Childs Nerv Syst DOI 10.1007/s00381-015-2706-6
CASE REPORT
Atypical extraventricular neurocytoma in a 3-year-old girl: case report with radiological-pathological correlation Hiroo Kawano 1 & Tokuhiro Kimura 2 & Koji Iwata 3 & Matakazu Furukawa 4 & Sadahiro Nomura 5 & Aya Ishii 2 & Shinsuke Tanaka 6 & Yoshinobu Hoshii 6 & Michiyasu Suzuki 5 & Eiji Ikeda 2
Received: 28 March 2015 / Accepted: 8 April 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Background Extraventricular neurocytoma (EVN) is a rare neuronal tumor histologically similar to central neurocytoma but arising in the brain parenchyma outside the ventricles. The minority of EVNs show atypical features including increased proliferative index, microvascular proliferation, or necrosis, and are called atypical EVN. Most of atypical EVNs occur in adults, and the tumors in children are extremely rare. A radiological-pathological correlation and radiological clue to atypical EVNs have not been clarified. Case report We report a case of atypical EVN in a 3-year-old girl. Magnetic resonance imaging (MRI) revealed an extraventricular intraparenchymal tumor in the left frontal lobe, which was composed of homogeneous welldemarcated cystic component and peripheral ill-delineated solid component with enhancement. Angiography demonstrated vascular proliferation and arteriovenous shunting in the tumor. Histologically, the resected tumor was diagnosed as atypical EVN. Types of the tumor borders (well-
* Tokuhiro Kimura [email protected] 1
Department of Basic Laboratory Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan
2
Department of Pathology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan
3
Yamaguchi University Hospital, Ube, Japan
4
Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Japan
5
Department of Neurosurgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
6
Division of Surgical Pathology, Yamaguchi University Hospital, Ube, Japan
circumscribed or infiltrative) and MRI findings correlated closely. Morphology of the tumor vasculature was remarkable for microvascular proliferation and dilated, thickened veins, which corresponded to the angiographic features. Conclusion Although rare, atypical EVN should be included in the differential diagnosis of a cystic mass in the cerebral hemispheres in children. Radiological evaluation of tumor borders and angiographic characteristics might be useful for predicting atypicality of the tumor. Keywords Extraventricular neurocytoma . Child . Neuroimaging . Angiography . Histology . Radiological-pathological correlation
Introduction Neuronal tumors are uncommon neoplasms of the central nervous system showing neuronal differentiation. Central neurocytoma (CN) is a neuronal tumor arising in the cerebral ventricles near the foramen of Monro. It consists of uniform, small, round neurocytes which often have perinuclear halos resembling oligodendroglioma cells. Rarely, tumors histologically similar to CNs arise in the brain parenchyma outside the ventricular system, and are called extraventricular neurocytoma (EVN). EVN has been listed as a distinct entity in the 2007 World Health Organization (WHO) Classification [6], and is categorized as a WHO grade II tumor [7]. Its histological features and biological behavior are similar to those of CN, but EVNs appear to exhibit a wider morphological spectrum [7]. The minority of EVNs show atypical histological features including increased proliferative index, microvascular proliferation, or necrosis, and are called atypical EVNs, which are regarded as a more aggressive variant [1, 5]. Most of the reported cases of atypical EVN are adults and, in fact,
Childs Nerv Syst
A 3-year-old girl was admitted to our hospital due to muscle weakness of the right side. Her birth and postnatal development were uneventful. Although she was right-handed, she began to use her left hand 1 month before the admission. Subsequently, she showed abnormal gait, frequent falling, and drooling. Neurological examination revealed right hemiparesis of the upper and lower extremities and papilledema. A computed tomography (CT) scan showed a well-demarcated cystic lesion in the left frontal lobe without
