The first experience of ultrasound-guided percutaneous microwave ablation for extracranial schwannoma of the cervical vagus nerve in carotid space and treatment response evaluation with contrast-enhanced imaging: A case report

2.1 Patient history

A 65-year-old female presented with a cervical schwannoma. The patient was admitted to another hospital 3 years ago due to repeated cough and expectoration with no obvious inducement. After various examinations were completed, she was diagnosed with non-small cell lung cancer (NSCLC). The result of Positron Emission Tomography-Computed Tomography (PET-CT) suggested the possibility of metastasis of lung cancer in the right clavicular region, mediastinum, double hilar lymph nodes, and bilateral pleura. The patient and her family refused to accept surgical treatment due to her age and poor health condition. After a comprehensive evaluation of the patient’s condition and taking the patient’s opinion into account, anti-tumor targeted therapy was administered from April 2019 to July 2020, with specific drug use changing among Gefitinib, Icotinib, and Anlotinib, and then changed to continuous Anlotinib monotherapy. In July 2020, the patient felt a mass above the anterior clavicle of the right neck, accompanied by hoarseness and persistent severe cough. The tumor was considered as cervical lymph node metastasis of lung cancer because of the lung cancer history, then she received intravenous chemotherapy twice in July 2020 and August 2020, with pemetrexed 800 mg D1 and nedaplatin 42 mg D1-D3. During both times of chemotherapy, the patient felt gastrointestinal discomfort, fatigue, depression, and other related side effects. The tumor showed no significant shrinkage after two rounds of chemotherapy. After a comprehensive evaluation, the treatment regimen was changed to local external radiotherapy to the cervical mass. The patient received 24 times of external local radiotherapy from September 2020, and the right anterior supraclavicular mass was slightly smaller than before. In November 2020, Anlotinib was changed into Erlotinib and has been taken ever since. Due to the patient’s persistent hoarseness and unimproved severe cough symptoms, which affected her sleep, she underwent a biopsy in March 2021. During the core-needle biopsy procedure, the patient presented an obvious symptom of an irritating cough caused by the tumor. The pathology indicated benign lesions with spindle mesenchymal proliferation, the immunohistochemistry and morphology suggested that the tumor was nerve origin and was diagnosed as schwannoma.

The patient’s current hoarseness and cough symptoms were considered to be caused by cervical schwannoma and the patient had poor sleep affected by the severe cough. Due to her basic diseases such as lung cancer and hypertension, the patient refused to accept surgery. In addition, even though the patient had received radiation therapy whereas had no significant improvement in symptoms. The patient was now admitted to our department with the requirement of minimally invasive ablation.

2.2 Preoperative examination

The preoperative examination was completed after the patient was admitted. Gray-scale ultrasound showed a slightly hypoechoic area above the right neck clavicle, with a size of 35×24×60mm, clear boundary, regular shape, inhomogeneous internal echo, and capsule. The hypoechoic “rat tail sign” was visible at both the upper and lower poles, and the lower pole was located at the angle between the beginning of the subclavian artery and the common carotid artery. Color Doppler flow imaging (CDFI) showed abundant blood flow signals around the mass and in the “rat tail” structures at both ends of the mass, but no significant blood flow signals were found in the central region of the mass. To clarify the specific anatomy around the lesion and to obtain a clear stereoscopic three-dimensional cognition, the patient was also subjected to enhanced scan Magnetic Resonance Imaging (MRI) of the neck. According to the MRI and ultrasound images, the cervical schwannoma was located in the carotid artery space between the common carotid artery and the internal jugular vein. Combined with the symptoms of a hoarse voice and irritating cough of the tumor, the diagnosis of cervical vagus schwannoma was suggested. In the biochemical examination, no significant abnormalities were observed except for the increase of the tumor marker CA724 (normal, < 6.9 U/ml) associated with NSCLC (Fig. 1).

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Fig. 1

Preoperative ultrasound examination. A. Grayscale US shows the schwannoma with a clear boundary, regular shape, inhomogeneous internal echo, and capsule. B. Color Doppler flow imaging (CDFI) shows abundant blood flow in the peripheral region and no blood flow in the central region of the schwannoma. C. The “rat tail sign” of schwannoma. D. Color Doppler flow imaging (CDFI) shows blood flow in the “rat tail” structure of schwannoma. E. Contrast-enhanced ultrasound (CEUS) shows isoenhancement in the peripheral region and remarkable hypoenhancement in the central region in the early stage (15 seconds after injection). F. Contrast-enhanced ultrasound (CEUS) shows hypoenhancement in the peripheral region and nonenhancement in the central region in late-stage (1 minute after injection). G. Contrast-enhanced ultrasound (CEUS) shows isoenhancement in the “rat tail” structure in the early stage (15 seconds after injection). H. Contrast-enhanced ultrasound (CEUS) shows hypoenhancement in the “rat tail” structure in the late stage (1 minute after injection).

