Review of Cervical Schwannomas: Presentation, Pathogenesis, Management, Complications and Future Directions

Michael Goutnik¹, Emma Earl², Ramya Reddy¹, Brandon Lucke-Wold^3*

¹University of Florida College of Medicine
²University of Utah College of Medicine
³University of Florida, Department of Neurosurgery

*Corresponding Author: Brandon P Lucke-Wold, Department of Neurosurgery, School of Medicine, West Virginia University, Morgantown, WV 26506, USA; Email: [email protected]

Published Date: 31-12-2022

Copyright^© 2022 by Goutnik M, et al. All rights reseved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Cervical schwannomas are benign peripheral nerve sheath tumors, relatively uncommon pathologies. The purpose of this review is to summarize and expand on the existing literature on cervical schwannomas, focusing on clinical presentation, pathogenesis, surgical and radiologic management and innovative therapies including ultrasound-guided techniques. Pubmed and SCOPUS databases were searched using combinations of terms including “cervical schwannoma”, “surgery”, “fusion”, “complications”, “radiosurgery” and others. The findings regarding these unique clinical entities are presented below.

Keywords

Cervical Schwannoma; Dumbbell Schwannoma; Intradural Spinal Tumor; Neurofibromatosis; Arthrodesis; Microwave Ablation

Introduction

Schwannomas, also known as neurilemmomas or neurinomas, are benign nerve sheath tumors that are derived from Schwann cells [1]. They are one of the most common peripheral nerve sheath tumors, that typically occur in the head or neck region about 25-45% of the time [1-3]. Schwannomas are often associated with neurofibromatosis, with the loss of chromosome 22q playing an instrumental role in both sporadic and neurofibromatosis-related cases [4]. A more extensive summary of pathogenesis is presented in Table 1. Cervical schwannomas originate from spinal nerves, typically from upper cervical spinal roots and occasionally from the sympathetic chain [5,6]. Among spinal schwannomas arising from C1, C2 and C3 roots, the most common schwannomas arise from C2, comprising 15% of all spinal schwannomas [6]. In addition, schwannomas may arise from sympathetic chains or the vagus nerve, although they are much rarer. Cervical Sympathetic Chain Schwannomas (CSCS) are quite rare, arising from the superior or middle portions of the cervical chain and typically occur in adults 20-50 years old [5]. Extradural schwannomas in high cervical spinal roots are rare in children [3]. Schwannomas of the Vagus Nerve (VNCS) are also very rare and can grow between the internal or common carotid artery and the internal jugular vein, causing separation of the two that may be seen on imaging [7]. This separation is not noted with CSCS [7].

Cervical schwannomas, in general, are considered slow growing tumors, with a growth rate of 5.3% per year [8]. One exception is during pregnancy. A case report described how growth can be accelerated during pregnancy, due to effects of estrogen and progesterone, although spinal schwannomas do not express these hormonal receptors [9]. Swelling and other symptoms can also present insidiously, due to the gradual increase in size [3]. If near C5-6 and of vagal origin, the schwannoma can displace the carotid sheath as well, or compress it [3]. They often present as a painless mass, although additional symptoms are related to size and specific nerve origin [10]. General symptoms can include neck swelling and pain and neurological symptoms in the upper extremities [9]. For instance, a case report of a cervical vagal schwannoma in the carotid space resulted in hoarseness and severe cough [10]. CSCS also do not present with specific symptoms, but surgical interventions may leave the patient with some degree of Horner’s syndrome, that is relatively well-tolerated [7]. CSCS and VCNS may have very similar presentations, but VNCS have higher potential for morbidity. Acute neurological deterioration, due to intratumoral or subdural hemorrhages, is very rare [11]. One case report detailed a probable mechanism being hyalinized vessels with spontaneous thrombosis [12]. Upon gross examination, besides findings associated with palpitation, there are typically no other clinical or radiological features of neurofibromatosis, such as café au lait spots [9].

