Brain Tumor Pathol DOI 10.1007/s10014-014-0204-2
CASE REPORT
Central neurocytoma with ependymoma-like glial component Fumi Kawakami • Junichi Nambu • Takanori Hirose • Takashi Sasayama Tomoo Itoh
•
Received: 9 September 2014 / Accepted: 20 October 2014 Ó The Japan Society of Brain Tumor Pathology 2014
Abstract We present the first case of central neurocytoma with a component suggesting ependymal-like differentiation as an unclassified glioneuronal tumor. The patient was a 26-year-old Japanese man with a brain tumor extending from the frontal wall of the bilateral lateral ventricles to the corpus callosum. Histologically, the tumor’s neuronal component consisted of small bland looking cells with fine, delicate, neuropil-like processes forming a rosette structure; its glial component consisted of tumor cells with thick processes arranged around the thinly walled vessels, resulting in a perivascular pseudo-rosette formation and indicating ependymal-like differentiation. Immunohistochemically, the cytoplasm of the tumor cells with ependymal-like features was positive for glial fibrillary acidic protein and negative for synaptophysin, while the tumor component with neuronal features showed the opposite immunohistochemical staining pattern. Most of the tumor cells were positive for Olig2, but EMA, D2-40, CD99, p53, and mutant IDH-1 (R132H) were totally F. Kawakami (&) J. Nambu T. Itoh Department of Diagnostic Pathology, Kobe University Hospital, 7-5-2, Kusunoki cho, Chuou-ku, Kobe, Hyogo 650-0017, Japan e-mail: [email protected] T. Hirose Division of Pathology for Regional Communication, Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki cho, Chuou-ku,, Kobe, Hyogo 650-0017, Japan T. Hirose Department of Diagnostic Pathology, Hyogo Cancer Center, 13-70, Kitaoji-cho, Akashi, Hyogo 673-0021, Japan T. Sasayama Department of Neurosurgery, Kobe University Hospital, 7-5-2, Kusunoki cho, Chuou-ku, Kobe, Hyogo 650-0017, Japan
negative. Its Ki-67 labeling index was less than 1 %. Histologically, this tumor was diagnosed as a central neurocytoma with an ependymoma-like glial component, and its tumor grade was estimated at grade II. The tumor location, infiltrating the corpus callosum, and histology were distinctive and might represent a peculiar subtype of glioneuronal tumor. Keywords Glioneuronal tumor Central neurocytoma Ependymoma Olig2
Introduction Neuronal and glioneuronal neoplasms are a group of slowgrowing, indolent tumors, generally affecting younger patients. According to the existing World Health Organization (WHO) classification, this group includes desmoplastic infantile astrocytoma and ganglioglioma, dysembryoplastic neuroepithelial tumors, ganglioglioma, gangliocytoma, central neurocytoma, extraventricular neurocytoma, cerebellar liponeurocytoma, papillary glioneuronal tumors (PGNTs), rosette-forming glioneuronal tumors of the fourth ventricle (RGNTs), and spinal paraganglioma [1]. The main components of these tumors are ganglion cells and/or neurocytes, but it is not uncommon for them to be associated with astrocytic glial components. Although anaplastic ganglioglioma is a highly aggressive grade III tumor, and central neurocytoma is classified as grade II tumor, most of the tumors in this category show a favorable prognosis and are thus classified as Grade I. However, some exceptional cases with a rapid progression have been reported [2, 3]. From another point of view, precious few cases of glioma show focal neuronal differentiation. The most notable
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Fig. 1 Radiological findings of the brain tumor extending from the frontal wall of the bilateral lateral cerebral ventricles to the corpus callosum. a On computed tomography images, the tumor was isointense and accompanied focal calcification. b–d T1-weighted
MRI revealing a slightly lower signal from the tumor than from the adjacent cerebral parenchyma (b) and on T2-weighted images, the tumor shows slightly higher signal intensity (c). The tumor image was enhanced by the administration of a contrast agent (d)
example is glioneuronal tumors with neuropil-like islands (GTNI). GTNI is a rare infiltrating astrocytoma and oligoastrocytoma accompanied by focal round islands composed of a delicate, neuropil-like matrix that is immunoreactive for synaptophysin and NeuN [4]; GTNI was originally described by Teo et al. [5]. Its clinical outcome and molecular background can be comparable to that of diffuse glioma, and the neuronal component of GTNI is thus presumed to be an aberrant neuronal differentiation of glial tumor cells [6–8]. In addition to this phenomenon, a small number of case reports of oligodendroglioma and ependymoma containing various neurocytic components, such as the neurocytic rosette, neuropil-like islands, ganglion cell differentiation, and others, has also been reported [9–13]. Here, we present the first case of central neurocytoma with a component indicating ependymal-like differentiation infiltrating the corpus callosum as an unclassified glioneuronal tumor.
