NMC Case Report Journal Advance Publication Date: May December 16, 2016 18, 2018
NMC Case Report Journal 2018; X: XX–XXX
DOI: 10.2176/nmccrj.cr.2018-0174
Case Report
A Case of Pleomorphic Xanthoastrocytoma with Intracranial Hemorrhage in a Child Yusuke Takamine,1 Shun Yamamuro,1 Koichiro Sumi,1 Takashi Ohta,1 Katsunori Shijo,1 Yoko Nakanishi,2 Taku Homma, 3 and Atsuo Yoshino1
Intracranial hemorrhage associated with lower grade glioma is unusual. Furthermore, pleomorphic xanthoastrocytoma (PXA) with intracranial hemorrhage, especially in a children, is extremely rare. We report here a rare case of child PXA with intracranial hemorrhage. An 11-year-old girl was admitted with headache and convulsions. A computed tomography scan demonstrated intracranial hemorrhage in the right temporal lobe. An angiogram revealed no vascular disease including arteriovenous malformation, angioma or aneurysm. Magnetic resonance (MR) imaging demonstrated no enhanced or cystic mass to suggest tumor presence. A follow-up study by MR imaging at 6 months after onset of the intracranial hemorrhage revealed a cystic mass lesion, with gadolinium-enhancement, in the right temporal lobe. This mass lesion was removed by surgery and diagnosed as PXA. Areas of tumor lesion could not be diagnosed immediately after the intracranial hemorrhage since bleeding lesion was prominent. Lower grade gliomas, including PXAs, should therefore be taken into consideration in the differential diagnosis of pediatric intracranial hemorrhage cases, separately from vascular disease and/or malignant brain tumor. Keywords: pleomorphic xanthoastrocytoma, intracranial hemorrhage, pediatric brain tumor
Introduction Pleomorphic xanthoastrocytoma (PXA) is rare, involving slowly growing neoplasms corresponding to World Health Organization (WHO) grade II. PXA accounts for less than 1% of all astrocytomas, and demonstrates a good clinical outcome compared to other gliomas. PXA typically arises from supra-tentorial locations in children or young adults.1) The most common clinical symptom of PXA is seizure, and intracranial hemorrhage associated with PXA is very rare. 1
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan 2 Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan 3 Division of Human Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan Received: July 18, 2018; Accepted: October 15, 2018 Copyright© 2018 by The Japan Neurosurgical Society This work is licensed under a Creative Commons AttributionNonCommercial-NoDerivatives International License.
We report here an extremely rare case of child PXA with intracranial hemorrhage.
Case Report An 11-year-old girl was admitted to another clinic with convulsions. She had a complaint of progressive headache 3 weeks before the convulsions. A computed tomography (CT) scan demonstrated intracranial hemorrhage in the right temporal lobe (Fig. 1A), and the patient was transferred to our hospital. Physical examinations displayed no abnormality, and there was no neurological deficit. Magnetic resonance (MR) imaging disclosed no enhanced or cystic mass to suggest tumor presence (Figs. 1B–1E). An angiogram revealed no vascular disease including arteriovenous malformation, angioma or aneurysm (Fig. 2A). She was observed conservatively and once discharged from our institution because repeated examinations by MR imaging and angiography had demonstrated no vascular disease and/or tumor mass (Figs. 2B–2D). MR imaging at 6 months after onset of the intracranial hemorrhage revealed a cystic mass lesion, with gadolinium-enhancement, in the right temporal lobe (Figs. 3A and 3B). She therefore underwent surgical resection and the tumor was completely removed (Figs. 3C and 3D). The intraoperative findings indicated that the tumor was reddish, soft, and vascular-rich. Pathological examinations of the tumor specimen demonstrated nuclear and cytoplasmic pleomorphism (Fig. 4A). Morphologically, the nuclei varied in their size, shape, and coarseness or dispersion of chromatin, but there was no mitosis or necrosis. Microvascular proliferation and bleeding scars were evident (Fig. 4B). The tumor revealed glial components including eosinophilic granular bodies, Rosenthal fibers and spindleshaped tumor cells (Figs. 4A and 4B). Hemosiderin was present near the tumor vessels, and the tumor cells demonstrated cytoplasmic pleomorphism and xanthomatous changes (Figs. 4C and 4D). Glial fibrillary acid protein (GFAP) and S-100 protein were positive immunohistochemically (Fig. 4E). Vimentin was also positive. Synaptophysin was positive immunohistochemically in the focal area. On silver staining, reticulin fibers were evident surrounded by tumor cells (Fig. 4F). Immuno-activity for CD34 was observed in the tumor and endothelial cells. The point mutation of BRAF gene at codon 600 (BRAF V600E) was negative on the polymerase chain reaction. The MIB-1 labeling index was 2.0%. Epithelial membrane antigen was negative immunohistochemically. These pathological findings were consistent with PXA. The patient was discharged from our institution without severe 1
NMC Case Report Journal Advance Publication Date: May December 16, 2016 18, 2018 Y. Takamine et al.
