Peripheral Nerve Sheath Tumor of the Vagus Nerve in a Dog Fui Yap, BVMS, MANZCVS, Kathryn Pratschke, MVB, MVM, CertSAS, DECVS

ABSTRACT A peripheral nerve sheath tumor was diagnosed in a female, neutered Labrador retriever with a 6 mo history of coughing, retching, ptyalism, and left-sided Horner’s syndrome. Computed tomography scan of the neck revealed a mass lesion between the carotid artery and esophagus in the mid-cervical region. Exploratory surgery was performed and an 18 cm section of thickened vagus nerve was excised. Histopathological findings and immunochemistry staining confirmed a malignant peripheral nerve sheath tumor. The tumor showed microscopic signs of malignancy, but there were no macroscopic signs of local extension or distant metastasis. This report documents a peripheral nerve sheath tumor of rare origin in dogs. (J Am Anim Hosp Assoc 2016; 52:57–62. DOI 10.5326/JAAHA-MS-6249)


nerve around the level of the tympano-occipital fissure and a

Peripheral nerve sheath tumors (PNSTs) are a heterogeneous group

functional thyroid carcinoma invading the vagosympathetic

of tumors affecting the peripheral nerves. They originate from

trunk.6,7 Lymphoma involving the right vagus nerve has been

Schwann cells, modified Schwann cells, fibroblasts, or perineural

reported in a cat.8

cells.1 They are relatively uncommon in dogs.2 The brachial plexus

This case report documents an extensive cervical vagal PNST

is the most commonly affected site in dogs, but PNST has also been

in a dog, which was managed through surgical resection allowing

reported in spinal and cranial nerves, of which the trigeminal nerve

resolution of the clinical signs induced by vagal dysfunction.

is the most commonly affected.


Reported cases of PNST of the

vagus are rare in both human and veterinary medicine. A literature

Case Report

search identified only two reported canine cases: an intrathoracic

A 9 yr, 8 mo old female neutered Labrador retriever was presented

malignant PNST of the right vagus nerve at the level of the

with a 6 mo history of left-sided Horner’s syndrome, waxing and

bronchus and a malignant PNST of the right proximal cervical

waning lethargy, a reluctance to exercise, and a retching cough.


The former dog presented with hyper-

These signs started after a single collapsing episode. Thoracic

trophic osteopathy secondary to a thoracic mass, and had a

radiographs were taken at this stage by the referring veterinarian,

vagotomy to excise a lesion measuring 20 mm in diameter and 50

which did not show obvious abnormality. The coughing and

mm in length, which was connected to the right vagus nerve

retching became more frequent over time with accompanying

cranially. The dog was still alive at 710 days postoperatively with no

ptyalism; it was also noted that tracheal palpation induced coughing

vagosympathetic trunk.


signs of local recurrence or metastasis. The second dog was

and retching. Routine hematology and serum biochemistry were

euthanized for necropsy without treatment following confirmation

unremarkable. Acute phase proteins were measured to assess the


of cervical neoplasia. Other neoplastic lesions reported to affect

presence of a concurrent inflammatory process and this showed a

the vagus nerve in dogs include a PNST derived from the

normal C-reactive protein with mildly increased haptoglobin.

hypoglossal nerve that encompassed the vagus and the accessory

Thoracic radiographs were not repeated; in preference, a computed

From the Small Animal Hospital, University of Glasgow, Glasgow, United Kingdom.

CT, computed tomography; PNST, peripheral nerve sheath tumors

Correspondence: [email protected] (F.Y.)