the tumor than from the adjacent cerebral parenchyma, which was located at the anterior part of the corpus callosum (Fig. 1b), and T2-weighted images revealed a slightly higher signal from the same (Fig. 1c). The tumor was enhanced with the addition of a contrast agent to the MRI (Fig. 1d). Radiologically, astrocytoma and ependymoma were listed as the presumptive diagnoses. The tumor was removed by craniotomy. The patient’s postoperative course was uneventful, without recurrence for 3 months.
Clinical summary The patient was a 26-year-old Japanese man with a brain tumor extending from the frontal wall of the bilateral lateral ventricles to the corpus callosum. The tumor was incidentally detected by computed tomography (CT) (Fig. 1a) for intracranial injury screening following a traffic accident. The patient had no appreciable medical history. None of his consanguine family had a history of brain tumor. A physical and neurological examination indicated no abnormalities. Six months later, he was reevaluated using CT and no clear tumor growth was detected. The tumor was solid with focal cystic changes and calcification (Fig. 1a). T1-weighted magnetic resonance images (MRI) revealed a slightly lower signal from
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Pathological findings Formalin-fixed paraffin-embedded tissue sections were used for hematoxylin and eosin (HE) staining and immunohistochemistry. Immunohistochemical staining was performed using BenchMark XT (Ventana, Tucson, AZ) (GFAP, D2-40, CD99, Olig2, Synaptophysin, p53, and KiTM 67) and BOND-MAX (Leica Biosystems, Wetzlar, Germany) [epithelial membrane antigen (EMA) and mutant IDH1 (R132H)]. The primary antibodies used were as follows: glial fibrillary acidic protein (GFAP) (EP672Y; Roche, Basel, Switzerland), Olig2 (1:20 dilution; ImmunoBiological Laboratories, Gunma, Japan), synaptophysin (SP1; Roche), EMA (E29, 1:2 dilution; Dako, Carpinteria, CA), D2-40 (1:30 dilution; Dako), CD99 (12E7, 1:200 dilution; Dako), p53 (DO-7; Dako), mutant IDH1 (R132H) (H09, 1:40 dilution; Optistain Medical, Marion, VA), and Ki-67 (Mib-1, 1:5 dilution; Dako). The tumor was located at the corpus callosum. It was mostly well demarcated and showed an expansile growth pattern. It was composed of two characteristic components (Fig. 2a). In most of the area, tumor cells with small bland looking oval- to round-shaped nuclei and fine delicate neuropil-like processes formed rosette structures, suggesting neuronal differentiation (Fig. 2b). In a small area, the
Brain Tumor Pathol
Fig. 2 Histological findings of the central neurocytoma with an ependymoma-like glial component. a A glial component (lower right area) and neuronal component existed alongside each other in the same tumor. b The neuronal component of the tumor. Tumor cells with small, bland looking, oval- to round-shaped nuclei and fine delicate neuropil-like processes formed a rosette structure. c In the glial component, tumor cells had relatively thick processes and were arranged around thinly walled vessels, resulting in a perivascular pseudo-rosette formation, and indicating ependymal-like
differentiation. d–i Immunohistochemically, the neuronal component was negative for GFAP (e), and positive for synaptophysin (h), while the glial component showed the opposite staining pattern: GFAP positive (f) and synaptophysin negative (i). Olig2 was positive for the tumor cells of both components (g). The Ki-67 labeling index was generally low (less than 1 %); however, a relatively large number of Ki-67 positive cells were identified in a part of the glial component (d)
nuclei of tumor cells were large and showed mild irregular contours and pleomorphism with coarse hyperchromasia. Although there was no true rosette or microrosette structure, the tumor cells had relatively thick processes and were arranged around thinly walled vessels resulting in a perivascular pseudo-rosette formation, indicating ependymal-like differentiation (Fig. 2c). In this area, three mitoses were detected in the whole section. Tumor necrosis and microvascular proliferation were not found in either component. Immunohistochemically, the cytoplasm of the tumor cells with ependymal features was positive for GFAP (Fig. 2f) and negative for synaptophysin (Fig. 2i), while the tumor component with neuronal features showed the opposite immunohistochemical staining pattern: negative for GFAP (Fig. 2e) and positive for synaptophysin (Fig. 2h). Most of the tumor cells were positive for Olig2
