Clear Cell Ependymoma Research Articles

PATH-16. HISTOPATHOLOGICAL EPENDYMOMA VARIANTS ARE ASSOCIATED WITH DISTINCT CLINICAL PARAMETERS AND DNA METHYLATION PATTERNS

Abstract According to the current WHO classification, ependymal tumors are classified as subependymomas, myxopapillary ependymomas, classic ependymomas, anaplastic ependymomas and RELA-fusion positive ependymoma (RELA-EPN). Among classic ependymomas, the WHO defines rare histological variants, i.e. the clear-cell, papillary, and tanycytic ependymoma. In parallel to this WHO classification scheme, DNA methylation patterns can distinguish nine distinct molecular ependymoma subgroups, some of which tightly overlap with certain histopathological subgroups, e.g. subependyomas or myxopapillary ependymomas. Since very little is known about the molecular background of histological classic ependymoma variants, we analyzed histomorphology, clinical parameters and global DNA methylation patterns of diagnosed tanycytic ependymomas (n=12), clear-cell ependymomas (n=14) and papillary ependymomas (n=19). Surprisingly, up to 42% of these variants did not match to ependymomas using a previously published DNA methylation-based classifier for brain tumors. Among the tumors with a match to one of the nine known ependymoma methylation classes, tanycytic ependymomas were predominantly located in the spine, but showed diverse molecular methylation patterns. Most clear-cell ependymomas showed a common histomorphology, were found supratentorially and fell into the methylation class of RELA-EPN. Papillary ependymomas showed a “papillary”, “trabecular” or “pseudo-papillary” growth pattern. Interestingly, a true papillary growth pattern was strongly associated with the molecular class B of posterior fossa ependymoma (PFB), but tumors displayed DNA methylation sites that were significantly different when compared to PFB ependymomas without papillary growth. Our results show that the diagnosis of classic histological ependymoma variants can be challenging. While clear-cell and papillary ependymomas harbor common molecular features, tanycytic ependymoma may not represent a molecularly distinct subgroup.

Molecular characterization of histopathological ependymoma variants.

According to the WHO classification, ependymal tumors are classified as subependymomas, myxopapillary ependymomas, classic ependymomas, anaplastic ependymomas, and RELA-fusion-positive ependymomas (RELA-EPN). Among classic ependymomas, the WHO defines rare histological variants, i.e., the clear cell, papillary, and tanycytic ependymoma. In parallel, global DNA methylation patterns distinguish nine molecular groups, some of which tightly overlap with histopathological subgroups. However, the match of the aforementioned histological variants to DNA methylation classes remains unclear. We analyzed histomorphology, clinical parameters, and global DNA methylation of tumors with the initial histological diagnoses of tanycytic (n = 12), clear cell (n = 14), or papillary ependymoma (n = 19). Forty percent of these tumors did not match to the epigenetic profile of ependymomas, using a previously published DNA methylation-based classifier for brain tumors. Instead, they were classified as low-grade glioma (n = 3), plexus tumor (n = 2), CNS high-grade neuroepithelial tumor with MN1 alteration (n = 2), papillary tumor of the pineal region (n = 2), neurocytoma (n = 1), or did not match to any known brain tumor methylation class (n = 8). Overall, integrated diagnosis had to be changed in 35.6% of cases as compared to the initial diagnosis. Among the tumors molecularly classified as ependymoma (27/45 cases), tanycytic ependymomas were mostly located in the spine (5/7 cases) and matched to spinal or myxopapillary ependymoma. 6/8 clear cell ependymomas were found supratentorially and fell into the methylation class of RELA-EPN. Papillary ependymomas with a positive ependymoma match (12/19 cases) showed either a "papillary" (n = 5), a "trabecular" (n = 1), or a "pseudo-papillary" (n = 6) growth pattern. The papillary growth pattern was strongly associated with the methylation class B of posterior fossa ependymoma (PFB, 5/5 cases) and tumors displayed DNA methylation sites that were significantly different when compared to PFB ependymomas without papillary growth. Tumors with pseudo-papillary histology matched to the methylation class of myxopapillary ependymoma (4/6 cases), whereas the trabecular case was anatomically and molecularly a spinal ependymoma. Our results show that the diagnosis of histological ependymoma variants is challenging and epigenetic profiles may improve diagnostic accuracy of these cases. Whereas clear cell and papillary ependymomas display correlations between localization, histology, and methylation, tanycytic ependymoma does not represent a molecularly distinct subgroup.

