial tumors developed isolated spinal metastasis, whereas 3 of 14 patients with infratentorial tumors did so.

Regarding the late neurotoxicity of radiotherapy, one of the 15 long-term (>4 years) survivors whose psychosocial status could be evaluated showed marked cognitive impairment. It was suggested that the use of new treatment strategies to improve local control would be warranted, and that prophylactic whole spinal axis irradiation appeared to be of more benefit in patients with infratentorial tumors than in those with supratentorial tumors.


Intracranial ependymomas: an analysis of prognostic factors and patterns of failure.

Paulino AC, Wen BC, Buatti JM, Hussey DH, Zhen WK, Mayr NA, Menezes AH.

Department of Radiology, Division of Radiation Oncology, The University of Iowa College of Medicine, Iowa City, Iowa, USA.

Am J Clin Oncol 2002 Apr;25(2):117-22 Abstract quote

From 1965 to 1997, 49 patients were diagnosed and treated for intracranial ependymoma at one institution. Tumor location was infratentorial in two thirds, and pathology was low grade in 38 patients (78%).

Gross total resection of the primary tumor was achieved in 21 (43%). Thirty-six patients received adjuvant radiotherapy; the entire neuraxis was treated in 14, whole brain in 10, and local field only in 12. Median follow-up was 9.6 years (range, 2-33 years). The 5-, 10-, and 15-year overall survival rates were 71.4%, 63.5%, and 63.5% for craniospinal radiotherapy, 60.0%, 60.0%, and 40.0% for whole brain radiotherapy, and 80.8%, 64.6%, and 64.6% for local field radiotherapy (p = 0.88). The 5-, 10-, and 15-year local control rates were 60.3%, 54.4%, and 48.9%.

The prognostic factors for a better local control rate were gross total resection (p = 0.021) and low grade histology (p = 0.031). Seventeen of 43 (39.5%) M0 patients did not respond to treatment; all had local failure and 4 also had a spinal relapse. Spinal relapse developed in 3 of 31 (10%) M0 patients who did not receive spinal radiotherapy, whereas 1 of 12 (8%) who had spinal radiotherapy did not respond to treatment in the spine.

The results of this study indicate that local radiotherapy is sufficient for M0 patients with intracranial ependymoma

SPINAL
 


Spinal intramedullary ependymomas: surgical results and immunohistochemical analysis of tumour proliferation activity.

Iwasaki Y, Hida K, Sawamura Y, Abe H.

Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Br J Neurosurg 2000 Aug;14(4):331-6 Abstract quote

This study analysed the outcome of 35 consecutive patients with intramedullary ependymoma who underwent a radical surgical resection between 1983 and 1996. The median age of patients was 47 years.

Tumour location was cervical in 22 patients, cerviothoracic in eight and thoraco lumber in five. The proliferative activity of 24 spinal and 14 intracranial ependymomas were determined by MIB-1 immunolabelling. Total removal of tumour was achieved in 26 patients and subtotal removal was performed in nine patients of whom six received postsurgical radiation therapy. Twenty-nine patients out of 35 could be followed over 3 years (follow-up periods: 168-36 months: mean 70). Moreover many patients could be followed over 4 years. In 27 of those 29 patients, the neurological symptom was stabilized or improved.

The proliferation indices of spinal ependymomas were significantly lower than those of intracranial ependymomas. Tumour regrowth occurred only in a young patient 29 months after a subtotal removal of the tumour which was not treated with irradiation and showed a high proliferation index on the second operation.

Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.


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