calcification and hemorrhage. Magnetic resonance imaging (MRI) demonstrated an extraventricular cystic mass of 65× 50×56 mm with midline shift. Peritumoral edema was not evident. On contrast-enhanced MRI, the medial and posterior parts of the lesion were composed of thin enhancing rim that was well-demarcated, while the lateral and anterior parts were relatively ill-delineated solid enhancing component (Fig. 1a, b). MR angiography suggested vascular proliferation in relation to the solid component of the lesion (Fig. 1c). Digital subtraction angiogram of the left internal carotid artery revealed vascular proliferation at the site corresponding to the solid component of the mass (Fig. 1d). It also showed early venous drainage in an arterial phase (Fig. 1e), indicating arteriovenous (AV) shunting associated with the mass. Resection was performed except for the portion attached to the motor area. The postoperative course was uneventful. No regrowth of the tumor was detected on follow-up 1 year after the surgery. Histological examination of the resected tissue revealed that most of the lesion was located in the white matter and was composed of a proliferation of uniform, small, round cells with perinuclear halos (Fig. 2a). Neuropil islands and ganglion-like large neuronal cells were occasionally seen (Fig. 2a), suggesting neuronal differentiation of the tumor
Fig. 1 Neuroradiological findings of the tumor. a, b Gadoliniumenhanced T1-weighted MR images (a axial, b coronal) show a welldemarcated cystic mass with peripheral solid component in the left frontal lobe. c MR angiography reveals increased vascular signal
corresponding to the solid component of the tumor (arrows). d, e Digital subtraction angiogram of the left internal carotid artery in lateral views (d arterial phase, e late arterial phase) shows vascular proliferation associated with the mass (arrow) and early venous drainage (arrowhead)
more than half of the patients of atypical EVN are reported to be in their sixth decade and above [5]. Atypical EVNs in children are extremely uncommon, but have been increasingly recognized in recent years in several case reports [1–3, 9, 11–13]. Although neuroradiological and histological findings were briefly mentioned in the previous reports, a precise radiological-pathological correlation of atypical EVN and a radiological clue to diagnosis of atypical tumors have not been described. Here, we report a case of atypical EVN in a 3-yearold girl with special reference to correlation of neuroradiological findings and histopathology.
Case report
Childs Nerv Syst
cells. Mitoses were found, ranging from 1 to 18/10 highpower fields. Immunohistochemically, both of the round cells with perinuclear halos and ganglion-like large cells were positive for NeuN (Fig. 2b) and synaptophysin (Fig. 2c).
Synaptophysin positivity was accentuated in neuropil islands (Fig. 2c). The tumor cells were negative for Olig2, glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), and mutant isocitrate dehydrogenase 1 (IDH1-
Fig. 2 Histological findings of the tumor. a The tumor is composed of a proliferation of round cells with perinuclear halos. Neuropil islands (arrowheads) and ganglion-like large neuronal cells (arrow) were occasionally seen. b–d Immunohistochemically, both of the round cells and ganglion-like large cells (b arrows) are positive for NeuN (b) and synaptophysin (c). Synaptophysin positivity was accentuated in neuropil islands (c arrowhead). Ki-67 (MIB-1) labeling index is approximately 20 % (d). e Necrosis (N) of the tumor tissue is focally observed. f Vasculature of the tumor tissue shows branching capillary network. g
Endothelial hyperplasia and glomeruloid microvascular proliferation are frequently observed. h Dilated veins with thickened walls (V) are found near the microvascular proliferation (arrows). i Low-power view showing well-circumscribed, thin tumor tissue. Cystic cavity is seen at the left. Inset shows magnified view of boxed area. j Low-power view of the solid area (SA) of the tumor. At the periphery of the solid area, there is infiltrative area (IA) where the tumor cells infiltrate the brain parenchyma in a single-cell manner. Insets show magnified view of boxed areas. Scale bars: (a–g) 50 μm, (h–j) 250 μm
Solid and cystic Solid ND Cystic and solid Headache Nausea ND Hemiparesis Frontoparietal Frontal Temporoparietal Frontal 9/M 2/F 7/F 3/F 5 6 7 The present case
yryear, mo month, wk week, MIB-1 LI MIB-1 labeling index, ND not described, NF1 neurofibromatosis type 1, AV shunting arteriovenous shunting, MA increased mitotic activity, MV microvascular proliferation, C calcification, N necrosis, STR subtotal resection, GTR gross total resection; CT chemotherapy, DOD dead of disease
[2] [3] [11] ND DOD, 11 wk Stable lesion, 47 mo Stable lesion, 1 yr Decompression GTR STR+radiation STR 10 % 20 % ND 20 % MA, MV, C ND ND MA, MV, N
[13] [12] [9]
[1] Stable lesion, 42 mo
ND Recurrence, 8 mo No recurrence, 1 yr STR GTR+CT GTR+radiation
STR+radiation ND
13 % 4% 5% MA, MV, N C MA, N, C
ND ND
ND ND Minimal vascularity, no AV shunting ND ND ND Vascular proliferation, AV shunting Solid Solid and cystic Solid
Cyst and nodule ND
Paraparesis NF1 Seizure Spinal cord Occipital Frontal
Frontal 5/M
8/M 7/M 3/F
1
Symptoms Location Age (yr)/sex Case no.
