- Email: [email protected]
A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report
NEUCIR-339; No. of Pages 5
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 8;x x x(x x):xxx–xxx
NEUROCIRUGÍA www.elsevier.es/neurocirugia
Case Report
A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report Yuya Hanashima a , Taku Homma b,∗ , Toshiya Maebayashi c , Takahiro Igarashi a , Toshiyuki Ishige b , Hiroyuki Hao b , Atsuo Yoshino a a
Department of Neurological Surgery, Nihon University School of Medicine, Itabashi 173-8610, Tokyo, Japan 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 b
a r t i c l e
i n f o
a b s t r a c t
Article history:
A subependymoma is a benign primary brain tumor classified as a World Health Organiza-
Received 14 February 2018
tion grade I tumor; it is asymptomatic in most cases. We present the case of a 66-year-old
Accepted 3 June 2018
Japanese man with a complaint of recurrent vomiting that led to the discovery of a large
Available online xxx
mass with hemorrhage, peritumoral edema, and a midline shift in the posterior horn of the right lateral ventricle. The patient was pathologically diagnosed with subependymoma after
Keywords:
undergoing total tumor resection; a year after the surgery, he was free from tumor recur-
Cerebrum
rence. Although symptomatic subependymomas are rare, they tend to show hemorrhage
Lateral ventricle
with peritumoral edema on neuroradiological tests and tend to be confused with high-grade
Subependymoma
brain tumors. In the present case, we highlight the importance of the appropriate diagnosis
Neuroradiology
for subependymomas showing neuroradiological features that mimic high-grade gliomas.
Symptomatic
This diagnosis will help in providing suitable treatment for subependymomas. ˜ © 2018 Sociedad Espanola de Neurocirugía. Published by Elsevier España, S.L.U. All rights reserved.
Gran subependimoma sintomático de características neurorradiológicas que imita a un glioma de alto grado: presentación de un caso clínico r e s u m e n Palabras clave:
Un subependimoma es un tumor cerebral primario benigno, clasificado por la Organización
Cerebro
Mundial de la Salud como un tumor grado I. En la mayoría de los casos es asintomático.
Ventrículo lateral
˜ Presentamos el caso de un varón japonés de 66 anos de edad que reportaba vómitos recu
Subependimoma
rrentes, los que lo llevaron al descubrimiento de una gran masa con hemorragia, edema
Neurorradiología
peritumoral y una desviación de la línea media del cuerno posterior del ventrículo la
Sintomático
teral derecho. Se le realizó un diagnóstico patológico de subependimoma luego de que se
∗
Corresponding author. E-mail address: [email protected] (T. Homma). https://doi.org/10.1016/j.neucir.2018.06.001 ˜ 1130-1473/© 2018 Sociedad Espanola de Neurocirugía. Published by Elsevier España, S.L.U. All rights reserved.
Please cite this article in press as: Hanashima Y, et al. A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report. Neurocirugia. 2018. https://doi.org/10.1016/j.neucir.2018.06.001
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2
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˜ después de la cirugía no presentaba le sometiera a una resección total del tumor. Un ano recurrencia del tumor. Aunque los subependimomas sintomáticos son raros, en las pruebas neurorradiológicas tienden a presentar hemorragia con edema peritumoral y se tiende a confundirlos con tumores cerebrales de alto grado. En el presente caso, destacamos la importancia de un diagnóstico adecuado de los subependimomas que presentan características neurorradiológicas que imitan a gliomas de alto grado. Este diagnóstico ayudará a brindar el tratamiento adecuado para dichos subependimomas. ˜ © 2018 Sociedad Espanola de Neurocirugía. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.
Introduction A subependymoma is a benign subtype of ependymoma that corresponds to a World Health Organization (WHO) grade I tumor.1 Subependymomas usually occur in middle-aged adults and are only occasionally symptomatic.2 Furthermore, neuroradiological characteristics mimicking high-grade glioma, such as hemorrhage and peritumoral edema, are rare in subependymomas.3–7 In this case report, we present a rare case of a large symptomatic subependymoma with unique neuroradiological findings that mimic a high-grade glioma.