Clear cell ependymoma with an atypical localisation mimicking intracranial glial tumour: A case report

Introduction Ependymomas are tumours of the central nervous system, originating from the ependymal cells which line the ventricles and the central canal of the spinal cord. Less than one-third of all ependymomas are located supratentorially, most of the time in close proximity to the ventricle walls around the trigone area. Case 34 year-old patient came into the outpatient clinic with headache and seizure. After radiological examination, she was operated on for an extra axial lesion located next to the left frontal gyrus. Pathological examination revealed a clear-cell ependymoma, WHO grade II, after which follow-up without any additional therapy was decided since the patient was young and total resection had been achieved. Conclusion Because of low incidence, radiological diagnosis is difficult. Even if total resection has been achieved, long term follow-up should be planned because of high rates of recurrence.

The Clinical Results of Radiation Therapy for Spinal Cord Ependymoma with Adverse Prognostic Features: A Single-Institution Experience

The primary treatment for spinal ependymoma is surgical resection. However, some cases cannot achieve complete resection because of either neurological compromise or disseminated feature. In these cases, radiotherapy (RT) is generally recommended, however, the role of RT has not been fully elucidated. This study evaluated the clinical outcome of RT on spinal ependymoma with the adverse feature, such as incomplete resection or disseminated disease. Between 1991 and 2016, 25 patients with spinal cord ependymoma treated with radiotherapy (RT) in a single institution were retrospectively reviewed. All except one patient with anaplastic ependymoma had gross disease in spinal MRI before RT. Eighteen (64%) underwent subtotal resection, while 6 (24%) did not undergo surgical resection. Six (24%) had multiple disseminated diseases. World Health Organization grade was I in 12 patients, II in 12 patients, and III in 1 patient. Nineteen (76%), 5 (20%), and 1 (4%) patients received RT to the localized disease, craniospinal area, and whole spinal cord with posterior cranial fossa, respectively. Median RT dose was 50.4 Gy (range, 44.0–59.4). With a median follow-up period of 49 months (range, 9–321 months), disease progression was observed in 4 patients, of whom 2 had clear cell ependymoma (grade II), and 2 had classic ependymoma (grade II). There was no failure or death in 12 patients with grade I ependymoma. Of 6 patients with disseminated disease, 3 had not experienced disease progression with follow-up of 111 months, 45 months, and 49 months, respectively. Of 18 patients with localized disease, 16 had not experienced disease progression until the last follow-up. In all patients, the 2- and 5-year progression-free survival rates were 91.7% and 79.6%, respectively, and overall survival rates were 95.7% and 83.7% respectively. Of patients with grade I ependymoma, the 2- and 5-year overall survival rates were 100%, while those were 91.7% and 69.4%, respectively, in patients with grade II or III ependymoma. Twelve (48%) showed improved neurologic function after RT. Late toxicity (hypopituitarism) occurred in 1 patient who received craniospinal irradiation. Favorable PFS and OS could be achieved with RT in spinal ependymoma with adverse features. RT appears to be an effective treatment option for spinal ependymoma in cases when complete tumor removal cannot be achieved.

Prognostic Implications of Histological Clear Cells in High-Grade Intracranial Ependymal Tumors: A Retrospective Analysis from a Tertiary Care Hospital in Pakistan.

