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.     

Pigmented ependymoma with lipofuscin and neuromelanin production

We report an unusual case of ependymoma with pigmentation, a phenomenon that has only been described in a few cases, to our knowledge. This tumor occurred in the fourth ventricle of a 45-year-old man. It showed the typical histologic appearance of ependymoma with perivascular pseudorosettes and rare ependymal rosettes. Some tumor cells contained brown cytoplasmic pigment, which was shown histochemically to represent a mixture of lipofuscin and neuromelanin. The pigment was positive for acid-fast and periodic acid-Schiff stains and was also focally positive for Masson-Fontana and Schmorl stains (bleached by pretreatment with potassium permanganate). In addition, some other tumor cells showed a signet ring morphology as a result of prominent intracytoplasmic vacuolation. Immunohistochemically, all the tumor cells expressed glial fibrillary acidic protein, and rare pigmented tumor cells also expressed HMB-45. Ultrastructural examination showed irregularly shaped heterogeneous electron-dense bodies corresponding to the pigment, and the cytoplasmic vacuoles were formed by dilatation of intracytoplasmic lumens lined by microvilli. Since lipofuscin production can occur in normal ependymal cells and neuromelanin has been suggested to be a melanized form of lipofuscin, it is not surprising that these 2 pigments can be found in ependymoma. In all the previously reported cases, the pigment was shown to represent melanin only. In our case, the HMB-45 positivity in rare tumor cells indicated that there might also be a minor melanin component in the pigment in addition to lipofuscin and neuromelanin.     

Clear-cell Ependymoma of the Cerebellum: A Case Report

A case of clear-cell ependymoma occurring in the cerebellum of a 3-year-old girl is reported. Light-microscopically, the tumor consisted mainly of clear cells with a perinuclear halo and showed some vague perivascular pseudorosettes, not true rosettes. In addition, the histological features of anaplasia, characterized by increased mitosis and focal pseudopalisading necrosis, were also observed. Immunohistochemically, the tumor cells were focally positive for glial fibrillary acidic protein and weakly positive for epithelial membrane antigen. Ultrastructurally, the intermediate junctions and rudimentary cilia confirmed the ependymal differentiation. Fifteen cases of infratentorial clear-cell ependymoma have been reported to date, and this case is the second childhood tumor among them, to the best of the authors' knowledge.     

Clear-cell ependymoma of the cerebellum: a case report

A case of clear-cell ependymoma occurring in the cerebellum of a 3-year-old girl is reported. Light-microscopically, the tumor consisted mainly of clear cells with a perinuclear halo and showed some vague perivascular pseudorosettes, not true rosettes. In addition, the histological features of anaplasia, characterized by increased mitosis and focal pseudopalisading necrosis, were also observed. Immunohistochemically, the tumor cells were focally positive for glial fibrillary acidic protein and weakly positive for epithelial membrane antigen. Ultrastructurally, the intermediate junctions and rudimentary cilia confirmed the ependymal differentiation. Fifteen cases of infratentorial clear-cell ependymoma have been reported to date, and this case is the second childhood tumor among them, to the best of the authors' knowledge.     

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.     

Case of clear cell ependymoma of medulla oblongata: clinicopathological and immunohistochemical study with literature review

Clear cell ependymoma has been included in the WHO classification of the central nervous system in 1993, after the first report by Kawano et al. Since then, only a few cases have been reported. Most clear cell ependymoma cases reported in the literature so far were located in the supra-tentorial compartment and/or cerebellum, and one case was in the cervical spinal cord. We report a case of clear cell ependymoma whose histological features were sufficient for the diagnosis and was unusually located in the fourth ventricle originating from the medulla oblongata. The tumor showed uniform tumor cells with perinuclear halo, nuclei being centrally located. Most of the tumor cells were arranged as perivascular pseudorosettes, and no ependymal canals or rosettes were evident. Mitotic figures were not frequent. Immunohistochemically, the tumor cells were strongly reactive for glial fibrillary acidic protein and vimentin, and weak and dot-like positive for epithelial membrane antigen. Clear cell change of the tumor cells appeared to be fixation artifact because this feature was not evident in the frozen section.     