Table 1
Atypical EVN is defined as EVN with atypical histological features including increased proliferative index, microvascular proliferation, or necrosis. The practical criteria for histological diagnosis of atypical EVN have been described as Bgeographic necrosis, vascular proliferation, or increased mitotic activity (≥3 mitoses/10 high-power fields)^ [1] or BMIB1 labeling index greater than 3 %, or features consistent with higher-grade tumors defined as frequent mitoses, vascular proliferation, or presence of necrosis^ [5]. The present case fulfilled both of these criteria. Radiologically, the preoperative differential diagnosis of the present case included pilocytic astrocytoma, desmoplastic infantile astrocytoma/ganglioglioma, and supratentorial primitive neuroectodermal tumor, but it was difficult to predict the histological type of the tumor from the CT and MRI findings. Histological examination revealed that the tumor was composed of round cells with perinuclear halos, which resembled oligodendroglioma or clear cell ependymoma. However, the cells were positive for neuronal markers (NeuN and synaptophysin) and negative for glial (Olig2 and GFAP) and ependymal (EMA) markers, suggesting neuronal character of the tumor. These immunohistochemical studies are particularly useful for the diagnosis of neurocytic neoplasms like this case. Atypical EVNs in children are very rare and, to our knowledge, only seven cases were reported previously (Table 1).
Reported cases of atypical extraventricular neurocytoma in children
Discussion
Neuroimaging
Angiographic findings
Histological features
MIB-1 LI
Treatment
Follow-up
R132H). Ki-67 (MIB-1) labeling index was approximately 20 % (Fig. 2d). Necrosis was focally observed (Fig. 2e). Morphology of the tumor vasculature was characteristic: in addition to branching capillary network (Fig. 2f), microvascular proliferation characterized by endothelial hyperplasia and formation of glomeruloid blood vessels were frequently found (Fig. 2g). Occasionally, dilated veins with thickened walls were observed near the microvascular proliferation (Fig. 2h). These findings indicated the diagnosis of atypical EVN. The microvascular proliferation and dilated, thickened veins in the tumor tissue are thought to be related directly to the angiographic signs of vascular proliferation and AV shunting, respectively. As the MRI suggested, the tumor tissue showed two patterns of growth: thin cyst-wall-like component (Fig. 2i) and solid component (Fig. 2j, inset 1). The tumor border of the former component is microscopically wellcircumscribed (Fig. 2i, inset), corresponding to thin enhancing rim on MRI. On the other hand, at the periphery of the latter component, the neoplastic cells infiltrated the cerebral cortex in a single-cell manner (Fig. 2j, inset 2), reaching the brain surface. The relatively indistinct border of the solid part on MRI could be explained by this infiltrative behavior of the tumor cells.
