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.     

Mucin-secreting cellular ependymoma: a light and electron microscopy study

Mucin accumulation in ependymomas is thought to be limited to the myxopapillary variant and represents an important diagnostic feature. Similarly, signet-ring cells in ependymomas have been shown by electron microscopy to represent microrosette instead of mucin secretion. This study describes an infratentorial ependymoma largely composed of mucinous areas and signet-ring cells. The ependymal nature of mucin-secreting cells was confirmed by ultrastructural analysis. This case widens the variable spectrum of ependymal morphology. The value of electron microscopy in differentiating central nervous system neoplasms showing mucous secretion is stressed.     

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.     

cIMPACT‐NOW update 7: advancing the molecular classification of ependymal tumors

Advances in our understanding of the biological basis and molecular characteristics of ependymal tumors since the latest iteration of the World Health Organization (WHO) classification of CNS tumors (2016) have prompted the cIMPACT‐NOW group to recommend a new classification. Separation of ependymal tumors by anatomic site is an important principle of the new classification and was prompted by methylome profiling data to indicate that molecular groups of ependymal tumors in the posterior fossa and supratentorial and spinal compartments are distinct. Common recurrent genetic or epigenetic alterations found in tumors belonging to the main molecular groups have been used to define tumor types at intracranial sites; C11orf95 and YAP1 fusion genes for supratentorial tumors and two types of posterior fossa ependymoma defined by methylation group, PFA and PFB. A recently described type of aggressive spinal ependymoma with MYCN amplification has also been included. Myxopapillary ependymoma and subependymoma have been retained as histopathologically defined tumor types, but the classification has dropped the distinction between classic and anaplastic ependymoma. While the cIMPACT‐NOW group considered that data to inform assignment of grade to molecularly defined ependymomas are insufficiently mature, it recommends assigning WHO grade 2 to myxopapillary ependymoma and allows grade 2 or grade 3 to be assigned to ependymomas not defined by molecular status.     

Tanycytic Ependymoma

Tanycytic ependymoma is an uncommon fibrillar variant of ependymoma characterized by streams of piloid, or hair-like, cells having “ependymal” nuclei. True ependymal rosettes are absent, and perivascular rosettes are inconspicuous. Misinterpretation as schwannoma or astrocytoma is a diagnostic problem and well-documented cases are scarce. The purpose of this report is to document the ependymal features of the neoplasm and to increase awareness of the entity's existence. Biopsy tissues from three patients with tanycytic ependymoma were examined. All tumors consisted of sheets of spindle cells that were positive for glial fibrillary acidic and S-100 proteins. Ultrastructural examination showed characteristic ependymal features, including intracytoplasmic intermediate filaments, prominent intercellular junctions, numerous slender surface microvilli, and microvilli-lined lumina. Accurate recognition of the ependymal nature of this spindle neoplasm requires a high index of suspicion. Because the spindle cells are immu-noreactive with antibodies to both glial fibrillary acidic and S-100 proteins, ultrastructural confirmation of ependymal features is necessary.     

Ovarian ependymoma. A case report

We present the case of a 30-year-old woman who was referred to our institution with an erroneous diagnosis of poorly differentiated carcinoma of the ovary. The patient presented pelvic pain for one year prior to surgery. A second laparotomy revealed a bilateral pure ovarian ependymoma that infiltrated the uterus and presented implants on the omentum. Differential diagnosis included mainly endometrioid and small cell carcinoma of the ovary. Presence of typical ependymal rosettes and positivity to GFAP confirmed the diagnosis of ependymoma. Other teratomatous elements were not observed. Ovarian ependymomas are rare tumors; only eight cases, to our knowledge, have been reported in the literature. They have a favorable prognosis; patients with advanced stage disease are reported alive and well after treatment with surgery and chemotherapy.     

