Eosinophilic globules in a classic ependymoma: evidence of a possible secretory role.

A number of neoplasms of the central nervous system can demonstrate diffuse eosinophilic globules, known to be secretory products of the corresponding cell type, but they have not been a salient feature in descriptions of classic ependymoma. Here, we present a case of a posterior fossa ependymoma demonstrating glassy PAS-positive, diastase-resistant, eosinophilic globules with light microscopic and ultrastructural features resembling Reissner fiber, the secretory product of the subcommissural organ. While there has been a single published description of an ependymoma with intra- and extracellular granulofibrillary material suggested to be evidence of secretory differentiation, ours is the first case to demonstrate diffuse eosinophilic globules in an ependymoma. The extent of globules allowed full study by electron microscopy to provide new insight into the secretory material and the surrounding structures. Our findings suggest that neoplastic ependymal cells can recapitulate the secretory capacity of the subcommissural organ.

Ultrastructural pathology of anaplastic and grade II ependymomas reveals distinctive ciliary structures--electron microscopy redux.

Ependymoma tumors likely derive from the ependymal cells lining the CNS ventricular system. In grade II ependymomas, tumor cells resemble typical ependymocytes, while anaplastic ependymomas are poorly differentiated. We studied three grade II and one anaplastic ependymoma, focusing on the ciliary structures. To unambiguously characterize the ultrastructure and number of cilia, we performed electron microscopy serial section analysis of individual cells. Differentiated ependymomas contained large basal bodies and up to three cilia, and lacked centrioles. Anaplastic ependymoma cells showed instead two perpendicularly oriented centrioles and lacked cilia or basal bodies. These findings could contribute to understand the mechanisms of ependymoma aggressiveness.

Cerebral and spinal cord tanycytic ependymomas in a young adult with a mutation in the NF2 gene.

We studied one frontal lobe tumor and multiple spinal cord tumors (one in an extramedullary location) that had been resected from a 24-year-old man. The frontal lobe tumor was well demarcated and non-infiltrating, and consisted of eosinophilic, elongated fibrillary cells arranged in a fascicular pattern. A similar histology was reproduced in the spinal cord tumors, with additional areas showing standard features of ependymoma. Immunohistochemical and ultrastructural observations revealed that all the tumors were ependymal in nature with positivity for GFAP and epithelial membrane antigen and negativity for oligodendrocyte transcription factor 2, showing intra- and intercellular microrosettes, leading us to a diagnosis of tanycytic ependymoma for the frontal lobe tumor and tanycytic ependymoma with ordinary ependymomatous component for the spinal cord tumors. The spinal extramedullary tumor was a schwannoma. Importantly, a heterozygous truncating mutation in the NF2 gene was identified in the blood lymphocytes from the patient. It is known that multiple nervous system tumors can occur in neurofibromatosis type 2 (NF2), which is caused by mutation in the NF2 gene, and that occurrence of ependymoma, including the tanycytic variant, can be associated with this genetic condition. The present case provides further information about the clinicopathology of tanycytic ependymoma with details of the immunohistochemical, ultrastructural and genetic features.

Cortical ependymoma with unusual histologic features.

Cortical ependymomas are rare gliomas with classic ependymal features but are unusual in primarily involving the cerebral cortex. Here, we present a 19-year old woman with new-onset seizures who was found to have a large, cortically based non-enhancing lesion with scalloping of the overlying calvarium. Abundant ependymal features were present including classic ependymal cytology, diffuse GFAP and dot-like EMA positivity, and well developed cilia, microvilli, and intercellular junctions on ultrastructural analysis. Additionally, the tumor showed areas of infiltrative growth similar to angiocentric glioma as well as striking mucin-filled microcystic spaces somewhat reminiscent of myxopapillary ependymoma. Thus far, the patient shows no evidence of recurrence following gross total resection. This case demonstrates detailed morphologic, immunohistochemical, and ultrastructural evidence supporting a relationship between cortical ependymoma and angiocentric glioma and suggesting that cortical ependymomas can have myxopapillary as well as classic features.

Clinical presentation, immunohistochemistry and electron microscopy indicate neurofibromatosis type 2-associated gliomas to be spinal ependymomas.