Background:Clear cell variant in ependymal tumors is rare. We aimed to compare the features and outcome of the World Health Organization (WHO) Grade 3 ependymal tumors with clear cells to the WHO Grade 3 classic anaplastic ependymoma (AE).Materials and Methods:A retrospective cohort study conducted at the Department of Neurosurgery, Aga Khan University, Pakistan, from 2003 to 2013. The medical records and radiology of patients with proven histopathology were reviewed. The analysis was done on SPSS 20.Results:Nine cases of clear cell variant and 23 cases of classic AE were found, both of which combined equated to 4% of the total tumor burden in 11 years. The median age of clear cell ependymoma (CCE) and AE were 49 and 37 years, respectively. Presenting symptoms included headache in 66% of CCE and 63% in AE, raised intracranial pressure accounting for 33% of CCE and 54% of AE, dizziness in 22% CCE and 39% AE, while seizures presented equally in both. Supratentorial location was observed in 77% CCE and 48% AE. Both showed hypointense signals on T1-weighted images of magnetic resonance imaging (MRI) while T2-weighted images showed hyperintensity in all cases of CCE but only 80% of AE. MRI characteristics such as the presence of cystic component were found in 89% of CCE and 68% of AE, necrosis in 33% CCE, and 22% AE, hemorrhagic in 22% CCE and 9% AE, and equivalent contrast enhancement. Gross total resection was achieved in 5 (55%) patients of CCE, compared to 6 (26%) patients in AE. Subtotal resection was done in 4 (44%) patients of CCE and 15 (65%) patients of AE. Radiotherapy was given to 5 (55%) patients of CCE and 12 (52%) patients of AE. Recurrence was observed in 77% cases of CCE and 70% of AE, with metastasis in 29% of AE and in only one patient of CCE. Repeat surgery was done in 3 (33%) cases of CCE and 8 (35%) cases of AE. Median progression-free survival and overall survival were 9 and 13 months, respectively, in CCE while 14 and 18 months, respectively, for AE.Conclusion:Clear cells in the WHO Grade 3 ependymal tumors are found mainly in a comparatively older adult population with a predilection for supratentorial location and are more aggressive in behavior with poorer outcome than AE.

Sellar/suprasellar extraventricular neurocytoma

Objective To explore the clinicopathological features of extraventricular neurocytoma located in the sellar/suprasellar region. Methods The clinical manifestations, neuroimaging, histopathological, immunohistochemical and molecular genetic features were retrospectively analyzed in one case of sellar/suprasellar extraventricular neurocytoma, and the related literatures were reviewed. Results A 27-year-old female presented with intermittent headache, accompanied by blurred vision for 5 months. Head MRI demonstrated a mass with a well-defined margin measuring 3.80 cm × 2.50 cm × 3.40 cm located in the sellar/suprasellar region. The tumor showed isointense to hyperintense signals on T 1 WI and hyper-hypointense mixed signals on T 2 WI, and slightly hyperintense signal on diffusion-weighted imaging (DWI). The pituitary was not shown. A transsphenoidal sellar tumor resection, cerebrospinal fluid (CSF) rhinorrhea repairing and optic decompression were performed. The mass was lightly yellow and tough with abundant blood supply and filled with old hemorrhage. The pituitary tissue was pushed to the left rear. Microscopy examination showed a diffuse invasive growth pattern with neuropil background in some area. The tumor cells were uniform on size and shape with round to oval, exquisite and hyperchromatic nuclei. No mitosis was found. Immunohistochemical staining showed the tumor cells were positive for neuronal nuclei (NeuN) and thyroid transcription factor-1 (TTF-1) in nuclei, calretinin (CR) in nuclei and cytoplasm, synaptophysin (Syn), chromogranin A (CgA), E-cadherin, matrix metalloproteinase-9 (MMP-9) in cytoplasm, and focally positive for S-100 protein (S-100) in nuclei, and neurofilament protein (NF), cytokeratin 8 (CK8) and vimentin (Vim) in cytoplasm. The Ki-67 labeling index was about 3%. The tumor tissue was negative for reticular fiber staining. Molecular genetic analysis showed that isocitrate dehydrogenasel (IDH) gene was not mutated, and 1p/19q was intact in tumor cells. The final pathological diagnosis was extraventricular neurocytoma, WHO grade Ⅱ. Conclusions Extraventricular neurocytoma located in the sellar/suprasellar region is very rare. The histological features are similar to central neurocytoma in ventricle. Tumor cells were in diffusely invasive growth and were uniform in size and shape, with round nuclei. Fibrillary areas mimicking neurophil and branching thin-walled capillaries can be seen. The differential diagnosis includes pituitary adenoma, oligodendroglioma, clear cell ependymoma, and so on. DOI: 10.3969/j.issn.1672-6731.2017.12.009

Cerebellar ependymoma with overlapping features of clear-cell and tanycytic variants mimicking hemangioblastoma: a case report and literature review