Q 2016 by American Animal Hospital Association



performed at the time of the CT scan to assess the laryngeal function. Endoscopic examination of the upper gastrointestinal tract identified inflammation around the gastro-esophageal junction that suggested esophageal reflux together with an area of mild esophageal mucosal scarring. Based on the diagnostic findings, the patient underwent exploratory cervical surgery for a suspected PNST. Laryngeal function was assessed at induction of general anesthesia, which confirmed unilateral left-sided paralysis with normal function on the right hand side. At surgery, a mass 12 cm in length was identified involving the left vagus nerve (Figures 2A, B). There was no visible local extension and the local lymph nodes were macroscopically normal. A vagotomy incorporating the tumor was performed, with 3 cm margins cranially and caudally to maximize the chance of a complete resection. This resulted in the resection of a total length of 18 cm of the cervical vagal nerve. The sympathetic chain was dissected free of the tumor and preserved, Computed tomography (CT) scan of the mid-cervical

although this meant potentially compromising the lateral margins

region—immediate post-contrast with IV administration of Ioversol

of resection. No complications were seen during anesthetic

300mg/ml. Note the hypoattenuating structure with a hyperattenuat-

recovery. There was a subjective, mild improvement of the

ing rim (white arrows). The structure was located dorsal to the

Horner’s syndrome the day after surgery and no further episodes

hyperattenuating carotid artery (blue arrow) and lateral to the

of coughing and retching were noted postoperatively. The heart


esophagus (yellow arrows).

rate and respiratory rate were also closely monitored during the postoperative period as decreased heart rate and respiratory rate are

tomography (CT) scan of the thorax and neck was performed

reported in unilateral vagotomy. The heart rate was similar between

instead. This showed thickening of the left vagosympathetic trunk at

the pre-operative period (80–98 beats per min) and postoperative

the level of the third cervical vertebra (Figure 1), which gradually

period (80–108 beats per min). The respiratory rate also remained

became a mass lesion as it extended caudally to the left subclavian

consistent pre- (20–36 per min) and postoperatively (16–36 per

artery and brachiocephalic trunk. A laryngeal examination was not


FIGURE 2 (A) Intra-operative picture of vagotomy (the head of the patient is to the right). The cranial part of the vagotomy was elevated.

(B) The excised vagus nerve. Note the thickening of the central portion of the vagus nerve affected by the peripheral nerve sheath tumors (PNSTs).




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PNST of the Vagus Nerve in a Dog

FIGURE 3 (A) The neoplastic cells (green arrows) arranged in bundles are visible in the circled area. Areas of hemorrhage (yellow arrows)

are also visible around the upper half of the image (40x power field). (B) Multiple mitotic figures (arrows) are visible in this high power field (100x). (C, D) The immunohistochemistry staining with S-100 shows diffuse, granular staining of the cytoplasm of the neoplastic cells (40x and 100x power fields).

The histopathology report identified a spindle cell sarcoma

differential for canine PNSTs.9 There was diffuse granular

with features of a PNST. Neoplastic cells were arranged in bundles

cytoplasmic staining of neoplastic cells with vimentin and S-100

(Figure 3A), expanding and replacing the nerve. There was also

(Figures 3C, D), which differentiated the tumor from a carcinoma

evidence of necrosis, pleomorphism, and a mitotic rate of 4 per 10

and supported a diagnosis of PNST.

high power fields (Figure 3B). The margins proximal and distal to

A follow-up phone call 19 mo postoperatively revealed that

the tumor were free of neoplastic cells, which suggested complete

the dog has not had any further episodes of coughing, retching,

resection in these planes. The lateral margins, the epineurium, had

ptyalism, or exercise intolerance, although her left-sided Horner’s

evidence of neoplastic cells invasion. Immunohistochemistry was

syndrome persisted. Periodic monitoring for clinical signs of local

performed to further classify the tumor and to confirm the cell of

recurrence and/or pulmonary metastasis was recommended at the

origin. The immunohistochemistry stain was negative for desmin

time of discharge. However, due to the positive outcome and

and smooth muscle actin. These results excluded tumor of smooth

financial constraint, the owner had elected not to repeat thoracic

muscle origin as well as those of vascular lineage, such as

radiographs for metastasis evaluation. The owner was happy with

hemangiopericytoma, which is the most important histological

the clinical outcome.




