Introduction

Tumors developing from the peripheral nervous system are collectively named nerve sheath tumors (NSTs).^1–2 Canine NSTs are associated with more aggressive behavior than their human counterpart; consequently, the designation malignant NSTs (MNSTs) is commonly used.^3–4 Cranial nerve (CN) involvement is rare in dogs, with the trigeminal nerve being the most frequently reported.^4–8 In people, primary NSTs of the hypoglossal nerve (HN) are very uncommon, probably because they very rarely affect purely motor CNs.⁹ They represent 1–7% of nonvestibular schwannomas, and malignancy occurs very rarely.⁹ We describe here the clinical presentation, MRI, and histologic examination of an MNST of the HN in a dog.

Case Report

A 4 yr old, male Maltese dog presented with a 1 wk history of intermittent neck pain and progressive difficulty walking. No history of dysphagia was reported. On neurological examination, the dog showed a depressed mental status, inconstant turning of the head and neck to the left, vestibular ataxia with left-sided drifting, episodic falls to the left, proprioceptive deficits in all four limbs, and ventrolateral positional strabismus of the left eye. In addition, oral examination showed left lingual hemiatrophy (Figure 1A). Based on these findings, the neuroanatomical localization was the left brain-stem with involvement of the left HN.

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Main differential diagnoses were neoplastic and inflammatory disease. Glioma, meningioma compressing the brainstem and the hypoglossal root, lymphoma, or a left caudal fossa metastasis were considered the most probable neoplasias. An MNST affecting the HN root and compressing the brainstem was considered possible but unlikely because it had not been previously described. Meningoencephalitis of unknown origin affecting the left brainstem was the main differential among inflammatory diseases. Toxoplasmosis and neosporosis were considered the most likely infectious diseases, because they can affect both the brainstem and nerve, but bacterial and fungal infections could not be completely ruled out either.

Complete blood cell count and serum biochemistry were unremarkable. MRI^a of the brain under general anesthesia revealed an extra-axial, space-occupying lesion in the left side of the caudal fossa causing marked contralateral displacement of the medulla oblongata and extending extracranially through the ipsilateral hypoglossal canal as a tubular dumbbell-shaped mass. The intracranial component of the mass measured approximately 1.7 × 1.0 × 0.9 cm, with distinct borders. The mass was isointense to gray matter on T1-weighted (T1W) images, heterogeneously hyperintense on T2-weighted (T2W) images, and enhanced homogeneously after IV administration of contrast medium^b except for a poorly enhancing core consistent with a necrotic center (Figures 1B, C). On the basis of the clinical signs and MRI findings, a presumptive diagnosis of a neoplasia involving the HN was made. Main differential diagnoses were round cell tumors (lymphoma) and MNST. Radiation therapy was considered the only therapeutic option. The owner declined this, and, after an initial improvement following steroid administration, the clinical signs rapidly deteriorated. The owner then elected for euthanasia and consented to a necropsy examination. At gross examination, the left lingual hemiatrophy was severe, with a seemingly crenated tongue. After the brain was removed, a hemorrhagic mass compressing the ventral surface of the medulla oblongata was visible. The mass extended through an enlarged hypoglossal canal (Figure 1D) into the extracranial parapharyngeal space assuming a tubular, multinodular, pink-gray appearance (Figure 2A). Brain, HN, and tongue were fixed in 10% neutral buffered formalin for routine histological examination. On transverse section, the left half of the brainstem revealed a large, necrotic-hemorrhagic area extending from the floor of the fourth ventricle to the pyramids (Figure 2B). At histological examination (Figures 2C, D), the HN was diffusely infiltrated by fusiform neoplastic cells arranged in Antoni A and Antoni B patterns (referring to highly cellular areas of spindle cells in a generally scant collagen stroma or sparsely cellular areas in abundant myxoid extracellular matrix, respectively). A pseudopalisading pattern of nuclei was also observed. Nuclear atypia were evident at high magnification with up to four mitotic figures/high-power field. Large areas of necrosis were present. Neoplastic infiltration did not occur either in the brainstem or in the tongue. Based on gross and histological features, a diagnosis of left hypoglossal MNST was made. Hemorrhagic and necrotizing lesions of the brainstem were considered secondary to the compression by the mass.