BackgroundImaging and histology of clear-cell ependymoma and cerebellum-based hemangioblastoma are similar; distinguishing between them is a diagnostic challenge.Case presentationA 62-year-old Chinese woman presented with an intermittent headache of 8 years’ duration. Computed tomography and magnetic resonance imaging revealed a mass in the cerebellum. Neurological imaging suggested hemangioblastoma (HB). Histologically, the tumor included cellular and paucicellular areas, in which cells were arranged in nests or diffusely distributed; and a highly vascular area, in which tumor cells were arranged in clusters and separated by capillaries. At low magnification, the tumor mimicked cellular HB, but at high magnification, tumor cells showed clear cytoplasm instead of the vacuolated cytoplasm typically observed in HB. Moreover, spindly, bipolar elements resembling tanycytes were observed within the nest structures. Although these features indicated the possibility of ependymoma, neither true ependymal rosettes nor an ependymal-lined profile was observed. The tumor was characterized by prominent vascularity, but glomeruloid formation was absent. We saw pleomorphism in foci of some tumor giant cells, but pathologic mitosis and palisaded necrosis were absent. Most tumor cells were positive for glial fibrillary acidic protein and S100. Epithelial membrane antigen was expressed with a paranuclear dot-like or a ring-like pattern. The Ki-67 index was approximately 2%. Considering the patient’s symptom, neurological imaging, and pathological findings, she was diagnosed as cerebellar ependymoma (WHO grade II).ConclusionsHere, we report a case of ependymoma with overlapping clear-cell and tanycytic features, and review the literature to evaluate its real incidence. Pathologists should consider this rare diagnosis when confronted with a similar presentation.

Supratentorial clear cell ependymomas with branching capillaries demonstrate characteristic clinicopathological features and pathological activation of nuclear factor-kappaB signaling.

Clear cell ependymoma is one of the 4 main histological subtypes of ependymomas defined by the World Health Organization (WHO) classification of tumors of the CNS. DNA methylation profiling can distinguish 4 subgroups of intracranial ependymomas, including supratentorial (ST) ependymomas with Yes-associated protein 1 fusion (YAP1), ST ependymomas with fusion of v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA), posterior fossa ependymomas with balanced genome, and posterior fossa ependymomas with chromosomal instability. In addition, trisomy 19 is a genomic hallmark of ependymomas with rich branching capillaries. However, the relation of histological and molecular subtypes is unclear. Here, we report a series of 20 ependymomas histologically defined by clear cells and branching capillaries. We observed a strong male predominance. Median age at surgery was 10.4 years (range, 0.8-68.4). All cases were ST, cortical, contrast enhancing, and most often frontal, cystic, and calcified. All tumors qualified as WHO grade III. Some of them exhibited neuronal differentiation. Trisomy 19 was recorded in 13 cases. All samples strongly accumulated p65RelA protein within nuclei, indicating pathological activation of the nuclear factor-kappaB pathway. We identified causative C11ORF95-RELA fusion in almost all cases. Median progression-free survival and overall survival were 11.4 years (95% CI: 5.1-17.8) and not reached, respectively. ST clear cell ependymomas with branching capillaries display characteristic clinicopathological features and are associated with pathological activation of nuclear factor-kappaB signaling, which may indicate a potential novel target for therapy in these patients.

Third Ventricular Ependymoma Mimicking Foster Kennedy Syndrome- A Case Report

Authors' contributions This work is carried out in collaboration of all authors. Authors ELT and RK designed the study, wrote the first draft of the manuscript and managed the literature search. Authors RK, WHWH and LSAT revised it critically for intellectual contents. Authors ELT, RK, WHWH and TLK were involved in the assessment and treatment of the patient. All authors read and approved the final manuscript. ABSTRACT Aims: To report a case of a third ventricular tumour mimicking Foster Kennedy Syndrome in a young adult. Presentation of Case: A 21-year-old female presented with bilateral blurring of vision with preceded by generalized headache, nausea and vomiting. Fundoscopy revealed optic nerve atrophy of the right eye and a swollen optic disc on the left in keeping with features of Foster Kennedy Syndrome. MRI of the brain revealed a third ventricular tumor extending into the suprasellar region with hydrocephalus. Surgical excision of the tumour was done and the subsequent histopathological report confirmed it to be a clear cell ependymoma. Discussion: Foster Kennedy syndrome is a rare clinical constellation describing a pattern of ocular findings typically related to extraaxial tumours involving the anterior skull base. It is characterized

