Subcutaneous tumor seeding after biopsy in gliomatosis cerebri.

Abstract

We observed a patient with subcutaneous seeding from gliomatosis cerebri with a low-grade histopathology. A 33-year-old woman with neurofibromatosis type 1 presented with progressive headache, diplopia, dysphagia, and a rightward instability. On neurological examination dysarthria, gait ataxia, and left-sided central facial and hypoglossal palsies were determined. MRI of the brain demonstrated diffuse, infiltrative non-enhancing lesions in the pons, both cerebellar hemispheres, the parahippocampal gyrus, and the thalamus. A stereotactic biopsy demonstrated an astrocytoma WHO grade 2. These characteristics confirmed gliomatosis cerebri. Three months later, the patient presented with hydrocephalus and a subcutaneous swelling directly underneath the surgical scar. The subcutaneous swelling was removed and the hydrocephalus was treated by ventriculoperitoneal shunting. Histopathological examination confirmed a subcutaneous manifestation of low-grade oligoastrocytoma. Gliomatosis cerebri with low-grade histology can seed subcutaneously.

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LETTER TO THE EDITOR
Subcutaneous tumor seeding after biopsy in gliomatosis cerebri
Dennis R. Buis•Paul van der Valk•
Philip C. De Witt Hamer
Received: 17 April 2011/Accepted: 30 July 2011/Published online: 12 August 2011
? The Author(s) 2011. This article is published with open access at Springerlink.com
Abstract
seeding from gliomatosis cerebri with a low-grade histo-
pathology. A 33-year-old woman with neurofibromatosis
type 1 presented with progressive headache, diplopia,
dysphagia, and a rightward instability. On neurological
examination dysarthria, gait ataxia, and left-sided central
facial and hypoglossal palsies were determined. MRI of the
brain demonstrated diffuse, infiltrative non-enhancing
lesions in the pons, both cerebellar hemispheres, the
parahippocampal gyrus, and the thalamus. A stereotactic
biopsy demonstrated an astrocytoma WHO grade 2. These
characteristicsconfirmedgliomatosis
months later, the patient presented with hydrocephalus and
a subcutaneous swelling directly underneath the surgical
scar. The subcutaneous swelling was removed and the
hydrocephalus was treated by ventriculoperitoneal shunt-
ing. Histopathological examination confirmed a subcuta-
neousmanifestationoflow-grade
Gliomatosis cerebri with low-grade histology can seed
subcutaneously.
We observed a patient with subcutaneous
cerebri.Three
oligoastrocytoma.
Keywords
Glioma ? Pathology
Tumor seeding ? Stereotactic biopsy ?
Case report
A 33-year-old female with neurofibromatosis type 1 pre-
sented with progressive headache since one year. Daily
nausea and vomiting progressed since six months. Diplo-
pia, dysphagia, and right-ward instability were present
since one month. On neurological examination dysarthria
and gait ataxia were confirmed. Left-sided central facial
and hypoglossal palsies were noted. She had diplopia,
when looking to the right with a grade 1 nystagmus and a
central hypesthesia of the right side of the face. Babinski’s
sign and right-sided hyperreflexia were noted. An MRI of
the brain demonstrated a diffuse infiltrative, non-enhancing
lesion reaching from the pons to both cerebellar hemi-
spheres, and extending to the basal ganglia and thalamus.
This resulted in bilateral diffuse swelling of the thalamus,
hypothalamus, and basal ganglia. Additionally, there were
manifestations around the right frontal lobe, the insula,
amygdala, and the parahippocampal gyrus. These radio-
logical characteristics were compatible with gliomatosis
cerebri (Fig. 1).
To establish a histopathological diagnosis, she had a
frameless stereotactic needle biopsy of the right mesio-
temporal region with a Sedan side cutting needle through a
regular burrhole (Fig. 2). A total number of three biopsies
at the same location were taken. The small dura opening
was covered with a Novacol pad (Taureon, Rijswijk, The
Netherlands), but left otherwise unclosed and unsealed.
The skin and subcutaneous tissue, and temporal fascia were
closed in layers.
The histopathological examination demonstrated irreg-
ular cells with a clear atypia of the GFAP positive staining
cells (Fig. 3). Given the relative paucity of these cells and
their diffuse spread throughout the biopsy, a diagnosis of
gliomatosis of the astrocytic subtype (WHO grade 2) was
D. R. Buis (&) ? P. C. De Witt Hamer
Department of Neurosurgery,
ZH 2F005, Neurosurgical Center Amsterdam,
VU University Medical Center, PO Box 7057,
1007 MB Amsterdam, The Netherlands
e-mail: drbuis@gmail.com
P. van der Valk
Department of Neuropathology, VU University Medical Center,
Amsterdam, The Netherlands
123
J Neurooncol (2012) 106:431–435
DOI 10.1007/s11060-011-0678-2

