Lengyel, Zsolt

Molnár, Péter Pál

Novák, László

Trón, Lajos

Neurology India

University of Debrecen Electronic Archive

105Neurology India March 2005 Vol 53 Issue 1
CMYK 105
Case Report
Novak Laszlo
University of Debrecen, Health and Life Sciences Center, Department of Neurosurgery, Nagyerdei krt. 98, P. O. Box. 31, 4012 Debrecen, Hungary.
E-mail: lnovak@jaguar.dote.hu
Does increased 18FDG uptake reflect malignant transformation
of a low-grade glioma? A diagnostic dilemma
Novak Laszlo, Molnar Peter*, Lengyel Zsolt**, Tron Lajos**
Departments of Neurosurgery and *Pathology, **PET Study Group of the Hungarian Academy of Sciences. University of Debrecen, Health
and Life Sciences Center, Hungary
Benign gliomas of the brain show decreased uptake of 18F
fluorodeoxyglucose (FDG) on positron emission tomogra-
phy (PET). Malignant transformation is usually manifested
by an increase of 18FDG uptake. A 45-year-old female has
been followed up since 1987 by means of 18FDG-PET for a
right hemispheric World Health Organization Grade II
oligoastrocytoma. In 1996, increased epileptic activity was
accompanied by increased 18FDG uptake within the tempo-
ral part of the tumor. After surgery, the epileptic seizures
diminished. Histological examination of the resected tumor
showed no change in the pathology when compared with
the first biopsy. Localized temporal increase of 18FDG up-
take was not associated with malignant progression. The
decrease of seizure frequency might shed light on a puta-
tive connection of hyperglycolysis and epileptic discharges.
Key Words: 18FDG-PET, malignant transformation, ictal
scan, low-grade glioma.
Introduction
Benign gliomas of the brain appear as hypometabolic areas
on 18F fluorodeoxyglucose positron emission tomography
(18FDG-PET).[1-3] Malignant transformation and tumor pro-
gression results in an increased 18FDG uptake.[2-3] We present
a case of a World Health Organization (WHO) Grade II
oligoastrocytoma with a total present length of 17 years’ sur-
vival time, despite indication – based on elevated 18FDG up-
take - of malignant progression eight years previously (Table
1).
Case Report
A right frontal WHO Grade II oligoastrocytoma in a 28-year-old
female was operated on in 1987. The patient stayed seizure-free un-
til 1994, when an infiltrating recurrence was detected. 18FDG up-
take was not elevated (Figure 1a). Partial temporal seizure activity
became uncontrollable in 1996 with tumor extension towards the
temporal lobe and the midline structures. The 18FDG-PET showed
increased tracer uptake in the temporal region suggesting the possi-
bility of malignant transformation (Figure 1b). The tumor then was
repeatedly resected with evidence of residual parts in surgically in-
accessible ganglionic structures. After surgery, the patient became
seizure-free again. Histology of the second partial resection from the
region of highest 18FDG uptake turned out to be the same WHO
Grade II. oligoastrocytoma (GFAP positive gemistocytes and tumor
cells with fried egg appearance, no necrosis, no atypia, slight en-
dothelial proliferation and infrequent mitosis). The repeated post-
operative 18FDG-PET revealed no elevated tracer uptake within the
residual parts. Following recovery from surgery, conventional irra-
diation and PCV chemotherapy were administered. Eight years later,
to date, the patient is in clinical remission. The follow-up 18FDG-
PET scans have revealed gradual elevation of tracer uptake in the
residual tumor, and thus a new cycle of PCV chemotherapy has been
indicated (Figure 1c).
PET investigations
All static cerebral PET scans were performed using a GE 4096
Plus PET scanner (GE Medical Systems AB, Uppsala). The patient
received 104 ± 44 ìCi/kg (mean ± SD) 18FDG as an intravenous
bolus injection in a dark, silent room 30 minutes prior to scanning.
Axial scans with spatial resolution of 6.5 mm full width at half-maxi-
mum were obtained. Corrections for tissue attenuation were allowed
by transmission measurements (25 min) performed before emission
scans using a 68Ge source of 8 mCi activity. The tumor-to-white mat-
ter (T/WM) and tumor-to-cortex (T/C) uptake ratios were used to
substitute true 18FDG utilization (Table 1). The most accepted cut-
off level in the differentiation of high-grade from low-grade tumors
is 1.5 for T/WM and 0.6 for T/C ratios.[2] The co-registered MRT
(Shimadzu SM 100X, 1 Tesla) and PET images were merged (Reg-
ister, McConnel Brain Imaging Center, Montreal Neurological Insti-
Table 1: The tumor-to-white matter (T/WM) and tumor-to-frontal
cortex (T/C) uptake ratios in consecutive 18FDG-PET scans*
1994 1996 1997 2000 2003
T/WM (highest) 2.36