intestines are partly innervated by branches of the vagus nerve, and

The vagus nerve carries both sensory and motor supplies to the

vagotomized dogs have been shown to have delayed gastric

palate, pharynx, larynx, trachea, esophagus, and the thoracic and abdominal organs.10 After arising from the dorsolateral aspect of the medulla oblongata, it exits the jugular foramen and tympanooccipital fissure and courses down the neck in the carotid sheath.10 Within the carotid sheath, the vagus nerve is bound to the sympathetic trunk within a common epineurium to form the vagosympathetic trunk, before separating from the sympathetic chain at the level of the thoracic inlet.10 The lesion in the cervical vagosympathetic trunk in this dog most likely resulted in Horner’s syndrome due to disruption of the sympathetic supply to the ipsilateral eye. The separation of the vagus nerve and the sympathetic chain is usually indistinct at this level in healthy animals; in this case, the separation was clearer due to the underlying pathological changes in the vagus nerve, enabling vagotomy with preservation of the sympathetic chain. The mild improvement in the patient’s Horner’s syndrome after the vagotomy indicated that the neoplastic lesion was restricted to the vagus nerve with the sympathetic supply affected due to compression from the lesion and local inflammation. However, the absence of further improvement at long-term follow-up suggests that the injury to the sympathetic chain was more severe than simple neurapraxia, possibly due to the chronicity of the lesion.

emptying and slower intestinal transit.13 Efferent vagus nerves provide parasympathetic innervation to the stomach and stimulate gastric motility, as well as the secretion of gastric acid, pepsin, and gastrin.14 A cervical vagal tumor has been previously suggested to stimulate vomiting in a dog.5 It seems reasonable to suggest that the vagal lesion in this dog, which was involving much of the cervical length of the vagus, may have altered gastric and small intestinal motility, resulting in gastro-esophageal reflux with retching, ptyalism, and esophagitis as seen on endoscopy. All laryngeal muscles, except for the cricothyroideus, are innervated by the recurrent laryngeal nerve, which branches from the vagus nerve at the level of the heart base (on the left) or rostral to the heart base (on the right).10 Therefore, a lesion in the cervical vagosympathetic trunk can be expected to induce ipsilateral laryngeal hemiplegia, which could predispose affected patient to aspiration. This would, in turn, worsen any respiratory signs and contribute to exercise intolerance and lethargy. Aspiration was not present in our patient, but our patient did show signs of lethargy and a reluctance to exercise. Various diagnostic imaging modalities have been reported in the diagnosis of PNST, including radiography, ultrasonography, CT, and MRI.4–6,15,16 MRI is the diagnostic modality of choice as it provides excellent soft tissue resolution and the ability to

Although neoplastic extension to the sympathetic chain cannot be

distinguish nerve bundles from vessels.3 Electromyography can

excluded without repeat advanced imaging and further diagnostics,

also be a useful diagnostic test in identifying the affected nerve.5,6 A

the lack of any progression of clinical signs or development of new

CT scan was performed on this dog rather than MRI due to the

clinical signs supports secondary dysfunction associated with

owners’ financial constraints. The lesion was visible in the

damage from the local vagal tumor.

immediate post-contrast sequence as a mass lesion with a

Given the structures innervated by the vagus nerve, loss of a

hyperattenuating rim, located between the carotid artery and

normal cough reflex might be anticipated with a primary vagal

esophagus. The involvement of the vagus nerve was suspected due

tumor. However, the cough reflex was preserved in this dog

to the location of the lesion. The rim enhancement effect on the

because of the cranial laryngeal nerve innervation. The cranial

post-contrast CT scan observed in this case was also a common

laryngeal nerve, which provides an afferent supply for the cough

finding in a retrospective study of dogs with mass lesions in the

reflex, branches off the vagus nerve at the level of the larynx.10 This

brachial plexus.15 The central, uneven distribution of hypoattenua-

is rostral to the lesion identified in our case. The cause of the

tion was likely to be due to necrosis, as noted on histopathology.

patient’s coughing was unclear, but thought likely to reflect gastro-

Histopathology findings and positive S-100 immunohisto-

esophageal reflux and laryngeal/tracheal mucosa irritation as such a

chemistry staining confirmed the diagnosis of a PNST of the vagus

link is well-recognized in people with chronic reflux.11 Motor

nerve in this dog. S-100 aids in differentiating a nerve sheath tumor

innervation of the esophagus is derived from branches of the vagus

from a carcinoma and has traditionally been regarded as the best

nerves, and experimental studies in dogs have previously shown

marker for identifying a malignant PNST.17 However, a recent

that transection of one vagus will not affect esophageal motility, but

publication has questioned its diagnostic utility as it was positive in


only about 50–90% of cases reported.18 Vimentin stains cells of

Stimulation of the central part of the vagus can cause episodes of

mesenchymal origins and was used to rule out a carcinoma.

