Clinical Neurology and Neurosurgery 106 (2003) 38–40

Short communication
Multicentric glioblastoma multiforme determined by positron
emission tomography: a case report
Ajay Jawahar, Christina Weilbaecher, Cedric Shorter, Nancy Stout, Anil Nanda∗
Department of Neurosurgery, Louisiana State University Health Sciences Center, 1501 Kings Highway,
P.O. Box 33932, Shreveport, LA 71130-3932, USA

Received 14 March 2003; accepted 31 March 2003

Abstract

The actual incidence of true multicentric glioblastoma multiforme (GBM) varies between 2.4 and 4.9% of all GBMs. True multicentric
tumors are described as widespread lesions in different lobes or hemispheres, which cannot be explained by spreading along the cerebrospinal
fluid or blood pathways. We present here a case of multicentric GBM identified with positron emission tomography. Case report: A 73-year-old
woman with sudden onset headaches, balance problems, and one episode of syncope was diagnosed as having an irregular, contrast-enhancing,
space-occupying lesion in the left-temporal–parietal region on magnetic resonance imaging (MRI). The tissue diagnosis was confirmed as
GBM, and she received stereotactic radiosurgery using the Leksell Gamma Knife® (Elekta Instruments, Atlanta, GA). A 3-month, follow-up,
MRI scan showed a remarkable decrease in the size of the contrast-enhancing area that was targeted during radiosurgery. A suspicious area of
enhancement was detected on the right side, although no surrounding edema was evident. Fluorodeoxyglucose (FDG)-PET scanning revealed
a large irregular neoplasm extending from the inferior left-temporal lobe into the deep parietal lobe with extremely intense FDG uptake,
suggesting a very aggressive tumor. A smaller lesion was also discovered in the deep right-frontal lobe, representing a second neoplastic
focus. The patient refused any further treatment. Conclusion: PET scans, in conjunction with MRI scans, allow for the best possible and most
comprehensive diagnosis and treatment plans.
© 2003 Elsevier B.V. All rights reserved.

Keywords: Multicentric glioblastoma multiforme; Positron emission tomography scan

1. Introduction
Glioblastoma multiforme (GBM) is the most common
primary brain tumor, accounting for 12–15% of all intracra-
nial neoplasms and 50–60% of all astrocytic tumors. Adults
with an average age between 40 and 60 years old most
commonly present with GBM. The prognosis of survival
for patients with GBM is approximately 50 weeks, and only
5% of patients survive for more than 5 years [1]. Multiple
tumors are determined by the dissemination or growth by
an established route such as spread by commissural or other
pathways including cerebrospinal-fluid channels or local
metastasis through satellite formation [2]. True multicentric
tumors are described as widespread lesions in different lobes
or hemispheres, which cannot be explained by spreading
along one of the previously mentioned pathways. The inci-
∗ Corresponding author. Tel.: +1-318-675-7352;
fax: +1-318-675-7111.
E-mail address: ananda@lsuhsc.edu (A. Nanda).
dence of true multicentric GBM varies between 2.4 and 4.9%
of all GBMs [3]. Yet, great controversy still surrounds this
issue because to be multicentric, the tumor would have to be
polyclonal in origin, which is usually only found in inher-
ited neoplastic syndromes or following exposure to environ-
mental carcinogens. We present here a case of multicentric
GBM identified with positron emission tomography (PET).
2. Case report
2.1. Clinical history
A 73-year-old white woman presented to the neurosurgery
clinic with sudden onset headaches, balance problems, and
one episode of syncope. Her medical history was signifi-
cant for longstanding hypertension, ischemic heart disease,
chronic obstructive pulmonary disease, and osteo-arthritis.
Neurological examination revealed short-term memory re-
call deficit (patient recalled one out of three words after