Upon microscopic examination, schwannomas are encapsulated, solid/cystic tumors, composed of two cellular zones: spindle-shaped Schwann cells and palisading nuclei (Antoni type A) as well as hypocellular arrangement and myxoid collagenous tissue (Antoni type B) [3,5,9]. This histopathology is quite characteristic of schwannomas. This is reflected in imaging, particularly MRI, which shows dishomogenous signals, due to the distribution of Antoni A and B cells [13]. Generally, schwannomas appear hypointense on T1-weighted images and hyperintense on T2-weighted images, depending on their cellularity [13]. CT imaging can show the relationship between the tumor and the carotid sheath, with CSCS and VNCS typically displacing the internal/common carotid artery anteriorly [14]. Angiography typically show hypovascular or moderately hypervascular tumors [15]. The less common hypervascular tumors display tortuous vessels, but no arteriovenous shunting or luminal narrowing [16]. While imaging is crucial for diagnosis and for further intervention, especially surgical, one limitation is that it cannot reveal the exact origin of the tumor, although it can help narrow the differential diagnosis depending on the anatomical compartment the tumor is found in [7]. Ultimately, surgical observation of the lesion and the nerve it originates from, along with histopathological examination, leads to a correct diagnosis [7]. However, an in-depth history and physical examination, along with imaging, can help inform interventions and narrow down the differential diagnosis.

Table 1: Summary of Schwannoma Pathophysiology.

Surgical Resection and Complications

Cervical schwannomas are often amenable to Gross Total Resection (GTR), albeit less so than thoracic and lumbosacral lesions [23-28]. GTR is associated with improved overall survival.28 Larger tumor size and encasement of the vertebral artery are associated with greater odds of Subtotal Resection (STR) [25,27,29,30]. In particular, the size of the foraminal and extraforaminal tumor components appear to influence the ability to fully resect tumor [25,31]. Ryu, et al., demonstrated that high cervical level (C2 and above) is associated with greater odds of GTR [25]. Meanwhile, Jinnai, et al., previously demonstrated that rostral spinal nerve sheath tumors are more frequently strictly extradural and more frequently extend outside the spinal canal, compared to more caudal tumors [27]. Considering that tumor extension distal to the spinal canal makes surgery more technically challenging, Jinnai, et al., and Ryu, et al., appear to contradict each other. This contradiction is explained by the more easily accessible anatomy of C2 schwannomas, in particular [25,32]. In fact, Jinnai, et al., had 100% GTR for all C1-C2 lesions [27]. Nonetheless, surgical resection is associated with significant improvements in patient-reported outcomes and satisfaction [33,34].

STR is associated with higher likelihood of tumor recurrence [30]. However, the recurrence rate for residual cervical schwannoma is low and often takes several years to develop [25,26,31,35].  Ryu, et al., found that in 31 cases of STR, there were no significant factors to explain which residual tumors grew and which didn’t [30]. Thus, Ryu, et al., advocate for frequent MRI follow-up for residual cases [30]. Sohn, et al., found the Ki-67 labeling index to predict regrowth for subtotally resected spinal schwannomas [35]. In cases where incomplete resection must be done for cervical dumbbell schwannomas, using the entrance of the intervertebral foramen as a landmark for surgical margins and resecting distally from this entrance may lower the risk of remnant tumor growth into the spinal canal [36].

A posterior approach is the usual surgical strategy for cervical schwannomas [23-25,29,30,37,38,39]. Gu, et al., reported success using a posterior approach with facetectomy for intra and extraforaminal dumbbell-shaped subaxial cervical schwannomas when the extraforaminal tumor measured less than 5.4 mm [29]. A combined anterolateral and posterior approach was preferred when the extraforaminal tumor was larger than 10 mm [29]. When there is a significant extradural component of tumor outside the spinal cord, an anterior approach may be needed [27,28]. A far lateral approach may be used for C1-2 tumors involving the foramen magnum [26,40]. Zhang, et al., report employing a less invasive transforaminal approach in 12 patients with concurrent cervical dumbbell schwannomas and other tumors [41]. For rare cervical sympathetic chain schwannomas, intracapsular enucleation appears to be an effective, function-sparing surgery that reduces the rate of permanent post-operative Horner’s syndrome compared to extracapsular resection [42-46].

