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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Histopathological features&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The lateral ventricular mass displayed a slightly increased cellularity&#44; frequent microcyst formation&#44; and hemorrhage &#40;A&#44; 40&#215;&#41;&#46; The tumor had a biphasic structure&#58; one area had scattered small clusters of neoplastic cells with a fibrillary background &#40;B&#44; 100&#215;&#41; and the other area had frequent microcyst formation &#40;C&#44; 100&#215;&#41;&#46; Intracytoplasmic eosinophilic dot&#47;ring-like inclusions &#40;black arrow&#41; were observed &#40;D&#44; 400&#215;&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">A subependymoma is a benign subtype of ependymoma that corresponds to a World Health Organization &#40;WHO&#41; grade I tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> Subependymomas usually occur in middle-aged adults and are only occasionally symptomatic&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">2</span></a> Furthermore&#44; neuroradiological characteristics mimicking high-grade glioma&#44; such as hemorrhage and peritumoral edema&#44; are rare in subependymomas&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3&#8211;7</span></a> In this case report&#44; we present a rare case of a large symptomatic subependymoma with unique neuroradiological findings that mimic a high-grade glioma&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical case</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 66-year-old Japanese man was admitted to a local hospital due to vomiting&#59; his initial symptoms included headache&#44; nausea&#44; and left homonymous hemianopsia&#44; which had been present for 10 days before visiting the hospital&#46; Computed tomography and nuclear magnetic resonance imaging &#40;nMRI&#41; revealed a calcified brain tumor with hemorrhage in his right occipital lobe&#46; The patient was transferred to our hospital for further examination and treatment&#46; Brain computed tomography confirmed the presence of a poorly defined large mass with calcification and hemorrhage in the right occipital lobe&#44; as well as widespread peritumoral edema of the surrounding white matter &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; The nMRI showed a 6-cm mass with hemorrhage in the posterior horn of the right lateral ventricle&#46; The mass appeared to be isointense to slightly hypointense on T1-weighted images&#44; isointense to slightly hyperintense on T2-weighted images&#44; and exhibited partial enhancement on T1-weighted gadolinium-enhanced images &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#8211;D&#41;&#46; Additionally&#44; the hemorrhagic area in the tumor was homogenously enhanced &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D&#41;&#46; A slight midline shift was apparently caused by the right lateral ventricular mass&#46; Therefore&#44; a high-grade glioma&#44; such as a glioblastoma&#44; was preoperatively suspected&#46; We performed total tumor resection on the ninth day after the patient&#39;s admission&#46; Although the hemianopsia originating from the primary visual cortex was still present 50 days after the surgery&#44; the patient&#39;s headache and nausea resolved&#44; and he was free from tumor recurrence at least one year after the operation&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Histopathology revealed that the resected specimen was a slightly hypercellular neoplasm with frequent microcysts and hemorrhage &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; The neoplasm included small&#44; scattered clusters of neoplastic cells with a fibrillary background &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#44; and the neoplastic cells formed microcysts frequently &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C&#41;&#46; The neoplastic cells had round to oval nuclei and light-eosinophilic to clear cytoplasms &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>D&#41;&#46; In addition&#44; the neoplastic cells frequently had intracytoplasmic eosinophilic dots&#44; although we did not observe other pathological features&#44; such as ependymal rosettes&#47;canals&#44; perivascular pseudorosettes&#44; microvascular proliferation&#44; or necrosis&#46; Mitotic figures were rarely observed within the tumor&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Immunohistochemical analyses revealed that the neoplastic cells were positive for S100 protein&#44; glial fibrillary acidic