After a comprehensive evaluation of the specific general condition with certain symptomatic and supportive treatment, the patient was arranged to receive microwave ablation therapy.

After obtaining the patient’s consent, we performed an ultrasound-guided microwave ablation of cervical schwannoma under general anesthesia considering her disability of cooperation with local anesthesia due to the uncontrollable severe cough. The thermal effect of microwave irradiation during ablation can lead to protein degeneration and dehydration of cells, resulting in coagulation necrosis of schwannoma after ablation, to inactivate the tumor, reduce the volume, and reduce the compression of important structures such as peripheral nerve, trachea, and blood vessels.

The main procedures were carried out as follows: 1. Pretreatment conventional ultrasound was performed to measure the size of schwannoma and plan the path of the microwave antenna puncture route. CDFI was carried out to demonstrate the vascularity in this schwannoma. 2. Pretreatment contrast-enhanced ultrasound (CEUS) was performed. The images showed isoenhancement in the early stage and hypoenhancement in the late stage in the peripheral region of the mass, with obvious hypoenhancement in the early stage, and nonenhancement in the late stage in the central region of the mass (Fig. 1). SonoVue® (Bracco, Milan, Italy) was used as the contrast agent for CEUS. 3. The anesthesiologist treated the patient with general anesthesia. After anesthesia, the patient was disinfected with the supine neck hyperextension position. 4. About 20 ml saline solution was injected into the neck to separate and protect the surrounding structure from the heat damage in ablation as isolation fluid under the guidance of ultrasound. 5. Under the guidance of real-time ultrasound, the microwave antenna was inserted into a predetermined position in the schwannoma and MWA with a “moving shot” technique was performed in each puncture path and all levels until the observation of hyperechoic gas with gasification reaction. The output power for microwave ablation was set at 30 W, and the total ablation time was 25 min and 8 seconds (Fig. 2). 6. CDFI was performed immediately after ablation, and no obvious blood flow signal was found in the tumor. 7. CEUS was performed immediately to evaluate the local treatment response, indicating that there was no enhancement in the ablated area. The size of the ablation area was equal to the pretreatment size of the schwannoma. 8. Ice compression was applied to the patient’s neck postoperatively to alleviate postoperative neck discomfort and to protect the neck skin.

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Fig. 2

Ultrasound-guided percutaneous MWA procedure. A. The microwave antenna (solid arrow) is inserted into the target area of the schwannoma under ultrasound guidance. B. Remarkable hyperechoic gas formation (dotted arrow) is observed around the antenna throughout the ablation. C. The microwave antenna (solid arrow) is inserted into the target area of the “rat tail” structure of schwannoma under ultrasound guidance. D. Remarkable hyperechoic gas formation (dotted arrow) is observed around the antenna throughout the ablation of the “rat tail” structure of schwannoma.

The patient’s condition was stable after the operation, and none of the complications such as fever, bleeding, dyspnea, dysphagia occurred. The second day posttreatment cervical MRI showed the tumor was slightly smaller after ablation than before the treatment. And there was no edema of various structures around the tumor which means there was no thermal injury caused by the ablation. She was discharged after 3 days of routine anti-infective and supportive treatment. The severe cough that affected her sleep completely disappeared after the patient woke up from anesthesia, while the hoarseness symptom was not improved.

2.5 Follow-up

The patient returned to the hospital for reexamination one month after the treatment, ultrasound examination indicated that the right anterior supraclavicular schwannoma was heterogeneous and hypoechoic, with a reduced tumor size of 30×22×24 mm and a volume reduction rate (VRR) of 68%. CDFI indicated that there was no obvious blood flow signal inside the tumor. Three months after the operation, the size of schwannoma was about 23×17×32 mm, and the VRR was about 75%. The patient’s severe cough has disappeared without recurrence since the MWA operation, while the symptom of hoarseness has not changed significantly (Table 1, Fig. 3).

