Keywords
spinal accessory nerve tumor - schwannomatosis - schwannoma - neck mass - diffusion
tensor imaging
Introduction
Schwannomas are benign peripheral nerve tumors that can be sporadic or familial in
nature and typically associated with neurofibromatosis type-2 (NF2).[1] These tumors can affect any point along the peripheral nerve, including the cranial
nerves, spinal roots, nerve plexi, and major peripheral nerves. They can cause symptoms
such as pain, weakness, changes in sensation, and cranial nerve deficits, depending
on the nerve in question.
Certain syndromes such as NF2 are associated with an increased frequency of schwannomas.
For example, NF2 is associated with bilateral vestibular schwannomas. Schwannomatosis
is another syndrome that appears to be a distinct entity from NF2 in that patients
may have multiple schwannomas without any evidence of a vestibular nerve schwannoma
or other findings associated with NF2.[2]
[3]
[4] Prior reports have demonstrated cases of schwannomatosis involving the cranial nerves,
spinal roots, major peripheral nerves, and brachial or lumbar plexi.[3]
[5] However, as with neurofibromas, cases of schwannomatosis involving the lower cranial
nerves (apart from the vestibulocochlear nerve) are rare.[3]
[6]
[7]
[8]
[9] Here, we report on a rare case of schwannomatosis involving the left spinal accessory
nerve and provide imaging findings and a description of the surgical approach.
Case Report
History, Physical Examination, and Imaging Findings
This case is of a 55-year-old female who initially presented with a palpable left
neck mass. The mass had been noted by the patient 8 years ago and had progressively
grown in size. A computed tomography (CT) of the neck was obtained, which demonstrated
a 3.5 × 2.3 × 4.6 cm lesion deep to the left sternocleidomastoid (SCM) muscle in addition
to a smaller 1 × 1 × 1.8 cm left posterior neck-enhancing mass. A fine needle aspiration
(FNA) had been performed 2 years prior at an outside hospital with pathology indicating
a low-grade spindle cell proliferation. She was thus referred to our institution for
further evaluation. At the time of initial presentation to our group, the patient
had noted dysphagia, left ear ache and tinnitus, and neck pain localized to the two
masses. A positron emission tomography (PET) CT was performed, which demonstrated
increased fluoro-2-deoxy-d-glucose uptake in the high cervical mass and, to a lesser degree, in the mass located
within the posterior triangle of the neck ([Fig. 1]). The outside tissue blocks were reviewed at our institution and felt to be consistent
with a peripheral nerve sheath tumor compatible with schwannoma from both lesions.
Because of the patient's ongoing symptoms and because malignancy could not be completely
excluded based on the results of the prior FNA, the decision was made to proceed with
surgical excision of both lesions. Prior to proceeding, a magnetic resonance neurogram
was obtained ([Fig. 2]). Tractography demonstrated that the two lesions appeared to originate from the
spinal accessory nerve and that apparent diffusion coefficient values were elevated
in both masses, supporting the diagnosis of a less aggressive tumor ([Fig. 3]).
Fig. 1 (A–C) Positron emission tomography–computed tomography (PET CT) was performed, which demonstrated
increased fluoro-2-deoxy-d-glucose uptake in both masses (standardized uptake value
of 7.3 for the larger mass and 2.7 for the smaller mass).
Fig. 2 Magnetic resonance imaging (MRI) neurogram demonstrated a larger 4.6 × 3.2 × 2.5
cm mass deep to the left sternocleidomastoid muscle just below the angle of the mandible
(A–C) and a bilobed 2.4 × 2.2 × 1.3 cm mass in the left posterior supraclavicular region
(D–F).
Fig. 3 Further imaging characterization of lesions. (A) Diffusion tensor imaging with tractography demonstrated abnormal thickened nerve
fibers coursing through the two spinal accessory nerve tumors. (B) Axial diffusion weight imaging (left) and apparent diffusion coefficient (ADC) images
(right) of the lesions. ADC values were 1.3 × 10−6 and 1.8 × 10−6 mm2/second for the larger and smaller masses, respectively.
Treatment Course
The patient was taken to the operating room for surgical resection. The patient was
positioned with her head turned slightly to the right with the neck extended ([Fig. 4A]). The smaller lesion was approached first through the posterior triangle of the
neck. Stimulation mapping of the tumor was conducted. The tumor was found to be located
on the distal spinal accessory (cranial nerve XI) nerve, with evidence of trapezius
activation with nerve stimulation ([Fig. 4B]). After identifying no overlying nerve fibers, the tumor was removed en bloc. A
separate incision was made in the upper cervical region to approach the larger second
mass located lateral and deep to the SCM muscle, which was reflected medially ([Fig. 4C]). During dissection of the tumor away from the nerve, motor evoked potentials (MEPs)
to the trapezius were lost. As the tumor was of significant size, view of the proximal
aspect of the afferent nerve was initially obstructed. Distally, the tumor was mapped,
and the fascicle of origin was identified, which appeared to activate the SCM. After
significant debulking of the mass, the proximal fascicle of origin was identified
but did not provide any muscle activation after stimulation. The tumor was therefore
removed in its entirety. All parameters for brachial plexus monitoring remained stable.
