Glioblastoma multiforme: a rare manifestation of extensive liver and bone metastases
Department of Biomedical Imaging (Radiology), Faculty of
Medicine, University of Malaya, Kuala Lumpur, Malaysia
Glioblastoma multiforme (GBM) is the most aggressive form
of primary brain tumours known collectively as gliomas. Gliomas are graded by
their microscopic appearance. As a rule, their behaviour can be predicted from
histology: Grade I (pilocytic astrocytomas) and Grade II (benign astrocytomas) tumours
are of low grade and grow slowly over many years. Grade IV tumours (GBM) are
the most aggressive and, unfortunately, also the most common in humans, growing
rapidly, invading and altering brain function. These tumours arise from the
supporting glial cells of the brain during childhood and in adulthood.
These growths do not spread throughout the body like other
forms of cancer, but cause symptoms by invading the brain. Untreated GBMs are
rapidly lethal. Most patients with GBM die of their disease in less than a year
and none have long term survival.
Extracranial metastases from GBM are extremely rare, with
a reported frequency of only 0.44% because of the absence of lymphatics in the
brain and the difficulty of tumours to penetrate blood vessels. A case of
glioblastoma multiforme with the rare features of extensive liver and bone
metastases is presented in this paper. � 2008 Biomedical Imaging and
Intervention Journal. All rights reserved.
Keywords: Glioblastoma multiforme, GBM, extracranial metastases, glioma
Gliomas are malignant brain tumours of glial cells growing
along white matter tracts. Glioblastoma multiforme (GBM) is the most aggressive
form of these primary brain tumours, which usually arise de novo or may
develop from lower grade gliomas after many years. Distinct genetic alterations
in GBM cases have been identified but as a rule there is no familial history.
The peak age of presentation is in late adult life. Reported series from the USA give an incidence of approximately 20,000 cases of GBM per year.
GBM is usually located in the cerebral hemispheres, with a
predilection for the white matter of the centrum semiovale and corpus callosum.
There is relative sparing of the basal ganglia and grey matter. Posterior fossa
and brain stem gliomas are seen in a younger age group. Multifocal tumours
occur in 2-5% . Contrast-enhanced CT scans of the brain demonstrate a
variable tumour pattern from diffuse homogenous enhancement to heterogenous and
ring enhancing patterns. The tumour, which rarely calcifies, usually extends
beyond the margins of the enhancement. MR imaging demonstrates ill-defined tumour
of a predominantly low signal on T1WI and heterogenous high signal on T2WI with
slight gadolinium enhancement and usually accompanied by extensive vasogenic
oedema. Areas of haemorrhage and central tumour necrosis may also be seen.
Additional imaging methods are PET scanning where an increase in glucose
utilization rates is seen and MR spectroscopy where increased choline peaks are
The diagnosis of GBM requires tissue obtained by surgical
methods. Surgery may vary from stereotactic needle biopsy of deep tumours to
open surgical excision of surface tumours using frameless stereotaxis. As the
name implies, GBM is multilobulated in appearance on gross pathology,
demonstrating quite extensive vasogenic edema. It is a deeply infiltrating
tumour with areas of haemorrhage and necrosis. Histologically, it is highly
cellular, often bizarrely pleomorphic, undifferentiated multipolar astrocytes
with prominent vascular endothelial proliferation and no capsule is
A 45-year-old woman had complained of progressive headache
over a period of one year with associated disturbances in speech and blurring
of vision over the last three weeks. A contrast-enhanced MRI of the brain was
performed in February 2004, showing a heterogeneously enhancing lesion in the
left temporal lobe with an associated cystic component (Figure 1). She then
underwent a craniotomy with excision of the left temporal lobe tumour, which
was diagnosed as a glioblastoma multiforme (WHO Grade 4) based on the histopathological
findings. She received three cycles of radiotherapy, commencing three months
post surgery. Post operatively, the patient�s condition improved and she was
discharged well five days after the surgery.
She then presented 9 months post-surgery with complaints
of back pain. An MRI of the lumbosacral spine revealed features suggestive of
bone metastases. A radionuclide bone scan performed two weeks later
demonstrated extensive skeletal metastases. A subsequent MRI of the
thoraco-lumbar spine demonstrated multiple areas of metastases with evidence of
spinal cord compression at the T7 level (Figure 2).