Clinical case A 66-year-old Japanese man was admitted to a local hospital due to vomiting; his initial symptoms included headache, nausea, and left homonymous hemianopsia, which had been present for 10 days before visiting the hospital. Computed tomography and nuclear magnetic resonance imaging (nMRI) revealed a calcified brain tumor with hemorrhage in his right occipital lobe. The patient was transferred to our hospital for further examination and treatment. Brain computed tomography confirmed the presence of a poorly defined large mass with calcification and hemorrhage in the right occipital lobe, as well as widespread peritumoral edema of the surrounding white matter (Fig. 1A). The nMRI showed a 6-cm mass with hemorrhage in the posterior horn of the right lateral ventricle. The mass appeared to be isointense to slightly hypointense on T1-weighted images, isointense to slightly hyperintense on T2-weighted images, and exhibited partial enhancement on T1-weighted gadolinium-enhanced images (Fig. 1B–D). Additionally, the hemorrhagic area in the tumor was homogenously enhanced (Fig. 1D). A slight midline shift was apparently caused by the right lateral ventricular mass. Therefore, a high-grade glioma, such as a glioblastoma, was preoperatively suspected. We performed total tumor resection on the ninth day after the patient’s admission. Although the hemianopsia originating from the primary visual cortex was still present 50 days after the surgery, the patient’s headache and nausea resolved, and he was free from tumor recurrence at least one year after the operation. Histopathology revealed that the resected specimen was a slightly hypercellular neoplasm with frequent microcysts and hemorrhage (Fig. 2A). The neoplasm included small,
scattered clusters of neoplastic cells with a fibrillary background (Fig. 2B), and the neoplastic cells formed microcysts frequently (Fig. 2C). The neoplastic cells had round to oval nuclei and light-eosinophilic to clear cytoplasms (Fig. 2D). In addition, the neoplastic cells frequently had intracytoplasmic eosinophilic dots, although we did not observe other pathological features, such as ependymal rosettes/canals, perivascular pseudorosettes, microvascular proliferation, or necrosis. Mitotic figures were rarely observed within the tumor. Immunohistochemical analyses revealed that the neoplastic cells were positive for S100 protein, glial fibrillary acidic protein (Fig. 3A), and the alpha-thalassemia/mental retardation syndrome X-linked protein. We did not observe immunoreactivity to oligodendrocyte transcription factor 2 (Fig. 3B), synaptophysin, mutant isocitrate dehydrogenase (IDH) 1 R132H, or p53. The neoplastic cells frequently had intracytoplasmic dots/rings that were positive for EMA/D240 (Fig. 3C and D), and the MIB-1 labeling index was <1%. These pathological and immunohistochemical features led us to update our diagnosis to a subependymoma corresponding to a WHO grade I tumor.1
Discussion Subependymomas account for 3.4–7.5% of all ependymal neoplasms8,9 ; they frequently affect middle-aged adults (mainly 42.5–51.0 year-olds, ranging from 1.5 to 85 years old),3,10 and predominantly affect adult males. The most common site for subependymomas is the fourth ventricle (55%), followed by the lateral ventricle (19–45%).3,10 In the present case, the subependymoma was located in the posterior horn of the right lateral ventricle. The tumor was relatively large (6 cm in diameter) and the patient was relatively old (66 years old). Most subependymoma cases are asymptomatic. Symptomatic subependymomas were identified in only 7 out of 1000 surgical specimens from intracranial subependymomas.2 Patients with symptomatic subependymomas are generally younger (with a mean age of 39–43 years), compared to patients with asymptomatic subependymoma (mean age: 59–75 years old).2,11 The major clinical symptoms of symptomatic subependymomas include headache (61%), gait ataxia (42%), visual disturbance (33%), memory/psychiatric disturbance (31%), paresis (31%), cranial nerve abnormalities (25%), nystagmus/vertigo (22%), and nausea/vomiting (19%).11
Please cite this article in press as: Hanashima Y, et al. A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report. Neurocirugia. 2018. https://doi.org/10.1016/j.neucir.2018.06.001
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Fig. 1 – Neuroradiological images. Brain computed tomography revealed a poorly-defined large mass with calcification (yellow arrow), hemorrhage (red arrow), peritumoral edema, and a midline shift in the right occipital lobe (A). Axial brain nuclear magnetic resonance imaging revealed that the mass was localized in the posterior horn of the right lateral ventricle, was isointense to slightly hypointense on T1-weighted images (B), and was isointense to slightly hyperintense on T2-weighted images (C). T1-weighted gadolinium-enhanced images revealed partial enhancement in the mass (D). The hemorrhagic area in the mass was homogenously enhanced (D, red arrow).