0303-8467/$ – see front matter © 2003 Elsevier B.V. All rights reserved.
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 A. Jawahar et al. / Clinical Neurology and Neurosurgery 106 (2003) 38–40
Fig. 1. Gadolinium-enhanced, T-1-weighted, axial MRI of the brain show-
ing left-parietal GBM.
a 5-min interval), occasional difficulty finding words, and
mild weakness (Grade 4 out of 5) in the right-upper and
-lower limbs. Based on these findings, a magnetic reso-
nance imaging (MRI) scan of the brain was ordered that
revealed an irregular, contrast-enhancing, space-occupying
lesion in the left-temporal–parietal region with edematous
tissue surrounding the brain. A shift of the midline to the
right was also noted (Fig. 1). A tissue biopsy was performed,
as her pre-existing medical conditions rendered her as a
high-risk case for a formal craniotomy and excision of the
tumor.
2.2. Histology
The patient’s histology slides revealed several cores of
brain tissue containing a highly cellular pleomorphic astro-
cytic neoplasm. There was marked proliferation of blood
vessels in focal areas, and numerous mitotic figures were
detected with areas of focal necrosis. The histological diag-
nosis, therefore, was GBM.
2.3. Treatment
The patient would not consent to a craniotomy and/or ex-
ternal beam radiation therapy, but agreed to take the option of
stereotactic radiosurgery using the Leksell Gamma Knife®
(Elekta Instruments, Atlanta, GA). The contrast-enhancing
lesion seen on MRI scan was targeted, delivering 14 Gy to
the tumor margin in a single session.
39
Fig. 2. Post-radiosurgery, contrast T-1 axial MRI of the brain showing
a remarkable decrease in the area of enhancement. Note the absence of
enhancement in the opposite hemisphere.
2.4. Follow-up
At the 3-month follow-up, the patient showed marked im-
provement in her headaches and other symptoms. A neuro-
logic examination revealed normal neurological functions,
and a follow-up MRI scan at that time showed a remarkable
decrease in the size of the contrast-enhancing area (Fig. 2)
that was targeted during radiosurgery. A suspicious area of
enhancement was detected on the right side, however, no
surrounding edema was noted. To investigate this area fur-
ther, an F-18 fluorodeoxyglucose (FDG)-PET study of the
brain was ordered. It revealed a large irregular neoplasm ex-
tending from the inferior left-temporal lobe into the deep
parietal lobe and into the calcrine area on the left with ex-
tremely intense FDG uptake, suggesting a very aggressive
tumor. A smaller, somewhat less FDG avid lesion was also
detected in the deep right-frontal lobe representing a sec-
ond neoplastic focus (Fig. 3). She refused any further treat-
ment and exhibited severe symptoms from her right-frontal
tumor (left hemiparesis Grade was 2 out of 5) over the next
3 months. Despite repeated requests, she refused any fur-
ther investigations and/or treatments and succumbed to the
disease 6 months after radiosurgery.
3. Discussion
The existence of true multicentric GBM has been widely
debated and discussed throughout the years. Diagnosis of
40 A. Jawahar et al. / Clinical Neurology and Neurosurgery 106 (2003) 38–40
Fig. 3. FDG-PET scan of the brain showing (a) the left-parietal tumor and (b) areas of increased uptake in the opposite hemisphere.
multiple lesions as such is very rare and, although it is dif-
ficult to estimate the frequency of true multicentric GBM, a
wide range of frequencies have been reported through histo-
logical studies. Frequencies of true multicentric GBM have
been reported to be as low as 2.3% and as high as 7.5–9%
in patients with multiple lesions [3–5]. Only rare cases of
multiple lesions can be diagnosed as true multicentric le-
sions without the evidence of possible intracranial spread
[2]. Even with detection of a lesion or multiple lesions by
traditional neuroradiological scanning, there are still prob-
lems in correctly identifying the lesions as GBM. First, as
was noted by Batzdorf and Malamud [2], interpreting ra-
diological scans can be difficult because of the balancing
of opposing pressures when tumors are located bilaterally.
Furthermore, the presence of multiple tumor foci raises the
question of a possible intracranial metastasis, especially if
extracranial masses are present. Another compounding fac-
tor making the diagnosis of a multicentric GBM difficult is
the absence of localizing signs from one or more of the tu-
mor foci. Conversely, localizing signs may be present, yet
not correspond to the lesions detected by neuroimaging [2].
For these reasons, it is imperative to investigate new meth-
ods to screen and subsequently detect multicentric GBM
tumors.
The development and use of PET scanner have improved
the ability to discover and diagnose multicentric lesions [6].
Though MRI scans are a mainstay in diagnosing and plan-
ning a treatment for patients suffering from brain lesions,
PET scanning offers sensitivity beyond the capabilities of
MRI scanning. Detection of early lesions by a neuroradio-
logic method, such as CT scans and MRI scans, may not
provide a definitive existence of a brain tumor or discrimi-
nate neoplastic tissue from edema [7]. FDG-PET scanning
allows for the discovery of very small lesions by measur-
ing the glucose utilization of the tumor that might go un-
detected by normal MRI scans. Glucose utilization of the
tumor can also be useful for tumor grading. Di Chiro et al.
[7] have reported the ability to grade tumors solely on the
uptake of FDG by tumors. The utilization of glucose is
higher in rapidly growing tumors (Grades 3 and 4) because
of the partiality of the malignant tumors towards anaerobic
metabolism [8]. Increased tumor grades can be correlated
with the increase in anaerobic glycolysis.
Our case report demonstrates the superior sensitivity of
FDG-PET scanning in comparison to MRI scanning for de-
tecting multicentric GBM. In the follow-up period, only
FDG-PET scan detected a small lesion in the right-frontal
lobe, in addition to the large irregular neoplasm found in the
left-temporal lobe. Though the patient refused further treat-
ment after being diagnosed with multicentric disease, we
believe a more comprehensive strategy of treatment could
have been planned with earlier FDG-PET scanning, as op-
posed to use of MRI alone.
4. Conclusion
The diagnosis of true multicentric GBM is very rare, but
with the increased availability of PET scanning the opportu-
nity for discovering multicentric lesions has increased. PET
scans, in conjunction with MRI scans, allow for the best
possible and most comprehensive diagnosis and treatment
plans.
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