tetanic contraction in the lower part of the pharynx and the cervical

Histologically, the most important differential for canine PNSTs is

esophagus.12 The stomach and the mesenteric portion of the small

a hemangiopericytoma.19 Most hemangiopericytomas show

bilateral transection results in dilation of the thoracic esophagus.




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PNST of the Vagus Nerve in a Dog

positive smooth muscle actin expression due to the vascular

the benign PNST group were alive without evidence of metastasis

lineage, whereas PNSTs are negative for smooth muscle actin, as

or recurrence during the study, but the duration of the follow-up


In addition,

was not stated in the study. The fifth dog in this study was later

hemangiopericytomas stain negative for S-100 and may stain

diagnosed with a recurrent malignant PNST. Due to the

positive for desmin, which are in contrast to the immunohisto-

retrospective nature of this study, little information is provided

chemistry result of this case since it was positive for S-100 and

regarding disease progression pre- and postoperatively or the cause

negative for desmin.9 The diagnosis of a malignant PNST has been

of death. In addition, the exact nerves involved and the

described to be based on macroscopic signs of local extension,

postoperative follow-up period were also not recorded.

was the tumor in the case reported here.

pulmonary metastasis, along with cellular evidence of anaplasia, necrosis, increased mitotic rate, and hemosiderin deposition.1 In


this case, there were cellular features of malignancy with

In conclusion, PNST of the vagus nerve should be considered as a

pleomorphism, necrosis and increased mitotic rate noted.

possible, albeit unusual, differential if animals are presented with

However, there was no grossly visible local extension and the

clinical signs consistent with combined sympathetic and vagal

cranial and caudal margins appeared to be free of tumor. The

nerve dysfunction. Even with the entire cervical length of one vagus

lateral margins were formed by the epineurium, into which there

nerve compromised by tumor growth, a good clinical outcome was

was invasion of neoplastic cells. Lateral margins of PNSTs have

achieved through surgical resection with preservation of the

not been clarified in previously reported cases of PNSTs.4–6,19 As a result, direct comparison of this with previous literature is not

sympathetic nerve and, therefore, treatment should be considered for such cases.

possible. There was no evidence of metastasis within the thoracic cavity, although, for completeness, an abdominal ultrasound


could have been additionally performed to confirm no identifiable distant metastasis. Overall, therefore, a diagnosis of lowgrade, malignant PNST was felt more appropriate by the authors despite the malignant changes on histopathology; the benign indications from absence of gross local extension and either local or distant metastasis were felt to offset the histological findings such that, from a clinical viewpoint, the tumor was more likely benign in behavior. The prognosis for PNSTs varies in the available literature. PNSTs have been reported to have a poor prognosis previously.20 This study, however, did not classify the PNSTs into benign or malignant categories.20 In this study, 72.3% (34 out of 47) of the dogs diagnosed with PNSTs had documented recurrence or were strongly suspected to have tumor recurrence after surgical excision; 69.4% (25 out of 36) of the documented deaths were PNST related and only 12.8% of the dogs (6 out of 47) had a relapse-free period of more than 1 yr.20 It is worth noting that the documented PNSTs in this study only involved those of brachial or lumbosacral plexuses, peripheral nerves, and spinal nerve roots. In contrast, another study reported a good prognosis in benign PNSTs but a poor prognosis for malignant PNSTs.19 In this retrospective study, eight of the PNSTs were from fore or hind limbs, four involved the head, and five involved other body parts (cervix, base of tail, ventral abdomen, fifth and sixth cervical vertebrae, and mammary gland). Most of the dogs in the malignant PNST group showed metastasis or recurrence, and all the dogs in this group died within 2 yr of surgical excision of the PNSTs. In contrast, four of the five dogs in