(Fig. 2g), but EMA, D2-40, CD99, p53, and mutant IDH-1 (R132H) were totally negative. The Ki-67 labeling index was less than 1 %, but 10 % of the tumor cells were positive for Ki-67 in the area with ependymal features (Fig. 2d). The histological and immunohistochemical profiles of this tumor suggested that it was a combined glial and neuronal tumor, and histologically, its neuronal and glial components mimicked central neurocytoma and ependymoma, respectively.
Discussion We described a peculiar lesion characterized by a neurocytic neoplasm fulfilling the histological criteria of a central neurocytoma containing glial components with ependymoma-like features, and immunohistochemical
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staining patterns, which confirmed its histology. The glial component was characterized by its thick processes, the perivascular pseudo-rosette arrangement of the tumor cells, and cytoplasmic positivity for GFAP, suggesting its ependymal-like differentiation. The neuronal component consisted of synaptophysin positive, bland looking, small tumor cells with fine and delicate neuropil-like processes showing an occasional rosette formation, suggesting central neurocytoma. Although a variety of brain tumors with biphasic histology consisting of neuronal and glial components have been described, reported cases of a central neurocytoma with glioma components are scarce. There have been only few descriptions of GFAP positive cells in cases of central neurocytoma, and none of them formed a morphologically evident gliomatous component [14, 15]. Usually, GFAP positive cells in a neurocytoma are considered to be intervening reactive astrocytes. To date, a case of central neurocytoma accompanied by ependymoma has not been reported in the English-language literature. As an intriguing case, a recurrent cerebellar liponeurocytoma with ependymal differentiation was described by Jouvet et al. [16], and might have a link to our case regarding its histogenesis. On another front, rare ependymomas could demonstrate neuronal differentiation. There have been three reported cases of ependymoma with neuropil-like islands. All three cases occurred in either children or adolescents and were supratentorial lesions: a 29-month-old girl with a huge mass in her left lateral ventricle [9], a 6-year-old boy with a large, partially cystic, parieto-occipital lesion [11], and a 16-year-old boy with a frontoparietal solid and cystic, superficially situated, tumor [10]. Rodriguez et al. reported a case of another ependymoma arising in the fourth ventricle of a 5-year-old girl with a peculiar type of neuronal differentiation, pale islands [10]. According to their study, a considerable number of cases of ependymoma without morphologically apparent neuronal elements show neuronal differentiation immunohistochemically and ultrastructurally. Although our case had ependymal-like differentiation of the glial component in common with these cases, the clinical features, including patient age, tumor location, and the histology of the neuronal component, were significantly different. Various alternatives may be proposed for the pathogenesis of the current case. Interestingly, most of the tumor cells were positive for Olig2. Although among the previous reports the pure central neurocytoma, extraventricular neurocytoma, and neurocytoma-like neural components in glioneuronal tumors were usually negative for Olig2 [17– 19], a small number of PGNTs and RGNTs containing Olig2 positive tumor cells with neuronal morphology have been reported [20]. It was experimentally revealed that
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Olig2 positive cells could differentiate into both glial and neuronal cells [21]. The subventricular zone (SVZ) of the forebrain, the tumor location of our case, is one of areas where the adult mammalian brain is capable of neurogenesis [22–24], and previous research has suggested that the SVZ is not only a source of new cells but also a potential source of brain tumors [25]. Olig2 positive cells in the SVZ may have a similar nature to progenitor cells of the CNS, and play important roles in the histogenesis of this tumor. In this report, we describe the case of an unusual glioneuronal tumor showing central neurocytoma with a glial component showing ependymoma-like histology. The tumor location, infiltrating the corpus callosum, as well as its histology, is distinctive and might represent a peculiar subtype of glioneuronal tumor. Because both components are classified as Grade II tumors, we presume this tumor will behave as a Grade II. However, its actual malignancy potential is unknown, and a careful follow-up will be needed in this particular case. Conflict of interest
There is no conflict of interest to be declared.
