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PubMedDate not supplied

Histological spectrum of ependymomas and correlation of p53 and Ki-67 expression with ependymoma grade and subtype.

BACKGROUND: Clinical and histological criteria for ependymoma prognosis are well recognized. Recently few studies have been done based on Immunohistochemistry for prognostication of these tumours. In this study we have correlated the histological spectrum with immmunoexpression of p53 and Ki67 in these tumors. AIMS: To know the incidence of ependymomas; study their morphological spectrum and to evaluate expression of P53 and Ki 67 in different morphological subtypes. MATERIAL AND METHOD: A retrospective study was preformed on 70 ependymomas received in a period between 1994 and 2001. Entire tissue received was processed for routine paraffin embedded H&E stained sections. Immunocytochemistry was performed using antibodies to GFAP, EMA, Pancytokeratin and synaptophysin, to differentiate papillary ependymoma from choroid plexus papilloma; clear cell ependymoma from oligodendroglioma and central neurocytoma; ependymoblastoma from other embryonal tumours. p53 and Ki-67 immunohistochemistry was performed to correlate their expression with various tumour grades and subtypes. RESULTS: There were 3 cases (4.2%) of Grade I ependymoma (2 cases of myxopapillary ependymoma and 1 case of subependymoma); 57 cases (81.5%) of ependymoma grade II (43 of these were of classical variety, 11 of clear cell ependymoma, 2 of papillary and 1 case of cellular ependymoma). There were 9 cases (12.8%) of anaplastic ependymoma (one of these was a clear cell ependymoma and 1 case (1.5%) of ependymoblastoma CONCLUSION: p53 and Ki67 indices can be used in routine diagnostic laboratories to supplement the tumor grade on histology and more studies with follow up should be performed to analyse the prognosis of different subtypes. The expression of Ki 67 and p53 was significantly higher in anaplastic ependymomas. 4 out of 11 cases of clear cell ependymomas showed higher Ki 67 indices as compared to classical grade II ependymomas, thus further highlighting the importance of differentiating the various subtypes.

Adolescent↗
PubMed2006

Identification of relevant prognostic histopathologic features in 69 intracranial ependymomas, excluding myxopapillary ependymomas and subependymomas.

BACKGROUND: The results of attempts to identify histopathologic parameters that contribute to the clinical outcome of patients with ependymomas have been controversial. This may be due to the relative rareness of ependymomas. Furthermore, in many investigations, myxopapillary ependymomas and subependymomas were included and may have confounded results, because those tumors should be considered clinicopathologic entities distinct from the other ependymomas. METHODS: In this retrospective study, the influence of the histologic subtype of ependymoma and of individual histologic features on the outcome of 69 patients with ependymomas was investigated. Myxopapillary ependymomas, subependymomas, and ependymomas with spinal localizations were excluded from the analysis. The ependymomas were subdivided into cellular, papillary, clear cell, and tanycytic subtypes. The study extended over a period of 30 years. RESULTS: No differences in clinical outcome between the four histologic subtypes of ependymomas were revealed. Neither tumor localization (either infratentorial or supratentorial), patient age, nor gender affected survival. The survival of patients who underwent complete tumor resection differed significantly from that of patients who underwent partial resection. In univariate analysis, the features of nuclear atypia, the mitotic index, and the MIB-1 labeling index (LI) significantly influenced survival. With regard to survival, the presence of microcysts, blood vessel density, and the feature of vascular hyalinization demonstrated a trend but did not reach significance. In multivariate analysis, only the mitotic index and the MIB-1 LI were identified as factors with independent prognostic significance (P = 0.027 and P = 0.023, respectively). Both proliferation indices were correlated strongly with each other. CONCLUSIONS: The results of the univariate analysis indicated that, for patients with intracranial ependymoma, nuclear atypia, the mitotic index, and the MIB-1 LI significantly influenced survival. In the multivariate analysis, the mitotic index and the MIB-1 LI were the only features that had independent prognostic significance. Because both showed strong correlations, only one of them should be included in a grading scheme for intracranial ependymomas.

Adolescent↗
PubMed2001

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

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.

Adolescent↗
PubMed2004

Infratentorial giant cell ependymoma: a rare variant of ependymoma.

