Keywords
brain neoplasms - glioblastoma - arachnoid - extra-axial
Palavras-chave
neoplasias cerebrais - glioblastoma - aracnoide - extra-axial
Introduction
Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant
brain tumor in adults, accounting for 14.6% of all tumors and 48.3% of malignant tumors.[1] It is usually located intra-axially in the deep white matter of the supratentorial
region, mainly in the frontal and temporal lobes.[2] Several neoplastic and nonneoplastic (granulomatous, lymphoproliferative, autoimmune)
dural-based entities are reported to clinically and radiographically mimic meningioma.[3]
[4] Glioblastoma multiforme with primary extra-axial involvement has rarely been reported
in the literature.[5] Here, we report a case of left temporal GBM with extra-axial features.
Case Report
A 76-year-old, previously healthy, nonsmoker, and nonalcoholic female patient, presented
with verbal paraphasia and attention deficit that had begun in the month prior to
her visit. Upon neurological examination, expressive aphasia was noted, and the three-word
recall test, along with the backward digit span test, was impaired. There were no
other neurological signs, such as focal deficits, motor weakness, cranial nerve deficit,
gait instability, or pronator drift. The vital signs and the initial laboratory testing
were unremarkable.
A brain magnetic resonance imaging (MRI) scan performed upon admission showed a 5.1-cm
left temporal tumor broadly abutting the dural surface at its anterior inferior and
medial aspects, with heterogeneous enhancement and surrounded by extensive vasogenic
edema. The dura showed a thickened appearance and enhancement (dural tail sign, DTS)
surrounding the middle cranial fossa. A mass effect was produced by the tumor, with
compression of the left lateral ventricle and shift of the midline structures to the
right by ∼ 3 mm ([Fig. 1]). The mass also presented a cerebrospinal fluid (CSF) cleft sign ([Fig. 2]).
Fig. 1 Axial (A), sagittal (B), and coronal (C) T1-weighted MRI scans with contrast demonstrating a heterogeneously-enhancing mass
(asterisk) with broad dural contact anteroinferiorly (red arrow) with a dural tail
sign (yellow arrow).
Fig. 2 Coronal (A) and axial (B) T2-weighted MRI scans showing CSF cleft sign (red arrows).
A computerized tomography (CT) scan of the chest, abdomen, and pelvis was performed,
and failed to reveal a primary tumor. The patient was submitted to appropriate intravenous
(IV) hydration, and dexamethasone 8 mg IV every 6 hours to decrease the edema.
The case was discussed in a tumor board meeting, and the main differential diagnoses
considered were malignant meningioma and glioblastoma multiforme. The decision was
made to proceed with craniotomy to resect the lesion. The patient received standard
preoperative medication, including valproate, dexamethasone, cefazolin, and mannitol
on the morning of the surgery. Intraoperatively, the tumor was soft, gray, round,
extra-axial, and attached to the dura of the left middle cranial fossa inferiorly,
and it was indenting but easily resectable from the temporal lobe superiorly and medially.
A gross total resection was performed under microscopic magnification.
A postoperative brain MRI showed complete resection of the middle cranial fossa tumor
([Fig. 3]). The postoperative course was smooth, and the patient demonstrated progressive
clinical improvement in her neurological status. The histopathological result of the
specimen was consistent with an isocitrate dehydrogenase 1 (IDH1) mutated glioblastoma
with arachnoid infiltration ([Fig. 4]). Moreover, there was a glial proliferation of the neoplastic cells within the arachnoid,
along with fibrous and angiomatous components, containing necrotic sites, pleomorphism,
and a multinucleate and a moderate to marked anisonucleosis with important mitotic
activity. The neoplastic cells expressed glial fibrillary acidic protein (GFAP), and
30% were expressing p53. They were positive for S-100 protein and IDH1. The IDH1 mutation
was assessed by immunohistochemistry ([Fig. 4]).
Fig. 3 Sagittal (A) and coronal (B) T1-weighted MRI scans with contrast showing complete surgical resection of the left
middle fossa tumor with thickened enhancing dura at the site of dural invasion (yellow
arrow).
