Keywords
cerebellopontine angle - neurofibromatosis type I - glioblastoma multiforme
Introduction
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, comprising
15 to 20% of all intracranial tumors.[1]
[2]
[3] They usually present in the supratentorial region within the cerebral hemispheres.
Posterior fossa or cerebellopontine angle (CPA) occurrence is unusual and may pose
a clinical challenge as it may mimic other, more commonly seen neoplasms in this location.[4]
[5] Within the CPA, they typically arise intra-axially from the cerebellum or pons with
lateral exophytic extension.[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11] Internal auditory canal (IAC) involvement is rare, with very few cases reported
in the literature.[3]
[5]
[12] There is no documented association between CPA glioblastomas and genetic or syndromic
disorders. We present a case of a 48-year-old patient with neurofibromatosis type
I (NFI) with an intra-axial GBM arising within the CPA.
Case Report
Clinicoradiographic Presentation
A 48-year-old male patient presented with a 1-month history of progressive right-sided
facial numbness and pain. He denied any other neurologic symptoms. His past medical
and surgical history were significant for NFI, chronic vocal cord paralysis secondary
to numerous procedures in childhood to excise laryngeal neurofibromas, and a Whipple
procedure for pancreatic ampullary carcinoma.
Physical examination demonstrated right facial hypesthesia, but all other cranial
nerves were intact. An audiogram was obtained with normal hearing bilaterally.
Magnetic resonance imaging (MRI) of the brain and brainstem revealed a right heterogeneous
T1 hypointense, T2 hyperintense contrast-enhancing 3.7 cm intra-axial mass with central
necrosis centered within the right ventral pons with extension superiorly to the midbrain.
Additionally, there was an 8-mm satellite lesion in the anteromedial paramedian pons
([Fig. 1]). There was surrounding regional mass effect with partial effacement of the right
fourth ventricle and midline shift at the level of the midsuperior pons with no IAC
involvement.
Fig. 1 Axial T1 weighted contrast enhancing lesions in the right cerebellopontine angle
(long white arrow) without internal auditory canal involvement (double arrow) and
ventral brainstem (short white arrow).
Surgical Approach
The patient underwent a combined transpetrosal-retrosigmoid approach, and the tumor
had an ill-defined plane separating it from the cerebellum and adjacent pons. Frozen
section histopathology showed poorly differentiated malignant neoplasm with focal
rhabdoid features, suggesting a tumor of glial origin. The patient underwent a subtotal
tumor resection due to the dangerous medial plane of dissection.
Postoperative Course
The patient’s postoperative course was uncomplicated, and he was discharged on postoperative
day 3. The final pathology revealed this to be a diffuse, high-grade astrocytoma,
and WHO grade IV. Immunohistochemical stains showed glial fibrillary acidic protein
positivity, consistent with glioblastoma.[13] The IDH1 mutant was negative. After his scheduled visits with hematology and radiation
oncology, protocol-based therapy for GBM was initiated and he began temozolomide with
planned concurrent radiation therapy.
Discussion
Cerebellopontine angle tumors are the most common neoplasms in the posterior fossa
and may be classified based on their site of origin as either intra-axial or extra-axial.[14]
[15] Although the majority of tumors that arise in this location are benign, more sinister
entities may occur. Only 11 cases of primary glioblastoma have been reported in the
CPA ([Table 1]). Most of these tumors have an intra-axial site of origin within the cerebellum
or pons and appear to exhibit secondary exophytic extension into the CPA.[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11] Only three of the described lesions involved the IAC.[3]
[5]
[12] None of the patients in the literature had syndromic or genetic predispositions
that contributed to tumorigenesis.
Table 1
Summary of cerebellopontine angle glioblastoma case reports
|
Authors
|
Sex/Age (y)
|
Site of origin
|
IAC involvement
|
Symptom duration
|
Treatment
|
Prognosis
|
|
Abbreviations: CN, cranial nerve; F, female; IAC, internal auditory canal; M, male;
RT, radiation therapy.
