Case Report - Cases of glioblastoma multiforme metastasizing to spinal cord

Abstract

Cases of glioblastoma multiforme (GBM) metastasizing to the leptomeninx or the intramedullary spine are quite rare and prognoses are relatively poor. We present three cases of GBM with spinal metastasis, one of which also had leptomeningeal dissemination. Three patients with GBM were admitted to our clinic for postoperative radiotherapy after surgery. Leptomeningeal metastasis and dissemination were diagnosed with magnetic resonance imaging. Radiotherapy provided only temporary relief from pain with small improvement in neurological deficit but no survival advantage.

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Case Report?
Cases of glioblastoma multiforme metastasizing to spinal
cord
Metehan Karaca, Meltem Nalca Andrieu, Ayse Hicsonmez, Yildiz Guney, Cengiz Kurtman
Department of Radiation Oncology, Ankara University Faculty of Medicine, Cebeci Hospital, Dikimevi Ankara, Turkey
Cases of glioblastoma multiforme (GBM) metastasizing to
the leptomeninx or the intramedullary spine are quite rare
and prognoses are relatively poor. We present three cases
of GBM with spinal metastasis, one of which also had
leptomeningeal dissemination. Three patients with GBM
were admitted to our clinic for postoperative radiotherapy
after surgery. Leptomeningeal
dissemination were diagnosed with magnetic resonance
imaging. Radiotherapy provided only temporary relief from
pain with small improvement in neurological deficit but no
survival advantage.
metastasis and
.medknow.com).
Key words: Glioblastoma multiforme, intramedullary
metastasis, leptomeningeal dissemination, radiotherapy
Introduction
Glioblastoma multiforme (GBM) is the most common primary
malignancy of the central nervous system (CNS). Cerebrospinal
fluid (CSF) seeding is observed in approximately 15-25% of
cases of supratentorial GBM,[1-3] while a higher incidence is seen
in patients with infratentorial GBM.[3] However, the exact
complete neurological examination and radiological evaluation,
tumor recurrence in the operation field and a new lesion in the
prepontine interpedincular system were found [Figure 1]. Also,
thoraco-lumbar spinal MRI revealed an expansive intramedullar
lesion at the T11-L1 junction measuring 3.5 x 2 x 1 cm in
diameter [Figure 2]. After palliative external radiotherapy to T10-
L2 with a total dose of 21 Gy in 3-Gy fractions, neurological
findings were diminished. Additionally, two cycles of CCNU
adjuvant chemotherapy were given. One month after the end of
RT, control MRI demonstrated no progression of the lesion.
Figure 1: The leptomeningeal implant in prepontine interpedincular
system (from first case)
performed routinely. In addition, CSF cytology is not useful due
to the high number of false negative results.[4]
Case Reports
Case 1
In February 2004, a 67-year-old man presented with a history
of headache and disarthria of two months duration. Brain MRI
demonstrated a contrast-enhancing lesion with edema measuring
7.5 x 5.5 x 5 cm in the left temporal lobe. Gross total resection was
performed. Histopathological findings showed GBM (WHO Grade
4). After surgery, cranial radiotherapy (RT) was delivered with a
total dose of 60Gy in 2-Gy fractions. The patient complained of
left leg weakness and back pain in the second week of RT.After a
Figure 2: An expansive intramedullar lesion at T11-L1 junction
(from first case)
Yildiz Guney
Department of Radiation Oncology, Cebeci Hospital, Dikimevi Ankara Turkey. E-mail: yildiz_guney@yahoo.com
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meningeal and spinal spread discovered at autopsy. Metastases,
Karaca M, et al.: Glioblastome multiforme
Although good local control and palliation of symptoms were
achieved with RT, the patient survived only about four months
after diagnosis of metastases.
Case 2
In November 2003, a 20-year-old woman was admitted to the
emergency unit with a history of headache and diplopia. After
radiological evaluation, a lesion measuring 3.5 x 3.5 x 2.2 cm from
the left lateral ventricule to the frontal lobe was found. Gross total
resection was performed. Histopathological findings showed GBM.
mm) and T12-L1 (3 x 1.5 x 1 cm) were found by MRI. In
consideration of the high performance status of the patient and no
change in the diameter of the primary lesion during the 17-months
period of postoperative cranial RT, spinal RT was to be delivered to
the limit dose of the cord. Palliation of symptoms was achieved with
RT, but the patient died in September 2005.
Discussion
The most common clinical features of leptomeningeal metastases
Postoperative cranial RT was delivered with a total dose of 60Gy in
are radicular pain in the upper and lower limbs, lower back,
2-Gy fractions. There was no complain for one year after RT.
interscapular area and neck. This is frequently followed by