protein &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A&#41;&#44; and the alpha-thalassemia&#47;mental retardation syndrome X-linked protein&#46; We did not observe immunoreactivity to oligodendrocyte transcription factor 2 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>B&#41;&#44; synaptophysin&#44; mutant isocitrate dehydrogenase &#40;IDH&#41; 1 R132H&#44; or p53&#46; The neoplastic cells frequently had intracytoplasmic dots&#47;rings that were positive for EMA&#47;D2-40 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>C and D&#41;&#44; and the MIB-1 labeling index was &#60;1&#37;&#46; These pathological and immunohistochemical features led us to update our diagnosis to a subependymoma corresponding to a WHO grade I tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Subependymomas account for 3&#46;4&#8211;7&#46;5&#37; of all ependymal neoplasms<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8&#44;9</span></a>&#59; they frequently affect middle-aged adults &#40;mainly 42&#46;5&#8211;51&#46;0 year-olds&#44; ranging from 1&#46;5 to 85 years old&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3&#44;10</span></a> and predominantly affect adult males&#46; The most common site for subependymomas is the fourth ventricle &#40;55&#37;&#41;&#44; followed by the lateral ventricle &#40;19&#8211;45&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3&#44;10</span></a> In the present case&#44; the subependymoma was located in the posterior horn of the right lateral ventricle&#46; The tumor was relatively large &#40;6<span class="elsevierStyleHsp" style=""></span>cm in diameter&#41; and the patient was relatively old &#40;66 years old&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Most subependymoma cases are asymptomatic&#46; Symptomatic subependymomas were identified in only 7 out of 1000 surgical specimens from intracranial subependymomas&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">2</span></a> Patients with symptomatic subependymomas are generally younger &#40;with a mean age of 39&#8211;43 years&#41;&#44; compared to patients with asymptomatic subependymoma &#40;mean age&#58; 59&#8211;75 years old&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">2&#44;11</span></a> The major clinical symptoms of symptomatic subependymomas include headache &#40;61&#37;&#41;&#44; gait ataxia &#40;42&#37;&#41;&#44; visual disturbance &#40;33&#37;&#41;&#44; memory&#47;psychiatric disturbance &#40;31&#37;&#41;&#44; paresis &#40;31&#37;&#41;&#44; cranial nerve abnormalities &#40;25&#37;&#41;&#44; nystagmus&#47;vertigo &#40;22&#37;&#41;&#44; and nausea&#47;vomiting &#40;19&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> Although the patient in this present case report was relatively old compared to previously reported cases&#44; his primary symptom &#40;recurrent vomiting&#41; was consistent with those reports&#46; The large size of the patient&#39;s subependymoma &#40;6<span class="elsevierStyleHsp" style=""></span>cm&#41; may have been associated with the presence of symptoms&#44;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">11&#44;12</span></a> as symptomatic subependymomas in the lateral ventricle have an average diameter of 5<span class="elsevierStyleHsp" style=""></span>cm&#44; while those that are asymptomatic have an average diameter of only 0&#46;8<span class="elsevierStyleHsp" style=""></span>cm&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a> Furthermore&#44; large subependymomas tend to show cyst formation&#44; calcification&#44; and hemorrhage&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">5&#8211;8</span></a> Thus&#44; this large subependymoma with neuroradiological and neuropathological evidence of calcification and hemorrhage is consistent with reports on symptomatic subependymomas&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">5&#8211;7&#44;11&#44;12</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">During the brain nMRI&#44; we observed peritumoral edema&#44; a midline shift&#44; and partial T1-weighted gadolinium enhancement&#46; In frequent&#44; glioblastomas&#44; IDH-wildtype&#44; revealed MRI features characterized by irregular-shaped tumor with ring-shape enhancement&#44; peritumoral edema&#44; and central hypointense area suggesting tumor necrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">13</span></a> Intraventricular glioblastoma&#44; although extremely rare&#44; also exhibited the same MRI findings as intraparenchymal ones&#59; namely irregular-shape&#44; heterogeneous or ring-like enhancement&#44; peritumoral