References 1. Nakazato Y, Figarella-Branger D, Becker AJ, Scheithauer BW, Rosenblum MK (2007) Chapter 6 neuronal and mixed neuronalglial tumours, Papillary glioneuronal tumor. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system, 4th edn. IARC Press, Lyon, pp 113–114 2. Chiba K, Aihara Y, Eguchi S, Tanaka M, Komori T, Okada Y (2014) Rosette-forming glioneuronal tumor of the fourth ventricle with neurocytoma component. Childs Nerv Syst 30:351–356 3. Garcı´a Cabezas S, Serrano Blanch R, Sanchez-Sanchez R, Palacios Eito A (2014) Rosette-forming glioneuronal tumour (RGNT) of the fourth ventricle: a highly aggressive case. Brain Tumor Pathol (Epub ahead of print) 4. Kleihues P, Burger PC, Rosenblum MK et al (2007) Chapter 1 Astrocytic tumours, Anaplastic astrocytoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system, 4th edn. IARC Press, Lyon, pp 30–32 5. Teo JG, Gultekin SH, Bilsky M, Gutin P, Rosenblum MK (1999) A distinctive glioneuronal tumor of adult cerebrum with neuropillike (including ‘‘rosetted’’) islands. Report of 4 cases. Am J Surg Pathol 23:502–510 6. Huse JT, Nafa K, Shukla N, Kastenhuber ER, Lavi E, Hedvat CV, Ladanyi M, Rosenblum MK (2011) High frequency of IDH-1 mutation links glioneuronal tumors with neuropil-like islands to diffuse astrocytomas. Acta Neuropathol 122:367–369 7. Schlamann A, von Bueren AO, Hagel C, Zwiener I, Seidel C, Kortmann RD, Mu¨ller K (2014) An individual patient data metaanalysis on characteristics and outcome of patients with papillary glioneuronal tumor, rosette glioneuronal tumor with neuropil-like islands and rosette forming glioneuronal tumor of the fourth ventricle. PLoS One 9:e101211 8. Ishizawa K, Hirose T, Sugiyama K, Kageji T, Nobusawa S, Homma T, Komori T, Sasaki A (2012) Pathologic diversity of glioneuronal tumor with neuropil-like islands: a histological and
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CASE REPORT
Central neurocytoma with ependymoma-like glial component Fumi Kawakami • Junichi Nambu • Takanori Hirose • Takashi Sasayama Tomoo Itoh
•
Received: 9 September 2014 / Accepted: 20 October 2014 Ó The Japan Society of Brain Tumor Pathology 2014
Abstract We present the first case of central neurocytoma with a component suggesting ependymal-like differentiation as an unclassified glioneuronal tumor. The patient was a 26-year-old Japanese man with a brain tumor extending from the frontal wall of the bilateral lateral ventricles to the corpus callosum. Histologically, the tumor’s neuronal component consisted of small bland looking cells with fine, delicate, neuropil-like processes forming a rosette structure; its glial component consisted of tumor cells with thick processes arranged around the thinly walled vessels, resulting in a perivascular pseudo-rosette formation and indicating ependymal-like differentiation. Immunohistochemically, the cytoplasm of the tumor cells with ependymal-like features was positive for glial fibrillary acidic protein and negative for synaptophysin, while the tumor component with neuronal features showed the opposite immunohistochemical staining pattern. Most of the tumor cells were positive for Olig2, but EMA, D2-40, CD99, p53, and mutant IDH-1 (R132H) were totally F. Kawakami (&) J. Nambu T. Itoh Department of Diagnostic Pathology, Kobe University Hospital, 7-5-2, Kusunoki cho, Chuou-ku, Kobe, Hyogo 650-0017, Japan e-mail: [email protected] T. Hirose Division of Pathology for Regional Communication, Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki cho, Chuou-ku,, Kobe, Hyogo 650-0017, Japan T. Hirose Department of Diagnostic Pathology, Hyogo Cancer Center, 13-70, Kitaoji-cho, Akashi, Hyogo 673-0021, Japan T. Sasayama Department of Neurosurgery, Kobe University Hospital, 7-5-2, Kusunoki cho, Chuou-ku, Kobe, Hyogo 650-0017, Japan
