Neurol Med Chir (Tokyo) 43, 404¿408, 2003

Pontine Malignant Astrocytoma With Hemorrhagic Onset
—Case Report—
Yosuke NISHIMUTA, Masaki NIIRO, Takashi KAMEZAWA, Koichi ISHIMARU,
Shunichi YOKOYAMA, and Jun-ichi KURATSU
Department of Neurosurgery, Faculty of Medicine, University of Kagoshima, Kagoshima

Abstract
A 7-year-old boy presented with acute onset of left hemiparesis and headache, followed by disturbance
of consciousness. Neuroimaging studies showed pontine hemorrhage. Surgery was performed to remove
a massive hematoma. Histological examination of the wall revealed anaplastic astrocytoma. Postoperative radiation therapy and several types of chemotherapy were administered. However, the tumor
recurred and he died 9 months after onset. Hemorrhagic onset of pontine glioma is rare and carries an
extremely poor prognosis.
Key words: pontine glioma,
chemotherapy

hemorrhage,

hemorrhagic onset,

Introduction

On admission, he was somnolent. Neurological
examination revealed bilateral abducens palsy
dominant on the right and facial palsy, dysarthria,
swallowing disturbance, cerebellar ataxia, and left
hemiparesis. Computed tomography (CT) obtained 2
days after onset showed a hematoma with surrounding edema in the pons (Fig. 1). Magnetic resonance
(MR) imaging on admission disclosed a hypointense
area on the T1-weighted image and a mixed hyperand hypointense area on the T2-weighted image in
the pons. The pons was remarkably expanded and
the fourth ventricle was compressed backwards
(Fig. 2A, B). The lesion showed irregular ring-like
enhancement by contrast medium (Fig. 2C).
Cerebral angiography revealed a remarkable mass
effect of the basilar artery. No tumor stain or vascular malformation was observed.
Surgery was performed to remove the hematoma
and identify the bleeding origin. A midline suboccipital craniectomy was performed. A bulge was
found in the floor of the fourth ventricle 2 cm above
the obex. A 7 mm-long midline incision was added.
Dark red clot was evacuated from 5 mm under the
surface. The brain tissue surrounding the hematoma
was pinkish gray and bled easily. Biopsy samples of
the abnormal tissue were taken.
Histological examination confirmed high cellularity, pleomorphic tumor cells, and atypical
nuclei with increased mitotic activity (Fig. 3A).
Most tumor cells were glial fibrillary acidic protein-

Pontine gliomas account for 5–15% of all pediatric
brain tumors.4,6,15,19) The vast majority of these
tumors are astrocytomas including malignant astrocytoma.3,15) The prognosis of pontine gliomas is
poor6,7,15) despite the administration of radiation
therapy and different regimens of combined
chemotherapy. Pontine gliomas usually manifest as
progressive, typically asymmetric symptoms and
signs resulting in a 2- to 5-month history of ataxia
and cranial nerve dysfunction.15) Presentation with
an acute, stroke-like onset is rare. We treated a
pediatric patient with a malignant pontine glioma
manifesting as stroke-like onset and atypical imaging features due to the presence of hemorrhage.

Case Report
A 7-year-old boy suddenly developed left hemiparesis and swallowing disturbance on April 15, 1999.
Two days later, he complained of headache and
gradually became unconscious. His level of consciousness slightly improved after conservative
treatment with osmotic agents and steroids, but
dysarthria and diplopia appeared. He was transferred to our hospital on April 26.
Received
2003

August 30, 2002;

Accepted

malignant astrocytoma,

March 24,

404

Pontine Glioma With Hemorrhagic Onset
positive and the MIB-1 labeling index was extremely
high (68%) (Fig. 3B). No necrosis or endothelial
proliferation was observed. The histological diagnosis was anaplastic astrocytoma.
He recovered consciousness after the operation,
but the focal neurological deficits remained unchanged. Postoperatively, he received chemoradiation therapy consisting of interferon-beta (100 U/day
for 15 days), ACNU (80 mg/kg), and radiation
(50 Gy), otherwise called IAR therapy. However, the
tumor continued to grow (Fig. 4A) and his neurolog-

405

ical condition worsened. Therefore, three cycles of
chemotherapy with carboplatin (400 mg/m2) and
etoposide (300 mg/m2) were added. Subsequently he
could walk with a stick and eat by himself. MR imaging showed remarkable reduction of the tumor size
(Fig. 4B).
His neurological state was relatively stable during
August through September. However, he complained of headache followed by consciousness
disturbance and tetraplegia in October. Imaging
studies disclosed tumor growth and cerebrospinal
fluid (CSF) dissemination (Fig. 4C). Another round
of chemotherapy with ifosfamide, cisplatin, and
etoposide was administered, followed by wholebrain radiation (21.6 Gy) against CSF dissemination.
However, he died of the tumor on December 30,
1999. Autopsy was not permitted.

Discussion

Fig. 1

Computed tomography scan obtained 2 days
after onset showing a round high-density
area with a surrounding low-density area in
the pons. The low-density area in the anterior part of the right temporal lobe is an
arachnoid cyst.

