Neurol Med Chir (Tokyo) 50, 414¿417, 2010

Glioblastoma Detected at the Initial Stage
in its Developmental Process
—Case Report—
Hirofumi OYAMA, Yusuke ANDO, Shinichirou AOKI*, Akira KITO,
Hideki MAKI, Kenichi HATTORI, and Kuniaki TANAHASHI
Departments of Neurosurgery and *Neurology, Ogaki Municipal Hospital, Ogaki, Gifu

Abstract
A 73-year-old male presented with a glioblastoma that was detected at the initial stage in the developmental process. He suffered cerebral infarction. Follow-up magnetic resonance (MR) imaging showed
no abnormality. Ten months later, he had transient right hemiparesis. Diffusion-weighted and fluid-attenuated inversion recovery (FLAIR) MR imaging showed a hyperintense area in the left frontal lobe.
The diagnosis was cerebral infarction and antiplatelet drug treatment was begun. The patient's right
hemiparesis subsided. Ten days later, right hemiparesis reappeared. Diffusion-weighted and FLAIR
MR imaging showed an enlarged hyperintense area in the left frontal lobe. Three weeks after the onset
of right hemiparesis, MR imaging revealed an irregular ring-enhanced mass lesion that had further increased in size. The diagnosis was brain abscess and antibiotic treatment was initiated. However, the
lesion did not respond and had further enlarged 5 weeks after the onset of right hemiparesis. The lesion
was partially removed and the histological diagnosis was glioblastoma with Ki-67 labeling index of
26%. After surgical treatment, the patient received irradiation of 60 Gy and chemotherapy with
temozolomide. Follow-up MR imaging showed regrowth of the tumor and aggravation of edema. The
rapid progression of the tumor ultimately resulted in the patient's death 12 months after the onset of
right hemiparesis. Diffusion-weighted imaging is a good method for the early detection of glioblastoma.
Key words: glioblastoma, developmental process,
cerebral infarction, brain abscess

diffusion-weighted magnetic resonance imaging,

Introduction

imaging and the tumor apparent diffusion coefficient may
provide useful information about the anaplastic grade of
glioblastomas.1,3,11,13) However, the differential diagnosis
of a cerebral infarction and an abscess is also very important.11,17)
We report a case of de novo glioblastoma which was detected early in the course by diffusion-weighted imaging.

Glioblastoma may occur de novo or secondary to another
tumor. The developmental process of a de novo glioblastoma remains obscure. We found only three previous reports
in which the developmental process was observed at an
early stage.5,18,23) There is accordingly no consensus regarding the best method of detecting a glioblastoma during its development. The early diagnosis of glioblastoma
using magnetic resonance (MR) imaging is difficult. One
case of de novo glioblastoma appeared as a well circumscribed hyperintense lesion without mass effect on T2weighted MR imaging, which could not be differentiated
from cerebral infarction, since gadolinium caused no contrast enhancement on T1-weighted MR imaging. Three
months after onset, gadolinium disclosed a small enhanced lesion.23) Another case appeared as a poorly
demarcated, hyperintense area on T2-weighted MR imaging, with no visible abnormalities or contrast enhancement by gadolinium on T1-weighted MR imaging. About 4
months after onset, brain MR imaging disclosed a ringshaped, irregular enhanced lesion.18) Diffusion-weighted
Received

July 27, 2009;

Accepted

Case Report
A 73-year-old male had previously suffered cardiac infarction, hypertension, and cerebral infarction. Follow-up
head MR imaging using a 1.5 T MR unit showed no abnormality (Fig. 1A, B). Ten months later, the patient suffered
transient right hemiparesis and was hospitalized.
Diffusion-weighted and fluid-attenuated inversion recovery (FLAIR) MR imaging showed a hyperintense area in
the left frontal lobe (Fig. 1C–E). The diagnosis was
cerebral infarction. The patient's symptom subsided after
treatment with glycerol, edaravone, and argatroban, followed by antiplatelet agent.
Ten days later, right hemiparesis reappeared and he was
re-admitted. Diffusion-weighted and FLAIR MR imaging
showed a hyperintense area in the left frontal lobe, which

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Initial Stage Detection of Glioblastoma With Diffusion-Weighted MR Imaging

415

Fig. 2 A: Photomicrograph of the tumor which predominantly
consists of proliferated atypical cells with irregular syncytium
and chromatin-condensed heterogeneous nuclei. Hyperplasia
of the vascular endothelium and pseudopalisading necrosis formation are also prominent. The tumor is a glioblastoma.
Hematoxylin and eosin stain, original magnification ×100.
B: Photomicrograph showing the Ki-67 labeling index is 26%.
Ki-67 stain, original magnification ×100.