negative. Its Ki-67 labeling index was less than 1 %. Histologically, this tumor was diagnosed as a central neurocytoma with an ependymoma-like glial component, and its tumor grade was estimated at grade II. The tumor location, infiltrating the corpus callosum, and histology were distinctive and might represent a peculiar subtype of glioneuronal tumor. Keywords Glioneuronal tumor Central neurocytoma Ependymoma Olig2
Introduction Neuronal and glioneuronal neoplasms are a group of slowgrowing, indolent tumors, generally affecting younger patients. According to the existing World Health Organization (WHO) classification, this group includes desmoplastic infantile astrocytoma and ganglioglioma, dysembryoplastic neuroepithelial tumors, ganglioglioma, gangliocytoma, central neurocytoma, extraventricular neurocytoma, cerebellar liponeurocytoma, papillary glioneuronal tumors (PGNTs), rosette-forming glioneuronal tumors of the fourth ventricle (RGNTs), and spinal paraganglioma [1]. The main components of these tumors are ganglion cells and/or neurocytes, but it is not uncommon for them to be associated with astrocytic glial components. Although anaplastic ganglioglioma is a highly aggressive grade III tumor, and central neurocytoma is classified as grade II tumor, most of the tumors in this category show a favorable prognosis and are thus classified as Grade I. However, some exceptional cases with a rapid progression have been reported [2, 3]. From another point of view, precious few cases of glioma show focal neuronal differentiation. The most notable
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Fig. 1 Radiological findings of the brain tumor extending from the frontal wall of the bilateral lateral cerebral ventricles to the corpus callosum. a On computed tomography images, the tumor was isointense and accompanied focal calcification. b–d T1-weighted
MRI revealing a slightly lower signal from the tumor than from the adjacent cerebral parenchyma (b) and on T2-weighted images, the tumor shows slightly higher signal intensity (c). The tumor image was enhanced by the administration of a contrast agent (d)
example is glioneuronal tumors with neuropil-like islands (GTNI). GTNI is a rare infiltrating astrocytoma and oligoastrocytoma accompanied by focal round islands composed of a delicate, neuropil-like matrix that is immunoreactive for synaptophysin and NeuN [4]; GTNI was originally described by Teo et al. [5]. Its clinical outcome and molecular background can be comparable to that of diffuse glioma, and the neuronal component of GTNI is thus presumed to be an aberrant neuronal differentiation of glial tumor cells [6–8]. In addition to this phenomenon, a small number of case reports of oligodendroglioma and ependymoma containing various neurocytic components, such as the neurocytic rosette, neuropil-like islands, ganglion cell differentiation, and others, has also been reported [9–13]. Here, we present the first case of central neurocytoma with a component indicating ependymal-like differentiation infiltrating the corpus callosum as an unclassified glioneuronal tumor.
the tumor than from the adjacent cerebral parenchyma, which was located at the anterior part of the corpus callosum (Fig. 1b), and T2-weighted images revealed a slightly higher signal from the same (Fig. 1c). The tumor was enhanced with the addition of a contrast agent to the MRI (Fig. 1d). Radiologically, astrocytoma and ependymoma were listed as the presumptive diagnoses. The tumor was removed by craniotomy. The patient’s postoperative course was uneventful, without recurrence for 3 months.