Fig. 4 Intraoperative findings. (A) Two separate incisions were required to remove both lesions. (B) The smaller bilobed lesion mass was accessed through the posterior triangle of the
neck and was located on the distal spinal accessory nerve. (C) The larger more proximal mass was approached medial to the sternocleidomastoid muscle
in the upper neck. Both masses underwent a gross total resection.
Pathological Findings and Clinical Outcome
Pathology for both lesions was consistent with schwannoma without malignant features.
Next-generation sequencing analyzing the coding regions of 479 cancer genes as well
as select introns of 47 genes using the UCSF 500 Cancer Gene Test revealed a small
in-frame insertion at codon p.R177 of the Sox 10 gene. There were no identifiable
alterations in NF1, NF2, LZTR1, SMARCB1, and TRAF7 genes. Despite the change in MEPs,
the patient was noted to be full strength in all muscle groups in the left upper extremity
including shoulder shrug and head turning immediately postoperatively. At follow-up,
her neck pain and prior dysphagia had improved significantly.
Discussion
Schwannomatosis is a syndrome characterized by multiple peripheral nerve schwannomas
usually without involvement of the vestibular nerve and can be sporadic or familial
in nature. In a retrospective analysis of 87 patients with schwannomatosis, 89% had
peripheral tumors, 74% had spinal tumors, and 9% had intracranial nonvestibular tumors.[9] The typical age of presentation is between 30 and 60 years, with pain being the
most common presenting symptom.[9] Prevalence has been reported to be approximately 1 in 140,000 to 150,000,[3]
[10] and life expectancy is reported to be near-normal (76.9 years) and significantly
longer than for patients with NF2.[3]
Although there is phenotypic overlap with the other syndromes under neurofibromatosis,
such as NF2, schwannomatosis is a distinct entity. Diagnostic criteria include at
least two nonintradermal anatomically distinct schwannomas (at least one histologically
confirmed) with no radiographic evidence of bilateral vestibular schwannomas on MRI
and NF2 mutation negative in a patient at least 30 years of age. Other criteria include
one biopsy-proven nondermal schwannoma or intracranial meningioma plus a first-degree
relative with schwannomatosis. Although diagnostic criteria initially excluded patients
with vestibular schwannomas, recent reports suggest that schwannomatosis patients
may still develop unilateral vestibular schwannomas.[11]
[12] Furthermore, intracranial meningiomas or cutaneous neurofibromas do not exclude
a diagnosis of schwannomatosis, although other features of other neurofibromatosis
syndromes such as Lisch's nodules and café au lait macules are not present.
The most well-described genetic alteration is a mutation in the SMARCB1 gene or LZTR1
gene on chromosome 22q11.2.[13] In our case, these mutations were not present and instead a mutation in SOX10 was
observed. While SOX10 has been used previously as an identifying marker for schwannomas,
mutation of SOX10 as a contributor to the pathogenesis of schwannomatosis, to our
knowledge, has not been previously reported.
Management of schwannomatosis patients represents a therapeutic challenge. Typically,
surgical intervention is indicated for symptomatic lesions.[5] We recommend the use of intraoperative neuromonitoring for all cases with the use
of stimulation to help identify functional fascicles that should be preserved. In
this case, although injury was sustained to the fibers of the spinal accessory nerve,
trapezius muscle innervation was maintained likely because of the additional innervation
of the trapezius muscle by branches of the cervical plexus.[14] Asymptomatic tumors may be observed, but close imaging surveillance is required.
Further management considerations include referral to a pain management specialist.
In the study by Merker et al, 68% of schwannomatosis experienced chronic pain. Despite
surgery and pain medications, the majority did not become pain-free.[9] Thus, ongoing treatment under the care of a pain management specialist is important
from a quality-of-life standpoint. Additionally, higher rates of depression and anxiety
can be seen in these patients, likely in the setting of chronic pain, the source of
which is often undiagnosed for years. Active surveillance and treatment of mood disorders
is therefore another critical component of medical care.[9]
Conclusion
Here, we report a rare case of schwannomatosis in addition to a genetic aberration
that has not been previously reported in this disease context. Using intraoperative
mapping and microsurgical technique, safe resection may be attempted for symptomatic
lesions.