Although the patient in this present case report was relatively old compared to previously reported cases, his primary symptom (recurrent vomiting) was consistent with those reports. The large size of the patient’s subependymoma (6 cm) may have been associated with the presence of symptoms,11,12 as symptomatic subependymomas in the lateral ventricle have an average diameter of 5 cm, while those that are asymptomatic have an average diameter of only 0.8 cm.8 Furthermore, large subependymomas tend to show cyst formation, calcification, and hemorrhage.5–8 Thus, this large subependymoma with neuroradiological and neuropathological evidence of calcification and hemorrhage is consistent with reports on symptomatic subependymomas.5–7,11,12 During the brain nMRI, we observed peritumoral edema, a midline shift, and partial T1-weighted gadolinium enhancement. In frequent, glioblastomas, IDH-wildtype, revealed MRI features characterized by irregular-shaped tumor with ring-shape enhancement, peritumoral edema, and central hypointense area suggesting tumor necrosis.13 Intraventricular glioblastoma, although extremely rare, also exhibited the same MRI findings as intraparenchymal ones; namely irregular-shape, heterogeneous or ring-like enhancement, peritumoral edema, and hypointense areas indicating
necrosis.14 Thus, our differential diagnosis included a highgrade glioma, such as glioblastoma, although the presence of calcification suggested a slow-growing brain tumor,15 rather than a high-grade glioma. Therefore, caution is needed when analyzing neuroradiological images, and careful examination may increase the reliability of the pathological diagnosis. Despite differences in tumor sizes and/or symptoms, the histopathological features of subependymomas are similar to those of ependymomas.11 For example, subependymomas are characteristic hypocellular neoplasms with small glial-cell clusters and a fibrillary background of glial cells,1 in which mitotic figures are rare. Specimens from large subependymomas also frequently exhibit cyst formation, calcium deposition, and vascular hyalinization However, these findings are less common in small tumors.1,11 Immunohistochemistry rarely reveals dot and/or ring immunoreactivity to EMA, as subependymomas are considered a variant of ependymal tumors.1,16,17 In the present case, the tumor’s histopathological features were indicative of subependymoma, and there were no ependymoma components, such as ependymal rosettes, ependymal canals, and/or perivascular pseudorosettes. Furthermore, the immunohistochemical findings were compatible with the immunoprofile of
Please cite this article in press as: Hanashima Y, et al. A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report. Neurocirugia. 2018. https://doi.org/10.1016/j.neucir.2018.06.001
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Fig. 2 – Histopathological features. The lateral ventricular mass displayed a slightly increased cellularity, frequent microcyst formation, and hemorrhage (A, 40×). The tumor had a biphasic structure: one area had scattered small clusters of neoplastic cells with a fibrillary background (B, 100×) and the other area had frequent microcyst formation (C, 100×). Intracytoplasmic eosinophilic dot/ring-like inclusions (black arrow) were observed (D, 400×).