Fig. 4 (A) Fibrous and vascular connective tissue (arachnoid: green arrow) invaded by astrocytes
with marked atypia and mitotic figures (hematoxylin and eosin stain, original magnification:
X200); (B) cluster of invasive cells positive for GFAP infiltrating the connective tissue (arachnoid)
(GFAP immunoperoxidase staining, original magnification: X100); (C) immunohistochemical staining reveals strongly positive results for the anti-IDH1
R132H mutation (original magnification: X400).
After the surgery, the patient was treated with radiotherapy and concomitant temozolomide
followed by adjuvant temozolomide. The last examination six months after the surgery
confirmed that the patient was doing well.
Discussion
Extra-axial brain tumors, which are responsible for approximately half of all intracranial
neoplasms in the United States, include a wide spectrum of pathologic tumors grouped
by their primarily extraparenchymal involvement, typically involving the meningeal
layers of the brain.[6] According to the most recent data from The Central Brain Tumor Registry of the United
States (CBTRUS, 2012–2016), the most commonly occurring malignant brain tumor was
glioblastoma (14.6% of all tumors), and the most common non-malignant tumor was meningioma
(37.6% of all tumors).[1] Besides, 1% to 3% of meningiomas are classified as malignant meningiomas, which
are characterized by higher rates of recurrence, morbidity, and mortality.[7] Meningioma exhibits a broad-based dural contact, inward displacement of the cortical
gray matter, and DTS.[8]
On the other hand, glioblastoma is usually an intra-axial tumor located in the subcortical
white matter of the brain hemispheres.[9] Moreover, GBM can extend to the dura, and rarely shows dural thickening and DTS.[10]
[11] The onset of GBMs occurs at a median age of 64 years, but they can occur at any
age, including during childhood. Ionizing radiation is one of the few known risk factors
to show an increased risk of glioma development. Radiation-induced GBM typically occurs
years after therapeutic radiation for another tumor or disease, or due to environmental
exposure to vinyl chloride, pesticides, smoking, petroleum refining, and synthetic
rubber.[12] Around 10% of all GBMs are IDH-mutant, which develop secondarily to progression
from a World Health Organization (WHO) grades II or III astrocytoma.[13] The vast majority of IDH-mutated gliomas occur in persons younger than 55 years
of age. In a study cinducted by Robinson and Kleinschmidt-DeMasters,[14] from a total of 578 gliomas tested for IDH1 mutation, 88 were IDH-mutant gliomas,
and only 4 occurred in persons aged 70 or older. The median overall survival in cases
of IDH-mutant GBMs carry is significantly better than that of IDH-wildtype GBMs following
the standard treatment (31 months versus 15 months respectively).[15] The standard treatment for GBM is surgery, which consists of maximum surgical resection
of tumor tissue, even if complete resection is not possible, followed by a course
of chemotherapy and/or radiotherapy. Currently, temozolomide, which is approved by
the US Food and Drug Administration (FDA), is the preferred chemotherapeutic agent
for GBM, and it can be tailored based on the characteristics of the patient.[16]
As therapeutic options remain scarce and prognosis, poor, alternative options such
as targeted therapies and immunotherapy are actively examined in clinical trials.
Apart from prolonged progression-free, but not overall, survival afforded by the vascular
endothelial growth factor antibody, bevacizumab, no pharmacological intervention has
been demonstrated to change the course of the disease.[17]
[18]
[19]
The classic imaging feature of GBM is a ring-enhancing intra-axial lesion on MRI or
CT; however, peripheral lesions rarely present dural thickening and DTS.[9]
[10]
[11] “Dural thickening”, “DTS”, “flare sign,” and “meningeal sign” are synonyms referring
to the thickening of the dura adjacent to an intracranial neoplasm on contrast-enhanced
T1-weighted MRI scans. Originally thought to be pathognomonic for meningioma, DTS
was reported in CNS lymphoma, metastasis, multiple myeloma, GBM, chordoma, schwannoma,
pleomorphic xanthoastrocytoma, hemangiopericytoma, medulloblastoma, eosinophilic granuloma,
and pituitary adenoma.[11] Additionally, gliosarcoma, which accounts for 1% to 8% of glioblastomas and demonstrates
