Keywords
vestibular schwannoma - internal auditory canal - magnetic resonance imaging - neurofibromatosis
type 2
Introduction
The majority of vestibular schwannomas (VSs) are unilateral, while less than 5% are
associated with neurofibromatosis type 2 (NF2), a high-penetrance autosomal dominant
disease hallmarked by the development of bilateral VS. Approximately half of newly
diagnosed cases of NF2 have no known family history of disease and arise from a de
novo mutation in the NF2 gene occurring during the postzygotic stages of embryogenesis.
Phenotypic expression within the NF2 population is variable, with some patients manifesting
a mild disease variant with small bilateral VS diagnosed at an old age, while others
presenting at a young age with innumerable intracranial and spinal tumors resulting
in severe debilitation and premature death. Patients with moderate or severe phenotypes
may develop collision tumors or multiple separate tumors along the course of the eighth
cranial nerve.[1] This phenomenon is generally considered to be unique to the NF2 population. To the
authors' knowledge, only two cases of unilateral multifocal VS have been reported
in the English literature.[2]
[3] Herein, the authors present a case of a medial VS isolated to the cerebellopontine
angle (CPA) and a discretely separate small intracanalicular VS in the same ear.
Case Presentation
An otherwise healthy 41-year-old female was referred for treatment of a recently diagnosed
left-sided 1.8-cm CPA tumor centered on the internal auditory canal (IAC) and a separate
ipsilateral 3-mm intracanalicular tumor appearing to arise from the superior vestibular
nerve ([Fig. 1]). The patient reported a history of several separate episodes of sudden sensorineural
hearing loss that were steroid responsive, the first occurring 3 years prior. A magnetic
resonance imaging (MRI) was ultimately obtained after her third episode of sudden
hearing loss, establishing the diagnosis of VS. The patient denied a family history
of NF2. Neurotologic examination was unremarkable and close review of MRI did not
find any other stigmata of NF2. Audiometric testing revealed AAO-HNS (American Academy
of Otolaryngology-Head and Neck Surgery) class A hearing bilaterally, with asymmetrical
pure tone thresholds and 92% word recognition in the left ear. Genetic testing for
NF2 was discussed with the patient but not pursued. After reviewing management options,
the patient was brought to the operating room and underwent a left retrosigmoid craniotomy
with resection of the larger cisternal tumor and the separate smaller intracanalicular
tumor ([Fig. 2]). Final histologic analysis revealed benign schwannoma for both separate specimens.
Postoperatively, the patient had normal facial nerve function and an uneventful recovery.
A 3-month postoperative MRI confirmed gross total resection and audiometry demonstrated
class D hearing with a 47-dB pure tone average and a 30% word recognition score. The
INI1/SMARCB1 staining pattern did not suggest NF2 or schwannomatosis.[4]
Fig.1 (A) Coronal and (C) axial T1-weighted magnetic resonance imaging (MRI) with contrast demonstrating a
1.8-cm cerebellopontine angle lesion (thick white arrow) centered on the internal
auditory canal, without meatal extension. A separate 3-mm tumor (thin white arrow)
can be seen in the distal internal auditory canal, distinctly separate from the cisternal
tumor. (B) Axial precontrast T1-weighted MRI demonstrates a left-sided isointense cerebellopontine
angle lesion. Without contrast administration, the meatal tumor cannot be identified.
(D) Axial heavy T2-weighted MRI (constructive interference steady state) further characterizing
two separate tumors involving the left cerebellopontine angle and internal auditory
canal consistent with multiple unilateral vestibular schwannomas.
Fig. 2 (A) Left-sided retrosigmoid craniotomy with resection of the larger cisternal vestibular
schwannoma (white arrow). (B) Endoscopic view of the separate smaller intracanalicular vestibular schwannoma (white
arrow).