|
|
Swaroop and Whittle[5]
|
M/22
|
Pons
|
Yes
|
12 months
|
Subtotal resection
|
Unknown
|
|
Kasliwal et al[7]
|
M/11
|
Cerebellum
|
No
|
15 days
|
Subtotal resection
|
Died after 2 months
|
|
Rasalingam et al[10]
|
M/9
|
Pons
|
No
|
2 weeks
|
Subtotal resection
|
Alive after 2 months
|
|
Wu et al[3]
|
M/60
|
CN VIII
|
Yes
|
2 months
|
Subtotal resection
|
Died after 2 months
|
|
Salunke et al[11]
|
M/59
|
Pons
|
No
|
3 months
|
Subtotal resection and RT
|
Unknown
|
|
Matsuda et al[9]
|
M/69
|
Cerebellum
|
No
|
1 hour
|
Subtotal resection with chemotherapy and RT
|
Alive after 24 months
|
|
Lee et al[8]
|
F/71
|
Cerebellum
|
No
|
3 months
|
Stereotactic biopsy with chemotherapy and RT
|
Alive after 12 months
|
|
Panigrahi et al[4]
|
F/52
|
Possible cerebellum
|
No
|
2 months
|
Subtotal resection and RT
|
Alive after 3 months
|
|
Chen et al[6]
|
F/5
|
Pons
|
No
|
5 months
|
Subtotal resection
|
Died after 2 months
|
|
Yang et al[1]
|
M/55
|
CN VIII
|
No
|
3 months
|
Subtotal resection
|
Died after 2.5 months
|
|
Takami et al[12]
|
M/55
|
Possible CN VIII
|
Yes
|
19 months
|
Subtotal resection and RT
|
Alive after 5 months
|
|
Present case
|
M/48
|
Pons
|
No
|
1 month
|
Subtotal resection, RT, and chemotherapy
|
Alive after 3 months
|
Based on the current literature, we report the first case of primary CPA GBM arising
from two distinct foci in a patient with NFI. This is an autosomal dominant genetic
disorder due to mutations in the NFI, tumor-suppressor gene on chromosome 17, which
results in loss of or reduced function of the protein neurofibromin.[16]
[17] Ultimately, this is responsible for a wide spectrum of clinical manifestations ranging
from café-au-lait macules to central nervous system tumors causing neurologic complications.[18] Despite no previously documented association between this genetic syndrome and CPA
GBM, it is known that there are thousands of distinct and unique pathogenic mutations
in affected patients with NFI. Correlations between genotype and phenotype in patients
with NF1 are more difficult to predict in patients with smaller mutations (<20 base
pairs) in the NFI gene.[19] It is known, however, that a mutation in the NFI gene places patients at increased
risk to develop both benign and malignant tumors throughout their lifetime.[20]
[21] More specifically, they have an increased propensity to develop gliomas in the brainstem.[16]
[22] Independent risk factors associated with mortality and tumor aggressiveness in this
cohort include symptomatic tumors, extra-optic location, and adult patients.[22]
Our patient’s neoplasm manifested acutely with a complete, right-sided trigeminal
sensory deficit. Based on our imaging findings and, specifically, the lack of IAC
involvement, a vestibular schwannoma was unlikely. The formulated differential diagnosis
included trigeminal schwannoma, meningioma, primary brain malignancy, or metastatic
disease. Due to the complexity of our patient’s clinical characteristics, a diagnosis
was only established after histopathological studies were finalized.
As with the other reported cases of CPA GBM, our patient’s clinical characteristics
made preoperative diagnosis difficult as the tumor mimicked more benign and commonplace
lesions that typically arise within that site. In terms of management, the postoperative
ramifications that accompanied the diagnosis were significant. Treatment for GBM follows
a triple-based protocol regimen involving gross tumor resection, chemotherapy, classically
with the alkylating drug temozolomide, and concurrent radiotherapy.[2]
[9] Despite this aggressive approach to treatment, prognosis of GBM is dismal, with
most patients only surviving 1 year after the initial diagnosis.[23] This is in stark contrast to CPA schwannomas, which can be managed with radiographic
surveillance, radiotherapy, or surgical resection.[24]
[25] After his initial hematology-oncology evaluation, our patient was started on 140
mg of temozolomide daily with a plan to initiate RT. Long-term prognosis for CPA GBM
is not well described and is based on a limited number of anecdotal case reports.
It is worth noting that longer survival was observed in the patients receiving all
three therapeutic options concurrently.[8]
[9]
In conclusion, we provided a case of primary intra-axial CPA GBM mimicking a more
benign entity in a patient with NFI with the intention of providing insight into the
clinicoradiographic presentation and natural history of this tumor. Although rare,
GBM should be considered in the differential diagnosis, especially if the clinical
course is rapid and progressive with multifocal brain involvement. Special attention
should be directed to patients with NF1, as they have a higher likelihood of presenting
with rare and more aggressive pathology.