MS-10 * CLEAR CELL EPENDYMOMA: A RARE VARIANT FIRST TIME REPORTED BY A TERTIARY CARE HOSPITAL IN PAKISTAN

OBJECTIVES: Clear Cell Ependymoma has never been reported from Pakistan. We aim to see the features and outcomes of this rare entity in Pakistan. METHODS: A retrospective case-series conducted at the Department of Neurosurgery, Aga Khan University. The medical record files of patients with Clear Cell Ependymoma from 2003 - 2012 were reviewed, MRI/C.T scans and Histopathological slides were reviewed. Patients lost to follow-up were contacted on telephone. Analysis was done on SPSS 20. RESULTS: Nine cases of CCE were found. The median age was 47 years. The symptoms included Headache 66.6%, seizures, hemiparesis, raised ICP 33.3% patients. Seven patients had supra-tentorial and 2 had infra-tentorial tumor. MRI showed hypo-intense signals on T1 and hyper-intense signals on T2 weighted images. Contrast enhancement was found in 7 patients (77.8%). Histopathology: Clear cells were found frequently in 5 cases. Immunohistochemistry showed GFAP and EMA positivity in all cases. Ki-67 showed high proliferative index in 5 patients. WHO class was II in 1 patient and III in 8 patients. Gross total resection was done in 5 (55.5%), Subtotal Resection in 4 patients (44.4%). 5 patients underwent radiotherapy, 3 patients underwent Radiotherapy + chemotherapy, post-surgery. Recurrence was there in 7 patients. Repeat surgery was done in 3 patients. Six patients died of the disease. Median Progression free survival was 8 months (range 5-28 months), the median overall survival was 15 months (range 6-52months). CONCLUSION: CCE is a significantly aggressive tumor in Pakistan with prognosis worse than other parts of the world.

Functionally tailored transcortical approach of deep-seated lesions: An alternative to the transulcal approach? A technical case report

It is commonly believed that sulci offer a natural path to reach deep-seated lesions. However, it has also been argued that this approach carries a risk of damaging the vessels during the opening of the sulcus. We therefore were prompted to test the possibility of finding a transcortical path identified as non-functional by intraoperative brain mapping. A successful resection is presented of a left posterior isthmus clear cell ependymoma through a selected corridor based on functional mapping in an awake patient. MRI performed at 12 months showed no tumour recurrence. Pre- and postoperative extensive testing confirmed an improvement of the patient's cognitive functions. Therefore, we were able to demonstrate the feasibility of a functionally tailored transcortical approach as an alternative to the transulcal approach for deep-seated lesions. This concept should be validated in a larger patient series.

Anaplastic oligodendroglioma arising from the brain stem and featuring 1p/19q co‐deletion

With respect to localization, oligodendrogliomas are characterized by a marked preponderance of the cerebral hemispheres. Outside these typical sites, any tumor histopathologically reminiscent of oligodendroglioma a priori is likely to represent one of its morphological mimics, including clear cell ependymoma, neurocytoma, pilocytic astrocytoma or glioneuronal tumors. This is particularly relevant as several of the latter are in principle curable by surgery. Among extrahemispherical sites, bona fide oligodendroglioma - as characterized by loss of heterozygosity (LOH) of chromosome arms 1p and 19q - so far has not been documented to occur in the brain stem. Here, we report the case of a 55-year-old female patient with an anaplastic oligodendroglioma (WHO grade III) of the brain stem and cerebellum diagnosed by stereotactic biopsy and featuring combined LOH of 1p and 19q. A morphological peculiarity was a population of interspersed tumor giant cells, a phenomenon that has been referred to as polymorphous oligodendroglioma. Our findings confirm the notion that - although very infrequently - true oligodendrogliomas do occur in the infratentorial compartment.

Clear Cell Ependymoma in a Dog

A 13-year-old, mixed breed dog presented with a 1-month history of seizures. Magnetic resonance imaging of the brain revealed a 2.2×1.0×0.9cm ovoid and elongate cystic mass within the white matter of the left frontal lobe extending caudally from the cribriform plate to the rostral left lateral ventricle. Three fractions of stereotactic radiotherapy were administered and resulted in reduction of the volume of the tumour; however, the clinical signs failed to improve. On post-mortem examination, a single mass 1.5×0.3×1cm was found within the left frontal lobe. It consisted of gelatinous, grey, friable tissue bordering a central empty cavity. Microscopical evaluation revealed polygonal neoplastic cells with distinct cytoplasmic borders and one or more intracytoplasmic solid, brightly eosinophilic, sharply defined globules. Immunohistochemically, the neoplastic cells expressed glial fibrillary acidic protein and S100 but were negative for pan cytokeratin, vimentin, olig-2 and synaptophysin. Ultrastructurally, neoplastic cells had dense whorls of intracytoplasmic intermediate filaments and were connected by multiple intermittent long zonula adherens-type junctions. Based on these findings, a diagnosis of clear cell ependymoma was made. This is the first report of this subtype in the dog.