Fig. 2

Unusual manifestations of pontine glioma include
acute onset with pure motor hemiplegia, upbeat nystagmus, and internuclear ophthalmoplegia, which
were histologically identified as glioblastoma.12,14,18)
However, these cases were not associated with
hemorrhage on CT. Only three of 1861 brain tumors
were pontine gliomas associated with hemorrhage.20) Pontine gliomas associated with hemorrhage identified by neuroimaging7,11,20) or histological study9) may not be very rare, but our case of pontine glioma associated with massive hemorrhage
also presented with unusual stroke-like onset.
CT usually demonstrates pontine glioma as a
diffuse low-density area with mass effect with or
without contrast enhancement. In our case, CT ob-

Magnetic resonance images obtained on admission. (A) T1-weighted image showing a hypointense area, (B) T2-weighted image showing a mixed hyper- and hypointense area in the pons
and the forth ventricle compressed backwards, and (C) T1-weighted image with contrast medium showing irregular ring-like enhancement of the lesion.

Neurol Med Chir (Tokyo) 43, August, 2003

Y. Nishimuta et al.

406

Fig. 3

Photomicrographs of the hematoma wall
showing pleomorphic astrocytic tumor
cells, increased cellularity, and atypical
nuclei with increased mitotic activity (A:
hematoxylin-eosin stain, ×100); and Ki-67
staining showing an extremely high number
of positive nuclei with a MIB-1 labeling
index of 68% (B: ×50).

Fig. 4

tained 2 days after onset revealed a high-density area
in the central part of the tumor, which reflected the
presence of hemorrhage. Lesions with mixed hypoand hyperintensity on both T1- and T2-weighted MR
imaging may reflect intratumoral hemorrhage.5,11) In
our case, the signal intensity on T1-weighted imaging was not typical of intratumoral hemorrhage, but
the presence of a massive, fluid-containing hematoma was confirmed intraoperatively.
The indications for surgery in patients with pontine glioma are restricted because the tumor usually
diffusely infiltrates the brain stem. Therefore, the
ablation of diffuse-type brain stem tumors is usually
abandoned unless the tumor extends exophytically
or is present in both poles of the brain stem.6,16)
Biopsy is sometimes performed to confirm tumor
histology and the degree of malignancy,10,17) but this
entails additional and unnecessary risks. Therefore,
the diagnosis of pontine gliomas should be established by imaging studies.2,6)
The onset and imaging findings were atypical for
pontine glioma in our case, so we performed hematoma removal and open biopsy to establish the
differential diagnosis from vascular malformations
such as cavernous angioma. Histologically, the
biopsy specimens identified a highly malignant astrocytic tumor, but diagnosis was anaplastic astrocytoma due to the absence of necrosis and endothelial
proliferation. The microscopic pathology of brain
stem tumors is often inhomogeneous.3,19) Our specimens were small and few in number, so we could
not confirm necrosis. However, the histologically
verified malignancy and the extremely high MIB-1
labeling index suggested that the tumor was a highly
malignant anaplastic astrocytic tumor, i.e. a glio-

Serial T1-weighted magnetic resonance images with contrast medium (A) after the course of
radiochemotherapy showing growth of the tumor, (B) after three cycles of chemotherapy with
carboplatin and etoposide showing reduction of the enhanced area and less compression of
the fourth ventricle, and (C) 2 months later showing increased tumor size and cerebrospinal
fluid dissemination.

Neurol Med Chir (Tokyo) 43, August, 2003

Pontine Glioma With Hemorrhagic Onset
blastoma. Therefore, we conclude that pontine gliomas with hemorrhagic- and stroke-like onset are
highly malignant and carry a very poor prognosis.
Spontaneous hemorrhage from brain tumors is
associated with malignant brain tumors, such as
glioblastoma, oligodendroglioma, and metastatic
brain tumor.1,8,20) Excluding pituitary adenoma,
the incidence of hemorrhage from brain tumor
was 2.4–5.4% macroscopically1,8,9,20) and 9.2%
microscopically.8) The incidence of hemorrhage in
pediatric patients was higher, at 5.3%20) and 10%,13)
respectively, than in adults. The site of the hemorrhage varies. Our case was intratumoral hemorrhage
as in three previous patients with pontine astrocytoma.20) The histological features of tumors with
intratumoral hemorrhage include tumor necrosis as
well as vascular changes such as vessel-wall hyalinization, degeneration or necrosis of vessel walls,
thrombosis, and presence of many thin-walled vessels and ruptured vessels.8) Our surgical specimens
were too small to clarify the pathological mechanisms of bleeding from the tumor. The high MIB-1
labeling index suggested that rapid tumor growth
may have caused vessel compression and/or distortion, and additional tumor invasion of the vessel
walls may have resulted in the intratumoral hemorrhage. The incidence of hemorrhagic onset in the
patients with brain tumor is not high, but direct
proof of the hemorrhagic origin is necessary for the
diagnosis and treatment planning for an intracerebral hematoma with atypical location,
imaging findings, or clinical course.
Irradiation is the main therapy for pontine gliomas, but cannot improve the prognosis satisfactorily. IAR therapy is one of the most widely accepted
postoperative treatment modalities for astrocytic
tumors in Japan. However, some tumors are
resistant to this treatment, as in our case.
Radiochemotherapy achieved only temporary remission despite the addition of carboplatin and etoposide treatment. Development of a new treatment
approach is needed to improve the currently dismal
prognosis of patients, such as ours, with brain stem
gliomas that exhibit malignant behavior.

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Address reprint requests to: Y. Nishimuta, M.D., Department of Neurosurgery, Faculty of Medicine, University of Kagoshima, 8–35–1 Sakuragaoka, Kagoshima
890–8520, Japan.
e-mail: yosuke-ns＠po.minc.ne.jp

Neurol Med Chir (Tokyo) 43, August, 2003