1. Koestner A, Higgins RJ. Tumors of the Nervous System. In: Tumors in Domestic Animals. 4th ed. Iowa City (IA): Iowa State Press; 2008:731– 735. 2. Withrow SJ, Vail DM, Page R. Small Animal Clinical Oncology. 5th ed. St. Louis: Saunders; 2013:592–596. 3. Kraft S, Ehrhart EJ, Gall D, et al. Magnetic resonance imaging characteristics of peripheral nerve sheath tumors of the canine brachial plexus in 18 dogs. Vet Radiol Ultrasound 2007;48(1):1–7. 4. Hara Y, Tagawa M, Ejima H, et al. Regression of hypertrophic osteopathy following removal of intrathoracic neoplasia derived from vagus nerve in a dog. J Vet Med Sci 1995;57(1):133–135. 5. Ruppert C, Hartmann K, Fischer A, et al. Cervical neoplasia originating from the vagus nerve in a dog. J Small Anim Pract 2000;41:119–122. 6. Davis EG, Coates JR, Johnson GC, et al. What is your neurologic diagnosis? Peripheral nerve sheath tumor. J Am Vet Med Assoc 2011; 239:189–191. 7. Melian C, Morales M, Espinosa de los Monteros A, et al. Horner’s syndrome associated with a functional thyroid carcinoma in a dog. J Small Anim Pract 1996;37:591–593. 8. Walker MC, Schaer M. Percutaneous ethanol treatment of hyperthyroidism in a cat. J Feline Med Surg 1998;26:10–12. 9. Mazzei M, Millanta F, Citi S, et al. Haemangiopericytoma: histological spectrum, immunohistochemical characterization and prognosis. Vet Dermatol 2002;13:15–21. 10. Evans HE, Kitchell RL. Cranial nerves and cutaneous innervation of the head. In: Evans HE, eds. Miller’s Anatomy of the Dog. 3rd ed. Philadelphia: Saunders; 1993:981–984. 11. Smith JA, Houghton LA. The oesophagus and cough: laryngopharyngeal reflux, microaspiration and vagal reflexes. Cough 2013; 9(1):12. 12. Hwang K, Grossman MI, Ivy AC. Nervous control of the cervical portion of the esophagus. Am J Physiol 1948;154(2):343–357. 13. Chen J, Koothan T, Chen JD. Synchronized gastric electrical stimulation improves vagotomy-induced impairment in gastric accommodation via



the nitrergic pathway in dogs. Am J Physiol Gastrointest Liver Physiol 2009;296:G310–318. 14. Magne ML, Twedt DC. Diseases of the stomach. In: Tams TR, ed. Handbook of Small Animal Gastroenterology. Philadephia: Saunders; 1996:218–220. 15. Rudich SR, Feeney DA, Anderson KL, et al. Computed tomography of masses of the brachial plexus and contributing nerve roots in dogs. Vet Radiol Ultrasound 2004;45(1):46–50. 16. da Costa RC, Parent JM, Dobson H, et al. Ultrasound-guided fine needle aspiration in the diagnosis of peripheral nerve sheath tumors in 4 dogs. Can Vet J 2008;49:77–81.




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17. Guo A, Liu A, Wei L, et al. Malignant peripheral nerve sheath tumors: differentiation patterns and immunohistochemical features - a minireview and our new findings. J Cancer 2012;3:303–309. 18. Stasik CJ, Tawfik O. Malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation (malignant triton tumor). Arch Pathol Lab Med 2006;130(12):1878–1881. 19. Chijiwa K, Uchida K, Tateyama S. Immunohistochemical evaluation of canine peripheral nerve sheath tumors and other soft tissue sarcomas. Vet Pathol 2004;41(4):307–318. 20. Brehm DM, Vite CH, Steinberg HS, et al. A retrospective evaluation of 51 cases of peripheral nerve sheath tumors in the dog. J Am Anim Hosp Assoc 1995;31:349–359.

Peripheral Nerve Sheath Tumor of the Vagus Nerve in a Dog.

A peripheral nerve sheath tumor was diagnosed in a female, neutered Labrador retriever with a 6 mo history of coughing, retching, ptyalism, and left-s...
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