A
B
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D
E
Fig. 1 Initial radiological findings. (A) Initial computed tomography (CT) scan revealing intracranial hemorrhage in the right temporal lobe (axial view). (B–E) Magnetic resonance (MR) imaging, taken at the following day of the CT scan, demonstrating no clear evidence of tumor mass (axial view. B; T1-weighted image, C; T1-weighted image with gadolinium-enhancement, D; T2-weighted image E; fluid attenuated inversion recovery image).
A
B
C
D
Fig. 2 Pre-operative radiological findings. (A) Angiogram, performed at 13 days after the hemorrhage, showing no abnormality. (B–D) Repeated MR imaging, taken at 2 months after the hemorrhage, demonstrating no tumor mass (axial view. B; T1-weighted image, C; T2-weighted image, D; fluid attenuated inversion recovery image).
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Fig. 3 Pre and post-operative magnetic resonance imaging. (A and B) A cystic mass lesion, with gadolinium-enhancement, was found at 6 months after onset of the intracranial hemorrhage (axial view, A; T1-weighted image, B; T1-weighted image with gadolinium-enhancement). (C and D) The tumor was removed surgically (axial view, C; T1-weighted image, D; T1-weighted image with gadolinium-enhancement).
complications, except for slightly left-side hemi-motor palsy due to the tumor resection (Karnofsky Performance Status score: 80). Adjuvant therapy including chemotherapy or radiation was not required. There has been no sign of recurrence over a period of 24 months since the operation.
Discussion Pleomorphic xanthoastrocytoma develops in children and young adults. The majority of symptoms include a fairly long 2
history of seizures, and accordingly PXA tends to arise on the brain surface. The incidence of hemorrhage in gliomas is approximately 1.4–2.6%.2) In general, the frequency of hemorrhage increases with degree on the WHO classification, i.e. it is more common in high-grade gliomas such as glioblastomas and anaplastic astrocytomas. Thus, high-grade gliomas tend to display microvascular proliferation and necrosis. The cause of the hemorrhage occurring in lower grade gliomas is poorly understood. Vascular proliferation is an occasional
NMC Case Report Journal Advance Publication Date: May December 16, 2016 18, 2018 Pleomorphic Xanthoastrocytoma with Intracranial Hemorrhage
A
B
C
D
E
F
Fig. 4 Photomicrographs obtained by hematoxylin and eosin (H&E) staining (A–D) and immunohistochemical staining (E and F). (A) Pleomorphic neoplastic cells and spindle-shaped cells surrounded by tumor vessels (original magnification ×100, bar = 200 µm). (B) Microvascular proliferation and eosinophilic granular bodies (original magnification ×200, bar = 100 µm). (C) Lymphocyte cells surrounded by tumor vessels (original magnification ×400, bar = 50 µm). (D) Microvascular proliferation and xanthomatous neoplastic cells (original magnification ×400, bar = 50 µm). (E) Photomicrograph showing representative GFAP immunostaining (original magnification ×100, bar = 200 µm). (F) Photomicrograph showing representative silver staining (original magnification ×100, bar = 200 µm). Table 1 Case of pleomorphic xanthoastrocytoma with intracranial hemorrhage Authors
Age (year-old)
Sex
Location
Type of hemorrhage
Cyst
Pathological diagnosis
Outcome
46
F
Left temporal
ICH/SAH
–
PXA
Dead
Yoshida et al. 2005
61
F
Lef temporal
ITH
+
PXA
Survived
8)
59
F
Left temporal
ICH
–
Anaplastic PXA
Dead