edema&#44; and hypointense areas indicating necrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">14</span></a> Thus&#44; our differential diagnosis included a high-grade glioma&#44; such as glioblastoma&#44; although the presence of calcification suggested a slow-growing brain tumor&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">15</span></a> rather than a high-grade glioma&#46; Therefore&#44; caution is needed when analyzing neuroradiological images&#44; and careful examination may increase the reliability of the pathological diagnosis&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Despite differences in tumor sizes and&#47;or symptoms&#44; the histopathological features of subependymomas are similar to those of ependymomas&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> For example&#44; subependymomas are characteristic hypocellular neoplasms with small glial-cell clusters and a fibrillary background of glial cells&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> in which mitotic figures are rare&#46; Specimens from large subependymomas also frequently exhibit cyst formation&#44; calcium deposition&#44; and vascular hyalinization However&#44; these findings are less common in small tumors&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">1&#44;11</span></a> Immunohistochemistry rarely reveals dot and&#47;or ring immunoreactivity to EMA&#44; as subependymomas are considered a variant of ependymal tumors&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">1&#44;16&#44;17</span></a> In the present case&#44; the tumor&#39;s histopathological features were indicative of subependymoma&#44; and there were no ependymoma components&#44; such as ependymal rosettes&#44; ependymal canals&#44; and&#47;or perivascular pseudorosettes&#46; Furthermore&#44; the immunohistochemical findings were compatible with the immunoprofile of subependymomas&#58; positive for glial fibrillary acidic protein and S100 protein&#44; negative for oligodendrocyte transcription factor 2&#44; and an extremely low MIB-1 labeling index&#46; However&#44; the present case also involved cytoplasmic EMA-positive dots&#47;rings&#46; Such EMA-immunoreactivity is&#44; contrary to ependymomas&#44; unusual for subependymomas&#44;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">18&#44;19</span></a> but was the characteristic pathological feature in the present case&#46; It appears that subependymomas and ependymomas can co-exist and it is possible that subependymomas represent a variant of ependymomas&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> We believe that our histopathological and immunohistochemical findings also support this theory&#44; and that the neoplastic cells exhibit ependymal differentiation at the cellular level but not at the structural level&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion&#44; we encountered a Japanese man with a symptomatic large subependymoma&#44; who exhibited signs of hemorrhage&#44; peritumoral edema&#44; and a midline shift&#44; mimicking high-grade-gliomas&#44; such as a glioblastoma&#46; Thus&#44; the clinical and neuroradiological findings could have supported the diagnosis of a high-grade glioma&#46; This case highlights the importance of conducting detailed clinical and neuroradiological analyses in order to reach an appropriate diagnosis and provide the best treatment possible&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Authors&#8217; contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">Yuya Hanashima collected the patient&#39;s clinical data and prepared the manuscript&#46; Taku Homma performed the pathological examination and prepared the manuscript&#46; Toshiya Maebayashi analyzed and prepared neuroradiological imaging data&#46; Takahiro Igarashi and Atsuo Yoshino collected the patient&#39;s clinical data and checked clinical sections of the manuscript&#46; Toshiyuki Ishige and Hiroyuki Hao performed pathological examinations&#46; Finally&#44; all authors read and approved the final version of the manuscript&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A subependymoma is a benign primary brain tumor classified as a World Health Organization grade I tumor&#59; it is asymptomatic in most cases&#46; We present the case of a 66-year-old Japanese man with a complaint of recurrent vomiting that led to the discovery of a large mass with hemorrhage&#44; peritumoral edema&#44; and a midline shift in the posterior horn of the right lateral ventricle&#46; The patient was pathologically diagnosed with subependymoma after undergoing