2 3 4
Reference
Childs Nerv Syst
Childs Nerv Syst
Most of those tumors arose in the cerebral hemispheres but the spinal cord was involved in one case. Symptoms were sitespecific. In neuroimaging, the tumors tended to show a wellcircumscribed, cystic, and solid pattern. Histologically, microvascular proliferation was reported in two cases, and necrosis was present in two cases. Calcification was sometimes found. MIB-1 labeling index was typically higher than 10 %. Although angiographic findings have rarely been reported in the previous cases of EVNs, they were described in case # 4 in Table 1. Notably, in case # 4, the angiography showed minimal vascularity and no AV shunting, and the tumor tissue lacked microvascular proliferation histologically [9]. In contrast, the present case exhibited vascular proliferation and AV shunting in the angiogram, and microvascular proliferation and dilated, thickened veins in histology, implying that angiographic findings might be a good indicator of the presence of atypical vascular features in EVN tissues. Compatibly, intratumoral AV shunting is often observed in glioblastomas in which microvascular proliferation is one of the histological hallmarks [8]. There have been several reports on radiological features of EVNs, in which most EVNs were reported to be wellcircumscribed [4, 10, 11, 14]. Histologically, Brat et al. described that most EVNs showed pushing borders and focal infiltration of tumor cells into adjacent brain tissue was observed more frequently in atypical EVNs than in typical ones [1]. In the present case, tumor infiltration was noted in histological examination, and the relatively indistinct border of the solid part on MRI probably reflected it. Although it is difficult to distinguish atypical EVNs from typical ones radiologically, the presence of infiltrative pattern and signs of vascular proliferation or AV shunting might be important clues to predict atypical features. Prognosis of the previously reported 85 cases of EVN was meta-analyzed by Kane et al., and they reported that atypical EVNs show higher rates of recurrence and mortality compared with typical ones [5]. However, most of the reported cases of atypical EVN were adults, and patients of atypical EVN tend to be older than those of typical EVN [5]. Therefore, the prognosis of atypical EVNs in children is still not clear because of its rarity. As shown in Table 1, the postoperative courses of atypical EVNs in children seem variable, and the actual recurrence rate or indication of radiation therapy remains unclear in this population. Accumulation of pediatric
cases of atypical EVN is important to clarify its biological behaviors and diagnostic clues. Conflict of interest The authors declare that they have no conflict of interest.
References 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Brat DJ, Scheithauer BW, Eberhart CG, Burger PC (2001) Extraventricular neurocytomas: pathologic features and clinical outcome. Am J Surg Pathol 25:1252–1260 Ghosal N, Dadlani R, Somorendra Singh S, Hegde AS (2011) Atypical extraventricular neurocytoma: a rare and challenging case diagnosed on intraoperative cytology. Cytopathology 23:270–273 Han L, Niu H, Wang J, Wan F, Shu K, Ke C, Lei T (2013) Extraventricular neurocytoma in pediatric populations: a case report and review of the literature. Oncol Lett 6:1397–1405 Huang WY, Zhang BY, Geng DY, Zhang J (2013) Computed tomography and magnetic resonance features of extraventricular neurocytoma: a study of eight cases. Clin Radiol 68:e206–e212 Kane AJ, Sughrue ME, Rutkowski MJ, Aranda D, Mills SA, Lehil M, Fang S, Parsa AT (2012) Atypia predicting prognosis for intracranial extraventricular neurocytomas. J Neurosurg 116:349–354 Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) (2007) World Health Organization classification of tumours of the central nervous system. IARC, Lyon Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109 Mariani L, Schroth G, Wielepp JP, Haldemann A, Seiler RW (2001) Intratumoral arteriovenous shunting in malignant gliomas. Neurosurgery 48:353–357 Mpairamidis E, Alexiou GA, Stefanaki K, Sfakianos G, Prodromou N (2009) Extraventricular neurocytoma in a child: case report and review of the literature. J Child Neurol 24:491–494 Myung JK, Cho HJ, Park CK, Chung CK, Choi SH, Kim SK, Park SH (2012) Clinicopathological and genetic characteristics of extraventricular neurocytomas. Neuropathology 33:111–121 Patil AS, Menon G, Easwer HV, Nair S (2014) Extraventricular neurocytoma, a comprehensive review. Acta Neurochir (Wien) 156:349–354 Raja AI, Yeaney GA, Jakacki RI, Hamilton RL, Pollack IF (2008) Extraventricular neurocytoma in neurofibromatosis type 1: case report. J Neurosurg Pediatr 2:63–67 Singh A, Chand K, Singh H, Sarkar C, Sharma MC (2007) Atypical neurocytoma of the spinal cord in a young child. Childs Nerv Syst 23:207–211 Yang GF, Wu SY, Zhang LJ, Lu GM, Tian W, Shah K (2009) Imaging findings of extraventricular neurocytoma: report of 3 cases and review of the literature. AJNR Am J Neuroradiol 30:581–585
