Primary diffuse leptomeningeal glioneuronal tumors.

Diffuse leptomeningeal disseminated glioneuronal tumor (DL-GNT) is a rare brain tumor that presents as a plaque-like subarachnoid tumor, commonly involving the basal cisterns and interhemispheric fissure of children but lacking intraparenchymal tumor. Histologically, the tumors are composed of sheets of monotonous rounded cells. Here, we report three cases of DL-GNTs, focusing on clinicopathologic features. Two patients were adult male, but one patient was child. The patients presented with seizures (n = 1) or headaches (n = 2). In all patients, radiography revealed characteristic leptomeningeal thickening and enhancement with minor superficial parenchymal lesions. All three cases were diffusely positive for both GFAP and synaptophysin, and scattered positive for OLIG2 and NeuN, but negative for IDH-1 (H09). Electron microscopic examination showed astrocytic and neuronal differentiation. The patient with the anaplastic tumor died due to aggressive progression of the tumor, but the remaining two patients were stable without tumor recurrence for 23 and 37 months. Thus, these findings suggest that DL-GNT can occur in both children and adult and both supra- and infra-tentorial leptomeninges. It has unique radiological and histopathological features and biological behavior. Further clinicopathological data with molecular genetic study are required for establishing DL-GNT as a unique entity.

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.

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".

Meningioma de cels claras. Una rara variante de meningioma / Clear cell meningioma. A rare variant of meningioma

Presentamos en nuestro trabajo, los hallazgos morfológicos e inmunohistoquímicos de carácter diagnóstico observados en un meningioma de células claras localizado a nivel de la cauda equina en un paciente de 25 años. El tumor mostró un patrón morfológico de predominio nodular en el que destacaban las células de citoplasma claro, positivas para la tinción de PAS. El hallazgo de áreas de aspecto meningoteliomatoso dentro del mismo tumor así como la inmunohistoquímica (positividad de las células tumorales para vimentina y EMA y negatividad para citoqueratinas, CD10, HMB-45 y proteína glial fibrilar ácida) permitió establecer un diagnóstico diferencial con otras neoplasias principalmente con las metástasis de carcinoma renal. De igual modo se comentan con brevedad las características de esta variante de meningioma de grado intermedio de malignidad (meningioma grado ii de la OMS)(AU)

The morphological and immunohistochemical findings of a clear cell meningioma found in the cauda equina of a 25 year old patient are reported. The tumour was predominately nodular with a marked presence of cells with clear cytoplasm which stained positively for PAS. The presence of meningoteliomatous areas in the tumour, together with the immunohistochemistry of the tumour cells (positivity for vimentin and EMA and negativity for cytokeratins, CD10, HMB45 and PGFA) were the diagnostic features that differentiated the tumour from other possible diagnoses, principally metastases from a renal carcinoma. The characteristics of this type of meningioma, which has an intermediate grade of malignancy (WHO grade ii meningioma) are discussed(AU)

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.

An immunohistochemical and electron microscopic study of atypical teratoid/rhabdoid tumor.

We report two infant cases with atypical teratoid/rhabdoid tumor (AT/RT) located in the cerebellar vermis and spinal cord. MRI showed the tumors were isointense on T1-weighted images and mixed intensity of isointense and slight high intensity on T2-weighted images. Postcontrast MRI demonstrated clear margin of tumor and heterogeneous strong enhancement. It was difficult to differentiate the tumor from medulloblastoma by hematoxylin and eosin staining. However, immunohistochemical staining showed that these tumor cells react positively for cytokeratin, smooth muscle actin (SMA), and epithelial membrane antigen (EMA) and helped us with the differentiation. Electron microscopic study has confirmed the presence of mesenchymal components, such as filaments and desmosome junctions in the rhabdoid cells, but no neuronal components. The tumors rapidly increased in size, showing high MIB-1 index, and the prognosis was gave.

Spinal glioma: platelet-derived growth factor B-mediated oncogenesis in the spinal cord.