Clear cells are associated with proliferative activity in ependymoma: a quantitative study

Ependymomas comprise WHO Grade (G) II tumors (ependymomas) and WHO Grade III tumors (anaplastic ependymomas). Clear cell ependymoma, a subtype of ependymoma characterized by proliferation of clear cells, generally corresponds to WHO Grade III. On the other hand, clear cells are common in otherwise conventional ependymomas. This study aims to reveal the direct relationship between clear cells and proliferative activity in ependymomas. A total of 14 ependymomas with clear cells, comprising 6 WHO Grade II tumors and 8 Grade III tumors, were studied. The sections were stained with hematoxylin and eosin (H&E), and also immunostained with PHH3, a marker of mitosis, and MIB-1, an anti-Ki-67 antibody. Each case was assessed on H&E sections for necrosis and microvascular proliferation, and semi-quantified for clear cells in an increasing order as Grades I - III (clear cell grade). Mitoses were counted on H&E and PHH3-stained sections, under a light microscope, in 4 areas showing a high amount of mitosis. The MIB-1 index was manually determined on 4 images captured from the area showing the highest amount of Ki-67-positive nuclei. The results were as follows: 1) Necrosis or microvascular proliferation was present irrespective of the clear cell grade (amount of clear cells). 2) A higher amount of clear cells was associated with a higher proliferative activity. These results indicate that clear cells could be an independent prognostic factor other than necrosis, microvascular proliferation, or the WHO grade. It seems important to assess clear cells, apart from the concept of clear cell ependymoma, when diagnosing an ependymoma.

Anaplastic Clear Cell Ependymoma of the Conus Medullaris and Cauda Equina in a 3-year-old Child

Only a minority of ependymomas present in the spinal cord. We report on a child with recurrence of a rare anaplastic clear cell type of ependymoma. This was initially misdiagnosed as a World Health Organization grade I myxopapillary ependymoma because this type of ependymoma occurs more commonly and the magnetic resonance imaging features and location at the conus medullaris were considered characteristic.

A case of anaplastic clear-cell ependymoma presenting with high erythropoietin concentration and 1p/19q deletions

We describe a 19-year-old woman with onset of epileptic seizure, and a small mural nodule and multicystic lesions with severe brain edema located in the right frontal lobe. At surgery, the tumor and a clear margin was removed, and symptoms improved postoperatively. Extended local radiotherapy (60Gy) was performed. Histopathological examination revealed oligodendroglioma-like tumor cells with a perinuclear halo. The tumor cells extended processes toward CD34-positive proliferating vessels, which resemble a basement membrane. These proliferating vessels formed a tumor membrane so that there was a clear margin between the tumor and brain tissue. Tumor cells were positive for epithelial membrane antigen in a dot-like pattern. MIB-1 staining index was 50.6%. Electron microscopy showed cilia and zipper-like junctions, and anaplastic clear-cell ependymoma grade III was diagnosed. A characteristic of the case was formation of a tumor membrane by proliferating tumor blood vessels. Fluorescence in situ hybridization showed 1p/19q deletions, and the concentration of erythropoietin in the cyst fluid was abnormally high, at 1,859.4mIU/ml. Erythropoietin and erythropoietin receptors were verified with immunohistochemical staining.

Glycogen-rich pleomorphic xanthoastrocytoma with clear-cell features: Confirmatory report of a rare variant with implications for differential diagnosis

