Ependymoma: Ultrastructural Studies of Two Cases

Several unusual ultrastructural findings in two ependymomas are reported. In case 1, a grade I ependymoma of the fourth ventricle, there were rosettes, perivascular pseudorosettes, and tumor cells having unusual intracytoplasmic vacuoles by light microscopy. Ultrastructurally, these vacuoles were frequently microrosettes as well as scattered, degenerated cytoplasmic processes of tumor cells. The lumina of some of the microrosettes were bordered by abnormally long and malformed zonulae adherentiae. In case 2, a recurrent grade III ependymoma of the third ventricle, there were rosettes and perivascular pseudorosettes as well as more cellular and anaplastic areas by light microscopy. Ultrastructurally, the cytoplasmic processes of tumor cells in perivascular pseudorosettes contained frequent dense-core vesicles and occasional parallel arrays of microtubules. These structures do not occur in normal mammalian ependymal cells but do occur in the ependymal tanycyte, a related cell that is plentiful in the walls of the third ventricle. Thus some of the tumor cells of this third ventricle ependymoma appear to have differentiated as tany-cytes.     

Ependymoma: Ultrastructural Studies of Two Cases

Several unusual ultrastructural findings in two ependymomas are reported. In case 1, a grade I ependymoma of the fourth ventricle, there were rosettes, perivascular pseudorosettes, and tumor cells having unusual intracytoplasmic vacuoles by light microscopy. Ultrastructurally, these vacuoles were frequently microrosettes as well as scattered, degenerated cytoplasmic processes of tumor cells. The lumina of some of the microrosettes were bordered by abnormally long and malformed zonulae adherentiae. In case 2, a recurrent grade III ependymoma of the third ventricle, there were rosettes and perivascular pseudorosettes as well as more cellular and anaplastic areas by light microscopy. Ultrastructurally, the cytoplasmic processes of tumor cells in perivascular pseudorosettes contained frequent dense-core vesicles and occasional parallel arrays of microtubules. These structures do not occur in normal mammalian ependymal cells but do occur in the ependymal tanycyte, a related cell that is plentiful in the walls of the third ventricle. Thus some of the tumor cells of this third ventricle ependymoma appear to have differentiated as tany-cytes.     

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.     

Gliosarcoma arising from an anaplastic ependymoma: a case report of a rare entity

We report the first case of a gliosarcoma arising from an anaplastic ependymoma and the second case of gliosarcoma arising from any type of ependymal neoplasm. The patient was a 48-year-old woman with a solid and cystic, peripherally enhancing, 7-cm right frontal mass lesion. Histologically, the lesion displayed characteristics of anaplastic ependymoma (grade III, World Health Organization scale). The tumor recurred despite multiple cycles of postoperative radiation and chemotherapy. After the fourth recurrence, the tumor displayed a biphasic pattern of differentiation. The first pattern was similar to the original anaplastic ependymoma, whereas there was a second new sarcomatous pattern resembling fibrosarcoma that was admixed with and overrunning the ependymal component. The spectrum of gliosarcoma is therefore expanded to include not only astrocytic and oligodendroglial components but ependymal components as well.     

Myxopapillary ependymoma with anaplastic features

A case of myxopapillary ependymoma with anaplastic features in 15-year-old boy is reported. The tumor was located in the intradural space extending to the 12th thoracic to 2nd lumbar vertebral level. It was excised with the accompanying spinal arch of the T12 to L2 vertebra. At operation, the tumor was not attached to the surrounding soft and bony tissues. The tumor, measuring 49 x 19 x 15 mm, was brownish-yellow in color and involved the conus medullaris and filum terminale. Histologically, the tumor was composed of biphasic features of a hypercellular papillary growth area and a hypocellular myxoid area. In the papillary growth area, ependymal rosettes and perivascular pseudorosettes were observed. These findings were consistent with those of a myxopapillary ependymoma, although multiple foci of punctate necrosis within the tumor and proliferation of endothelial cells showing glomeruloid structures were observed. Many mitotic figures were also observed. In addition, the Ki-67 labeling index of tumor cells was 10.1%. These findings are unusual for myxopapillary ependymoma, and therefore, it appeared that the diagnosis of myxopapillary ependymoma with anaplastic features was appropriate.     