Human platelet-derived growth factor B (hPDGFB) has been characterized in vitro and shown to mediate numerous cellular responses including glial proliferation and differentiation. Expression of PDGFB is thought to be important in the pathogenesis of glioma and several animal models of cerebral glioma based on PDGF expression have been described. To examine whether PDGF could contribute to the pathogenesis of spinal cord glioma, we developed transgenic mice that express hPDGFB under the control of a tetracycline-responsive element (TRE/hPDGFB). These TRE/hPDGFB mice were mated with transgenic mice expressing the tetracycline transcriptional activator (tet-off), tTA, regulated by the human glial fibrillary acidic protein (GFAP) promoter and exhibiting uniquely strong promoter activity in the spinal cord. These transgenic mice (GFAP/tTA:TRE/hPDGFB) expressed hPDGFB in GFAP-expressing glia in a manner responsive to doxycycline administration. Without doxycycline, almost all GFAP/tTA:TRE/hPDGFB mice developed spinal cord neoplasms resembling human mixed oligoastrocytoma. Tumorigenesis in these animals was suppressed by doxycycline. To further examine the importance of PDGFB in mouse primary intramedullary spinal cord tumors, we also created transgenic mice expressing hPDGFB under the control of the human GFAP promoter (GFAP/hPDGFB). These GFAP/hPDGFB mice also developed spinal oligoastrocytoma. PDGFB can mediate the development of mouse spinal tumors that are histologically and pathologically indistinguishable from primary intramedullary spinal tumors of humans and may provide opportunities for both novel insights into the pathogenesis of these tumors and the development of new therapeutics.

Cluster of cases of malignant schwannoma in cattle.

Between 1998 and 2001, several cases of ataxia and paresis followed by recumbency and death were reported in cows from different farms in a restricted area of the Argentinian Patagonia. Five cases of this cluster were studied and a diagnosis of malignant schwannoma was established. Electron microscopy (em) of tumour samples from three of the animals revealed intracytoplasmic or interstitial structures resembling retroviral particles. Attempts to isolate a viral agent from the tumours were unsuccessful but the epidemiological data and the em findings suggest a viral aetiology.

Intramedullary clear cell ependymoma in the thoracic spinal cord: a case with its crush smear and ultrastructural findings.

Clear cell ependymoma was included in the World Health Organization classification of the nervous system in 1993, and all the reported cases, except for two in the spinal cord, were located in the brain, mainly in the supratentorial compartment. Astrocytomas outnumber ependymomas in the spinal cord, and the two entities partly share cytologic findings such as long, bipolar glial processes and oval to round nuclei resembling those seen in pilocytic astrocytoma. Here, we report the first Korean case of intramedullary clear cell ependymoma of the spinal cord, which is the third case situated in the spinal cord in the literature. The crush smear revealed round-to-oval nuclei with occasional nuclear eosinophilic inclusion and rare nuclear grooves. Cytoplasm had fluffy eosinophilic glial processes, and acellular fibrillary zone. On hematoxylin-eosin stain, oval to round tumor cells had large central nuclei with indistinct nucleoli and a moderate amount of clear cytoplasm, i.e. perinuclear halo, mimicking oligodendroglioma. Perivascular pseudorosettes and ependymal clefts were rarely found. In retrospect, perinuclear halo was absent on crush smears. Ultrastructurally, they had extensive surface microvilli and edematous cytoplasm filled with abundant glial filaments and microlumens with or without microvilli. Intercellular long cell junctions of the zipper-like zonula adherens type were found.

Oncocytoma of the spinal cord causing paraplegia - a case report.

STUDY DESIGN: Case report. OBJECTIVES: To describe a rare case of oncocytoma arising from the spinal cord in a 40-year old woman. SETTING: Republic of Korea. METHODS: The patient's history, physical examination, radiological and pathological findings were reviewed. RESULTS: A 40-year-old woman presented with 3-month history of low back pain. Magnetic resonance imaging revealed an intradural extramedullary mass located between L1 and L4. She refused any surgical treatment and so was discharged. At 10 days after discharge, an emergency operation was performed because of sudden paralysis in both lower extremities. The confirmed diagnosis is oncocytoma. At 4 months after surgery, the patient failed to obtain neurological recovery from complete paraplegia. CONCLUSIONS: Since the progression of an intradural extramedullary mass that shows minor neurological symptoms can lead to complete paraplegia in a short time, close observation and early surgical decompression are necessary.

Spinal adrenal cortical adenoma with oncocytic features: report of the first intramedullary case and review of the literature.

Ectopic adrenal cortical neoplasms are extremely rare, and only a few have involved the CNS. We report the first case of an intramedullary oncocytic adrenal cortical neoplasm of the spinal cord with immunohistochemical (IMHC) confirmation. A 27-year-old man presented with progressive lower extremity weakness, spastic paraparesis, decreased reflexes, and hypoesthesia below T10. A spinal myelogram showed cauda equina blockade and obliteration of sacral nerve roots. This prompted emergent surgical intervention. A well-circumscribed, approximately 3 x 2 cm, light brown to tan, intramedullary tumor was identified at the level of the conus medullaris. Histologically, the tumor showed sheets and nests of plump, cytologically bland polygonal cells with abundant eosinophilic cytoplasm. A single mitosis, but no necrosis, was identified. By IMHC, the cells were positive for inhibin, melan-A, and synaptophysin, and negative for GFAP, EMA, cytokeratins, S-100, HMB-45, and chromogranin. Electron microscopy study performed from paraffin-embedded tissues demonstrated abundant mitochondria, and lipid vacuoles. This case confirms the occurrence of adrenal cortical neoplasms in the CNS and is the first report of an intradural, intramedullary adrenal cortical adenoma of the spinal cord, and the first to occur in a male. This tumor should be considered in the differential diagnosis of tumors of the CNS.