Fig. 3 – Immunohistochemical features. The mass was positive for glial fibrillary acidic protein (A, 200×) and negative for oligodendrocyte transcription factor 2 (B, 200×). The neoplastic cells had frequent intracytoplasmic dots/rings that were positive for epithelial membrane antigen (C, 400×) and D2-40 (D, 400×).
subependymomas: positive for glial fibrillary acidic protein and S100 protein, negative for oligodendrocyte transcription factor 2, and an extremely low MIB-1 labeling index. However, the present case also involved cytoplasmic EMA-positive dots/rings. Such EMA-immunoreactivity is, contrary to ependymomas, unusual for subependymomas,18,19 but was
the characteristic pathological feature in the present case. It appears that subependymomas and ependymomas can co-exist and it is possible that subependymomas represent a variant of ependymomas.11 We believe that our histopathological and immunohistochemical findings also support this theory, and that the neoplastic cells exhibit ependymal
Please cite this article in press as: Hanashima Y, et al. A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report. Neurocirugia. 2018. https://doi.org/10.1016/j.neucir.2018.06.001
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differentiation at the cellular level but not at the structural level.
Conclusions In conclusion, we encountered a Japanese man with a symptomatic large subependymoma, who exhibited signs of hemorrhage, peritumoral edema, and a midline shift, mimicking high-grade-gliomas, such as a glioblastoma. Thus, the clinical and neuroradiological findings could have supported the diagnosis of a high-grade glioma. 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.
5.
6.
7.
8.
9.
Authors’ contributions Yuya Hanashima collected the patient’s clinical data and prepared the manuscript. Taku Homma performed the pathological examination and prepared the manuscript. Toshiya Maebayashi analyzed and prepared neuroradiological imaging data. Takahiro Igarashi and Atsuo Yoshino collected the patient’s clinical data and checked clinical sections of the manuscript. Toshiyuki Ishige and Hiroyuki Hao performed pathological examinations. Finally, all authors read and approved the final version of the manuscript.
Acknowledgements
10.
11.
12.
13.
The authors thank Mrs. Yukari Hirotani (Department of Pathology, Nihon University School of Medicine) for her excellent technical assistance.
14.
references
15.
1. McLendon R, Rushing EJ, Schiffer D, Hirose T, Rosenblum MK, Santi M, et al. Subependymoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO classification of tumours of the central nervous system. Lyon: International Agency for Research on Cancer; 2016. p. 102–3. 2. Matsumura A, Ahyai A, Hori A, Schaake T. Intracerebral subependymomas. Clinical and neuropathological analyses with special reference to the possible existence of a less benign variant. Acta Neurochir (Wien). 1989;96:15–25. 3. Ragel BT, Osborn AG, Whang K, Townsend JJ, Jensen RL, Couldwell WT. Subependymomas: an analysis of clinical and imaging features. Neurosurgery. 2016;58:881–90. 4. Carrasco R, Pascual JM, Navas M, Fraga J, Manzanares-Soler R, Sola RG. Spontaneous acute hemorrhage within a
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subependymoma of the lateral ventricle: successful emergent surgical removal through a frontal transcortical approach. Neurocirugia (Astur). 2010;21:478–83. Landriel F, Besada C, Migliaro M, Christiansen S, Goldschmidt E, Yampolsky C, et al. Atypical hemorrhagic presentation of a fourth ventricle subependymoma: a case report. Neurol Med Chir (Tokyo). 2013;53:828–31. Akamatsu Y, Utsunomiya A, Suzuki S, Endo T, Suzuki I, Nishimura S, et al. Subependymoma in the lateral ventricle manifesting as intraventricular hemorrhage. Neurol Med Chir (Tokyo). 2010;50:1020–3. Lindboe CF, Stolt-Nielsen A, Dale LG. Hemorrhage in a highly vascularized subependymoma of the septum pellucidum: case report. Neurosurgery. 