Discussion
To the authors' knowledge, this is only the third report of a case with multiple unilateral
VSs occurring in a patient without other features of NF2.[2]
[3] In the following, we review the characteristic imaging features of VS and the radiologic
differential diagnosis, summarize the two prior reports of multifocal unilateral VS,
and finally offer several explanations for this rare and baffling phenomenon.
High-resolution MRI with gadolinium allows for accurate diagnosis of VS, even less
than 2 mm in size. VS classically exhibit hypo- to isointense signal on precontrast
T1-weighted imaging, iso- to hyperintense signal on T2-weighted sequences, and avid
enhancement with contrast administration. VSs involving the CPA are classically centered
on the IAC and usually exhibit meatal extension. In contrast, meningiomas are generally
eccentric to the porus acusticus, exhibit a broad base with dural tails, and often
display hyperostosis of underlying bone with intratumoral calcifications seen on computed
tomography. Epidermoids of the CPA are usually isointense to cerebrospinal fluid on
T1- and T2-weighted MRI and do not enhance with contrast. They are most easily distinguished
from other CPA lesions using diffusion-weighted imaging, uniquely revealing restricted
diffusion. Lastly, lipomas are distinctively hyperintense on precontrast T1- and hypointense
on T2-weighted sequences and readily suppress with fat saturation sequences. Additionally,
epidermoids and lipomas distinguish themselves from VS and meningioma by their propensity
to engulf coursing nerves and vessels rather than pushing them to the tumor periphery
and are more apt to acquiesce to the contour of the cistern before causing significant
brainstem compression.
The first report of a unilateral double VS was by Kennedy et al in 2005.[2] In this case, a subtle facial nerve paresis prompted an MRI study leading to the
diagnosis of unilateral multifocal VSs—one medially based cisternal tumor and a second
small intracanalicular VS. Additional clinical details, including patient age and
tumor dimensions, were not specified. Subsequently, Barbara et al[3] reported the case of a 47-year-old man who was discovered to have two unilateral
VSs after developing asymmetrical hearing loss. In this case, the patient did not
have any family history of disease, and genetic testing of blood and normal skin was
negative for NF2 mutation. Notably, however, the patient also had numerous uncharacterized
“fibromalike masses” of the scalp. In the currently presented case, the patient denied
a family history of NF2, and INI1/SMARCB1 staining suggested that the tumors were not associated with NF2 or schwannomatosis.
There are several plausible explanations for the development of multiple unilateral
VS. First, it is conceivable that this condition resulted from mosaic NF2, where a
mutation occurred sometime after conception, leading to two separate cell lineages.
In this scenario, if a de novo mutation of the NF2 gene develops late in embryogenesis,
segmental NF2 may progress explaining unilateral and often localized manifestations
of NF2. However, in such cases, patients may never truly fulfill Manchester criteria
for NF2, and lymphocyte genetic testing is frequently negative since the mutation
may never affect leukocyte lineages. This theory may explain the finding of Barbara
et al[3] where a patient had multifocal unilateral VSs and multiple subcutaneous “fibromas”
of the scalp, but negative blood genetic testing. It is also important to realize
that among patients without a family history of disease, a mutation can only be positively
detected in approximately 80% of patients and therefore a negative test does not guarantee
freedom from future NF2 diagnosis.
It is also possible that multifocal unilateral VS is the heralding presentation in
a minority of patients who will eventually fulfill diagnostic criteria for NF2. However,
it is well established that the great majority of patients with NF2 initially present
with bilateral tumors, and sequential VS development after the age of 40 is exceptionally
rare.[5] Lastly, it is conceivable that the occurrence of multiple unilateral VS is more
common than we realize and was only diagnosed in these select cases because the medial
tumor did not venture into the IAC and join with the intracanalicular tumor. That
is, perhaps a small fraction of sporadic VS are actually a confluent mass comprising
several adjacent tumors. This hypothesis is further supported by histologic studies
of sporadic tumors demonstrating multicentric involvement of the vestibular nerve.[6]