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.     

Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features – “Ependymosarcoma”

By analogy to gliosarcoma, the term “ependymosarcoma” has recently been coined to thematize the rare phenomenon of a malignant mesenchymal component arising within an ependymoma. We report on an example of this paradigm, involving tanycytic ependymoma as the host tumor in a 40-year-old female who underwent two tumor extirpation procedures at one-year interval. She first presented with severe headaches, and was seen by imaging to harbor a moderately enhancing mass 2.5 cm in diameter at the rostral septum pellucidum accompanied by occlusive hydrocephalus. Microscopically, the tumor consisted of solid, wavy fascicles of elongated cells that were occasionally interrupted by vague perivascular pseudorosettes. Mitotic activity was absent, and less than 1% of nuclei immunoreacted for MIB-1. A histological diagnosis of tanycytic ependymoma (WHO grade II) was rendered, and no adjuvant therapy given. At recurrence, the lesion was 3.5 cm in diameter, intensely enhancing, and had already seeded into the subarachnoid space. Histology showed a biphasic glial–sarcomatous architecture with remnants of the original ependymoma now displaying hypercellularity and atypical – yet not frankly anaplastic – features. The sarcomatous moiety consisted of spindle and epithelioid cells densely interwoven with reticulin fibers. While the ependymal component was GFAP and S100 protein positive, and featured punctate staining for EMA, none of these markers was expressed in the adjacent sarcoma. Instead, the latter reacted for vimentin and smooth muscle actin. To the best of our knowledge, this is the first documentation of tanycytic ependymoma undergoing malignant transformation, one driven by a highly anaplastic mesenchymal component, corresponding to “ependymosarcoma”.     

Cytogenetic evidence for a chromosome 22 tumor suppressor gene in ependymoma.

Although ependymomas comprise 5-10% of pediatric brain tumors, consistent cytogenetic aberrations have not been identified in these neoplasms. We report karyotypes for two ependymomas. A predominantly well-differentiated ependymoma contained several numerical chromosome aberrations, including monosomy 22. In contrast, an anaplastic ependymoma had a more complex karyotype that included loss of one chromosome 22 homologue and a balanced translocation at q13.3 in the remaining 22 homologue. These findings suggest the location of an ependymoma tumor suppressor gene on the long arm of chromosome 22.     

Multiple chromosomal monosomies are characteristic of giant cell ependymoma

Giant cell ependymoma, a rare ependymoma subtype, was recently recognized as a separate diagnostic entity with variations both in malignant potential and course of disease. We analyzed the first supratentorial giant cell ependymoma using G-band karyotyping, DNA ploidy analysis, and array comparative genomic hybridization. The tumor was hypodiploid, and the karyotype showed multiple monosomies. This novel cytogenetic pattern seems specific for giant cell ependymoma as the only previous cytogenetic analysis of a giant cell ependymoma found similar monosomies. We were also able to analyze cytogenetically the subsequent recurrent tumor, phenotypically an anaplastic ependymoma, allowing a first insight into the genetic events involved in disease progression.     

Extraspinal ependymoma of the broad ligament

Extraspinal ependymoma is a rare tumor, occurring most commonly in the sacrococcygeal region, and only a small number of cases have been reported to arise in the uterine ligament. Herein is reported a case of extraspinal ependymoma arising in the broad ligament of a 27‐year‐old woman. The lesion was 14 cm in diameter with an intra‐abdominal implant in the omentum. On cut section the tumor was found to be solid, and demonstrated hemorrhaging, necrosis, myxoid foci, and central cystic spaces. Microscopically the tumor was composed of a proliferation of short spindle or polygonal cells arranged in short fascicles or in a solid sheet‐like fashion with occasional perivascular pseudorosettes, together with myxoid areas and variable histological architectures exhibiting cribriform, pseudopapillary, and variable‐sized cystic patterns. On immunohistochemistry most tumor cells were positively reactive to glial fibrillary acidic protein (GFAP), CD99, estrogen receptor, and progesterone receptor. The patient has remained disease‐free for 6 months after the adjuvant chemoradiotherapy. Extraspinal ependymoma should be considered as a differential diagnosis when examining unusual intrapelvic tumors, especially in young female patients. The identification of characteristic histological features such as perivascular pseudorosettes and immunohistochemical expression of GFAP are helpful for confirming the diagnosis.     