64
M
Left frontal
ICH
+
PXA
Survived
5
F
Left temporal
ITH
–
PXA
Survived
Yoshikawa et al. 2010
60
F
Left temporal
ICH/SAH
–
PXA
Survived
Present case
11
F
Right temporal
ICH
+
PXA
Survived
Levy et al. 199610) 9)
Asano et al. 2006 7)
Lee et al. 2007
6)
Wind et al. 2009
5)
F: female, ICH: intracranial hemorrhage, ITH: intra tumor hemorrhage, M: male, PXA: pleomorphic xanthoastrocytoma, SAH: subarachnoid hemorrhage.
feature of such tumors. Retiform capillaries are sometimes observed in lower grade gliomas and have been found to be associated with hemorrhage.3,4) Intracranial hemorrhage associated with PXA is extremely rare. So far, only six cases have been reported in the English literature5–10) (Table 1). PXAs appear as hypovascular masses on angiogram, and histological hypervascularity has been reported in only one case.9) Our patient exhibited no tumor stain on angiogram, and microvascular proliferation with bleeding scars were evident in most of the tumor area without mitosis or necrosis on histological examination. These observations indicated that PXA with intracranial hemorrhage cases tend to display
microvascular proliferation. In our patient, lymphocyte cells were present surrounded by tumor vessels. These findings suggested that vasculitis had led to intratumor hemorrhage and intracranial hemorrhage. PXAs with significant mitotic activity and/or with areas of necrosis have been designated as pleomorphic xanthoastrocytomas with anaplastic features. Such tumors exhibited an increased risk of early recurrence. In a previous report, approximately 15–20% of PXAs were inferred to have undergone malignant transformation. 11) When a tumor became malignant, microvascular proliferation was more likely, and the volume of tumor vessels increased, leading to tumor bleeding.8) 3
NMC Case Report Journal Advance Publication Date: May December 16, 2016 18, 2018 Y. Takamine et al.
As described above, six cases of intracranial hemorrhage associated with PXA have been reported, and only one report described a pediatric case.6) The patient ages described in the other five reports ranged from 46 to 64 years old, and only one case demonstrated malignancy diagnosed as anaplastic PXA. 8) Every past case underwent surgical treatment urgently and could be diagnosed early. In the present case, the intracranial hemorrhage did not require surgical treatment. Even though she underwent repeated investigations, we were therefore unable to reveal the cause of the intracranial hemorrhage upon first examination. In general, low grade brain tumor, including PXA, demonstrates a slow course. We failed to detect any tumor therefore by MR imaging until 6 months after the onset of the intracranial hemorrhage. In the period immediately after the intracranial hemorrhage, no tumor could be detected on imaging studies because the mass was masked by hemorrhage. We thus need to be aware that low grade brain tumor, including PXA, should not be excluded in the differential diagnosis of pediatric intracranial hemorrhage cases other than vascular disease and/or malignant brain tumor, and film follow-up is strictly necessary.
Conflicts of Interest Disclosure The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.
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Corresponding author: Shun Yamamuro, MD, PhD, Department of Neurological Surgery, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
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