History
A 6-year-old sexually intact male Weimaraner presented to the Dick White Referrals neurology service with a history of 3 months of infrequent upper respiratory stertor, 1 week of changed bark, and 2 days of vestibular ataxia, right Horner syndrome, pain when opening the mouth, and occasional sneezing and retching. General physical examination was normal besides a respiratory rate of 30 breaths per minute.
Assessment
Anatomic diagnosis
The neurologic localization in this case was the vestibular system. Deciding whether the central or peripheral system is affected requires identifying any neurologic deficits that cannot be attributed to the peripheral vestibular system, such as proprioceptive deficits, altered mentation, cranial nerve deficits (besides nerves VII and VIII), and positional nystagmus that changes direction with head position. The lack of proprioceptive deficits in our patient is typically a good indicator of peripheral vestibular disease. Horner syndrome, facial nerve deficits (causing the diminished palpebral reflex on the right side) and rotatory nystagmus can be present in both central and peripheral vestibular disease. However, the depressed mentation and reduced swallow reflex could indicate a more central pathology.1
Arousal and mentation are generally mediated by the ascending reticular activating system (ARAS), located between the thalamus and the medulla; the swallow reflex is coordinated by the medullary nuclei of cranial nerves IX and X in particular; and the sympathetic nervous system output originates in the midbrain under control of the hypothalamus, before coursing along the tectotegmental tract within the brainstem and spinal cord. Therefore, a brainstem lesion, affecting the ARAS, sympathetic nervous system and several cranial nerve nuclei, would be possible in this case. However, such a widespread lesion would be expected to cause significant neurologic deficits, such as a profoundly altered mental status, upper motor neuron tetraparesis, proprioceptive deficits and ataxia in all four limbs, and possibly respiratory distress because the major respiratory centers are located in the pons and medulla.1
Likely location of the lesion
The pathology is therefore most likely causing a right peripheral vestibular syndrome, originating in the middle ear. The facial nerve courses through the facial canal in the petrosal bone to exit the skull at the stylomastoid foramen, dorsal to the tympanic bulla. The sympathetic innervation to the eye passes in similarly close proximity to the middle ear. Deficits in both the facial nerve and the sympathetic ocular innervation, in the absence of proprioceptive deficits, strongly suggest a peripheral lesion.1 Potential causes of a depressed mentation in peripheral vestibular disease include unobserved head trauma, extracranial toxins, motion sickness or metabolic pathologies, but pain was thought to be most likely. The reluctance to open the mouth could be due to pain or a mechanical difficulty. The diminished swallow reflex, although indicative of a central vestibular lesion, is subjective, and correct interpretation may be more difficult in a poorly cooperative dog or one with oral pain.1
Horner syndrome may be localized to postganglionic or preganglionic sympathetic neurons with pharmacological testing. The application of 0.1-10% phenylephrine will resolve the symptoms of a postganglionic (third order) lesion due to complete denervation hypersensitivity at the postsynaptic membrane.1,2 Low concentrations of phenylephrine will not dilate a normal pupil or the pupil of a patient with preganglionic (first or second order) lesions; in these cases the healthy third order neuron continues to release small quantities of norepinephrine.2 Unfortunately, the onset of denervation hypersensitivity is extremely variable and false negative results may occur in earlier stages.1,2 The Horner syndrome in our patient showed minimal response to phenylephrine, but only began two days before presentation.
Etiologic diagnosis
Key differential diagnoses for a peripheral vestibular localization include otitis media/interna and middle ear neoplasia. Other causes of peripheral vestibular syndrome, such as ototoxicity, hypothyroidism and idiopathic vestibular syndrome, would be unlikely to cause all the reported signs, including facial and sympathetic nerve dysfunction and pain. There was no trauma or use of ototoxic agents in the recent clinical history.
Diagnostic Test Findings
Hematology and biochemistry tests revealed a raised C-reactive protein (98 mg/L, reference < 10mg/L). Ocular 2.5% phenylephrine caused minimal change in the Horner syndrome after 90 minutes.
MRI of the head was performed using a 0.4T unit (Hitachi Aperto Aspire; Hitachi Medical Corp). Sequences acquired were T2W, FLAIR, T2*GE, T1W, and T1W post-gadolinium contrast in the transverse plane; T2W and T1W post-contrast in the sagittal plane; and T1W post-contrast in the dorsal plane. This showed a large and expansile mass lesion arising from the right tympanic bulla, causing osteolysis of the osseous bulla. It also extended into the medial part of the right external ear canal causing luminal distension. The mass was markedly heterogeneously T2, FLAIR and T2* hyperintense (relative to muscle), iso- to slightly hyperintense on T1, and showed strong heterogeneous contrast enhancement. Marked contrast enhancement was noted in the surrounding soft tissues, adjacent fascial planes and in the thickened adjacent meninges. The right medial retropharyngeal lymph node was enlarged and cranial nerves VII and VIII were not clearly identified on the right.