High-grade neuroepithelial tumor with BCL6 corepressor-alteration presenting pathological and radiological calcification: A case report

A 5-year-old girl presented with headache and vomiting. Head computed tomography and magnetic resonance imaging showed a right frontal lobe tumor with marked calcification. The patient underwent resection surgery with suspicion of anaplastic ependymoma, and the tumor was gross totally removed. Pathological examination revealed areas of dense tumor cells with a high nucleocytoplasmic ratio and myxoid areas consisting of tumor cells with a round-shaped nucleus and eosinophilic cytoplasm. Perivascular pseudorosette, necrosis, circumscribed growth, and microcalcification were also observed. Immunohistochemistry demonstrated negative staining for glial fibrillary protein and epithelial membrane antigen. Diagnosis of a high-grade neuroepithelial tumor (HGNET) with BCL6 corepressor (BCOR) alteration was made based on pathological findings and internal tandem duplication in the exon 15 of BCOR. Although calcification on radiological and pathological examination is not typical, it would be essential to recognize that calcification could appear in HGNET-BCOR.     

Ectopic cervical anaplastic ependymoma

Ependymomas generally arise in the central nervous system (CNS), although rare primary extraneural ependymomas have been observed. Reported herein for the first time is the case of a patient with primary ectopic cervical anaplastic ependymoma. The tumor was found in the right neck root region of a 35-year-old man. No additional tumor was found in the CNS or in other parts of the body. The patient received surgery and post-surgical local radiotherapy. Microscopically, the tumor consisted of round to oval cells with fine chromatin, distinct nucleoli, moderate nuclear atypia and numerous mitoses (>25/10 high-power fields) in a densely cellular growth pattern with characteristic fibrillary cytoplasm and formation of perivascular pseudorosettes. By immunohistochemistry, the tumor cells were positive for glial fibrillary acidic protein, epithelial membrane antigen (EMA), vimentin and S-100 protein. EMA staining showed a membranous as well as a paranuclear pattern of immunoreactivity. Electron microscopic studies revealed that tumor cells form micro rosettes, into which microvilli and cilia projected. The diagnosis was World Health Organization grade III anaplastic ependymoma. There is no evidence of local tumor recurrence or distant metastasis after 30 months follow up. The present case adds yet another unique example to the already diverse spectrum of head and neck neoplasms encountered in surgical pathology.     

A rare case of malignant pediatric ectomesenchymoma arising from the cerebrum

Malignant ectomesenchymoma is a rare tumor that contains both ectodermal and mesenchymal elements. So far, only 7 patients with a manifestation in the cerebrum (with confirmed clinicopathological data) have been reported. A 4-year-old girl was present at our hospital with a 3-week history of intermittent sudden dizzy with no apparent cause. MRI showed an irregular enhanced lesion in the left frontal-parietal lobe and lateral ventricle with peripheral gadolinium-enhancement with a significant surrounding edema. Total removal of the tumor was performed. Histological examination of the resected tumor revealed a mixed astrocytoma and anaplastic ependymoma component with undifferentiated mesenchymal spindle cell component. Generally speaking, the main malignant part in most cases of malignant ectomesenchymoma (MEM) is the mesenchymal component. In the present case, the malignant component was both in the mesenchymal and ectodermal part. In particular, the mesenchymal part was mainly composed of spindle cells, and the ectodermal part primarily consisted of gliomatous component and anaplastic ependymoma component. The patient was then treated with chemotherapy and as regard to the prognosis, there was no evidence of tumor recurrence at the 5 months’ follow-up. The long term follow-up is still in progress.     

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.     