There are several studies that investigate the role of arthrodesis in cervical schwannomas.  Laminectomy combined with lateral mass screw fixation is associated with less subsequent spinal instability and deformity compared to laminectomy alone [34]. Furthermore, Sebai, et al., found that total facetectomy was associated with a greater odds of the addition of arthrodesis compared to subtotal facetectomy, likely due to concern about spinal instability [47]. Safaee, et al., similarly found a significant relationship between extradural lesions and likelihood of adding fusion to resection, likely due to bony instability [48]. Of note, the addition of fusion does not appear to increase the rate of postoperative complications including sensory and motor deficits, infection and CSF leak [48].

Safaee, et al., examined 221 tumors including 163 schwannomas and found 30% of patients developed postoperative complications, which were most commonly sensory deficits (15% of patients) [24]. These appear to improve over time. In a different study of 75 cervical dumbbell schwannomas by Nakamura, et al., sensory and motor deficits respectively persisted in only 8 and 8% patients [31]. Of note, intraoperative neuromonitoring does not appear to prevent complications, but is associated with a higher rate of GTR [24]. Another possible complication of spinal surgery is CSF leak. CSF leak following spinal durotomy appears to happen in about 5% of cases and appears to be associated with prior surgery at the index level and cervical vs thoracic location, but does not appear to depend on dural closure technique or other covariates [24,34,48,49,50]. CSF leak is associated with serious infections including meningitis and healing disorders with subsequent repeat surgery [50].

Iatrogenic Vertebral Artery Injury (VAI) is a rare (~0.3%) but serious complication of anterior cervical spine surgery and may be controlled via hemostatic agents and postoperative endovascular embolization [51-54]. For posterior approaches, vertebral artery injury is uncommon and is associated with posterior atlantoaxial transarticular screw fixation (known as Magerl fixation) [32,53,55-57]. VAI may be prevented by careful preoperative planning with observation of the relevant anatomy via CT/MR angiography [53,54,57]. Furthermore, posterolateral and anterolateral approaches for schwannomas of the first two cervical nerve roots should include extraperiosteal VA control [58,59]. In a case report by Lee, et al., the authors encountered VAI during a posterior approach for a C2-3 extradural schwannoma and were able to treat the injury with compression, perfusion maintenance and endovascular embolization [57]. They were able to embolize the left VA due to preoperative CT angiography demonstrating right VA dominance with retrograde flow [57]. Jecko, et al., reported a case of C5-6 schwannoma involving a posterior approach followed by anterior approach, that was complicated by a subsequent vertebral artery pseudoaneurysm that was successfully treated with coil embolization [54]. Patsalides, et al., have shown that preoperative embolization of hypervascular cervical spinal tumors may be safe, but the one schwannoma in this study was not embolized due to low vascularity (Fig. 1) [60].

Figure 1: Management of Cervical Schwannoma.

Role of Radiation and Associated Complications

Radiosurgery is a safe and effective alternative for those who aren’t candidates of open surgery, including those with multiple or recurrent lesions, advanced age, or multiple comorbidities [61-65]. In 1995, Hamilton, et al., first demonstrated the use of Stereotactic Radiosurgery (SRS) for the treatment of metastatic spinal lesions in 5 patients who had failed to respond to traditional fractionated radiation therapy [61].  Dodd, et al., and Gerszten, et al., later extended on these findings by showing short-term safety and efficacy in benign spinal lesions, including schwannomas [62,63]. Monserrate, et al., then reported on the use of cone-beam CT image guidance to improve target selectivity [64]. Other than candidates described above, patients with neurofibromatosis type 2 and those with VA encasement represent special populations that may benefit from radiosurgery.  Dodd, et al., suggested that patients with neurofibromatosis type 2 are a population that may especially benefit from SRS due to schwannomas recurring more frequently [62]. Ryu, et al., suggest patients with difficult cases, such as those with VA encasement, may benefit from intentional STR followed by SRS [30].