1992;31:741–5. Schiffer D, Chiò A, Giordana MT, Migheli A, Palma L, Pollo B, et al. Histologic prognostic factors in ependymoma. Childs Nerv Syst. 1991;7:177–82. Kurt E, Zheng PP, Hop WC, van der Weiden M, Bol M, van den Bent MJ, et al. Identification of relevant prognostic histopathologic features in 69 intracranial ependymomas, excluding myxopapillary ependymomas and subependymomas. Cancer. 2016;106:388–95. Rushing EJ, Cooper PB, Quezado M, Begnami M, Crespo A, Smirniotopoulos JG, et al. Subependymoma revisited: clinicopathological evaluation of 83 cases. J Neurooncol. 2007;85:297–305. Scheithauer BW. Symptomatic subependymoma: report of 21 cases with review of the literature. J Neurosurg. 1978;49:689–96. Chiechi MV, Smirniotopoulos JG, Jones RV. Intracranial subependymomas: CT and MR imaging features in 24 cases. Am J Roentgenol. 1995;165:1245–50. Louis DN, Brat DJ, Ohgaki H, Stupp R, Suvà ML, Biernat W, et al. Glioblastoma, IDH-wildtype. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO classification of tumours of the central nervous system. Lyon: International Agency for Research on Cancer; 2016. p. 28–51. Sarikafa Y, Akcakaya MO, Sarikafa S, Ozkaya F, Akdemir O, Celik SE. Intraventricular glioblastoma multiforme: case report. Neurocirugia. 2015;26:147–50. Okuchi K, Hiramatsu K, Morimoto T, Tsunoda S, Sakaki T, Iwasaki S. Astrocytoma with widespread calcification along axonal fibers. Neuroradiology. 1992;34:328–30. Cunha AM, Brito AC, de Almeida Lima G, de Souza LA, Simões EL, Telles C, et al. Cerebellopontine angle subependymoma without fourth ventricle extension: an uncommon tumor in a rare location. Neuropathology. 2012;32:164–70. Iwasaki M, Hida K, Aoyama T, Houkin K. Thoracolumbar intramedullary subependymoma with multiple cystic formation: a case report and review. Eur Spine J. 2013;22:S317–20. Bi Z, Ren X, Zhang J, Jia W. Clinical, radiological, and pathological features in 43 cases of intracranial subependymoma. J Neurosurg. 2015;122:49–60. Limaïem F, Bellil SBH, Bellil K, Chelly I, Jemel H, Haouet S, et al. Subependymomas: a clinicopathological study of 6 symptomatic cases. Pathologica. 2008;100:401–4.
Please cite this article in press as: Hanashima Y, et al. A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report. Neurocirugia. 2018. https://doi.org/10.1016/j.neucir.2018.06.001
ARTICLE IN PRESS n e u r o c i r u g i a . 2 0 1 8;x x x(x x):xxx–xxx
NEUROCIRUGÍA www.elsevier.es/neurocirugia
Case Report
A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report Yuya Hanashima a , Taku Homma b,∗ , Toshiya Maebayashi c , Takahiro Igarashi a , Toshiyuki Ishige b , Hiroyuki Hao b , Atsuo Yoshino a a
Department of Neurological Surgery, Nihon University School of Medicine, Itabashi 173-8610, Tokyo, Japan 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 b
a r t i c l e
i n f o
a b s t r a c t
Article history:
A subependymoma is a benign primary brain tumor classified as a World Health Organiza-
Received 14 February 2018
tion grade I tumor; it is asymptomatic in most cases. We present the case of a 66-year-old
Accepted 3 June 2018
Japanese man with a complaint of recurrent vomiting that led to the discovery of a large
Available online xxx
mass with hemorrhage, peritumoral edema, and a midline shift in the posterior horn of the right lateral ventricle. The patient was pathologically diagnosed with subependymoma after
Keywords:
undergoing total tumor resection; a year after the surgery, he was free from tumor recur-
Cerebrum
rence. Although symptomatic subependymomas are rare, they tend to show hemorrhage
Lateral ventricle
with peritumoral edema on neuroradiological tests and tend to be confused with high-grade
Subependymoma
brain tumors. In the present case, we highlight the importance of the appropriate diagnosis
Neuroradiology
for subependymomas showing neuroradiological features that mimic high-grade gliomas.
Symptomatic
This diagnosis will help in providing suitable treatment for subependymomas. ˜ © 2018 Sociedad Espanola de Neurocirugía. Published by Elsevier España, S.L.U. All rights reserved.