However, at the last visit, the patient complained of left foot pain.
paraparesis or, infrequently, quadraparesis.[5] Accordingly,our
After a through neurological examination and radiological
patients presented with pain during leptomeningeal dissemination.
evaluation, tumor recurrence in the operation field was found in
The most common sites for spinal GBM metastases are the
December 2004. Also, lumbar MRI showed multiple lesions at the
lower thoracic, upper lumbar and lumbosacral regions.[6] Reports
lowest thoracic and upper lumbar vertebral region and between
of intramedullary metastases are quite rare in the literature.[5]
fibers of cauda equinea, but concurrent CSF study was negative
Since patients with GBM usually do not live long enough for
[Figure 3]. Palliative RT to T12-L2 with a total dose of 39Gy in 3-
small tumor implants to grow to the symptomatic size, it is difficult
Gy fractions was delivered in January 2005. Good palliation was
to clinically evaluate symptomatic metastasis. The rate of spinal
achieved with RT, but the patient died in June 2005.
leptomeningeal seeding after diagnosis of GBM has been variably
reported. A review of the literature by Erlich and Davis in 1978
revealed only 14 well-documented cases of spinal subarachnoid
In January 2003, a 28-year-old woman was admitted to the
seeding from primary intracranial GBM since 1931.[7] In a study
emergency unit with a history of headache and sudden weakness of
of 600 patients with GBM, only 2% had symptomatic CSF
the right side. After radiological evaluation, brain MRI
seeding.[5] This result suggests that the symptomatic involvement
demonstrated a contrast-enhancing lesion measuring 7 x 3.5 x 4.5
occurs relatively late in the course of GBM. In our cases, metastases
cm in the left frontal and parietal lobe. Gross total resection was
were diagnosed in the 2nd, 12th and 17th
performed. Histopathological studies showed GBM (WHO Grade
respectively. Stark et al[8] reported three patients (1.1%) of 267
4). Postoperative cranial RT was delivered with a total dose of
adult cases of GBM who developed spinal drop metastases 5, 8 or
60Gy in 2-Gy fractions. She received temazolamid as concurrent
11 months after craniotomy. The incidence of symptomatic
chemotherapy. After surgery and RT, there was no symptom or
metastasis is certainly lower than the incidence observed
complain for 17 months. Although a small residual lesion was found
postmortem. Most of the large series describe patients with
in all control MRIs, it was stable. At the last control in June 2005,
the patient complained of lower limb weakness and intradural-
which were associated with pain and/or neurological deficit, were
extramedullar lesions at T6 (5-6 mm), T8 (10-12 mm), T9 (7?
usually verified by radiological studies. We suspected CSF
spreading because of back pain and neurological deficit during
Case 3
months after RT,?
Figure 3: A metastatic lesion at lowest thoracic and upper lombar
vertebral region (from second case)
RT. Magnetic resonance imaging findings demonstrated the
dissemination of disease in Case 1.
Until recently, myelography with CT follow-up was the most
accurate diagnostic test for leptomeningeal metastasis,[6] but CT
myelography has now been replaced with MRI. Spinal MRI with
gadolinium enhancement is the current investigation of choice for
leptomeningeal metastasis.
Although there is still no satisfactory treatment for
leptomeningeal metastasis, RT is the most commonly used
treatment modality, with a total dose of 25 to 40Gy. Because of
the diffuse nature of the disease, leptomeningeal metastasis is
often unsuitable for surgical decompression. The advantage of
intravenous or intrathecal chemotherapy has not been proven for
intramedullary metastasis. Because curative treatment is not
applicable, the treatment modality for these patients is solely
palliative. Our patients were treated with a total dose of 21Gy,
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Karaca M, et al.: Glioblastome multiforme
39Gy or 46Gy and good palliation of symptoms was achieved.
Leptomeningeal metastasis with CSF tumor dissemination
almost always results in a fatal outcome. The median time from
diagnosis of the primary intracranial GBM to diagnosis of CSF
tumor dissemination ranges from 8 to 14 months, median
survival ranges from 11 to 17 months and the average time
interval between diagnosis of leptomeningeal metastasis and
death is two to three months.[9] As mentioned by Fakhrai et
al,[10] survival periods are shorter in patients who have GBM
with spinal seeding and these patients should be given adequate
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pain and/or associated spinal root nerve signs should cause
Accepted on 23-05-2006
clinicians to consider leptomeningeal and/or spinal dissemination
Source of Support: Nil, Conflict of Interest: None declared.
of GBM.?
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