Low-dose radiation therapy for a variety of conditions may rarely contribute to formation of benign peripheral nerve sheath tumors, including schwannomas [66]. The latency period appears to be two decades, with GTR being the preferred treatment [66]. Radiation therapy may also contribute to formation of Malignant Peripheral Nerve Sheath Tumors (MPNSTs), which require more aggressive treatment [67]. Patients with neurofibromatosis may be more likely to undergo malignant transformation following radiation, with no difference in survival compared to patients without neurofibromatosis undergoing malignant transformation [67]. One case described by Gilder, et al., features a patient with prior pelvic radiation history who developed what appeared to be a lumbar schwannoma, but subsequently recurred and was found to be a Malignant Peripheral Nerve Sheath Tumor (MPNST) [68]. The authors suggested a particular methylation immunostain to distinguish between low-grade MPNSTs and benign schwannomas [68].

Future Directions

In 2019, Yuce and colleagues evaluated the use of ultrasound-guided microsurgical excision of small (<3 cm, nonpalpable) brachial plexus schwannomas (n=11). Their data suggests skilled surgeons can effectively achieve complete resection without perioperative and postoperative complications [69]. Additionally, Sandler and colleagues suggest the combination of intermittent nerve mapping and continuous vagal nerve monitoring may represent the future standard of care in vagal schwannoma management, as their results suggest reduced postoperative morbidity [70].

In 2019, Ramirez and colleagues described their experience utilizing Microwave Ablation (MVA) in brain and skull-base tumors. Their clinical study (n=23) suggests MVA can be utilized as a minimally invasive single therapeutic option or as a complement to microsurgical techniques [71]. MVA has historically been utilized in liver and pancreatic tumors and has more recently been used to treat tumors in the bone, bladder, prostate, breast, adrenal gland and kidney [72-77]. Additionally, MVA has been utilized the management of cardiac arrhythmias and achieving hemostasis in surgery [78-83]. MVA is a thermal ablating technique that utilizes a microwave generator emitting an electromagnetic wave to destroy tumors [84]. Electromagnetic microwaves disrupt the water molecules of surrounding tissue, producing friction and heat that subsequent cell death via coagulation necrosis. This process eliminates tumor tissue with the goal of destroying the entire tumor and preserving as much of the surrounding healthy parenchyma [84,85]. Experimental studies have suggested a maximum ablation diameter of 5.5 cm with an intensity of 45 W to avoid damaging adjacent tissues [84].

In 2021, Sagoo, et al., published a systematic review involving microwave ablation in the treatment of spinal metastases [86]. They found significant improvements in analgesia and local tumor control, although many patients had concurrent surgery [86]. Furthermore, only 6.5% of patients undergoing percutaneous microwave ablation experienced complications, including transient radicular pain and skin burns [86]. In 2022, Zhu and colleagues published a case report describing treatment of a cervical vagus nerve schwannoma. The patient had a history of non-small cell lung cancer and presented with hoarseness and a severe cough. The diagnosis was made via core-needle biopsy after chemotherapy failed to shrink the tumor. Ultrasound-guided percutaneous Microwave Ablation (MVA) was utilized. Her tumor continued to shrink following treatment and her presenting symptoms resolved. Zhu and colleagues suggest MVA as a safe and innovative alternative to traditional surgical resection of cervical schwannomas [10]. More research is necessary to compare outcomes between MVA and traditional surgical resection in the treatment of cervical schwannomas.

Conclusion

This review highlights the implicated pathogenesis, surgical management and complications, role of radiation and potential application of ultrasound-guided microwave ablation in the treatment of cervical schwannomas. It is important to consider this diagnosis in patients presenting with a slowly enlarging, asymptomatic neck mass, with possible radicular symptoms. The usual surgical management involves a posterior approach, with the goal of gross total resection. Finally, for those with complicated lesions, neurofibromatosis and multiple tumors, radiation therapy and microwave ablation may be reasonable alternatives that need to be researched more extensively.

Conflict of Interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the manuscript.

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Article Type

Short Communication

Publication History

Received Date: 09-12-2022 
Accepted Date: 24-12-2022 
Published Date: 31-12-2022

Copyright© 2022 by Goutnik M, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation: Lucke-Wold BP, et al. Review of Cervical Schwannomas: Presentation, Pathogenesis, Management, Complications and Future Directions. J Neuro Onco Res. 2022;2(3):1-12.

Figure 1: Management of Cervical Schwannoma.