We describe a giant cell ependymoma occurring in a 50-year-old man. The mass was located in the posterior aspect of the foramen magnum, extending from the cerebellar tonsil to the upper cervical spine. The tumor was a highly cellular neoplasm showing biphasic histology. Diffuse sheets of non-cohesive atypical giant cells, having eccentrically located single or multiple nuclei and plump eosinophilic cytoplasm, partly infiltrated the desmoplastic inflammatory stroma. Parts of perivascular pseudorosette-forming or pseudopapillary areas were composed of atypically elongated cells, which looked like conventional anaplastic ependymoma. There was a transitional area between two patterns. Numerous mitoses and focal necrosis were observed. Immunohistochemically, the tumor cells were immunoreactive for glial fibrillary acidic protein, vimentin, S-100 protein, and CD99. None of the tumor cells showed immunoreactivity for epithelial membrane antigen except for the intracytoplasmic lumen of a few vacuolated cells. Ultrastructurally, tumor cells were ependymal in nature; we noted cytoplasmic intermediate filaments and intercellular microrosettes with microvilli, cilia, and long zonula adherens. The features of this tumor, e.g. its superficial location, mixed giant cells, perivascular pseudorosettes or papillaries, complicated its differentiation from rhabdoid/papillary meningioma. However, immunohistochemistry and electron microscopy confirmed the diagnosis of ependymoma. The giant cell variant should be included in the subclassification of the ependymoma.

Ependymoma↗
PubMed2003

Epithelioid ependymoma: a new variant of ependymoma: report of three cases.

OBJECTIVE: To describe the pathological features of three very similar and unusual primary central nervous system tumors that are not readily recognized as conventional ependymomas but which, by ultrastructural examination, have an ependymomatous character. METHODS: Three distinctive tumors were found in a review of our files for cases of ependymoma. In each case, hematoxylin and eosin-stained sections were reviewed, and immunostains for epithelial membrane antigen, cytokeratin, vimentin, and glial fibrillary acidic protein were performed on formalin-fixed, paraffin-embedded sections. Electron microscopy was performed in each case. RESULTS: The tumors had a diffuse myxoid background, often containing tightly clustered cells that mimicked multinucleated giant cells, but lacking perivascular pseudorosettes or central lumen rosettes. Glial fibrillary acidic protein and vimentin immunostains did not reveal perivascular processes. Epithelial membrane antigen immunostains showed a dot-like cytoplasmic immunoreactivity in some cell clusters in two of the three cases. Cytokeratin was negative in all three cases. However, ultrastructurally, the cells of each tumor had extensive surface microvilli; the giant cell-like clusters had cells with extensive close appositions, some junctions, and, in two cases, lumina with microvilli. Two of the patients were adults (both with temporal lobe tumors), and one patient was 13 years old and had a cervical spinal cord intramedullary tumor. Each tumor was sharply circumscribed from adjacent central nervous system tissue but was not encapsulated. One of the cases in an adult was mitotically highly active; this tumor recurred locally 4 years after initial gross total excision. CONCLUSION: These tumors are unusual variants of ependymoma. This pattern of ependymoma is sufficiently distinctive to be recognized in hematoxylin and eosin stains once the architecture of the epithelioid clusters is appreciated.

Adolescent↗
PubMed2005

Mediastinal myxopapillary ependymoma primary or late metastases of paracoccygeal ependymoma: a case report.

A 25-year-old woman presented in 2002 with progressive shortness of breath and weight loss. A computed tomographic scan of the chest showed a huge anterior mediastinal mass, and pathological examination of a mediastinoscopic needle biopsy revealed typical myxopapillary ependymoma, an extremely unusual diagnosis at this site. Further workup and questioning of the patient revealed that she had opted not to disclose a history of surgery for right gluteal fold mass in 1993, which was primarily treated with surgery followed by radiotherapy for relapse. Review of the histology of the excised mass showed a myxopapillary ependymoma, similar to current histology. Clinical examination of the local gluteal and paracoccygeal site, computed tomographic imaging, and magnetic resonance imaging failed to demonstrate any evidence of recurrent disease in soft tissue or bone. The case is presented, and this very unusual presentation is discussed.

Adult↗
PubMedDate not supplied

Cyclooxygenase-2 (cox-2) expression and angiogenesis in intracranial ependymomas.