CASE REPORT
Atypical extraventricular neurocytoma in a 3-year-old girl: case report with radiological-pathological correlation Hiroo Kawano 1 & Tokuhiro Kimura 2 & Koji Iwata 3 & Matakazu Furukawa 4 & Sadahiro Nomura 5 & Aya Ishii 2 & Shinsuke Tanaka 6 & Yoshinobu Hoshii 6 & Michiyasu Suzuki 5 & Eiji Ikeda 2
Received: 28 March 2015 / Accepted: 8 April 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Background Extraventricular neurocytoma (EVN) is a rare neuronal tumor histologically similar to central neurocytoma but arising in the brain parenchyma outside the ventricles. The minority of EVNs show atypical features including increased proliferative index, microvascular proliferation, or necrosis, and are called atypical EVN. Most of atypical EVNs occur in adults, and the tumors in children are extremely rare. A radiological-pathological correlation and radiological clue to atypical EVNs have not been clarified. Case report We report a case of atypical EVN in a 3-year-old girl. Magnetic resonance imaging (MRI) revealed an extraventricular intraparenchymal tumor in the left frontal lobe, which was composed of homogeneous welldemarcated cystic component and peripheral ill-delineated solid component with enhancement. Angiography demonstrated vascular proliferation and arteriovenous shunting in the tumor. Histologically, the resected tumor was diagnosed as atypical EVN. Types of the tumor borders (well-
* Tokuhiro Kimura [email protected] 1
Department of Basic Laboratory Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan
2
Department of Pathology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan
3
Yamaguchi University Hospital, Ube, Japan
4
Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Japan
5
Department of Neurosurgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
6
Division of Surgical Pathology, Yamaguchi University Hospital, Ube, Japan
circumscribed or infiltrative) and MRI findings correlated closely. Morphology of the tumor vasculature was remarkable for microvascular proliferation and dilated, thickened veins, which corresponded to the angiographic features. Conclusion Although rare, atypical EVN should be included in the differential diagnosis of a cystic mass in the cerebral hemispheres in children. Radiological evaluation of tumor borders and angiographic characteristics might be useful for predicting atypicality of the tumor. Keywords Extraventricular neurocytoma . Child . Neuroimaging . Angiography . Histology . Radiological-pathological correlation
Introduction Neuronal tumors are uncommon neoplasms of the central nervous system showing neuronal differentiation. Central neurocytoma (CN) is a neuronal tumor arising in the cerebral ventricles near the foramen of Monro. It consists of uniform, small, round neurocytes which often have perinuclear halos resembling oligodendroglioma cells. Rarely, tumors histologically similar to CNs arise in the brain parenchyma outside the ventricular system, and are called extraventricular neurocytoma (EVN). EVN has been listed as a distinct entity in the 2007 World Health Organization (WHO) Classification [6], and is categorized as a WHO grade II tumor [7]. Its histological features and biological behavior are similar to those of CN, but EVNs appear to exhibit a wider morphological spectrum [7]. The minority of EVNs show atypical histological features including increased proliferative index, microvascular proliferation, or necrosis, and are called atypical EVNs, which are regarded as a more aggressive variant [1, 5]. Most of the reported cases of atypical EVN are adults and, in fact,
Childs Nerv Syst
A 3-year-old girl was admitted to our hospital due to muscle weakness of the right side. Her birth and postnatal development were uneventful. Although she was right-handed, she began to use her left hand 1 month before the admission. Subsequently, she showed abnormal gait, frequent falling, and drooling. Neurological examination revealed right hemiparesis of the upper and lower extremities and papilledema. A computed tomography (CT) scan showed a well-demarcated cystic lesion in the left frontal lobe without