Neurofibromatosis type 2 (NF2) is a hereditary tumor syndrome. The hallmark of NF2 is bilateral vestibular schwannoma. In addition, glioma is one of the diagnostic criteria of NF2. In this retrospective study the clinical presentation and histopathological features of 12 spinal gliomas from NF2 patients were assessed. Ten tumors were previously diagnosed as ependymomas and two as astrocytomas. However, upon re-evaluation both astrocytomas expressed epithelial membrane antigen in a dot-like fashion and in one case it was possible to perform electron microscopy revealing junctional complexes and cilia typical for ependymoma. The findings suggest that NF2-associated spinal gliomas are ependymomas. Based on the fact that NF2-associated gliomas are almost exclusively spinal and that no NF2 mutations have been found in sporadic cerebral gliomas, we suggest that "glioma" in the current diagnostic criteria for NF2 should be specified as "spinal ependymoma".

Ependymoma with "granular cell" features: report of two cases.

We report two cases of ependymoma which showed prominent "granular cell" changes of the cytoplasm. The patients were a 7-year-old boy with a tumor in the cerebellum (case 1) and a 70-year-old man with a tumor in the frontal lobe (case 2). The tumor of case 1 showed a histopathological appearance of ependymoma containing many focal aggregates of large polygonal cells in which the cytoplasm was stuffed with numerous eosinophilic granules. The tumor of case 2 predominantly showed the features of papillary ependymoma, and some tumor cells were swollen and contained similar eosinophilic granules. Intracytoplasmic granules in both tumors were immunoreactive for GFAP and ubiquitin, but not for epithelial membrane antigen, CD68 or mitochondria. Ultrastructurally, they were found as aggregates of membrane-bound, electron-dense, globular structures. Karyotypic analysis of the tumor in case 1 demonstrated 2, 11 and 12 trisomies. Intracytoplasmic eosinophilic granules occasionally occur in astrocytic and oligodendroglial neoplasms, but an appearance of similar granules is very rare in ependymoma. The two cases presented here may represent a new histopathological variant of ependymoma, and the term "granular cell ependymoma" is appropriate for them.

Ependymoma in a dwarf goat.

Ependymomas are relatively rare neuroglial tumours that derive from ependymal cells, lining the ventricles of the brain and the central canal of the spinal cord. They occur particularly in dogs, while reports in goats are extremely scarce. A 15-year-old female dwarf goat was found in lateral recumbency, developed opisthotonus and was killed humanely. Necropsy revealed a well-demarcated, non-encapsulated mass in the diencephalon at the level of the interthalamic adhesion. Histologically, the neoplasm showed highly cellular sheets of tumour cells with occasional perivascular pseudorosettes and true rosettes. Immunohistochemistry revealed an extensive and perivascularly accentuated expression of S100 protein and glial fibrillary acidic protein, while vimentin expression was observed to a minor extent. Tumour cells were negative for cytokeratin and CNPase. Ultrastructurally, intercellular junctions were present, but cilia and blepharoblasts were lacking. The presented findings are consistent with a cellular subtype of an ependymoma. Ependymomas should be regarded as a rare cause of central nervous signs in goats.

Three-dimensional reconstructive analysis of intracytoplasmic lumina found in ependymomas.

Three-dimensional reconstructive analyses revealed that the intracytoplasmic lumina found in ependymomas were actually formed by subsidence of an extracellular membrane, resembling a volcano. This finding was compatible with cytologic and electron microscopic findings. In addition, there were many tiny thorns resembling a holly leaf on the extracellular membrane, such that cilia and microvilli on the cellular membrane discontinued cell-to-cell tight junctions.

Perivascular elastic fibers: a diagnostic feature of ependymoma.

To assess the diagnostic potential of perivascular elastic fiber detection as an indicator of ependymoma, the authors performed ultrastructural studies on a large series of pediatric brain tumors. Elastic fibers were demonstrated by electron microscopy in 38 of 50 (76%) ependymomas, 2 of 25 (8%) choroid plexus tumors, 0 of 100 (0%) medulloblastomas, and 0 of 100 (0%) astrocytomas. In some poorly differentiated examples, elastic fibers were initially the sole indicator of ependymal differentiation. The authors conclude that the sensitivity and specificity of this feature is sufficient to render demonstration of perivascular elastic fibers a useful diagnostic indicator of ependymoma.

A case of tanycytic ependymoma arising from the cerebral hemisphere.

