Introduction

A 6-year-old 7.72-kg neutered male domestic shorthair cat was examined because of a 1.5-month history of left head tilt and ataxia. The cat had initially been presented to an emergency clinic, and empiric treatment with clindamycin for suspected otitis media–otitis interna had resulted in a minimal response. A routine CBC and serum biochemical analyses were performed and revealed a slightly high symmetric dimethylarginine concentration (18 µg/dL; reference range, 0 to 14 µg/dL) in the absence of azotemia and slightly low alanine aminotransferase (18 U/L; reference range, 27 to 158 U/L) and alkaline phosphatase (9 U/L; reference range, 12 to 59 U/L) activities. The cat was subsequently prescribed a 3-week course of prednisolone at an anti-inflammatory dosage and had a partial response in mobility despite persistence of the head tilt and ataxia.

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On initial examination, the cat had a rectal temperature of 39.5 °C. The cat displayed a left head tilt, left-sided palpebral reflex deficit, decreased pinna sensation, and ambulatory vestibular ataxia. The left menace response and corneal reflex were incomplete. A large, firm, smooth subcutaneous mass attached to the deeper tissues was palpable in the left pharyngeal region. A smaller mass was palpable from the contralateral side.

Assessment

Diagnostic Plan

The diagnostic plan consisted of MRI of the head to detect structural abnormalities along the pathways of the cranial nerves, needle biopsy of the retropharyngeal mass to evaluate the nature of the mass, and CSF analysis to rule out inflammatory, infectious, and neoplastic processes.

Diagnostic Test Findings

Magnetic resonance imaging of the head was performed in sagittal, dorsal, and transverse planes (Intera 1.5-T MRI scanner; Philips Healthcare); T2-weighted, proton density, T2*-weighted, FLAIR, and diffusion-weighted imaging sequences were obtained. Apparent diffusion coefficient values were calculated with the diffusion-weighted imaging sequence. In addition, sagittal, dorsal, and transverse T1-weighted images were obtained before and after administration of contrast medium (ProHance).

Imaging revealed 2 large, asymmetric, hyperintense, smooth, lobulated, heterogeneously contrast-enhanced, space-occupying masses in the retropharyngeal area. The mass on the left extended rostrally to envelop the caudoventral aspect of the left tympanic bulla. Coincidentally, there was also diffuse contrast enhancement of the left cranial nerve VII, most notably of the portion near the internal acoustic meatus and the tympanic and mastoid segments (Figure 1). No other structural abnormalities of the brain or tympanic bullae were evident on MRI images. Cerebrospinal fluid analysis was not performed given the lack of leptomeningeal enhancement on brain MRI images. Multiple samples of the retropharyngeal masses were collected transcutaneously with a core biopsy needle while the cat was anesthetized.

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Transverse T1-weighted MRI images of the caudal brainstem obtained before (A) and after (B) contrast administration in a 6-year-old domestic shorthair cat with a 1.5-month history of left head tilt and ataxia. Notice the diffuse contrast enhancement of the left cranial nerve VII (facial nerve), particularly at the level of the internal acoustic meatus (arrow) and the tympanic and mastoid segments (arrowhead). Strong contrast enhancement is also associated with a left retropharyngeal mass that extended to the caudoventral aspect of the tympanic cavity.

Citation: Journal of the American Veterinary Medical Association 260, 10; 10.2460/javma.20.11.0611

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Histologic examination of the needle biopsy specimens identified sheets of neoplastic round to polygonal cells that contained a moderate amount of vacuolated cytoplasm and round to irregular nuclei with 1 or 2 prominent nucleoli. These cells displayed moderate cellular pleomorphism with frequent necrosis and a high mitotic count (8 mitotic figures/10 hpf). Because of poor differentiation of the neoplastic cells, immunohistochemical testing was performed. The cells showed diffuse strong CD20 and CD18 immunoreactivity, suggestive of B-cell lymphoma. There was no evidence of cytokeratin AE1/3 immunoreactivity detected.