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Fig. 3

Preablation and postablation MRI. A. Coronary section of preablation cervical magnetic resonance imaging (MRI) shows schwannoma locates between the common carotid artery (CCA, cross) and internal jugular vein (IJV, triangle), which separates the two vessels and squeezes the trachea (dotted arrow). B. Cross section of preablation cervical magnetic resonance imaging (MRI). C. Coronary section of postablation (two days after the ablation) cervical magnetic resonance imaging (MRI) shows the volume of schwannoma is slightly smaller than that before the ablation (VRR was 36%). D. Cross-section of postablation (two days after the ablation) cervical magnetic resonance imaging (MRI). E. Coronary section of postablation (three months after ablation) cervical magnetic resonance imaging (MRI) shows the volume of schwannoma is significantly smaller than that before the ablation (VRR was 75%). F. Cross-section of postablation (three months after ablation) cervical magnetic resonance imaging (MRI).

3.1 The clinical manifestation and diagnostic evaluation of schwannoma

The clinical manifestations of the disease are varied, and the symptoms are mainly related to the specific location of the tumor and the degree of compression on the corresponding nerve. Most of the time the tumor presents as an asymptomatic soft mass with occasional pain and tenderness [13]. When it involves the original nerve or peripheral nerve tissue, sensory disorders such as tingling, numbness, burning sensation may occur in the corresponding parts of the innervation. When the tumor originates from the auditory nerve, tinnitus, hearing loss, facial numbness, pain, or in large volume cause facial paralysis and other symptoms. Although most studies have focused on intracranial acoustic neurilemoma, most of these tumors are non-vestibular and extracranial [4]. About one-third of all extracranial schwannomas are located within the carotid space, and most often arise from the vagus and sympathetic nerves that traverse the space [14]. It may cause hoarseness, cough, dysphagia, Honor syndrome, and other related symptoms. Paroxysmal coughing may occur in some vagus schwannomas upon palpation [15, 16].

It is very important and difficult to make a definitive diagnosis and precise location of schwannoma before operation. Patients with this disease usually come to the hospital as painless masses and undergo CT, MR, ultrasound, or biopsy to confirm the diagnosis. According to previous literature, these methods have no significant difference in the preoperative correct diagnosis rate of schwannoma, and sometimes it is still difficult to give a clear conclusion [14, 15]. Due to ease of execution and relatively low cost, ultrasound is the most common way of first diagnosis and preoperative imaging examination for extracranial schwannomas. Schwannoma appears as a round or oval, well-defined, hypoechoic area with an inhomogeneous internal echo under the ultrasound exam. The “rat tail sign” may be seen in the upper and lower poles of the tumor when it originates from a nerve with a large diameter, which is a typical sign of schwannoma diagnosis by ultrasound and makes ultrasound more valuable in diagnosis [17, 18] (Fig. 1).

The diagnosis of schwannoma and its origin should be determined based on the location of the patient’s mass location, clinical symptoms, imaging examination, and biopsy pathology. In patients with a history of other tumors, lymph nodes should be distinguished. Accurate diagnosis of schwannoma and the specific nerve origin are important factors for the successful treatment and the reduction of posttreatment complications [14, 20].

3.2 Current treatment of schwannoma

Treatment of schwannoma depends on the clinical symptoms, the location, the growth rate, and the patient’s wishes. When the tumor grows slowly without peripheral vital organ structure and obvious clinical symptoms, follow-up observation can be selected in some cases based on the patients’ opinions. Treatment should be performed as early as possible when the tumor has rapid growth, poor growth location, or obvious clinical symptoms. The goal of treatment for schwannoma is to preserve neurological function while completely removing the tumor [13, 21]. The preferred treatment in the clinic is complete surgical resection of the tumor, which is the treatment that most patients receive. Sometimes radiation therapy is used to treat schwannoma alone or in combination with surgery, because of the poor tumor growth site or the rejection of patient on invasive surgery. In rare cases, chemotherapy may be used [4, 23].