We report a rare case of tanycytic ependymoma arising from the cerebral hemisphere. A 59-year-old man was admitted to our hospital because of the incidental detection by MRI of a tumor lesion in the right temporooccipital paratrigonal region. The mass showed low-to iso-intensity on T1-weighted images and high intensity on T2/proton-weighted images. Partial resection was performed using a transsulcal approach to avoid compromising the visual field. Most of the tumor cells showed elongated spindle shapes arranged in dense fascicles. A few true ependymal rosettes and perivascular pseudorosettes were visible. The tumor cells were positive for GFAP, S-100, and vimentin, but negative for synaptophysin, EMA, and keratin. The MIB-1 labeling index was approximately 1%. Ultrastructurally, the tumor cells had ependymal cell features, such as microvilli and cilia. From these findings, a pathological diagnosis of tanycytic ependymoma was made.

Lipomatous ependymoma: report of a rare differentiation pattern with a comprehensive review of literature.

We report the case of a 13-year-old girl presenting with left-sided hemiparesis, altered sensorium and episodic headache with bouts of projectile vomiting. Imaging revealed a large heterodense intraventricular mass lesion displaying focal calcification and hyperintensity on T1- and T2- weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance images suggesting the presence of intratumoral fat. Histologically, the tumour showed sheets of glial cells, focal perithelial rosettes and individual cells showing fat vacuoles. The morphological impression was of an ependymoma with lipomatous differentiation. Glial fibrillary acid protein (GFAP) immunohistochemistry revealed positivity in the cytoplasmic processes of the tumour cells as well as in the cytoplasmic rim of the cells having an adipocytic appearance. S100 and vimentin were also immunoreactive. Ultrastructural studies confirmed the ependymal differentiation of the tumour and the presence of an osmiophilic fat component confirming the diagnosis. After 1 year of follow-up, the patient presented with similar complaints and MRI evidence of recurrence of the tumour. A comprehensive literature review revealed that half of the reported cases of this pattern recurred suggesting a possibly tenacious clinical course.

Isolation of plasma membranes from murine ependymoblastoma and subcellular distribution of amphotericin B in this tumor.

A method for the isolation of plasma membranes from an experimental murine ependymoblastoma is described. In this procedure, 5'-nucleotidase was used as the plasma membrane marker, since cytochemical methods demonstrated that the enzyme was present on this subcellular structure only. The final plasma membrane preparation showed a 15-fold enrichment in 5'-nucleotidase activity and a 17-fold enrichment in the activity of phosphodiesterase I, another plasma membrane marker. The specific activity of beta-glucuronidase (lysosomal enzyme) was twice that of the whole homogenate, the specific activity of arylesterase (microsomal enzyme) was similar to that of the whole homogenate and succinate dehydrogenase (mitochondrial marker) was not detected. Electron microscopy of this fraction showed vesicles on which 5'-nucleotidase activity could be demonstrated. The subcellular distribution of [3H]amphotericin B per mg of protein was similar in the plasma membrane preparation and in the whole homogenate. It is concluded that, in ependymoblastoma, amphotericin B shows no selective affinity for the plasma membrane.

Woman aged 24 years with fourth ventricular mass.

April 2005. A woman aged 24 years presented with symptoms related to a tumor in the fourth ventricle. Cytologically, the tumor was biphasic with areas typical of a classic ependymoma, including rosettes, and other areas containing grossly atypical giant cells. Many tumor cells were GFAP-positive and ultrastructural examination revealed microvilli and cilia. The histopathologic abnormalities place this tumor among the ependymomas. Its focal giant cell phenotype is very rare, but has been reported in 4 intracranial or filum ependymomas.

A pigmented choroid plexus carcinoma: histochemical and ultrastructural studies.

A large tumor of the left lateral ventricle in a 3 1/2 year old male was diagnostic of malignant choroid plexus papilloma (choroid plexus carcinoma) as observed histologically. Focal neoplastic epithelial cells contained yellow-brown pigment which was not entirely compatible with melanin by histochemical techniques. Ultrastructurally, the tumor had definite evidence of choroid plexus origin. The neoplastic cells contained electron-dense and lamellar bodies, as well as structures of intermediate type. Premelanosomes were not observed. Thus there was no evidence for neural crest melanin. It is suggested that the pigment is probably lipofuscin and melanin derived from lipofuscin by "melanization" through pseudoperoxidation.

The cytogenetic basis for classifying ependymomas.