Papillary ependymoma: its differential diagnosis from choroid plexus papilloma.

Papillary ependymoma is a rare variant of ependymoma and often gives rise to confusion with choroid plexus papilloma because of topographic, light microscopic and ultrastructural similarities. Here, we report two cases of papillary ependymomas regarding their unique clinicopathologic features and differential points from choroid plexus papilloma. Brain MRI revealed a large mass in the left lateral ventricle in one case and a 3cm sized mass in the pineal area and the 3rd ventricle in the other. Microscopically, the tumor was characterized by papillary and tubular structures. Immunohistochemically, the tumor cells in both cases expressed cytokeratins(CK22 and CAM 5.2) but did not express glial fibrillary acidic protein(GFAP), vimentin, epithelial membrane antigen, and S100 protein. This is a very unusual immunohistochemical feature for papillary ependymoma. Ultrastructurally, the tumor showed a mosaic pattern of tumor cells with frequent intercellular microrosettes having a few stubby microvilli, a few cilia and zonulae adherentes. The cytoplasmic processes were markedly reduced compared to conventional ependymoma. The cytoplasm did not contain intermediate filaments. Interestingly, the mitochondria showed abnormal features with a pleomorphic shape and abnormal cristae in both cases. These ultrastructural features enabled differentiation between papillary ependymoma and choroid plexus papilloma in addition to the light microscopic findings.     

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.     

Multi-disciplinary treatment of a rare pelvic cavity ependymoma

Ependymomas usually develop from neuroectodermal organs. Here, we present an ependymoma arising from the pelvic cavity. A 27-year-old Korean female was admitted to the hospital with a sensation of abdominal fullness. Imaging studies revealed a huge heterogeneous nodular mass in the pelvis and lower abdomen. Laparotomy showed that two large masses with multiple nodules were located between the uterus and rectum and uterus and bladder, respectively. Histologically, the tumor was characterized by compact columnar neoplastic cells divided by fibrovascular septae. The neoplastic cells formed true ependymal rosettes and perivascular pseudorosettes. Immunohistochemical staining showed a strong positive reaction for glial fibrillary acidic protein (GFAP) and vimentin and a partial positive reaction for S100 and EMA. The tumor was thus diagnosed as an ependymoma arising from the pelvic cavity. The patient was treated with a debulking operation and chemotherapy based upon the in vitro chemosensitivity test results. The patient was free of cancer for 4 years following surgery. This is a rare case of extraneural ependymoma for which an in vitro chemosensitivity test was critical in determining the multidisciplinary approach for treatment.     

Signet-ring cell ependymoma: case report with implications for pathogenesis and differential diagnosis

We describe light microscopic, immunohistochemical and ultrastructural features of a signet-ring cell ependymoma (WHO grade II) identified in a surgically resected left cerebellar cystic tumor from a 64-year-old man. Part of the tumor showed clear-cell differentiation. Immunohistochemical coexpression of glial fibrillary acidic protein and epithelial membrane antigen, characteristic of ependymoma, was detected in both components. Sinuous intermediate junctions, cytoplasmic lumina, and scant astroglial filaments were demonstrated by electron microscopy. Signet-ring cell change was shown to be induced by disproportionate cavitation of either microvillus-bearing cytoplasmic lumina or microrosettes. The staining qualities of clear cells were mainly due to paucity and degeneration of subcellular organelles. Therefore, signet-ring cell ependymomas represent a unique anomaly of intra- and extracellular compartmentalization to be distinguished from various unrelated forms of cytoplasmic volume increase, resulting in an optically similar "empty" appearance of tumor cells. As a clinically relevant consequence, signet-ring cell ependymoma must be included in the differential diagnosis of primary or metastatic neoplasms of the central nervous system, having in common a phenotype characterized by overdeveloped optically lucent cell bodies.     