Cerebrospinal fluid (CSF) was not sampled in this case, but a fine needle aspirate (FNA) was taken from the mass under ultrasound guidance. FNA sampling identified necrosis with aggregates of keratinized anucleate superficial squamous epithelial cells and neutrophilic and macrophagic inflammation, suggestive of a tympanokeratoma (also known as cholesteatoma).
On recovery from his investigations, the patient developed acute respiratory distress syndrome secondary to suspected aspiration pneumonia and went into cardiopulmonary arrest. At post-mortem, the right tympanic bulla was grossly increased in size with a roughened appearance; on cut section the bulla was completely filled by a cream-colored material of a granular to creamy consistency. Histopathology was consistent with right middle ear squamous cell carcinoma and severe tympanic bone osteolysis. Lung pathology showed acute, unilateral bronchopneumonia compatible with aspiration pneumonia. The enlarged right medial retropharyngeal lymph node was consistent with lymphoid hyperplasia.
Comments
The lesion was found to originate in the middle ear on MRI (Figure 1). Differentials for a middle ear mass include papillary adenoma, squamous cell carcinoma, adenocarcinoma, lymphoma, fibrosarcoma, cholesterol granulomas, aural inflammatory polyps, cranial mandibular osteopathy and tympanokeratoma.3 Other tumors may originate from the external auditory meatus and invade the middle ear. A major differential diagnosis for this case was a tympanokeratoma. The MRI appearance of these masses has been described in humans, dogs and cats. The imaging findings from this case do not fully correlate with previously described canine tympanokeratomas. Human and canine tympanokeratomas typically show partial contrast enhancement of the bulla lining but no enhancement of the middle ear content. Conversely, a recent feline case report did find heterogeneous enhancement of the mass itself.4
A—T2 transverse image at the level of the tympanic bullae demonstrating the expansile, osteolytic lesion within the right tympanic bulla (red asterisk), extending to the right external ear canal and beyond ventrally (red arrows). The differences in relation to the normal left tympanic bulla (green asterisk) and margins (green arrows) are obvious. B—T1 transverse post-contrast, showing widespread heterogeneous contrast enhancement within the lesion and surrounding soft tissues with a more peripheral and ventral distribution (blue arrowheads).
Citation: Journal of the American Veterinary Medical Association 261, 11; 10.2460/javma.22.12.0591
Had the patient recovered uneventfully, further investigation would have included tumor biopsy and staging of disease. Staging would involve cytology of the enlarged local lymph node and checking for distant metastases with whole-body CT, or thoracic radiography and abdominal ultrasound. Good surgical margins would be impossible due to the proximity to vital structures, so surgical debulking of the tumor via a total ear canal ablation and lateral bulla osteotomy (TECA-LBO) procedure could be considered instead of a biopsy. This could be followed by palliative radiation therapy as has been previously described.5 Metastasis to local lymph nodes could be treated similarly with surgical excision and radiation therapy. The prognosis would likely be poor in this case due to the degree of local invasion, even without evidence of metastatic spread.
Squamous cell carcinomas are rarely described in the canine middle ear. Pain on opening the mouth is considered a typical finding among sporadic case reports, and the current case additionally developed acute onset neurologic signs.3,5 The clinical signs of ear neoplasia will often mimic those of chronic or recurrent otitis, but the majority of signs were acute in our patient.3 Squamous cell carcinomas, although rare, should be considered as a differential diagnosis for middle ear disease.
Acknowledgments
The authors declare that there were no conflicts of interest. No third-party funding or support was received in connection with this study or the writing or publication of the manuscript.
The manuscript has not been submitted for publication elsewhere, but the case has been presented as a poster at the ESVN-ECVN Symposium 2022.
References
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Neuron LM, Neuron UM. Vestibular system: special proprioception and the neurological examination. In: de Lahunta A, Glass E, Kent M, eds. de Lahunta’s Veterinary Neuroanatomy and Clinical Neurology. 5th ed. Saunders; 2021:203-245, 345-373, 531-546.
- 2.↑
Zwueste DM, Grahn BH. A review of Horner’s syndrome in small animals. Can Vet J. 2019;60(1):81-88.
- 3.↑
Sula MJM. Tumors and tumorlike lesions of dog and cat ears. Vet Clin North Am Small Anim Pract. 2012;42(6):1161-1178. doi:10.1016/j.cvsm.2012.08.004
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Herberger A, Hammond J, Miller A, Olson B. MRI of a middle ear cholesteatoma in a cat. Vet Radiol Ultrasound. 2022;63(5):E16-E20. doi:10.1111/vru.13137
- 5.↑
Yoshikawa H, Mayer MN, Linn KA, Dickinson RM, Carr AP. A dog with squamous cell carcinoma in the middle ear. Can Vet J. 2008;49(9):877-879.