The phylogeny of ependymal cells and astrocytes can be traced to a single primitive progenitor the ependymoglia or the tanycyte, respectively. Ependymoglia cells have ependymal perikarya having astrocyte-like processes that terminate subpially in primitive glial footplates. Such cells prevail in primitive nervous systems, but they also persist regionally in the mature mammalian brain. Their fine structure has been studied in many species. An electronmicroscopic study of 8 ependymomas reveals that the neoplastic cells possess features characteristic of primitive ependymoglia; in particular they possess cell processes filled with glial filaments, terminating submesenchymally in a primitive, piston-shaped footplate. The perivascular pseudorosettes of ependymomas are the equivalents of these cell poles. The dominant phenomenon of ependymoma structure appears to be a reversion of cellular organization to the stage of primitive ependymoglia cells. On reviewing 43 ependymomas and 71 astrocytomas 11 neoplasms were found having a tissue structure reminiscent of the evolution of piloid astrocytes from ependymoglia or tanycytes, respectively. These features correspond to transitional stages seen in normal primitive brains. Tumors of this type may be characterized as a tanycytic variant of ependymomas. They appear to be relatively common in the spinal cord and present a source of confusion with piloid astrocytomas.

Ependymoma of the broad ligament. A report of two cases.

The clinical and pathological features of two cases of ependymoma that originated in the broad ligament are reported. Metastases developed in both patients. The tumors had the distinctive features of ependymoma on light-microscopical examination, and the diagnosis was confirmed by ultrastructural study in one case and immunoperoxidase staining for glial fibrillary acidic protein in both cases. The tumors presented diagnostic difficulties because of their close resemblance to serous papillary carcinomas of the ovary and the absence of published reports of ependymoma occurring in the female genital tract.

Melanotic ependymoma and subependymoma.

We report two examples of melanin production by human gliomas. One was a grossly pigmented, well-differentiated ependymoma resected from the left frontoparietal region of a 13-year-old girl. The patient received radiotherapy and was free of tumor 12 years after operation. The second example was a pigmented subependymoma incidentally discovered at the autopsy of a 52-year-old man. Neoplastic cells containing an intracytoplasmic pigment satisfying histochemical criteria for melanin were present in both cases. Electron microscopic study of the melanotic ependymoma revealed electron-dense granules in the cytoplasm of cells forming rosettes. Premelanosomes were not detected. While the mechanism of melanogenesis in these cases is obscure, they support the potential of glial derivatives to produce melanin and indicate that melanogenesis in such neoplasms may have no adverse prognostic import.

Primary malignant ependymoma of the lung.

In a 64-year-old woman, a solitary pulmonary nodule developed 30 months after combination chemotherapy and thoracic irradiation had been administered for small-cell carcinoma of the ipsilateral lung. No evidence of extrapulmonary tumor was identified, and the nodule was excised. The well-circumscribed tumor had histologic features of a malignant ependymoma. Immunohistochemical staining showed strong reactivity for glial fibrillary acidic protein; staining for S-100 protein, Leu-7, and vimentin was less intense. Focal reactivity for epithelial membrane antigen was also present. Stains for keratin, synaptophysin, and chromogranin were negative. Electron microscopy showed cohesive cells, the cytoplasm of which contained intermediate filaments. Rare well-formed junctions were also noted. Flow cytometry of formalin-fixed paraffin-embedded tissue demonstrated DNA aneuploidy. Six months after the ependymoma was diagnosed, the patient, who had a history of hypertension, died of an intracerebral hemorrhage.

Cauda equina tumor with ependymal and paraganglionic differentiation.

We describe the case of a 31-year-old woman who was first treated for a pigmented choroid plexus papilloma of the fourth ventricle. Ten year later, she developed a new tumor in the region of the cauda equina. This second neoplasm contained areas of papillary ependymoma that displayed phosphotungstic acid hematoxylin-positive glial fibers and immunoreactivity for glial fibrillary acidic and S-100 proteins. Areas of ependymoma merged with others that displayed the appearance of a paraganglioma, including lobules and nests of chief cells immunoreactive for neuron-specific enolase, synaptophysin, chromogranin, and serotonin. Satellite cells, but not chief cells, stained for glial fibrillary acidic and S-100 proteins. Electron microscopy showed features of both ependymal and paraganglionic differentiation, including intercellular lumina with microvilli, junctional complexes, cell processes with closely packed filaments, and dense core granules. Our case represents a rare example of a cauda equina neoplasm with simultaneous ependymal and paraganglionic differentiation. To our knowledge, this is the first described example of a tumor of this region showing features of both ependymoma and paraganglioma.