calcification and hemorrhage. Magnetic resonance imaging (MRI) demonstrated an extraventricular cystic mass of 65× 50×56 mm with midline shift. Peritumoral edema was not evident. On contrast-enhanced MRI, the medial and posterior parts of the lesion were composed of thin enhancing rim that was well-demarcated, while the lateral and anterior parts were relatively ill-delineated solid enhancing component (Fig. 1a, b). MR angiography suggested vascular proliferation in relation to the solid component of the lesion (Fig. 1c). Digital subtraction angiogram of the left internal carotid artery revealed vascular proliferation at the site corresponding to the solid component of the mass (Fig. 1d). It also showed early venous drainage in an arterial phase (Fig. 1e), indicating arteriovenous (AV) shunting associated with the mass. Resection was performed except for the portion attached to the motor area. The postoperative course was uneventful. No regrowth of the tumor was detected on follow-up 1 year after the surgery. Histological examination of the resected tissue revealed that most of the lesion was located in the white matter and was composed of a proliferation of uniform, small, round cells with perinuclear halos (Fig. 2a). Neuropil islands and ganglion-like large neuronal cells were occasionally seen (Fig. 2a), suggesting neuronal differentiation of the tumor
Fig. 1 Neuroradiological findings of the tumor. a, b Gadoliniumenhanced T1-weighted MR images (a axial, b coronal) show a welldemarcated cystic mass with peripheral solid component in the left frontal lobe. c MR angiography reveals increased vascular signal
corresponding to the solid component of the tumor (arrows). d, e Digital subtraction angiogram of the left internal carotid artery in lateral views (d arterial phase, e late arterial phase) shows vascular proliferation associated with the mass (arrow) and early venous drainage (arrowhead)
more than half of the patients of atypical EVN are reported to be in their sixth decade and above [5]. Atypical EVNs in children are extremely uncommon, but have been increasingly recognized in recent years in several case reports [1–3, 9, 11–13]. Although neuroradiological and histological findings were briefly mentioned in the previous reports, a precise radiological-pathological correlation of atypical EVN and a radiological clue to diagnosis of atypical tumors have not been described. Here, we report a case of atypical EVN in a 3-yearold girl with special reference to correlation of neuroradiological findings and histopathology.
Case report
Childs Nerv Syst
cells. Mitoses were found, ranging from 1 to 18/10 highpower fields. Immunohistochemically, both of the round cells with perinuclear halos and ganglion-like large cells were positive for NeuN (Fig. 2b) and synaptophysin (Fig. 2c).
Synaptophysin positivity was accentuated in neuropil islands (Fig. 2c). The tumor cells were negative for Olig2, glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), and mutant isocitrate dehydrogenase 1 (IDH1-
Fig. 2 Histological findings of the tumor. a The tumor is composed of a proliferation of round cells with perinuclear halos. Neuropil islands (arrowheads) and ganglion-like large neuronal cells (arrow) were occasionally seen. b–d Immunohistochemically, both of the round cells and ganglion-like large cells (b arrows) are positive for NeuN (b) and synaptophysin (c). Synaptophysin positivity was accentuated in neuropil islands (c arrowhead). Ki-67 (MIB-1) labeling index is approximately 20 % (d). e Necrosis (N) of the tumor tissue is focally observed. f Vasculature of the tumor tissue shows branching capillary network. g
Endothelial hyperplasia and glomeruloid microvascular proliferation are frequently observed. h Dilated veins with thickened walls (V) are found near the microvascular proliferation (arrows). i Low-power view showing well-circumscribed, thin tumor tissue. Cystic cavity is seen at the left. Inset shows magnified view of boxed area. j Low-power view of the solid area (SA) of the tumor. At the periphery of the solid area, there is infiltrative area (IA) where the tumor cells infiltrate the brain parenchyma in a single-cell manner. Insets show magnified view of boxed areas. Scale bars: (a–g) 50 μm, (h–j) 250 μm
Solid and cystic Solid ND Cystic and solid Headache Nausea ND Hemiparesis Frontoparietal Frontal Temporoparietal Frontal 9/M 2/F 7/F 3/F 5 6 7 The present case
yryear, mo month, wk week, MIB-1 LI MIB-1 labeling index, ND not described, NF1 neurofibromatosis type 1, AV shunting arteriovenous shunting, MA increased mitotic activity, MV microvascular proliferation, C calcification, N necrosis, STR subtotal resection, GTR gross total resection; CT chemotherapy, DOD dead of disease
[2] [3] [11] ND DOD, 11 wk Stable lesion, 47 mo Stable lesion, 1 yr Decompression GTR STR+radiation STR 10 % 20 % ND 20 % MA, MV, C ND ND MA, MV, N
[13] [12] [9]
[1] Stable lesion, 42 mo
ND Recurrence, 8 mo No recurrence, 1 yr STR GTR+CT GTR+radiation
STR+radiation ND
13 % 4% 5% MA, MV, N C MA, N, C
ND ND
ND ND Minimal vascularity, no AV shunting ND ND ND Vascular proliferation, AV shunting Solid Solid and cystic Solid
Cyst and nodule ND
Paraparesis NF1 Seizure Spinal cord Occipital Frontal
Frontal 5/M
8/M 7/M 3/F
1
Symptoms Location Age (yr)/sex Case no.