Suprasellar giant cell ependymoma: a rare neoplasm in a unique location

Ependymomas are glial tumors that usually present in the posterior fossa in children and in the spinal cord in adults. Giant cell ependymoma, a rare ependymal subtype only recently recognized as a diagnostic entity in the last decade, demonstrates pleomorphic giant cells admixed with features of typical ependymoma. Although only 8 giant cell ependymomas have been reported to date, none have been reported in the suprasellar space. Moreover, as these neoplasms demonstrate a high incidence of anaplastic grade, recognition of this ependymal subtype is paramount. We describe the presentation and pertinent radiologic, histologic, immunologic, and ultrastructural findings in conjunction with relevant clinical implications of the first reported case of a suprasellar giant cell ependymoma occurring in a 34-year-old female 7 years after an initial diagnosis of a medullary ependymoma with rare atypical giant cells, a potential tumor seeding culprit.     

Giant cell ependymoma-report of three cases and review of the literature

Ependymomas constitute the most common type of primary spinal cord tumors, and are subclassified as myxopapillary ependymoma, classic ependymoma, and anaplastic ependymoma. Ependymomas can be further subclassified based on morphologic phenotype: cellular, papillary, tanycytic, clear cell, pigmented and epithelioid. Giant cell ependymoma (GCE), a rare variant, has recently been described. Reported cases have exhibited a wide anatomic distribution, including spinal cord, cerebrum and cerebellum. We report here three cases of GCE, arising from cerebrum in a 5-year-old girl, spinal cord in a 34-year-old female and cerebellum in an 86-year-old female respectively. Histologically those cases showed prominent pleomorphic giant cells with focal perivascular pseudorosettes in all cases. Tumor cells were immunopositive for GFAP and EMA. Only the first case was qualified for anaplastic ependymoma. No recurrence was noted in these three cases after 57, 46 and 6 months of follow-up respectively. By reviewing the literature, GCEs arising from spinal cord and cerebellum tended to have low-grade morphology while supratentorially located GCEs tended to have anaplastic features. GCEs were preferentially located in extraventricular regions. Anaplastic GCEs in adult population seemed to pursue a more aggressive behavior. Gross total resection should still be the main treatment for GCEs.     

The carcinoembryonic antigen (CEA) in carcinomata of the stomach

Summary The localization of CEA in gastric carcinomata of different histological types was studied by indirect immunofluorescence. In well differentiated adenocarcinomata CEA was present on the surface of the tumor cells. CEA was absent in anaplastic cancers. Signet ring cells contained both CEA and mucus in their cytoplasm; this may indicate that signet ring cells are fairly well-differentiated tumor cells. In areas with intestinal metaplasia, CEA was detected on the luminal surface of the cells similar to a malignant tumor.Supported in part by Fonds zur Förderung der wissenschaftlichen Forschung (Project No. 1543).     

Papillary carcinoma of the thyroid gland with anaplastic transformation in the metastatic foci. An immunohistochemical study

An immunohistochemical study was made on an autopsy case of papillary carcinoma of the thyroid with anaplastic transformation in the metastatic foci occurring in a 72-year-old woman. The anaplastic carcinoma cells were sarcomatous in appearance, and they were vimentin-positive and cytokeratin-negative. Whereas, papillary tumor cells which were intermingled in the anaplastic carcinoma contained both cytokeratin and vimentin. The close correlation between tumor cell anaplasia and the expression of the different intermediate filament proteins in thyroid carcinoma was briefly discussed.     

PAPILLARY CARCINOMA OF THE THYROID GLAND WITH ANAPLASTIC TRANSFORMATION IN THE METASTATIC FOCI An Immunohistochemical Study

An immunohistochemical study was made on an autopsy case of papillary carcinoma of the thyroid with anaplastic transformation in the metastatic foci occurring in a 72-year-old woman. The anaplastic carcinoma cells were sarcomatous in appearance, and they were vimentin-positive and cytokeratin-negative. Whereas, papillary tumor cells which were intermingled in the anaplastic carcinoma contained both cytokeratin and vimentin. The close correlation between tumor cell anaplasia and the expression of the different intermediate filament proteins in thyroid carcinoma was briefly discussed.     

Anaplastic Ependymoma of the Spinal Cord in Childhood A Case Report

We report a 6-year-old girl with anaplastic ependymoma probably originating in the region of the conus medullaris and probably spreading retrogradely to the region of the interventricular foramen (Monro) through the cere-brospinal fluid (CSF). Since ependymoma of the spinal cord rarely occurs in children, and retrograde spreading is extremely rare, the histological features and mechanism of metastasis of the tumor are discussed.