Molecular Genetic Analysis of Ependymal Tumors : NF2 Mutations and Chromosome 22q Loss Occur Preferentially in Intramedullary Spinal Ependymomas

Ependymal tumors are heterogeneous with regard to morphology, localization, age at first clinical manifestation, and prognosis. Several molecular alterations have been reported in these tumors, including allelic losses on chromosomes 10, 17, and 22 and mutations in the NF2 gene. However, in contrast to astrocytic gliomas, no consistent molecular alterations have been associated with distinct types of ependymal tumors. To evaluate whether morphological subsets of ependymomas are characterized by specific genetic lesions, we analyzed a series of 62 ependymal tumors, including myxopapillary ependymomas, subependymomas, ependymomas, and anaplastic ependymomas, for allelic losses on chromosome arms 10q and 22q and mutations in the PTEN and NF2 genes. Allelic losses on 10q and 22q were detected in 5 of 56 and 12 of 54 tumors, respectively. Six ependymomas carried somatic NF2 mutations, whereas no mutations were detected in the PTEN gene. All six of the NF2 mutations occurred in ependymomas of WHO grade II and were exclusively observed in tumors with a spinal localization (P = 0.0063). These findings suggest that a considerable fraction of spinal ependymomas are associated with molecular events involving chromosome 22 and that mutations in the NF2 gene may be of primary importance for their genesis. Furthermore, our data suggest that the more favorable clinical course of spinal ependymomas may relate to a distinct pattern of genetic alterations different from that of intracerebral ependymomas.     

Ependymoma of the sella turcica: a variant of pituicytoma

A broad spectrum of neoplasms affects the sellar region. Among these, gliomas are rare, most being tumors of pituicytes such as granular cell tumor and pituicytoma. Only 4 ependymomas of the human sellar region have been reported to date and all have had classic histologic features. Herein, we describe the clinicopathologic features of a sellar, low-grade ependymoma with unusual histology, but classic ultrastructural features, occurring in an elderly patient and thus expanding the spectrum of reported cases. The literature is reviewed and concepts of histogenesis are explored, particularly an origin in "ependymal pituicytes." The concept that sellar ependymoma is pituicyte-derived is explored.     

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.     

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.     

Myxopapillary ependymoma of the sacrococcygeal region. Report of a case

A case of subcutaneous myxopapillary ependymoma arising in the sacrococcygeal region of a 42-year-old woman is reported. Less than 60 cases of such tumors have so far been described in locations outside the central nervous system. Sacrococcygeal ependymomas are locally aggressive tumors that require a complete and wide surgical excision to prevent recurrences. They tend to metastasize in about 17% of cases.     

Ovarian ependymomas of extra-axial type or central immunophenotypes

We report the differential clinicopathologic and immunophenotypical features of 2 pure ovarian ependymomas of extra-axial type with a predominant microcystic, anaplastic pattern occurring in patients aged 22 and 32 years and a unique myxopapillary pigmented ependymoma that originated within an ovarian mature cystic teratoma in a 35-year-old woman. The latter had a central nervous system phenotype different from that previously reported in ovarian ependymomas of extra-axial types, being negative for estrogen and progesterone receptors, epithelial membrane antigen and cytokeratin 34βE12, cell adhesion molecule 5.2, and cytokeratin 7. Furthermore, its benign behavior contrasted with the aggressive course of the other 2 ependymomas of extra-axial types, in which peritoneal invasion was present at the time of diagnosis. These findings illustrate that both central and extra-axial types of ependymoma show phenotypic variations that may point to either a derivation from different precursors or differentiation along diverse pathways. Thus, whereas ependymomas of extra-axial types would represent neometaplastic phenomena, those originated from the nervous tissue of teratomas resemble central nervous system ependymomas. Moreover, the dissimilarities between central and peripheral types of ependymoma would parallel the phenotypic differences present in primitive neural tumors of the female genital tract.     