Clinical summary The patient was a 26-year-old Japanese man with a brain tumor extending from the frontal wall of the bilateral lateral ventricles to the corpus callosum. The tumor was incidentally detected by computed tomography (CT) (Fig. 1a) for intracranial injury screening following a traffic accident. The patient had no appreciable medical history. None of his consanguine family had a history of brain tumor. A physical and neurological examination indicated no abnormalities. Six months later, he was reevaluated using CT and no clear tumor growth was detected. The tumor was solid with focal cystic changes and calcification (Fig. 1a). T1-weighted magnetic resonance images (MRI) revealed a slightly lower signal from
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Pathological findings Formalin-fixed paraffin-embedded tissue sections were used for hematoxylin and eosin (HE) staining and immunohistochemistry. Immunohistochemical staining was performed using BenchMark XT (Ventana, Tucson, AZ) (GFAP, D2-40, CD99, Olig2, Synaptophysin, p53, and KiTM 67) and BOND-MAX (Leica Biosystems, Wetzlar, Germany) [epithelial membrane antigen (EMA) and mutant IDH1 (R132H)]. The primary antibodies used were as follows: glial fibrillary acidic protein (GFAP) (EP672Y; Roche, Basel, Switzerland), Olig2 (1:20 dilution; ImmunoBiological Laboratories, Gunma, Japan), synaptophysin (SP1; Roche), EMA (E29, 1:2 dilution; Dako, Carpinteria, CA), D2-40 (1:30 dilution; Dako), CD99 (12E7, 1:200 dilution; Dako), p53 (DO-7; Dako), mutant IDH1 (R132H) (H09, 1:40 dilution; Optistain Medical, Marion, VA), and Ki-67 (Mib-1, 1:5 dilution; Dako). The tumor was located at the corpus callosum. It was mostly well demarcated and showed an expansile growth pattern. It was composed of two characteristic components (Fig. 2a). In most of the area, tumor cells with small bland looking oval- to round-shaped nuclei and fine delicate neuropil-like processes formed rosette structures, suggesting neuronal differentiation (Fig. 2b). In a small area, the
Brain Tumor Pathol
Fig. 2 Histological findings of the central neurocytoma with an ependymoma-like glial component. a A glial component (lower right area) and neuronal component existed alongside each other in the same tumor. b The neuronal component of the tumor. Tumor cells with small, bland looking, oval- to round-shaped nuclei and fine delicate neuropil-like processes formed a rosette structure. c In the glial component, tumor cells had relatively thick processes and were arranged around thinly walled vessels, resulting in a perivascular pseudo-rosette formation, and indicating ependymal-like
differentiation. d–i Immunohistochemically, the neuronal component was negative for GFAP (e), and positive for synaptophysin (h), while the glial component showed the opposite staining pattern: GFAP positive (f) and synaptophysin negative (i). Olig2 was positive for the tumor cells of both components (g). The Ki-67 labeling index was generally low (less than 1 %); however, a relatively large number of Ki-67 positive cells were identified in a part of the glial component (d)
nuclei of tumor cells were large and showed mild irregular contours and pleomorphism with coarse hyperchromasia. Although there was no true rosette or microrosette structure, the tumor cells had relatively thick processes and were arranged around thinly walled vessels resulting in a perivascular pseudo-rosette formation, indicating ependymal-like differentiation (Fig. 2c). In this area, three mitoses were detected in the whole section. Tumor necrosis and microvascular proliferation were not found in either component. Immunohistochemically, the cytoplasm of the tumor cells with ependymal features was positive for GFAP (Fig. 2f) and negative for synaptophysin (Fig. 2i), while the tumor component with neuronal features showed the opposite immunohistochemical staining pattern: negative for GFAP (Fig. 2e) and positive for synaptophysin (Fig. 2h). Most of the tumor cells were positive for Olig2
(Fig. 2g), but EMA, D2-40, CD99, p53, and mutant IDH-1 (R132H) were totally negative. The Ki-67 labeling index was less than 1 %, but 10 % of the tumor cells were positive for Ki-67 in the area with ependymal features (Fig. 2d). The histological and immunohistochemical profiles of this tumor suggested that it was a combined glial and neuronal tumor, and histologically, its neuronal and glial components mimicked central neurocytoma and ependymoma, respectively.