As a minimally invasive treatment method, ultrasound-guided ablative therapy can accurately destroy the lesion under the guidance of real-time ultrasound imaging without damaging the surrounding important structures [24–26]. Commonly used ultrasound-guided ablation methods include radiofrequency ablation (RFA), microwave ablation, and cryoablation. In previous studies, these three methods have been used in individual cases of schwannoma. At present, RFA and MWA are more widely used than cryoablation in the ablation of various lesions under the guidance of ultrasound. Compared with RFA, MWA has the advantages of a higher power, higher temperature, and less affected by the heat sink effect [27]. This is a method of using microwave thermal effect to produce high temperature on target lesion to achieve the denaturation of proteins inside and outside cells, dehydration of cells, and finally coagulation necrosis of the lesions [28]. In recent years, MWA has been increasingly applied in the ablation of different types of tumors and volume reduction of some hypertrophy organs [29, 30]. As for schwannoma, ablation therapy in previous studies was mainly applied to trunk or limb tumors, and no cases of head and neck schwannoma treated by ultrasound-guided thermal ablation have been found [7–11]. The main complication of this treatment is damage to the origin and peripheral nerves, intraoperative attention should be paid to the extent of ablation not exceeding the sheath of the schwannoma. CEUS before and after the ablation should be performed to determine the specific area of ablation and the outcome of treatment [31, 32].

For the case we reported, due to her medical history of NSCLC and the possibility of metastasis in the lymph node and bilateral pleura when it was diagnosed, the cervical lymph node metastasis was considered when the neck mass was first found. The patient was confirmed to be cervical schwannoma by biopsy pathology while the cervical mass is nonresponsive to chemotherapy and slightly responsive to the radiation with no improvement of hoarseness and cough symptoms. Considering that MWA has an obvious cell dehydration effect, we chose MWA as the treatment for this patient [33–36]. MRI and ultrasound examinations were completed in our hospital before the operation, indicates the cervical tumor was in the carotid space and located between the common carotid artery (CCA) and the internal jugular vein (IJV), and made the two vessels separated [14, 17]. Combined with the symptoms of hoarseness and severe irritating cough, it was diagnosed as intrathecal carotid vagus schwannoma. The key to ensuring the safety, success, and effectiveness of this treatment is the definite diagnosis and the full knowledge of tumor location before ablation, real-time guidance of intraoperative ultrasound images, close attention to the ablation range during surgery, and evaluation of the ablation range by CEUS before and after ablation.

The patient’s severe cough symptom completely disappeared after ablation, while the hoarseness was not improved. It has been confirmed that the patient’s schwannoma is vagal schwannoma in the carotid space. According to the local neuroanatomy of the neck, the tumor location is close to the bifurcation of the right vagus nerve and the recurrent laryngeal nerve. The right recurrent laryngeal nerve leaves the right vagus nerve in front of the first segment of the right subclavian artery, loops around the right subclavian artery, and ascends along the tracheoesophageal groove [37]. In addition to the obvious compression of the vagus nerve, the large tumor compressed the recurrent laryngeal nerve in the tracheoesophageal groove as well as the trachea, causing it to deviate to the left. This causes damage to the vagus and recurrent laryngeal nerves, leading to obvious hoarseness and severe cough symptom.

Compared with RFA, MWA has a more obvious effect of cell dehydration which can make the lesions shrink rapidly after ablation to achieve an immediate reduction of tumor volume and reduce the compression. The severe cough disappeared when the patient awoke from general anesthesia after the treatment and did not recur at review. Two days after the operation, the cervical MRI showed that the tumor size was 35×24×38 mm with a VRR of 36%, which was significantly smaller than that before the ablation. The severe cough caused by compression was relieved due to the significant volume reduction caused by obvious cell dehydration of MWA (Table 1, Fig. 3).

Neurogenic tumors of the neck, such as the vagus schwannoma in this case, can themselves cause hoarseness, vocal cord paralysis, and generally poor prognosis for functional recovery [37, 38]. The vagus nerve has been injured by compression for a long time, and neither real-time image-guided ablation nor surgery can completely avoid the trauma caused by the invasion, nor can ablation remove the tumor completely [39]. Due to the slow growth of the tumor, the patient could have a good compensation, and there was no obvious aggravation of the symptoms of vagus nerve injury after the operation. Considering the overall situation, the patient’s persistent hoarseness symptoms are caused by the tumor itself and the operation, and long-term observation and follow-up are still needed to find out whether the patient may recover. Fluid isolation can be performed when necessary to reduce the impact and damage of thermal ablation on important structures surrounding the ablation target.

This treatment method is a relatively bold attempt, the important factors such as the specific output power, ablation time, ablation range to complete removal of the tumor while protecting the nerve in the operation still need to be determined by further prospective studies.

In conclusion, ultrasound-guided percutaneous MWA for extracranial cervical vagus schwannomas might be a minimally invasive, effective, and relatively safe alternative to conventional treatment for those patients with severe symptoms.