AIM: Cyclooxygenase-2 (Cox-2), the inducible key enzyme in the biosynthesis of prostaglandins, appears to play a role in the regulation of progression, invasiveness and angiogenesis of various neoplasms including some glial tumors. Little is known about the role of Cox-2 in angiogenesis and proliferation of ependymomas. We studied Cox-2 expression, Ki-67 labeling index (Ki-67 LI) and microvessel density (MVD) in 30 intracranial ependymomas and analyzed the relationship among these parameters to evaluate their importance in the tumor biology of ependymomas. RESULTS: The mean Ki-67 LI for all tumors ranged from 1 - 50% (mean 9%). Statistically significant difference was present for Ki-67 LI between ependymomas (grade II, WHO) and anaplastic ependymomas (grade III, WHO) (p < 0.001) (mean Ki-67 LI for ependymoma, 2.8%, for anaplastic ependymomas, 15.6%). Anaplastic ependymomas did not demonstrate a greater vascularization than ependymomas, and the MVD values were 84.5 +/- 39.7 for ependymomas, and 90.6 +/- 61.4 for anaplastic ependymomas. Cox-2 immunohistochemical expression was observed in 19 tumors (63%). Although Cox-2 expression was slightly higher in anaplastic ependymomas, it was not statistically significant. No correlation was found between Cox-2 expression and MVD and Ki-67 LI. CONCLUSION: Similar to morphologic and prognostic heterogeneity in ependymomas, Cox-2 expression, MVD and Ki-67 LI also show a great variability. Other factors may be more important for the proliferation and angiogenesis of ependymomas.

Adolescent↗
PubMed1980

[Brain tumors in infants and children--factors affecting prognosis. (Part 1) Ependymoma (author's transl)].

Ependymomas constitute 6.1 to 12.7 percent of pediatric intracranial neoplasms with a predominance of male patients, younger children and infratentorial involvement. Although there is a generally accepted pathological classification of ependymoma, the prognosis and surgical results of this tumor do not always correlate with the apparent tumor malignancy. We analyzed 38 ependymomas in children in light of the prognosis and its affecting factors. Thirty-three were intracranial and 5 were intraspinal. Among 33 intracranial ependymomas, 20 were infratentorial (4th ventricle) 9 were in the lateral ventricle or cerebral parenchyma and 4 were in the para third ventricular region. In age distribution, 3rd or 4th ventricular ependymomas were seen in younger children, under the age of 10 years, except for one child; while ependymomas in the lateral ventricle, cerebral parenchyma or spinal cord were more common in older children. Malignant ependymomas or ependymoblastomas were found in 14 intracranial ependymomas involving equally each location. The surgical mortality in 38 ependymomas was 0. The five year survival rates in malignat ependymomas and low grade ependymomas were not significantly different. However, the five year survivals in the 3rd or 4th ventricular ependymomas were extremely poor, 20% and 0% respectively, while lateral ventricular or intraparenchymal ependymomas had an excellent survival rate of 60% at five years. The patients with total tumor removal survived significantly longer (5 year survival 50%) than with subtotal resection (5 year survival 25.5%) or biopsy (5 year survival 16.6%). All patients except 4 were treated with radiation therapy. The clinical significance of radiation therapy will also be further discussed.

Cerebral Ventricle Neoplasms↗
PubMed2001

Tumor imprint cytology of ovarian ependymoma. A case report.

BACKGROUND: Ependymoma is a tumor that usually develops in the central nervous system and is extremely rare in the ovary. The first case of ovarian ependymoma was reported by Kleinman et al. (Kleinman GM, Young RH, Scully RE. Ependymoma of the ovary: report of three cases. Hum Pathol 1984;15:632-8.) in 1984, and only eight cases have been reported since then. Criteria for the histopathologic diagnosis of ependymoma are already established, but there has been no investigation of the cytologic diagnosis of ovarian ependymoma. METHODS: An imprint cytologic specimen was obtained from a recurrent ovarian ependymoma. The imprint cytologic features were compared with the findings of histologic examination, immunostaining, and electron microscopy. RESULTS: Imprint cytology revealed clusters of small cells with tapering cytoplasmic processes and a round nucleus. On the basis of these features, a neurogenic tumor could be included in the differential diagnosis. Furthermore, many rosette-like collections of cells that were suggestive of ependymal rosettes or perivascular pseudorosettes, characteristic of ependymoma, were found. The presence of ependymal rosettes and perivascular pseudorosettes also were confirmed by the histopathologic examination. Together with positive immunostaining for glial fibrillary acidic protein, this led to the diagnosis of ependymoma, which also was supported by the electron microscopic findings. CONCLUSIONS: Careful observation of the imprint cytologic specimen of an ovarian ependymoma should reveal numerous rosette-like collections of cells that were suggestive of ependymal rosettes or perivascular pseudorosettes. In addition, if we remember that ependymoma can develop in the ovary and find cells with tapering processes that suggest a neurogenic tumor, it may be possible to detect histologic features characteristic of ependymoma by the imprint cytology. To our knowledge, this is the first report on the imprint cytologic diagnosis of ependymoma originating in the ovary.

Adult↗
PubMed2002

Epithelial differentiation and proliferative potential in spinal ependymomas.