Discussion We described a peculiar lesion characterized by a neurocytic neoplasm fulfilling the histological criteria of a central neurocytoma containing glial components with ependymoma-like features, and immunohistochemical
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staining patterns, which confirmed its histology. The glial component was characterized by its thick processes, the perivascular pseudo-rosette arrangement of the tumor cells, and cytoplasmic positivity for GFAP, suggesting its ependymal-like differentiation. The neuronal component consisted of synaptophysin positive, bland looking, small tumor cells with fine and delicate neuropil-like processes showing an occasional rosette formation, suggesting central neurocytoma. Although a variety of brain tumors with biphasic histology consisting of neuronal and glial components have been described, reported cases of a central neurocytoma with glioma components are scarce. There have been only few descriptions of GFAP positive cells in cases of central neurocytoma, and none of them formed a morphologically evident gliomatous component [14, 15]. Usually, GFAP positive cells in a neurocytoma are considered to be intervening reactive astrocytes. To date, a case of central neurocytoma accompanied by ependymoma has not been reported in the English-language literature. As an intriguing case, a recurrent cerebellar liponeurocytoma with ependymal differentiation was described by Jouvet et al. [16], and might have a link to our case regarding its histogenesis. On another front, rare ependymomas could demonstrate neuronal differentiation. There have been three reported cases of ependymoma with neuropil-like islands. All three cases occurred in either children or adolescents and were supratentorial lesions: a 29-month-old girl with a huge mass in her left lateral ventricle [9], a 6-year-old boy with a large, partially cystic, parieto-occipital lesion [11], and a 16-year-old boy with a frontoparietal solid and cystic, superficially situated, tumor [10]. Rodriguez et al. reported a case of another ependymoma arising in the fourth ventricle of a 5-year-old girl with a peculiar type of neuronal differentiation, pale islands [10]. According to their study, a considerable number of cases of ependymoma without morphologically apparent neuronal elements show neuronal differentiation immunohistochemically and ultrastructurally. Although our case had ependymal-like differentiation of the glial component in common with these cases, the clinical features, including patient age, tumor location, and the histology of the neuronal component, were significantly different. Various alternatives may be proposed for the pathogenesis of the current case. Interestingly, most of the tumor cells were positive for Olig2. Although among the previous reports the pure central neurocytoma, extraventricular neurocytoma, and neurocytoma-like neural components in glioneuronal tumors were usually negative for Olig2 [17– 19], a small number of PGNTs and RGNTs containing Olig2 positive tumor cells with neuronal morphology have been reported [20]. It was experimentally revealed that
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Olig2 positive cells could differentiate into both glial and neuronal cells [21]. The subventricular zone (SVZ) of the forebrain, the tumor location of our case, is one of areas where the adult mammalian brain is capable of neurogenesis [22–24], and previous research has suggested that the SVZ is not only a source of new cells but also a potential source of brain tumors [25]. Olig2 positive cells in the SVZ may have a similar nature to progenitor cells of the CNS, and play important roles in the histogenesis of this tumor. In this report, we describe the case of an unusual glioneuronal tumor showing central neurocytoma with a glial component showing ependymoma-like histology. The tumor location, infiltrating the corpus callosum, as well as its histology, is distinctive and might represent a peculiar subtype of glioneuronal tumor. Because both components are classified as Grade II tumors, we presume this tumor will behave as a Grade II. However, its actual malignancy potential is unknown, and a careful follow-up will be needed in this particular case. Conflict of interest
There is no conflict of interest to be declared.
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