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.

Imprint cytologic features of intracytoplasmic lumina in ependymoma. A report of two cases.

BACKGROUND: Intracytoplasmic lumina have been recently recognized as a characteristic histologic feature of ependymoma. However, the cytologic diagnostic usefulness has not been discussed. We encountered two imprint cytology cases of spinal cord ependymomas in which there were intracytoplasmic lumina in the tumor cells. CASES: Two women had spinal cord tumors on magnetic resonance imaging. Imprint cytology study was carried out on the resected tumors. The cytologic specimen of the first case, aged 52, showed tumor clusters consisting of elongated epithelioid cells, a few of which also had intracytoplasmic lumina. Histologically, tumor cells formed ependymal rosettes and pseudoperivascular rosettes. There were a few tumor cells with intracytoplasmic lumina. The cytologic specimen of the second patient, aged 37, had scattered and isolated tumor cells with intracytoplasmic lumina resembling signet-ring cells and paired tumor cells forming small, glandlike structures. Histologically, the tumor was composed mainly of signet-ring-like cells containing intracytoplasmic lumina. CONCLUSION: Intracytoplasmic lumina were observed in the imprint cytologic specimens of spinal cord ependymoma. The diagnosis of ependymomas can be made cytologically when intracytoplasmic lumina are found since no other primary neuroepithelial tumors of the central nervous system possess such a characteristic feature.

Spinal tanycytic ependymomas.

Three cases of spinal tanycytic ependymoma are reported, a man aged 45 years and two women aged 36 and 55 years. Each patient developed gradual paraparesis over a few months prior to admission. Magnetic resonance imaging showed an enhancing, well-circumscribed tumor in the spinal cord in each case. Histologically, the tumors consisted of monotonous proliferation of long spindle cells with markedly eosinophilic cell processes; focally forming perivascular pseudorosettes. The tumor cells were strongly immunopositive for glial fibrillary acidic protein, S-100 protein and vimentin. Ultrastructurally, in addition to massive intermediate filaments, many tumor cells showed abundant microtubules. Well-developed desmosomes and microvilli/cilia-lined microlumina were occasionally observed. The tumors were grossly totally removed and the patients remain recurrence free at 9, 9, and 2 years postoperatively. Reviewing reported cases including our three cases, tanycytic ependymoma may occur frequently in spinal cord, especially in the cervical region of the spinal cord. Since histologically it resembles pilocytic astrocytoma and schwannoma, tanycytic ependymoma should be included in the differential diagnosis of benign spindle cell tumors of the central nervous system.

Solitary fibrous tumor of the spinal cord. Report of a case with scrape cytology.

BACKGROUND: Solitary fibrous tumor is a rare spindle cell tumor and has been forced at a variety of sites. To the best of our knowledge, only two cases of solitary fibrous tumor arising in the spinal cord have been reported; no cytologic findings were documented. CASE: A 62-year-old male presented with a spinal cord tumor. A scrape smear of the resected tumor revealed naked, spindle-shaped nuclei. Some nuclei were twisted or had long spindles. In the background, abundant, thin and thick collagen fibers were present. Immunohistochemically, the spindle cells were positive for CD34 and negative for S-100 protein and alpha-smooth muscle actin. Histologic diagnosis of the tumor was benign solitary fibrous tumor. CONCLUSION: Our case indicates that solitary fibrous tumor can occur in the spinal cord and should be differentiated from other benign spindle cell tumors, such as meningioma and schwannoma. The key cytologic features of solitary fibrous tumor may be the presence of abundant thin and thick collagen fibers in scrape specimens.

Pigmented schwannoma of the ventral spinal cord.

Pigmented schwannomas of the spinal canal are rare entities. We present a case of such in an unusual, ventral intradural, extramedullary location in a 27-year-old man. Imaging and histopathologic findings, including electron microscopy, showed an intradural, extramedullary pigmented schwannoma, densely adherent to the leptomeninges of the anterior median septum. This lesion is demonstrative of the neuroectodermal origin of these lesions and represents a rare location of these tumors.