The patient by this time had also complained of vague
abdominal pains, and a CT scan of the abdomen and pelvis showed multiple
massive hypodense liver lesions of varying sizes (Figure 3). An ultrasound-guided
core biopsy of one of these liver lesions was performed and was
histopathologically confirmed to be that of liver tissue demonstrating abnormal
sheets of small round �blue� cells with high nucleocytoplasmic ratio and
pleomorphism in keeping with glioblastome multiforme metastases (Figure 4a).
Based on the laboratory histopathology results and imaging
findings, a diagnosis was made of glioblastoma multiforme (GBM) of the brain,
with extensive liver and bone metastases.
Extracranial metastasis of GBM is extremely rare, with a
reported frequency of only 0.44%. Pasquier et al found metastases occurred in
regional lymph nodes (51%) and lungs and pleura (60%) and occasionally in the
bone (31%) and liver (22%) . Metastases from GBM are rare for a number of
reasons: the cerebrum does not have a lymphatic system; the intra-cranial
sinuses are enclosed in a dense dural membrane, which makes penetration by
tumour cells difficult; intracerebral veins are thin walled and would probably
collapse from compression before they could be penetrated by an expanding
tumour; and the immunological response of the host organ to neuroglial tumour
cells may prevent their growth outside the central nervous system . A
further explanation could be the short life span of patients with GBM who do
not survive long enough to develop metastases.
Extra-cranial metastases have been described following
stereotactic biopsy and few cases have been reported to occur in the absence of
previous craniotomy . Distant metastases generally occur after craniotomy,
when direct access via the dural vessels to the extra-cerebral tissue is
possible. When a tumour infiltrates the dura mater of the middle cranial fossa,
metastases tend to occur in the lungs and pleura given the fact that much of
the meningeal venous system flows back into the internal jugular venous system .
Haematogenous metastases may occur in the bone with the vertebrae being the
most common site of bony involvement . Lymph node metastasis is thought to
occur through connections between perineural spaces and lymphatic plexuses .
In the present case, the patient was initially thought to
have another malignancy giving metastases to the liver. However, histopathologic
confirmation obtained via a liver biopsy revealed highly cellular pleomorphic
cells similar to that seen in the primary cerebral glioblastoma multiforme. Therefore,
the extensive liver lesions were accepted as extra-neural metastases of GBM and
the patient was treated accordingly.
Much evidence now exists to support the notion that the
removal of a maximum volume of tumour in the brain improves function and
prolongs survival in the patients with GBM. Chemotherapy is a controversial
treatment as many studies have failed to show prolonged median survival in
treated patients, although the proportion of long term survivors may be
somewhat greater. With distant metastases, chemotherapy is the only appropriate
treatment but in these patients the prognosis is very poor.
A case of glioblastoma multiforme of the brain with the
rare occurrence of extensive extra-cranial metastases to the liver and bone is
Figure 1 A coronal contrast-enhanced MRI of the brain demonstrating the heterogeneously enhancing left temporal lobe mass (glioblastoma multiforme) with an associated cystic component (arrow).
Figure 2 A contrast-enhanced T1 weighted sagittal MRI of the spine demonstrating multiple enhancing lesions in the vertebral bodies in keeping with bony metastases and cord compression at T7 level (arrow).
Figure 3 An axial contrast-enhanced CT scan of the liver demonstrating multiple liver metastases of varying sizes (the largest marked with an asterisk).
Figure 4 The H&E; stained histopathological slide of the liver biopsy demonstrating a) abnormal sheets of small round �blue� cells with high nucleocytoplasmic ratio and pleomorphism in keeping with glioblastoma multiforme metastases (slide magnification x200); b) the normal appearance of the hepatocytes obtained from a normal part of the liver tissue (slide magnification x500).
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|Received 8 March 2007; received in revised form 17 December 2007; accepted 26 December 2007
Correspondence: Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. E-mail: firstname.lastname@example.org (Melanie Robert).
Please cite as: Robert MC, Wastie ML,
Glioblastoma multiforme: a rare manifestation of extensive liver and bone metastases, Biomed Imaging Interv J 2008; 4(1):e3
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