Highly anaplastic extraventricular ependymoma arising in an adult,mimicking metastatic adenocarcinoma with heavy stromal inflammation and emperiporesis

We report a case of extraventricular ependymoma arising in a 50-year-old woman that took an aggressive clinical course with recurrence three times. The initial tumor was a well-circumscribed nodule in the right temporal white matter measuring 2 cm in diameter. It showed variegated histological findings mimicking metastatic adenocarcinoma: an epithelioid arrangement of highly pleomorphic cells with pseudopapillary structures and perivascular pseudorosettes, and bizarre multinucleated giant cells with occasional emperiporesis surrounded by abundant mononuclear inflammatory cells, as well as a focal small area of conventional ependymoma. Emperiporesis and abundant mononuclear cell infiltration were not previously described in an ependymoma. The recurrent tumors predominantly showed an epithelioid pattern with frequent formation of astroblastoma-like pseudopapillary structures. Neoplastic cells were markedly atypical and had characteristic intracytoplasmic eosinophilic inclusion bodies. Much of the cells in both the initial and recurrent tumors showed a positive immunostaining for glial fibrillary acidic protein (GFAP) with accentuation to the cytoplasmic processes of the pseudorosettes and pseudopapillary structures. Epithelial membrane antigen (EMA) highlighted the epithelial differentiation of the tumor cells, while cytokeratin was completely negative. Although this tumor might be classified to at least WHO grade III from the histology and aggressive behavior, the exact grading is still controversial because of the rarity of such cases.     

Ovarian ependymoma

A 76-year-old woman presented with a large calcifying mass behind the bladder. The tumor contained solid areas of a yellowish white color. Microscopic examination revealed highly cellular solid areas with many typical ependymal perivascular pseudorosettes. The cells contained uniform round-to-oval nuclei, some of which had irregular contours, clumped chromatin and occasional prominent nucleoli. There was widespread geographic necrosis and there were 5 atypical mitotic figures per 10 high power fields. Glial fibrillary acidic protein (GFAP) immunopositivity was observed in the cytoplasm of the tumor cells. Based on the histopathologic and immunohistochemical features, the tumor was diagnosed as an anaplastic ependymoma. This is to the best of our knowledge only the second case of anaplastic ependymoma in the medical literature.     

Epithelial differentiation in medulloblastoma: comparison with other embryonal tumors of neuroectodermal origin

Three cases of medulloblastoma characterized by epithelial differentiation are described in patients 6-months-, 1-month- and 8-years-old. Histologically, tumors from the two infant patients showed a perivascular arrangement without apparent radiated cytoplasmic processes from the vessels. Tumor cells displayed round and/or pleomorphic vesicular nuclei and a more abundant eosinophilic cytoplasm than that found in classic medulloblastoma. Neither Homer-Wright rosettes nor ependymal or ependymoblastic rosettes were noted in these tumors. The tumor in the 8-year-old patient exhibited a classic medulloblastoma component intermingled with abundant eosinophilic cytoplasm forming a tubular structure. Immunohistochemically, tumor cells in all cases were positive for cytokeratin, synaptophysin, and vimentin. In the third case involving the 8-year-old patient, epithelial tumor cells were positive for cytokeratin, whereas classic medulloblastoma components were negative for cytokeratin. Positive staining for melanoma-specific antigen was seen only in the third case, where strong reactivity of tumor cells formed a tubulus. However, the classic medulloblastoma component was negative for melanoma-specific antigen. Ultrastructurally, basal laminae were observed around tumor cells in the 6-month-old patient. These morphological and immunohistochemical features suggest that medulloblastoma with epithelial differentiation is a rare but distinct variant of medulloblastoma, and that some of these tumors should show differentiation in ocular pigment epithelium.     

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.     