Table 1
Atypical EVN is defined as EVN with atypical histological features including increased proliferative index, microvascular proliferation, or necrosis. The practical criteria for histological diagnosis of atypical EVN have been described as Bgeographic necrosis, vascular proliferation, or increased mitotic activity (≥3 mitoses/10 high-power fields)^ [1] or BMIB1 labeling index greater than 3 %, or features consistent with higher-grade tumors defined as frequent mitoses, vascular proliferation, or presence of necrosis^ [5]. The present case fulfilled both of these criteria. Radiologically, the preoperative differential diagnosis of the present case included pilocytic astrocytoma, desmoplastic infantile astrocytoma/ganglioglioma, and supratentorial primitive neuroectodermal tumor, but it was difficult to predict the histological type of the tumor from the CT and MRI findings. Histological examination revealed that the tumor was composed of round cells with perinuclear halos, which resembled oligodendroglioma or clear cell ependymoma. However, the cells were positive for neuronal markers (NeuN and synaptophysin) and negative for glial (Olig2 and GFAP) and ependymal (EMA) markers, suggesting neuronal character of the tumor. These immunohistochemical studies are particularly useful for the diagnosis of neurocytic neoplasms like this case. Atypical EVNs in children are very rare and, to our knowledge, only seven cases were reported previously (Table 1).
Reported cases of atypical extraventricular neurocytoma in children
Discussion
Neuroimaging
Angiographic findings
Histological features
MIB-1 LI
Treatment
Follow-up
R132H). Ki-67 (MIB-1) labeling index was approximately 20 % (Fig. 2d). Necrosis was focally observed (Fig. 2e). Morphology of the tumor vasculature was characteristic: in addition to branching capillary network (Fig. 2f), microvascular proliferation characterized by endothelial hyperplasia and formation of glomeruloid blood vessels were frequently found (Fig. 2g). Occasionally, dilated veins with thickened walls were observed near the microvascular proliferation (Fig. 2h). These findings indicated the diagnosis of atypical EVN. The microvascular proliferation and dilated, thickened veins in the tumor tissue are thought to be related directly to the angiographic signs of vascular proliferation and AV shunting, respectively. As the MRI suggested, the tumor tissue showed two patterns of growth: thin cyst-wall-like component (Fig. 2i) and solid component (Fig. 2j, inset 1). The tumor border of the former component is microscopically wellcircumscribed (Fig. 2i, inset), corresponding to thin enhancing rim on MRI. On the other hand, at the periphery of the latter component, the neoplastic cells infiltrated the cerebral cortex in a single-cell manner (Fig. 2j, inset 2), reaching the brain surface. The relatively indistinct border of the solid part on MRI could be explained by this infiltrative behavior of the tumor cells.