Lipidized (foamy) tumor cells in a spinal cord ependymoma with collagenous metaplasia.

We report a 49-year-old woman with a spinal cord ependymoma located in the thoracolumbar region. At surgery, a soft dark-grayish tumor, which contained a hard whitish area, was removed. The specimen was a moderately cellular tumor with a central core made up of collagen nodules poor in cellular elements. Many of the tumor cells possessed ground glass-like eosinophilic cytoplasm, and frequently foamy tumor cells were evident. Perivascular pseudorosettes, ependymal rosettes and canals were present, the latter being rare. Many tumor cells, including those with foamy cytoplasm, were positive for glial fibrillary acidic protein. Similar tumor cells were also seen among, and even within, the collagen nodules. The MIB-1 labeling index was 0.66%. Ultrastructurally, the frequent lipidized tumor cells were ependymal in nature; cytoplasmic 10-nm-wide filaments, and intracytoplasmic lumina and intercellular microrosettes lined by microvilli were evident. Cilia were very rare. We considered the present case to be an unusual, lipidized variant of ependymoma. The collagen nodules appeared to be produced by the tumor cells themselves.

Nuclear grooves in ependymoma. Cytologic study of 21 cases.

OBJECTIVE: To study the efficacy of crush preparation smears in the diagnosis of ependymomas. STUDY DESIGN: The study group consisted of 21 patients aged 7-61 years. All were admitted to Shiraz University hospitals (Nemazi and Beheshti) with intramedullary tumors. Fourteen were ventricular (fourth ventricle), 1 was in the parietal lobe, 5 were in the lumbosacral region and 1 was in the cauda equina. Intraoperative crush preparation smears were obtained from tissue, which was sent for frozen section and diagnosed cytologically. The control group consisted of 123 intracranial tumors (meningiomas, schwannomas, astrocytomas, oligodendrogliomas, medulloblastomas, pituitary adenomas, choroid plexus papilloma, craniopharyngioma and metastatic tumors). RESULTS: The smears in 11 cases revealed perivascular pseudorosettes, and the smears in 21 cases revealed ependymal rosettes. Papillary clusters, calcification and intranuclear inclusions were seen in two cases. Acinar structures were seen in seven cases. Myxomatous material was seen in one case. Nuclear grooves were seen in 15 cases. All cases were diagnosed as ependymomas. Biopsy specimens confirmed the cytologic diagnosis. The tumors in the control group showed no evidence of nuclear grooves. CONCLUSION: Fifteen cases of ependymoma showed a substantial number of nuclear grooves. Intraoperative crush preparation smears were very useful in the diagnosis of ependymomas and helped with the rapid interpretation of frozen sections.

Myxopapillary ependymomas: a clinicopathologic study of 14 cases including MIB-1 and p53 immunoreactivity.

Few studies have examined cell proliferation or p53 immunoreactivity in myxopapillary ependymomas. This study retrospectively examines tumor MIB-1 and p53 immunohistochemical features in 14 patients (eight women, six men; age range, 12-69 yr; median, 32 yr) with myxopapillary ependymoma. Their preoperative symptoms lasted from 2 months to 18 years (median, 12 mo) and most commonly involved lower back pain. The tumor was in the lumbar spinal cord region in 12 patients, the sacral cord in 1, and both the lower thoracic and upper lumbar cord in 1. In three patients, cerebrospinal fluid protein levels were markedly elevated, with negative cytologic results. Thirteen patients underwent a gross total resection. All of the tumors demonstrated histologic features diagnostic of myxopapillary ependymoma. Four cases had focal, prominent, nuclear pleomorphism. From 1 to 5 mitotic figures per 10 high power fields were identified in four tumors. There was no vascular proliferation or necrosis. Nine patients are alive at last known follow-up with no evidence of tumor (median, 36 mo); four are alive with residual tumor (median, 40 mo); and one died after 74 months (tumor status unknown). Eleven patients received adjuvant radiation and/or chemotherapy. Six experienced at least one tumor recurrence at intervals of 20 to 132 months. MIB-1 indices on the initial tumor resection ranged from 0 to 5.5 (median, 0.9) in 12 cases. In three patients with recurrent tumor, MIB-1 indices were higher in the initial tumor in two cases and lower in one. p53 Immunostaining of 13 tumors showed rare positive-staining tumor cell nuclei. The conclusions are that myxopapillary ependymomas grow slowly; that MIB-1 labeling indices are unreliable predictors of tumor recurrence; and that the lack of p53 immunostaining in most myxopapillary ependymomas in this series suggests that this gene might not play a significant role in the pathogenesis of these tumors.