Ependymal variant of dysembryoplastic neuro-epithelial tumor

Dysembryoplastic neuro-epithelial tumors (DNET) are glioneuronal tumors with a common astrocytic or oligodendroglial differentiation. We report a case of DNET with an ependymal differentiation. A 13 years-old girl had refractory focal seizures for 3 years. Successive MRI showed a stable cortical lesion of the right temporal lobe with DNET characteristics. The lesion was resected. Histological examination revealed a pure ependymal differentiation characterized by perivascular pseudorosettes containing EMA immunoreactive cells. Mib1 positive cells were absent. In spite of histologic features of ependymoma, this tumor showed clinical, radiological and behaviour characteristics of DNET. We are not aware of any other case of DNET with ependymal differentiation in the literature. Our observation suggests that the glial component of DNET may show an ependymal differentiation.     

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.     

伸展细胞型室管膜瘤的病理学观察

目的 探讨伸展细胞型室管膜瘤的临床病理特点、诊断及鉴别诊断。方法 对6例伸展细胞型室管膜瘤进行光镜、免疫组化、特殊染色、电镜观察并结合文献进行分析。结果 肿瘤主要由长梭形细胞构成,呈束状交错状、车辐状排列,可见围绕血管分布,形成假菊形团。瘤细胞呈单极或双极突起细长,分化好,核分裂象罕见,未见坏死。免疫组化标记瘤细胞vimentin强阳性,GFAP、S-100蛋白、EMA阳性,Syn和HHF35阴性。超微结构观察见较多的中间细丝和发育好的的桥粒,以及细胞间腔隙内有微绒毛。结论 伸展细胞型室管膜瘤起源于脑室附近伸展细胞,是罕见的室管膜瘤的一个亚型,在诊断上往往易与其它梭形细胞为主的神经上皮肿瘤相混,病理诊断依赖于组织学、免疫组化、特殊染色和电镜观察。免疫组化和特殊染色在鉴别诊断中有重要价值。     

Primary extraneural myxopapillary ependymoma of the broad ligament

Primary extraneural ependymomas are rare tumors that arise in ectopic sites, including pulmonary, sacrococcygeal region, ovarian, and paraovarian tissues. Four such ependymomas reported in the literature involve the paraovarian tissues, including 2 broad ligament ependymomas. Here we describe a myxopapillary ependymoma of the broad ligament in a 22-year-old woman, which may be the first tumor of this type to be reported in this location. Cytology, histology, cytochemistry, immunohistochemistry, and flow cytometry ploidy analysis are studied and described. Identification of perivascular ependymal rosettes, ependymal canals, vimentin and glial fibrillary acidic protein immunoreactivity, cytochemical staining of blepharoplasts or terminal bars by phosphotungstic acid hematoxylin, and presence of multiple foci of myxoid degeneration among the ependymal rosettes characterized a myxopapillary ependymoma.     

November 2004: intradural mass of the cauda equina in a woman in her early 60s

November 2004. A 63-year-old woman presented with slowly aggravating lower back pain and recent urinary urge incontinence. MRI revealed a sharply-delineated, partly cystic intradural mass with inhomogenous contrast-enhancement and ectatic vessels at the upper pole. An ependymoma was suspected, and the tumor was resected in toto. Histologically, at first glance, the tumor strongly resembled an ependymoma, showing a monomorphic cellular pattern, perivascular pseudorosettes and ependymal canal-like structures. However, the finding of a delicate collagen capsule, compartmentation of tumor cells into zellballen and the presence of ganglionic cells were untypical. These features were indicative of a paraganglioma with a gangliocytic component. Immunoreactivity of the tumor cells for neuroendocrine antigens, the detection of GFAP-positive sustentacular cells and the ultrastructural confirmation of neurosecretory granules substantiated this diagnosis. The clinical, radiological and morphological similarity between ependymomas, which are far more common in the cauda equina region than paragangliomas, has led to substantial diagnostic confusion in the past.     

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.