CASE REPORTS
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)
Introduction
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.
1,3
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.
4,5
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.
4
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
5
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
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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
FIGURE 1
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
min).
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.
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Discussion
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
12
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
9,19
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
Conclusion
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
REFERENCES
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
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