Comments

Cranial nerve neuropathies, including vestibular disease and facial nerve neuropathy, are commonly classified into peripheral and central neurologic dysfunctions.^1–3 Central lesions should be suspected when the affected animal also has an abnormal level of consciousness, postural reaction deficits, multiple concurrent deficits involving cranial nerves other than cranial nerves VII and VIII, and vertical or dysconjugate nystagmus.^1,2 It is important to note that cranial nerves VII and VIII travel in close proximity after they emerge from the caudal brainstem, and thus, they may be affected concurrently by both central and peripheral diseases.³ In addition, it has been suggested that concomitant idiopathic vestibular disease can occur in 50% of dogs with idiopathic facial nerve neuropathy.³ The most common causes of facial nerve neuropathy in cats are nonsurgical trauma, middle ear neoplasia, and idiopathic dysfunction.⁴ The most common causes of peripheral vestibular disease in cats are otitis media–otitis interna and idiopathic dysfunction.² In humans, multiple cranial neuropathies were reported to be most commonly associated with malignancies (31.1%), vascular diseases, and trauma.⁵ Neoplastic processes may affect the cranial nerves by direct compression, infiltration, or paraneoplastic processes.⁶ As a result, tumors of the head and neck can be associated with cranial nerve palsy.⁶

To the authors’ knowledge, cranial nerve neuropathies secondary to direct compression of the nerves are infrequently reported in companion animals. On the other hand, cranial nerve neuropathies secondary to direct compression of the nerves are well recognized in humans, particularly those with lymphoma, skull base meningioma, schwannoma, or sarcoidosis.^6,7 When multiple cranial nerve involvement is evident, certain mechanisms, including direct compression, nerve infiltration (neurolymphomatosis), and paraneoplastic disease processes secondary to lymphoma, should be considered.⁷ In the present report, a presumptive diagnosis of left cranial nerve VII and VIII neuropathies secondary to direct compression by a large lymphomatous mass was made. However, lymphatic microinfiltration and paraneoplastic processes could not be completely ruled out. A definitive diagnosis would require a nerve biopsy. Cerebrospinal fluid analysis was not performed because it was considered unlikely to enable a more definitive diagnosis, given the known focal peripheral involvement. The contrast enhancement of cranial nerve VII likely represented secondary neuritis.

Lymphoma is a common cause of peripheral neuropathy in cats⁸ but has also been sporadically reported to affect cranial nerves and multiple peripheral nerves in cats as a result of neurolymphomatosis.^8,9 Neurolymphomatosis describes widespread malignant lymphocytic invasion of peripheral nerves and ganglia leading to diffuse neurologic dysfunction.^8,9 This was considered to be unlikely in the present case owing to the regional distribution of the neuropathy.

Although histopathology and cytology remain the gold standards for diagnosis of lymphoma, a recent study¹⁰ described a significant association between symmetric dimethylarginine concentration and feline lymphoma. In addition, a large portion of these cases had no overt increases in creatinine concentration.¹⁰ Although the pathophysiology of increased symmetric dimethylarginine concentration in these cases is currently unknown, the increase was proposed to be due to reversible acute kidney injury or a reversible reduction in symmetric dimethylarginine excretion secondary to spontaneous tumor lysis.¹¹

Treatment for solitary lymphoma in cats is most commonly based on the University of Wisconsin-Madison protocol, with or without adjunctive radiation therapy and surgical resection.^8,12 The overall survival time of cats with lymphoma in various anatomic localizations treated with a cyclophosphamide, vincristine, prednisone, and methotrexate (COP-M) protocol was 108 days,¹³ but responders had a significantly longer median survival time (591 days) than did nonresponders (73 days).¹³ The prognosis may improve with adjunctive radiation therapy, with a median complete remission time of 861 days reported in most cats with solitary lymphoma in 1 study.¹⁴

The cat of the present report was treated with palliative radiation therapy in combination with lomustine. The intended hypofractioned, palliative-intent radiation protocol was a total of 6 weekly 6-Gy fractions administered with a cobalt-60 teletherapy unit (Theratron T-1000 Cobalt-60 Radiotherapy; MDS Canada Inc). Five weeks after the diagnosis was made and treatment was initiated, the cat developed pleural effusion and dyspnea. Radiation therapy was subsequently discontinued, and a COP-M protocol was instituted. Three weeks later, the cat had a complete clinical response with resolution of the dyspnea, head tilt, facial paralysis, and palpable cervical masses. The plan was to continue treatment with the COP-M protocol for a minimum of 4 cycles.