total tumor resection&#59; a year after the surgery&#44; he was free from tumor recurrence&#46; Although symptomatic subependymomas are rare&#44; they tend to show hemorrhage with peritumoral edema on neuroradiological tests and tend to be confused with high-grade brain tumors&#46; In the present case&#44; we highlight the importance of the appropriate diagnosis for subependymomas showing neuroradiological features that mimic high-grade gliomas&#46; This diagnosis will help in providing suitable treatment for subependymomas&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Un subependimoma es un tumor cerebral primario benigno&#44; clasificado por la Organizaci&#243;n Mundial de la Salud como un tumor grado I&#46; En la mayor&#237;a de los casos es asintom&#225;tico&#46; Presentamos el caso de un var&#243;n japon&#233;s de 66 a&#241;os de edad que reportaba v&#243;mitos recurrentes&#44; los que lo llevaron al descubrimiento de una gran masa con hemorragia&#44; edema peritumoral y una desviaci&#243;n de la l&#237;nea media del cuerno posterior del ventr&#237;culo lateral derecho&#46; Se le realiz&#243; un diagn&#243;stico patol&#243;gico de subependimoma luego de que se le sometiera a una resecci&#243;n total del tumor&#46; Un a&#241;o despu&#233;s de la cirug&#237;a no presentaba recurrencia del tumor&#46; Aunque los subependimomas sintom&#225;ticos son raros&#44; en las pruebas neurorradiol&#243;gicas tienden a presentar hemorragia con edema peritumoral y se tiende a confundirlos con tumores cerebrales de alto grado&#46; En el presente caso&#44; destacamos la importancia de un diagn&#243;stico adecuado de los subependimomas que presentan caracter&#237;sticas neurorradiol&#243;gicas que imitan a gliomas de alto grado&#46; Este diagn&#243;stico ayudar&#225; a brindar el tratamiento adecuado para dichos subependimomas&#46;</p></span>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Neuroradiological images&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Brain computed tomography revealed a poorly-defined large mass with calcification &#40;yellow arrow&#41;&#44; hemorrhage &#40;red arrow&#41;&#44; peritumoral edema&#44; and a midline shift in the right occipital lobe &#40;A&#41;&#46; Axial brain nuclear magnetic resonance imaging revealed that the mass was localized in the posterior horn of the right lateral ventricle&#44; was isointense to slightly hypointense on T1-weighted images &#40;B&#41;&#44; and was isointense to slightly hyperintense on T2-weighted images &#40;C&#41;&#46; T1-weighted gadolinium-enhanced images revealed partial enhancement in the mass &#40;D&#41;&#46; The hemorrhagic area in the mass was homogenously enhanced &#40;D&#44; red arrow&#41;&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Histopathological features&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The lateral ventricular mass displayed a slightly increased cellularity&#44; frequent microcyst formation&#44; and hemorrhage &#40;A&#44; 40&#215;&#41;&#46; The tumor had a biphasic structure&#58; one area had scattered small clusters of neoplastic cells with a fibrillary background &#40;B&#44; 100&#215;&#41; and the other area had frequent microcyst formation &#40;C&#44; 100&#215;&#41;&#46; Intracytoplasmic eosinophilic dot&#47;ring-like inclusions &#40;black arrow&#41; were observed &#40;D&#44; 400&#215;&#41;&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Immunohistochemical features&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The mass was positive for glial fibrillary acidic protein &#40;A&#44; 200&#215;&#41; and negative for oligodendrocyte transcription factor 2 &#40;B&#44; 200&#215;&#41;&#46; The neoplastic cells had frequent intracytoplasmic dots&#47;rings that were positive for epithelial membrane antigen &#40;C&#44; 400&#215;&#41; and D2-40 &#40;D&#44; 400&#215;&#41;&#46;</p>"
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Case Report
A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report
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Yuya Hanashimaa, Taku Hommab,
Autor para correspondencia
homma.taku@gmail.com

Corresponding author.
, Toshiya Maebayashic, Takahiro Igarashia, Toshiyuki Ishigeb, Hiroyuki Haob, Atsuo Yoshinoa
a Department of Neurological Surgery, Nihon University School of Medicine, Itabashi 173-8610, Tokyo, Japan
b Division of Human Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, Itabashi 173-8610, Tokyo, Japan
c Department of Radiology, Nihon University School of Medicine, Itabashi 173-8610, Tokyo, Japan

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