Gran subependimoma sintomático de características neurorradiológicas que imita a un glioma de alto grado: presentación de un caso clínico r e s u m e n Palabras clave:
Un subependimoma es un tumor cerebral primario benigno, clasificado por la Organización
Cerebro
Mundial de la Salud como un tumor grado I. En la mayoría de los casos es asintomático.
Ventrículo lateral
˜ Presentamos el caso de un varón japonés de 66 anos de edad que reportaba vómitos recu
Subependimoma
rrentes, los que lo llevaron al descubrimiento de una gran masa con hemorragia, edema
Neurorradiología
peritumoral y una desviación de la línea media del cuerno posterior del ventrículo la
Sintomático
teral derecho. Se le realizó un diagnóstico patológico de subependimoma luego de que se
∗
Corresponding author. E-mail address: [email protected] (T. Homma). https://doi.org/10.1016/j.neucir.2018.06.001 ˜ 1130-1473/© 2018 Sociedad Espanola de Neurocirugía. Published by Elsevier España, S.L.U. All rights reserved.
Please cite this article in press as: Hanashima Y, et al. A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report. Neurocirugia. 2018. https://doi.org/10.1016/j.neucir.2018.06.001
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˜ después de la cirugía no presentaba le sometiera a una resección total del tumor. Un ano recurrencia del tumor. Aunque los subependimomas sintomáticos son raros, en las pruebas neurorradiológicas tienden a presentar hemorragia con edema peritumoral y se tiende a confundirlos con tumores cerebrales de alto grado. En el presente caso, destacamos la importancia de un diagnóstico adecuado de los subependimomas que presentan características neurorradiológicas que imitan a gliomas de alto grado. Este diagnóstico ayudará a brindar el tratamiento adecuado para dichos subependimomas. ˜ © 2018 Sociedad Espanola de Neurocirugía. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.
Introduction A subependymoma is a benign subtype of ependymoma that corresponds to a World Health Organization (WHO) grade I tumor.1 Subependymomas usually occur in middle-aged adults and are only occasionally symptomatic.2 Furthermore, neuroradiological characteristics mimicking high-grade glioma, such as hemorrhage and peritumoral edema, are rare in subependymomas.3–7 In this case report, we present a rare case of a large symptomatic subependymoma with unique neuroradiological findings that mimic a high-grade glioma.
Clinical case A 66-year-old Japanese man was admitted to a local hospital due to vomiting; his initial symptoms included headache, nausea, and left homonymous hemianopsia, which had been present for 10 days before visiting the hospital. Computed tomography and nuclear magnetic resonance imaging (nMRI) revealed a calcified brain tumor with hemorrhage in his right occipital lobe. The patient was transferred to our hospital for further examination and treatment. Brain computed tomography confirmed the presence of a poorly defined large mass with calcification and hemorrhage in the right occipital lobe, as well as widespread peritumoral edema of the surrounding white matter (Fig. 1A). The nMRI showed a 6-cm mass with hemorrhage in the posterior horn of the right lateral ventricle. The mass appeared to be isointense to slightly hypointense on T1-weighted images, isointense to slightly hyperintense on T2-weighted images, and exhibited partial enhancement on T1-weighted gadolinium-enhanced images (Fig. 1B–D). Additionally, the hemorrhagic area in the tumor was homogenously enhanced (Fig. 1D). A slight midline shift was apparently caused by the right lateral ventricular mass. Therefore, a high-grade glioma, such as a glioblastoma, was preoperatively suspected. We performed total tumor resection on the ninth day after the patient’s admission. Although the hemianopsia originating from the primary visual cortex was still present 50 days after the surgery, the patient’s headache and nausea resolved, and he was free from tumor recurrence at least one year after the operation. Histopathology revealed that the resected specimen was a slightly hypercellular neoplasm with frequent microcysts and hemorrhage (Fig. 2A). The neoplasm included small,