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made. Due to profound invasion, resulting in too extensive
radiation fields, radiotherapy was refrained and temozolo-
mide monotherapy was initiated. Her headaches improved
with Dexamethasone. However, three months later, the
headaches progressed, accompanied by a subcutaneous
swelling at the incision, due to which the patient was
unable to wear her glasses (Fig. 4). CT-imaging demon-
strated triventricular hydrocephalus. In order to relief her
headaches, she was given a ventriculoperitoneal shunt
and the swelling was removed completely through a
re-incision.
Histopathological examination of the subcutaneous
swelling demonstrated skin and subcutaneous tissue inva-
ded by glial tumor, which was diagnosed to be oligoastro-
cytoma, as the sample was dominated by oligodendrocytes
with a clear cytoplasm and slightly irregular nuclei, but
also a component of large, multinucleated astrocytic cells,
which were morphologically similar to the biopsy sample
(Fig. 5).
After placement of the shunt, her headaches improved,
but the intracranial tumor progressed clinically during
temozolomide, which was subsequently stopped. Although,
Fig. 1 The diffusely swollen mesencephalon, uncus and parahippo-
campal gyrus on FLAIR (A) and T2MRI-sequences (B), as well as
the absence of gadolinium enhancement (C and E) is compatible with
the radiological criteria for gliomatosis cerebri. There is diffuse
enlargement of the pons (D)
432J Neurooncol (2012) 106:431–435
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our patient was offered second line chemotherapy, she
refused further treatment and died shortly after.
Discussion
Approximately 20% of patients with neurofibromatosis type
1 develop low-grade gliomas [1], but gliomatosis cerebri is
rare, even in association with neurofibromatosis [2]. Glio-
matosis cerebri is a glioma with a diffuse, usually astrocytic
growth pattern, that widely invades the brain involving at
least three cerebral lobes, and usually with bilateral
involvement of the cerebral hemispheres, deep gray matter,
brainstem or cerebellum [3]. Although, mitotic activity is
generally low, and anaplastic characteristics, such as
microvascular proliferation and necrosis are generally
absent at presentation [4–6], its biologic behaviour corre-
sponds to a WHO grade 3 tumor in the majority of cases [3].
Subcutaneous metastasis from gliomas are rare [7].
However,in high-gradeglioma,remote cutaneous
Fig. 2 A needle biopsy was taken from tumor in the right mesiotemporal region (green tract)
J Neurooncol (2012) 106:431–435433
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metastasis [8–10], or metastatic seeding through the
stereotactic biopsy tract [11–14] have been reported. The
presumed mechanism includes seeding of tumor cells
during surgery [13], especially, when the biopsy tract was
not included in the irradiated volume [14]. Seeding of
tumor in the biopsy tract has not been reported in glio-
matosis cerebri or low-grade glioma. Alternatively, the
glioma grading may have been underestimated due to
biopsy sampling error.
We postulate that in the presented case, tumor cells were
spilled and implanted during removal of the needle, as the
intra- and extracranial tumor components were not con-
tinuous on CT imaging and at visual inspection during
removal of the lesion. Therefore our observation demon-
strates that gliomatosis cerebri with low-grade histopa-
thology has the potential to seed subcutaneously. This
observation warrants several practical advises. First, close
inspection for tumor fragments in the surgical field during
biopsy seems to be required. Second, extensive rinsing of
the surgical field may facilitate removal of tumor elements
that cannot be detected by inspection. Third, tight dural
sealing or closure to avoid secondary subcutaneous tumor
spill is advisable.
Fig. 3 Initial brain biopsy. The
left hand panel shows
hematoxilin–eosin-stained
section of cortical tissue with
slight increase in cellularity
(objective 92.5). The cells are
somewhat irregular, as is better
appreciated in the right hand
panel, a GFAP staining for
astrocytic cells (objective 940),
showing clear atypia of the
positive-staining cells. Given
the relative paucity of these
cells and their diffuse spread
throughout the biopsy a
histopathological diagnosis of
gliomatosis was made
Fig. 4 The subcutaneous lesion (blue arrow), in the biopsy tract is
not continuous with the intracranial compartment. The hyperdensity
in the pons is thought to be a tumor related bleeding, which was
probably not biopsy related
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Fig. 5 Resection specimen of
skin and subcutaneous tissues.
The inset in the top left hand
corner shows a low-power view,
showing epidermis and dermis.
In the larger figure, the image is
dominated by oligodendrocytes
with a clear cytoplasm and
slightly irregular nuclei; in
addition, there is a component
of large, multinucleated
astrocytic cells, warranting the
diagnosis of oligoastrocytoma
in this specimen. Both figures
are hematoxilin–eosin stained.
(The inset is a 91.25 objective,
the large figure a 940 objective)
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