Perivascular pseudorosettes in childhood brain tumours: an ultrastructural and immunohistochemical study

Perivascular pseudorosettes (PP) in childhood central nervous system tumours were examined with light and electron microscopy and immunohistochemistry for glial fibrillary acidic protein, S-100 protein and albumin. One kind of PP at light microscopy comprised a central thin-walled vessel surrounded by a thick mantle of eosinophilic fibrillary material and rings of usually regular nuclei. Adjacent tumour tissue was compact. This type was correlated closely with ultrastructural evidence of ependymal differentiation. The central vessel showed continuous endothelium in all. Another type of PP comprised a central vessel of varying thickness surrounded by hyaline material, clearly defined tapering processes, and rings of often irregular nuclei. Adjacent tissue showed extensive edema and microcystic change. Ultrastructurally, this type showed no ependymal differentiation except in one myxopapillary ependymoma. Fenestrated vessels were seen in half of the tumours associated with this kind of PP. It is proposed that variation in vascular permeability, rather than in the structure of tumour cells, is the main cause for the difference in histological appearance of the two types of PP. Fenestrated vessels may also be responsible for the "myxoid" change in myxopapillary ependymomas. The amount of extracellular albumin showed no consistent correlation with the presence of fenestrations in vessels. A variable degree of positivity to GFAP and S-100 protein was seen in the tumours associated with both types of PPs with no clear difference in pattern.     

Complex cytogenetic abnormalities including telomeric associations and MEN1 mutation in a pediatric ependymoma

Ependymomas are neuroectodermal tumors of the brain and spinal cord. Some recurrent cytogenetic aberrations have been reported in these tumors, including alterations involving chromosomes 22, 6, and 11. However, consistent molecular alterations have not been identified in ependymal tumors. We studied a recurrent ependymoma in a 3-year-old patient by standard cytogenetic and molecular analysis of TP53 and MEN1 genes. In the present case, we found many of the cytogenetic features previously described as being recurrent in ependymomas, including unstable telomeric alterations. Furthermore, we detected a novel acquired heterozygous mutation in the MEN1 gene. The chromosomal instability produced by the telomeric alterations and the mutation in the MEN1 gene could be important events in the tumorigenesis of ependymomas.     

Immunohistochemical study of ependymal neoplasms: histological subtypes and glial and epithelial characteristics

Summary An immunohistochemical study on ependymal tumours was performed in order to determine what relationships exist between histological subtypes and epithelial or glial characteristics. Thirty-eight ependymal tumours were examined with antibodies to cytokeratin (CK), epithelial membrane antigen (EMA), transthyretin (TTR) and glial fibrillary acidic protein (GFAP) using the avidin-biotin-complex technique. They included 23 ependymomas, 13 anaplastic ependymomas, and 2 myxopapillary ependymomas. Only 3 of the 23 ependymomas were positive with EMA but 19 reacted with GFAP. None of them were positive with CK. Six of the 13 anaplastic ependymomas were positive with EMA, 3 with CK and 10 with GFAP. Five of the 6 anaplastic ependymomas which had epithelial marker proteins were either negative or weakly positive for GFAP. The present study demonstrates that most benign ependymomas exhibit GFAP positivity while the anaplastic ones tend to suppress their glial nature in favour of epithelial differrentiation. However, ependymal tumours showed few characteristics of choroid plexus cells; only one of the examined cases was positive for TTR.     

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.     

Fine-needle aspiration diagnosis of metastatic anaplastic sacrococcygeal ependymoma to the lungs

Ectopic ependymomas are uncommon neoplasms, and most of them occur in the sacrococcygeal area. They usually present as subcutaneous sacral masses. The most common histological subtype is the myxopapillary. We describe a case of anaplastic sacrococcygeal ependymoma metastatic to the lungs diagnosed by fine-needle aspiration biopsy. Diagn Cytopathol 1996;15:228–230. © 1996 Wiley-Liss, Inc.     

Ovarian and omental ependymomas in peritoneal washings: cytologic and immunocytochemical features

The cytologic findings in peritoneal washings of two women, one of whom had an ovarian ependymoma and the other a primary omental ependymoma, are reported. The ependymomas were characterized by the presence of numerous, isolated, spindle and stellate cells as well as groups of cells forming true rosettes. The tumor cells displayed slightly pleomorphic, round-to-oval eccentric nuclei and abundant fibrillary cytoplasm with tapering cytoplasmic processes. In addition, one of the patients had numerous papillae and cell clusters with associated psammoma bodies indistinguishable from those found in low-grade serous carcinoma. The demonstration of glial fibrillary acidic protein (GFAP) in both cases by immunocytochemical procedures indicates the usefulness of this method in cytologic preparations to confirm the diagnosis of these uncommon neoplasms.