Fig. 1 Fluid-attenuated inversion recovery (FLAIR) (A, D, G,
J, M), T2-weighted (B, E, H, K, N), diffusion-weighted (C, F), and
T1-weighted with gadolinium (I, L) magnetic resonance images
taken before and after onset of the symptoms. A, B: Images
were taken 10 months before the onset of symptoms and show
no abnormality. C–E: Images were taken at the onset of symptoms. Note the hyperintense area in the left frontal lobe on the
diffusion-weighted and FLAIR images. F–H: Images were
taken when right hemiparesis reappeared 2 weeks after symptom onset. Diffusion-weighted and FLAIR images show an increase in the size of the hyperintense area in the left frontal
lobe, compared with the previous images. The lesion is also
visible on the T2-weighted image. I–K: Images were taken 3
weeks after symptom onset. All images confirm a further increase in the size of the irregular ring-enhanced mass lesion.
L–N: Images were taken 5 weeks after symptom onset. Note the
lesion has further increased in size.

was larger than on the previous images. T2-weighted MR
imaging also detected the lesion (Figs. 1F–H). Three weeks
after the onset of right hemiparesis, MR imaging showed
an irregular ring-enhanced mass lesion that had further increased in size (Fig. 1I–K). The diagnosis was brain ab-

Neurol Med Chir (Tokyo) 50, May, 2010

scess and antibiotic therapy was initiated. However, 5
weeks after the onset of right hemiparesis, the lesion had
not responded to treatment and continued to increase in
size (Fig. 1L–N). Therefore, the patient was admitted to
our neurosurgical department with a diagnosis of possible
tuberculoma or brain tumor.
Neurological examination found right hemiparesis, especially in the lower limb. The diagnosis was brain tumor.
The patient underwent partial tumor resection 7 weeks after symptom onset. A vascular, soft, gray tumor was located in the left premotor and motor area. Histological examination revealed predominant proliferation of atypical cells
with irregular syncytium and chromatin-condensed heterogeneous nuclei (Fig. 2A). Hyperplasia of the vascular endothelium and pseudopalisading necrosis formation were
also prominent. The Ki-67 labeling index was 26% (Fig.
2B). Immunohistochemical staining for glial fibrillary acidic protein was positive. The histological diagnosis was
glioblastoma.
The surgical treatment was followed by irradiation with
60 Gy and chemotherapy with temozolomide. Follow-up
MR imaging showed regrowth of the tumor and aggravation of edema. Motor aphasia appeared and his right
hemiparesis was aggravated with gait disturbance. Rapid
progression of the tumor ultimately resulted in the
patient's death 12 months after the onset of symptoms.

Discussion
In our patient, diffusion-weighted imaging detected the
glioblastoma in the early stage, whereas T1- and T2-weighted MR imaging showed almost no abnormality. Diffusionweighted MR imaging is a useful technique for assessing a
brain tumor,21) and shows glioblastoma, anaplastic astrocytoma, lymphoma, and metastases as hyperintense lesions, but these types of tumors are indistinguishable.3)
Tumor cellularity correlates well with the intensity on
diffusion-weighted imaging.11,21) Diffusion-weighted imaging can easily detect high-grade glioma, but not necessarily low-grade glioma.
Diffusion-weighted imaging also shows abscess or acute

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416

cerebral infarction as a hyperintense lesion.2) Diffusionweighted MR imaging shows almost no signal intensity
abnormality in stroke patients more than 2 weeks after
symptom onset since pseudo-normalization is occurring
during the subacute stage of cerebral infarction.2) In our
patient, cerebral infarction could be ruled out because
diffusion-weighted imaging revealed continuous enlargement of the lesion.
Differentiation of brain abscess from malignant glioma
can be difficult based on diffusion-weighted MR imaging.4,10,15) Brain abscess appears as markedly hyperintense
and malignant glioma appears as moderately hyperintense
on diffusion-weighted imaging.4,10,15,16) Furthermore, brain
abscess appears as homogeneously hyperintense and
malignant glioma appears as heterogeneously hyperintense.15) Diffusion-weighted imaging showed the lesion in
our patient as moderately hyperintense and heterogeneous. Therefore, retrospective differential diagnosis was
possible between malignant glioma and abscess. MR spectroscopy is another diagnostic method for the differential
diagnosis between abscess and glioblastoma.15)
Uptake of L-methyl-11C-methionine (11C-methionine) is
greater in glioma than in intact tissue. Therefore, methionine positron emission tomography (PET) is very useful
for the evaluation of gliomas.7,19,22) The Ki-67 proliferation
index is significantly correlated with 11C-methionine uptake.9,22) Angiogenesis, as assessed by microvessel count,
is also correlated with 11C-methionine uptake.9,12) Therefore, methionine uptake is highly useful for detecting gliomas and for differentiating between benign and malignant
gliomas.9,20) Furthermore, the metabolically active tumor
volume (as reflected by methionine uptake) is greater than
the volume of gadolinium-diethylenetriaminepenta-acetic
acid enhancement in high-grade glioma, and complete
resection of the tumor volume indicated by increased
methionine uptake prolongs the survival.6,19)
FLAIR MR imaging sequence can show the complete
extent of infiltrative gliomas with a sharp border.7,14,22) The
fast FLAIR sequence can provide additional information
about tumors with poor contrast enhancement and is useful for the evaluation of low-grade gliomas.8) In our case,
the glioblastoma was clearly detected by diffusion-weighted MR imaging. However, the lesion was also demonstrated by FLAIR imaging.
Glioblastoma can progress very rapidly, as in our
patient. T2-weighted and FLAIR MR imaging performed
10 months before the onset of symptoms did not detect the
tumor. After detection by diffusion-weighted imaging, the
tumor volume increased weekly. Prompt diagnosis is very
important in cases of glioblastoma since total removal may
be possible with an early and confident diagnosis. Combination of diffusion-weighted and FLAIR MR imaging with
11C-methionine PET is important for the prompt diagnosis
and treatment of glioblastomas.

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Address reprint requests to: Hirofumi Oyama, M.D., Department
of Neurosurgery, Ogaki Municipal Hospital, 4–86
Minamikawa–machi, Ogaki, Gifu 503–8502, Japan.
e-mail: oya3776＠arrow.ocn.ne.jp