The aim of this investigation was recognition of the epithelial differentiation and proliferative activity of ependymomas in the spinal cord compared with astrocytomas in the spinal cord and ependymoma in the brain. We investigated histopathological and immunohistochemical examination in thirty-five cases, including eleven ependymomas, thirteen astrocytomas in the spinal region and eleven ependymomas in the intracranial region. An anti-epithelial membrane antigen antibody (EMA), and two types of anti-cytokeratin antibodies, CAM 5.2 (45 and 52 kDa) and keratin (56 and 64 kDa) were applied as epithelial markers. The proliferative potential of the tumors was investigated using the Ki-67 labeling index (LI, %). Histologically, perivascular pseudorosettes were seen in all of the spinal and intracranial ependymomas. There were few ependymal structures in the spinal ependymomas except in the myxopapillary type. Immunohistochemical study demonstrated that nine (82%) were immunoreactive for EMA, eight (73%) were immunoreactive for CAM 5.2 and three (27%) were immunoreactive for keratin in the spinal ependymomas. In the spinal astrocytomas, no tumors were immunoreactive for EMA or CAM 5.2. One of thirteen cases was immunoreactive for keratin. The Ki-67 LI of the spinal ependymomas was lower than that of the intracranial ependymoma (p < 0.01). Epithelial differentiation was found in the ependymomas which may reflect the differences in histological and biological features between ependymomas and astrocytomas in the spinal cord. Regional differences in ependymomas may influence not only clinical features but also histo-pathological characteristics.

Adolescent↗
PubMed1998

Correlation of bcl-2, p53, and MIB-1 expression with ependymoma grade and subtype.

In this study, we report our results on the proliferative activity of ependymomas as determined by MIB-1 (also known as Ki-67) immunohistochemical analysis, and we compare our results with those obtained by immunolabeling with monoclonal antibodies to p53 and bcl-2 proteins to assess whether expression correlated with ependymoma subtype or tumor grade. The study included 4 myxopapillary ependymomas (Grade I of the World Health Organization [WHO] scale), 10 subependymomas (WHO Grade I), 17 ependymomas (WHO Grade II), 2 papillary ependymomas (WHO grade II), and 4 anaplastic ependymomas (WHO Grade III). The MIB-1 proliferation index was significantly higher in tumors diagnosed as anaplastic ependymoma (P < .001), with a moderate level of correlation (Kendall's tau-b = 0.557, asymptotic standard error = 108). In addition, one ependymoma (WHO Grade II) not considered overtly anaplastic by routine histologic criteria showed a high MIB-1 labeling index, suggesting that the MIB-1 proliferation index might be a more objective indicator of tumor grade. The remaining WHO Grade I and Grade II ependymomas showed low proliferative activity. bcl-2 oncoprotein expression was identified in all of the four myxopapillary and in both papillary ependymomas. An additional observation was the correlation of p53 expression with increasing WHO grade. These data suggest that high MIB-1 and p53 immunolabeling might be objective indicators of high grade in ependymomas that do not otherwise meet routine histologic criteria for high-grade ependymoma. Subsequent clinicopathologic analyses will be important in assessing whether these markers are useful as independent predictors of survival.

Adolescent↗
PubMed2001

Ependymoma in children and young adults (0-19 years): report of 25 consecutive cases.

The objective of this retrospective study was to evaluate the relative effect of surgery and radiotherapy (RT) on the survival of 25 consecutive children and young adults treated for ependymoma [18 in the posterior fossa (PF), 2 in supratentorial locations (ST) and 5 in intraspinal locations (IS)]. Five-year survival rates for patients with PF, ST and IS tumors were 28%, 0% and 100%, respectively. Total tumor resection was a positive prognostic factor in the case of PF tumors. No patients with subtotal removal of a PF tumor survived for longer than 5 years. The effect of RT on survival of patients with PF ependymomas in this series was uncertain. No patients with PF ependymoma had disseminated disease at diagnosis, and all tumor recurrences were local. Based on these observations, we see no indications for craniospinal RT of PF ependymomas, except in rare cases of disseminated disease. If RT is given, it should only be targeted to the tumor site. The two patients with ST ependymoma died within 3.8 years after primary treatment. Our series of ST ependymomas does not allow any specific treatment recommendations. One patient with IS ependymoma was cured by surgery alone. Four patients with IS ependymoma had documented residual tumor after surgery. RT induced remission in these patients. For IS ependymomas we recommend no RT if total tumor removal can be documented. In patients with subtotal removal of IS ependymomas local RT is effective and should be given.

Adolescent↗