scattered clusters of neoplastic cells with a fibrillary background (Fig. 2B), and the neoplastic cells formed microcysts frequently (Fig. 2C). The neoplastic cells had round to oval nuclei and light-eosinophilic to clear cytoplasms (Fig. 2D). In addition, the neoplastic cells frequently had intracytoplasmic eosinophilic dots, although we did not observe other pathological features, such as ependymal rosettes/canals, perivascular pseudorosettes, microvascular proliferation, or necrosis. Mitotic figures were rarely observed within the tumor. Immunohistochemical analyses revealed that the neoplastic cells were positive for S100 protein, glial fibrillary acidic protein (Fig. 3A), and the alpha-thalassemia/mental retardation syndrome X-linked protein. We did not observe immunoreactivity to oligodendrocyte transcription factor 2 (Fig. 3B), synaptophysin, mutant isocitrate dehydrogenase (IDH) 1 R132H, or p53. The neoplastic cells frequently had intracytoplasmic dots/rings that were positive for EMA/D240 (Fig. 3C and D), and the MIB-1 labeling index was <1%. These pathological and immunohistochemical features led us to update our diagnosis to a subependymoma corresponding to a WHO grade I tumor.1
Discussion Subependymomas account for 3.4–7.5% of all ependymal neoplasms8,9 ; they frequently affect middle-aged adults (mainly 42.5–51.0 year-olds, ranging from 1.5 to 85 years old),3,10 and predominantly affect adult males. The most common site for subependymomas is the fourth ventricle (55%), followed by the lateral ventricle (19–45%).3,10 In the present case, the subependymoma was located in the posterior horn of the right lateral ventricle. The tumor was relatively large (6 cm in diameter) and the patient was relatively old (66 years old). Most subependymoma cases are asymptomatic. Symptomatic subependymomas were identified in only 7 out of 1000 surgical specimens from intracranial subependymomas.2 Patients with symptomatic subependymomas are generally younger (with a mean age of 39–43 years), compared to patients with asymptomatic subependymoma (mean age: 59–75 years old).2,11 The major clinical symptoms of symptomatic subependymomas include headache (61%), gait ataxia (42%), visual disturbance (33%), memory/psychiatric disturbance (31%), paresis (31%), cranial nerve abnormalities (25%), nystagmus/vertigo (22%), and nausea/vomiting (19%).11
Please cite this article in press as: Hanashima Y, et al. A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report. Neurocirugia. 2018. https://doi.org/10.1016/j.neucir.2018.06.001
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Fig. 1 – Neuroradiological images. Brain computed tomography revealed a poorly-defined large mass with calcification (yellow arrow), hemorrhage (red arrow), peritumoral edema, and a midline shift in the right occipital lobe (A). Axial brain nuclear magnetic resonance imaging revealed that the mass was localized in the posterior horn of the right lateral ventricle, was isointense to slightly hypointense on T1-weighted images (B), and was isointense to slightly hyperintense on T2-weighted images (C). T1-weighted gadolinium-enhanced images revealed partial enhancement in the mass (D). The hemorrhagic area in the mass was homogenously enhanced (D, red arrow).