both glial and sarcomatous differentiation, when it's located peripherally in the
brain, may simulate meningioma by having DTS and homogenous enhancement.[20] The CSF cleft sign, which is defined as a thin rim of CSF between the tumor body
and the brain parenchyma, may be more advantageous in differentiating intracranial
extra-axial tumors from intra-axial tumors.[21] However, malignant or grade-III meningioma may lack the CSF cleft sign or clear
demarcation between the tumor and the brain parenchyma.[22]
In the literature, there is limited data regarding the diagnostic confusion between
malignant meningioma and GBM, and primary extra-axial involvement of GBM is rarely
reported. Patel et al.[5] described two cases of glioblastoma mimicking meningioma, with the first case being
a heterogeneous-enhancing right temporoparietal mass with broad contact along the
right tentorium, CSF cleft sign, and DTS, and the second, a case of a left parasagittal,
heterogeneous-enhancing mass abutting the falx with DTS. Moreover, Gheyi et al.[23] reported a case of right frontoparietal mass with both extra- and intra-axial components
causing inward displacement of the adjacent dura and calvarial destruction. Derrig
at al.[24] also presented a case of GBM involving the cavernous sinus and Gasserian ganglion
with retrograde extension along the trigeminal nerve. Taghipour Zahir et al.[25] described a case of GBM presenting as a right frontal calvarial mass. Additionally,
two cases of primary extra-axial GBM within the cerebellopontine angle were reported
by Wu et al.[26] and Lee et al.[27] Lastly, Karthigeyan et al.[28] described a case of extra-axial left petroclival giant-cell GBM. [Table 1] summarizes the major characteristics of the aforementioned cases of primary extra-axial
GBM.
Table 1
Major characteristics of primary extra-axial GBM case reports
|
Authors, year
|
Sex/Age (years)
|
Location
|
Duration of symptoms
|
Treatment
|
Prognosis
|
|
Derrig et al.,[24] 1986
|
Female/62
|
Base of right middle cranial fossa
|
6 weeks
|
Resection, neon heavy-particle radiation
|
Dead after 6 months
|
|
Gheyi et al.,[23] 2004
|
Male/68
|
Right frontoparietal calvarium
|
Few days
|
Near total
resection, EBRT
|
Dead after 143 days
|
|
Wu et al.,[26] 2011
|
Male/60
|
Left cerebellopontine angle
|
2 months
|
Subtotal resection
|
Dead after 2 months
|
|
Patel et al.,[5] 2016
|
Female/57
|
Right temporoparietal
|
1 month
|
Resection followed by concurrent WBRT and TMZ
|
Not available
|
|
Male/60
|
Left parasagittal
|
Not availabel
|
Resection followed concurrent WBRT and TMZ + 12 months of adjuvant TMZ
|
Dead after 28 months
|
|
Lee et al.,[27] 2017
|
Female/71
|
Left cerebellopontine angle
|
3 months
|
Navigation-assisted SB followed by conventional WBRT
concurrent with TMZ
|
Alive after 1 year of the diagnosis
|
|
Karthigeyan et al.,[28] 2017
|
Female/27
|
Left petroclival
|
4 months
|
Subtotal Resection + Radiotherapy
|
Not available
|
|
Taghipour Zahir et al.,[25] 2018
|
Male/60
|
Right frontal calvarium
|
1 year
|
Biopsy followed by WBRT and
concomitant TMZ +
adjuvant TMZ
|
Dead after 7 months
|
|
Present case report
|
Female/76
|
Left temporal
|
1 month
|
GTR followed by WBRT and concomitant TMZ + adjuvant TMZ
|
Alive after 6 months
|
* Abbreviations: EBRT, external-beam radiation therapy; GBM, gliobastoma multiforme;
GTR, gross total resection; TMZ, temozolamide; SB, stereotactic biopsy; WBRT, whole-brain
radiation therapy.
The case herein reported reveals that GBM may present as an extra-axial mass based
on imaging and intraoperative findings, which render the diagnosis challenging, while
the gold standard of diagnosis is still made through surgical pathology. Because of
the scarcity of reports of cases of extra-axial GBM in the literature, further studies
have to be conducted to define this new entity and whether the prognosis differs from
that of intra-axial GBM.
Conclusion
The present report demonstrates that, although GBM is the most common primary intra-axial
malignant brain tumor, it could present as an extra-axial mass with infiltration of
the meningeal layers despite the absence of a history of previous trauma, surgery
or radiotherapy. Glioblastoma should be considered in the differential diagnosis of
extra-axial masses with atypical malignant features, especially in elderly patients.