T/WM (85% cut-off) 0,96 0.98 0.86 1.17 1.82
T/C (highest) 1.25
T/C (85% cut-off) 0,48 0.52 0.5 0.63 0.83
*The second resection was performed after the 1996 scan. Afterwards, no
such heterogeneity of tracer uptake has been observed.
106 Neurology India March 2005 Vol 53 Issue 1
106 CMYK
Figure 1a: Neuroradiological features in 1994. The corresponding axial slice of MRT (i), 18FDG-PET (ii) and the merged co-registered scans (iii)
made after a diagnosis of the recurrent tumor. The 18FDG uptake of the whole tumor is less than the normal brain tissue’s
(i) (ii) (iii)
Figure 1b: Neuroradiological features in 1996. The corresponding axial slice of MRT (i), 18FDG-PET (ii) and the merged co-registered scans (iii)
made before second operation in 1996 after nine years from discovery. The red arrow points out the right temporal region of elevated 18FDG uptake.
The surrounding part of the tumor is hypometabolic
Figure 1c: Neuroradiological features in 2003. The corresponding axial slice of MRT (i), 18FDG-PET (ii) and the merged co-registered scans (iii)
made after 16 years of medical history. The tracer uptake of infiltrating right hemispheric tumor is elevated but does not approach the extent that
was detected in 1996
(i) (ii) (iii)
(i) (ii) (iii)
107Neurology India March 2005 Vol 53 Issue 1
CMYK 107
tute). The region of highest 18FDG uptake was defined within tumor
limits (10 pixels, 2x2 mm/pixel), and isocontour ROI was drawn with
an 85% cut-off value. Contralateral centrum semiovale served as an
area of white matter (10 pixels). Contralateral frontal cortex was
defined at the plane of the isocontour ROI (average uptake of 5 ROIs,
each contains 5 pixels).
Discussion
18FDG-PET studies have shown good correlation between
histological grade and tracer uptake that is intrinsically het-
erogeneous in gliomas.[1-3] Regionally elevated tracer uptake
is considered to be related to the presence of anaplasia, higher
proliferation rate and cell density, hypervascularization, and
inflammation.[2-3] The temporal hypermetabolic region had
been assumed to be a sign of malignant transformation but
histology proved WHO Grade II. oligoastrocytoma. It occurred
after a nine year long follow-up. In most cases of intracer-
ebral tumors, resection results in decrease of seizure frequency
and the regrowth often result in increase or in recurrence of
previously eliminated and temporarily absent fits, suggesting
that the pacemaker area is mainly represented in the tumor
and/or within a close vicinity.[4-5] There was no preserved gray
matter in the removed specimen, but the overlying cerebral
cortex might have acted as a pacemaker since in case of epi-
leptic activity the uptake rises because of excessive number of
action potentials generated. The patient was not having sei-
zures during the PET scans. EEG monitoring could help, but
in focal seizure activity conventional scalp electrodes might
not reveal spikes when the underlying tumor is expansive. In
our case, after temporal resection, the seizures subsided, a
fact that possibly implies that the elevated temporal 18FDG
uptake might have been a result of continuous epileptic activ-
ity.[6]
Acknowledgement
The authors wish to express grateful appreciation for technical assistance to Irma
Kari.
References
1. Derlon JM, Chapon F, Noel MH, Khouri S, Benali K, Petit-Taboue MC. Non-
invasive grading of oligodendrogliomas: Correlation between in vivo metabolic
pattern and histopathology. Eur J Nucl Med 2000;7:778-87.
2. Meyer PT, Schreckenberger M, Spetzger U, Meyer GF, Sabri O, Setani KS, et
al. Comparison of visual and ROI-based brain tumour grading using 18F-FDG
PET: ROC analyses. Eur J Nucl Med 2001;2:165-74.
3. Padma MV, Said S, Jacobs M, Hwang DR, Dunigan K, Satter M, et al. Predic-
tion of pathology and survival by FDG PET in gliomas. J Neurooncol
2003;64:227-37.
4. Luyken C, Blumcke I, Fimmers R, Urbach H, Elger CE, Wiestler OD, et al.
The spectrum of long-term epilepsy-associated tumors:long-term seizure and
tumor outcome and neurosurgical aspects. Epilepsia 2003;44:822-30.
5. Tandon PN, Mahapatra AK, Khosla A. Epileptic seizures in supratentorial glio-
mas. Neurol India 2001;49:55-9.
6. Meltzer CC, Adelson PD, Brenner RP, Crumrine PK, Van Cott A, Schiff DP, et
al. Planned ictal FDG PET imaging for localization of extratemporal epileptic
foci. Epilepsia 2000;2:193-200.
Accepted on 20.04.2004.


Does increased 18FDG uptake reflect malignant transformation of a low-frade glioma?: a diagnostic dilemma

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Does increased 18FDG uptake reflect malignant transformation of a low-frade glioma?: a diagnostic dilemma

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