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Discussion

This paper describes an MNST affecting the HN both intra- and extracranially. A tumor involving the left HN together with the ipsilateral glossopharyngeal, vagus, and accessory nerves has been described.¹⁰ In that paper, the HN was suspected to be the origin of the tumor at the post mortem gross examination, and a presumptive diagnosis of MNST was made histologically. The involvement of several nerves controlling the swallowing process justified both the reasons for presentation (dysphagia, coughing, and a change in the dog’s bark) and the deficits seen on neurological examination (lack of the gag reflex and difficulty in forming a bolus, moving the food into the oropharynx, and swallowing).

To the authors’ knowledge, this is the first report solely involving the HN in the dog. The dog presented herein was 4 yr old at the time of diagnosis, whereas MNSTs typically affect older dogs.¹³ Only 4 out of 61 dogs described in two reviews on MNST were 5 yr old or younger.^3,6 A recent case of vagal MNST was reported in a 5 yr old dog.¹⁴ Therefore, although rare, MNST should be considered in the differentials of younger dogs, too.

The dog presented here had no history of dysphagia. Dysphagia might have been expected because the voluntary component of the oropharyngeal phase of deglutition involves normal movements of the base of the tongue to transfer the food bolus into the oropharynx.¹⁵ In a review of human literature based on 160 case reports of HN NST, tongue atrophy was present at the time of diagnosis in 91.6% of patients but dysphagia in only 31.8%.¹⁶ In human beings, unilateral atrophy or paralysis of the tongue typically does not disturb prehension, deglutition, and mastication. Because of these minimal disabilities, HN paralysis usually appears as a sign rather than a symptom, and it is discovered as an incidental finding during the clinical workup.⁹ In our case, neurological deficits related to the compression of the brainstem, rather than the lingual hemiparesis, were the cause of the consultation, and a more direct involvement of the HN was suspected during the neurological evaluation because of the lingual hemiatrophy. On the basis of this observation, either the importance of the HN in the swallowing process could be less than previously hypothesized, or the activity of the contralateral HN could compensate in a satisfactory manner.

MRI showed an extra-axial caudal fossa mass lesion extending extracranially and assuming a tubular bilobed shape. The HN emerges from the medulla oblongata laterally to the pyramids, by means of several rootlets, and passes extracranially into the parapharyngeal space through the hypoglossal canal. The hypoglossal canal is located on a ridge of bone rostral to the ventral condyloid fossa that lies between the paracondylar process and the occipital condyle.¹⁷ In normal dogs, identification of both the intracranial component of the HN and the hypoglossal canal is difficult on MR images because of a lack of spatial resolution for such small structures.^18–19 In our case, both the intracranial and the extracranial component of the HN were easily identified in MRI because the disease process made them larger and caused enhancement after contrast medium administration. Their close proximity to the left occipital condyle justified the assumption that the dumbbell-shaped mass was developing internally and externally to the hypoglossal canal, along the course of the HN (Figure 1B).

Furthermore, the shape of the mass lesion seen on MRI resembles the most frequent one seen in humans, often described as dumbbell tumors, formed by two apparently separated components linked by an indistinct narrower part inside the hypoglossal canal.^9,16 A dumbbell-shaped presentation has been described in a dog affected by trigeminal MNST.²⁰ In the case described by Davis et al. the mass was extending from the brainstem through the tympano-occipital fissure, suggesting a major involvement of CNs IX, X, and XI.¹⁰

Features considered to be suggestive of, although not specific for, CN MNSTs include an extra-axial mass at the level of the brainstem and a unilateral enlarged nerve branch, typically iso-hyperintense on T2W sequences and iso-hypointense on the T1W sequences with heterogeneous contrast enhancement.²¹ In humans, hypoglossal schwannomas are usually heterogeneous on T2W and enhance on postcontrast T1W sequences.²² Possible additional findings include distortion of the adjacent brainstem and enlargement of the skull foramina. Similar findings in our case, together with the clinical signs, suggested an antemortem diagnosis of hypoglossal MNST.

Post mortem examination clearly demonstrated the extracranial extension in the parapharyngeal space and the secondary hypoglossal canal enlargement. This mirrors the pathogenesis in people in which these lesions frequently develop intracranially from the origin of the nerve or within the hypoglossal canal and show secondary extracranial extension and hypoglossal canal enlargement.^16,23

At histological examination, the presence of a spindle cell neoplastic population arranged in high- and low-density areas was consistent with a peripheral NST. Pseudopalisading nuclei were considered distinctive for a tumor of Schwann cell origin, and nuclear atypia and the high mitotic index were considered criteria of malignancy.²⁴

Conclusion

In conclusion, hypoglossal MNST is an extremely rare condition in dogs. The results of our diagnostic workup demonstrate how clinical and MRI evaluation can strongly support the diagnosis.