Central nervous system space-occupying lesions with clear-cell features encompass a nosologically heterogeneous array, ranging from reactive histiocytic proliferations to neuroepithelial or meningothelial neoplasms of various grades and to metastases. In the face of such differential diagnostic breadth, recognizing cytoplasmic lucency as part of the morphological spectrum of some low grade gliomas will directly have an impact on patient care. We describe a prevailing clear-cell change in an epileptogenic left temporal pleomorphic xanthoastrocytoma surgically resected from a 36-year-old man. Mostly subarachnoid and focally calcified, the tumor was composed of fascicles of moderately atypical spindle cells with optically lucent cytoplasm that tended to intermingle with a desmoplastic mesh of reticulin fibers. Immunohistochemically, coexpression of S100 protein, vimentin, GFAP, and CD34 was noted. Conversely, neither punctate staining for EMA nor positivity for CD68 was seen. Mitotic activity was absent, and the MIB1 labeling index was 2–3% on average. Diastase-sensitive PAS-positive granula indicated clear-cell change to proceed from glycogen storage. Electron microscopy showed tumor cell cytoplasm to be largely obliterated by non-lysosomal-bound pools of glycogen, while hardly any fat vacuole was encountered. Neither ependymal-derived organelles nor annular lamellae suggesting oligodendroglial differentiation were detected. The latter differential diagnosis was further invalidated by lack of codeletion of chromosomal regions 1p36 and 19q13 on molecular genetic testing. By significantly interfering with pattern recognition as an implicit approach in histopathology, clear-cell change in pleomorphic xanthoastrocytoma is likely to suspend its status as a “classic”, and to prompt more deductive differential diagnostic strategies to exclude look-alikes, especially clear-cell ependymoma and oligodendroglioma.

Supratentorial Clear Cell Ependymoma Mimicking Oligodendroglioma : Case Report and Review of the Literature

Clear cell ependymomas (CCEs) are rare variants of ependymomas. Tumors show anaplastic histological features and behave as an aggressive manner. CCEs have a predilection for extraneural metastases and early recurrence, and they demonstrate characteristic radiographic features. These tumors should be radiologically and pathologically differentiated from oligodendrogliomas. On microscopic examination, CCEs are composed of sheets of cells and resemble oligodendroglioma. However, upon closer examination, the nature of CCEs can be detected earlier, resulting in prompt treatment of the tumor. Although we report only one case, we emphasize the importance of early diagnosis and treatment. Future description of more cases of these rare cancers is necessary to aid in their diagnosis and treatment.

Intraparenchymal clear cell ependymoma

Clear cell ependymoma (CCE) is an uncommon variant of ependymoma having a predilection for the supratentorial region. Histologically, it bears an uncanny resemblance to oligodendroglioma, central neurocytoma, hemangioblastoma and metastasis from clear cell carcinoma. Here, we report a rare case of clear cell ependymoma in a 45-year-old male, which histomorphologically resembled anaplastic oligodendroglioma on intraoperative smears, frozen section and routine light microscopy. Immunohistochemistry, however, helped to arrive at the correct diagnosis. Unlike other clear cell tumors of the brain parenchyma, CCE is known to follow an aggressive course and, hence, obtaining a correct diagnosis is imperative since it has a direct therapeutic and prognostic connotation.

Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology

Isocitrate dehydrogenase 1 (IDH1) mutations are frequent in astrocytomas, oligoastrocytomas and oligodendrogliomas. We previously reported the generation of a mutation-specific antibody that specifically detects R132H mutated IDH1 protein (clone H09). Here, we investigate the feasibility of H09 immunohistochemistry to differentiate between oligodendrogliomas/oligoastrocytomas and other tumors with similar morphology. A total of 274 brain tumors presenting with focal or extensive clear cell morphology were investigated. High numbers of H09-positive cases were observed in adult grade II oligodendrogliomas (67 of 74, 91%), grade III oligodendrogliomas (65 of 69, 94%), grade II oligoastrocytomas (11 of 14, 79%) and grade III oligoastrocytomas (10 of 11, 91%). All cases of pediatric oligodendrogliomas (n = 7), neurocytomas (n = 41, 35 central, 4 extraventricular, 2 cerebellar liponeurocytomas), dysembryoplastic neuroepithelial tumors (n = 21), clear cell ependymomas (n = 8), clear cell meningiomas (n = 9) as well as 12 primary glioblastomas with oligodendroglial differentiation and 5 pilocytic astrocytomas with oligodendroglial-like differentiation were negative for H09 immunohistochemistry. Three oligodendrogliomas with neurocytic differentiation had evidence of IDH1/IDH2 mutations either by H09 immunohistochemistry or direct sequencing. We conclude that in tumors with an oligodendroglioma-like morphology, binding of H09 is highly specific for oligodendrogliomas or oligoastrocytomas and substantially helps in the discrimination from other clear cell tumors. Negative H09 immunohistochemistry of an adult oligodendroglioma or oligoastrocytoma should prompt the consideration of other clear cell neoplasms. Further, our observations firmly assign oligodendrogliomas with neurocytic differentiation to the group of oligodendrogliomas and demonstrate that H09 is especially helpful for the difficult discrimination of such lesions from extraventricular neurocytomas.