Although the patient in this present case report was relatively old compared to previously reported cases, his primary symptom (recurrent vomiting) was consistent with those reports. The large size of the patient’s subependymoma (6 cm) may have been associated with the presence of symptoms,11,12 as symptomatic subependymomas in the lateral ventricle have an average diameter of 5 cm, while those that are asymptomatic have an average diameter of only 0.8 cm.8 Furthermore, large subependymomas tend to show cyst formation, calcification, and hemorrhage.5–8 Thus, this large subependymoma with neuroradiological and neuropathological evidence of calcification and hemorrhage is consistent with reports on symptomatic subependymomas.5–7,11,12 During the brain nMRI, we observed peritumoral edema, a midline shift, and partial T1-weighted gadolinium enhancement. In frequent, glioblastomas, IDH-wildtype, revealed MRI features characterized by irregular-shaped tumor with ring-shape enhancement, peritumoral edema, and central hypointense area suggesting tumor necrosis.13 Intraventricular glioblastoma, although extremely rare, also exhibited the same MRI findings as intraparenchymal ones; namely irregular-shape, heterogeneous or ring-like enhancement, peritumoral edema, and hypointense areas indicating
necrosis.14 Thus, our differential diagnosis included a highgrade glioma, such as glioblastoma, although the presence of calcification suggested a slow-growing brain tumor,15 rather than a high-grade glioma. Therefore, caution is needed when analyzing neuroradiological images, and careful examination may increase the reliability of the pathological diagnosis. Despite differences in tumor sizes and/or symptoms, the histopathological features of subependymomas are similar to those of ependymomas.11 For example, subependymomas are characteristic hypocellular neoplasms with small glial-cell clusters and a fibrillary background of glial cells,1 in which mitotic figures are rare. Specimens from large subependymomas also frequently exhibit cyst formation, calcium deposition, and vascular hyalinization However, these findings are less common in small tumors.1,11 Immunohistochemistry rarely reveals dot and/or ring immunoreactivity to EMA, as subependymomas are considered a variant of ependymal tumors.1,16,17 In the present case, the tumor’s histopathological features were indicative of subependymoma, and there were no ependymoma components, such as ependymal rosettes, ependymal canals, and/or perivascular pseudorosettes. Furthermore, the immunohistochemical findings were compatible with the immunoprofile of
Please cite this article in press as: Hanashima Y, et al. A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report. Neurocirugia. 2018. https://doi.org/10.1016/j.neucir.2018.06.001
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Fig. 2 – Histopathological features. The lateral ventricular mass displayed a slightly increased cellularity, frequent microcyst formation, and hemorrhage (A, 40×). The tumor had a biphasic structure: one area had scattered small clusters of neoplastic cells with a fibrillary background (B, 100×) and the other area had frequent microcyst formation (C, 100×). Intracytoplasmic eosinophilic dot/ring-like inclusions (black arrow) were observed (D, 400×).
Fig. 3 – Immunohistochemical features. The mass was positive for glial fibrillary acidic protein (A, 200×) and negative for oligodendrocyte transcription factor 2 (B, 200×). The neoplastic cells had frequent intracytoplasmic dots/rings that were positive for epithelial membrane antigen (C, 400×) and D2-40 (D, 400×).
subependymomas: positive for glial fibrillary acidic protein and S100 protein, negative for oligodendrocyte transcription factor 2, and an extremely low MIB-1 labeling index. However, the present case also involved cytoplasmic EMA-positive dots/rings. Such EMA-immunoreactivity is, contrary to ependymomas, unusual for subependymomas,18,19 but was
the characteristic pathological feature in the present case. It appears that subependymomas and ependymomas can co-exist and it is possible that subependymomas represent a variant of ependymomas.11 We believe that our histopathological and immunohistochemical findings also support this theory, and that the neoplastic cells exhibit ependymal
Please cite this article in press as: Hanashima Y, et al. A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report. Neurocirugia. 2018. https://doi.org/10.1016/j.neucir.2018.06.001
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differentiation at the cellular level but not at the structural level.
Conclusions In conclusion, we encountered a Japanese man with a symptomatic large subependymoma, who exhibited signs of hemorrhage, peritumoral edema, and a midline shift, mimicking high-grade-gliomas, such as a glioblastoma. Thus, the clinical and neuroradiological findings could have supported the diagnosis of a high-grade glioma. 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.
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Authors’ contributions Yuya Hanashima collected the patient’s clinical data and prepared the manuscript. Taku Homma performed the pathological examination and prepared the manuscript. Toshiya Maebayashi analyzed and prepared neuroradiological imaging data. Takahiro Igarashi and Atsuo Yoshino collected the patient’s clinical data and checked clinical sections of the manuscript. Toshiyuki Ishige and Hiroyuki Hao performed pathological examinations. Finally, all authors read and approved the final version of the manuscript.
Acknowledgements
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The authors thank Mrs. Yukari Hirotani (Department of Pathology, Nihon University School of Medicine) for her excellent technical assistance.
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references
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Please cite this article in press as: Hanashima Y, et al. A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report. Neurocirugia. 2018. https://doi.org/10.1016/j.neucir.2018.06.001