2 3 4
Reference
Childs Nerv Syst
Childs Nerv Syst
Most of those tumors arose in the cerebral hemispheres but the spinal cord was involved in one case. Symptoms were sitespecific. In neuroimaging, the tumors tended to show a wellcircumscribed, cystic, and solid pattern. Histologically, microvascular proliferation was reported in two cases, and necrosis was present in two cases. Calcification was sometimes found. MIB-1 labeling index was typically higher than 10 %. Although angiographic findings have rarely been reported in the previous cases of EVNs, they were described in case # 4 in Table 1. Notably, in case # 4, the angiography showed minimal vascularity and no AV shunting, and the tumor tissue lacked microvascular proliferation histologically [9]. In contrast, the present case exhibited vascular proliferation and AV shunting in the angiogram, and microvascular proliferation and dilated, thickened veins in histology, implying that angiographic findings might be a good indicator of the presence of atypical vascular features in EVN tissues. Compatibly, intratumoral AV shunting is often observed in glioblastomas in which microvascular proliferation is one of the histological hallmarks [8]. There have been several reports on radiological features of EVNs, in which most EVNs were reported to be wellcircumscribed [4, 10, 11, 14]. Histologically, Brat et al. described that most EVNs showed pushing borders and focal infiltration of tumor cells into adjacent brain tissue was observed more frequently in atypical EVNs than in typical ones [1]. In the present case, tumor infiltration was noted in histological examination, and the relatively indistinct border of the solid part on MRI probably reflected it. Although it is difficult to distinguish atypical EVNs from typical ones radiologically, the presence of infiltrative pattern and signs of vascular proliferation or AV shunting might be important clues to predict atypical features. Prognosis of the previously reported 85 cases of EVN was meta-analyzed by Kane et al., and they reported that atypical EVNs show higher rates of recurrence and mortality compared with typical ones [5]. However, most of the reported cases of atypical EVN were adults, and patients of atypical EVN tend to be older than those of typical EVN [5]. Therefore, the prognosis of atypical EVNs in children is still not clear because of its rarity. As shown in Table 1, the postoperative courses of atypical EVNs in children seem variable, and the actual recurrence rate or indication of radiation therapy remains unclear in this population. Accumulation of pediatric
cases of atypical EVN is important to clarify its biological behaviors and diagnostic clues. Conflict of interest The authors declare that they have no conflict of interest.
References 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Brat DJ, Scheithauer BW, Eberhart CG, Burger PC (2001) Extraventricular neurocytomas: pathologic features and clinical outcome. Am J Surg Pathol 25:1252–1260 Ghosal N, Dadlani R, Somorendra Singh S, Hegde AS (2011) Atypical extraventricular neurocytoma: a rare and challenging case diagnosed on intraoperative cytology. Cytopathology 23:270–273 Han L, Niu H, Wang J, Wan F, Shu K, Ke C, Lei T (2013) Extraventricular neurocytoma in pediatric populations: a case report and review of the literature. Oncol Lett 6:1397–1405 Huang WY, Zhang BY, Geng DY, Zhang J (2013) Computed tomography and magnetic resonance features of extraventricular neurocytoma: a study of eight cases. Clin Radiol 68:e206–e212 Kane AJ, Sughrue ME, Rutkowski MJ, Aranda D, Mills SA, Lehil M, Fang S, Parsa AT (2012) Atypia predicting prognosis for intracranial extraventricular neurocytomas. J Neurosurg 116:349–354 Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) (2007) World Health Organization classification of tumours of the central nervous system. IARC, Lyon Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109 Mariani L, Schroth G, Wielepp JP, Haldemann A, Seiler RW (2001) Intratumoral arteriovenous shunting in malignant gliomas. Neurosurgery 48:353–357 Mpairamidis E, Alexiou GA, Stefanaki K, Sfakianos G, Prodromou N (2009) Extraventricular neurocytoma in a child: case report and review of the literature. J Child Neurol 24:491–494 Myung JK, Cho HJ, Park CK, Chung CK, Choi SH, Kim SK, Park SH (2012) Clinicopathological and genetic characteristics of extraventricular neurocytomas. Neuropathology 33:111–121 Patil AS, Menon G, Easwer HV, Nair S (2014) Extraventricular neurocytoma, a comprehensive review. Acta Neurochir (Wien) 156:349–354 Raja AI, Yeaney GA, Jakacki RI, Hamilton RL, Pollack IF (2008) Extraventricular neurocytoma in neurofibromatosis type 1: case report. J Neurosurg Pediatr 2:63–67 Singh A, Chand K, Singh H, Sarkar C, Sharma MC (2007) Atypical neurocytoma of the spinal cord in a young child. Childs Nerv Syst 23:207–211 Yang GF, Wu SY, Zhang LJ, Lu GM, Tian W, Shah K (2009) Imaging findings of extraventricular neurocytoma: report of 3 cases and review of the literature. AJNR Am J Neuroradiol 30:581–585
