Pathology in Practice

Sophia P. Topulos 1Department of Clinical Sciences, Department of College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Elizabeth C. Alloway 2Department of Population Health and Pathobiology, Department of College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Debra A. Tokarz 2Department of Population Health and Pathobiology, Department of College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Julien Guevar 1Department of Clinical Sciences, Department of College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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History

An indoor 10-year-old 5.1-kg (11.2-lb) castrated male domestic shorthair cat was presented for evaluation of chronic weight loss; dysphagia, anorexia, and impaired vision of 2 months’ duration; and recent episodes of sneezing. The clinical signs of a dropped jaw, ptyalism, and blepharospasm of the left eye were all reported by the owner to have had a sudden onset 2 months prior to the evaluation. One month later, acute blindness (with mydriasis, absent pupillary light reflexes, and absent menace responses in both eyes), anorexia, and a depressed mentation were noted. Episodic improvements in mentation and vision changes with anti-inflammatory glucocorticoid treatment were reported by the referring veterinarian; however, the dropped jaw persisted. The cat's vaccination status against rabies virus, feline herpesvirus-1, feline calicivirus, and panleukopenia virus was reportedly current. However, the cat was not receiving flea, tick, or heartworm preventatives or deworming medication. Results of a CBC, serum biochemical profile, and assessment of serum thyroxine concentration were unremarkable. Six months prior to the evaluation, testing revealed that the cat was negative for circulating anti-FIV antibody and FeLV antigen. Deterioration of the cat's condition (lethargy, altered mentation, and inability to eat or drink) over a 5-day period prompted emergency consultation at our institution.

Clinical and Gross Findings

The cat's physical examination findings were unremarkable with the exception of severe ptyalism and neurologic problems. Alertness and awareness were impaired. A dropped jaw was evident, but there was no evidence of an orthopedic problem; manually, the jaw could be closed easily but would not remain closed, and there appeared to be no facial asymmetry with no noted muscle atrophy, signs of pain, or loss of sensation (Figure 1). The menace response and pupillary light reflexes (direct and indirect) were decreased bilaterally, although worse in the left eye than in the right eye. Mydriasis was also present in the left eye. The remainder of the neurologic examination findings were considered normal. A fundic examination revealed no abnormalities. Further assessments, including MRI of the head, analysis of a CSF sample, abdominal ultrasonography, and thoracic radiography and investigation (eg, collection of fine-needle aspirate specimens) of any detected abnormalities, were declined by the owner. Supportive care and treatment with prednisolone were continued at home. Owing to the cat's poor quality of life, euthanasia was elected 4 days later. Propofol was used for sedation prior to euthanasia by IV injection of pentobarbital sodium and phenytoin sodium solution. A complete necropsy of the cat was performed immediately following euthanasia.

Figure 1—
Figure 1—

Photograph of an indoor 10-year-old domestic shorthair cat that was presented for evaluation of chronic weight loss; dysphagia, anorexia, and impaired vision of 2 months’ duration; and recent episodes of sneezing. A sudden onset of additional clinical signs (dropped jaw, ptyalism, and blepharospasm of the left eye) was reported 2 months prior to the evaluation. Notice mydriasis of the left eye; the dropped jaw allows protrusion of the tongue.

Citation: Journal of the American Veterinary Medical Association 257, 10; 10.2460/javma.2020.257.10.1017

Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page

Necropsy Findings

Gross postmortem lesions were confined to the head. An unencapsulated, infiltrative, firm, pale tan, irregular mass had bilaterally effaced and replaced the ventral, middle, dorsal, and ethmoidal conchae; rostral aspect of the frontal sinus; ethmoid bone; and frontal bone.1,2 Bilaterally, the frontal bones were soft and easily crushed. The trigeminal ganglia and nerves were diffusely, moderately thickened; the nerves measured 3 mm in diameter (Figure 2).

Figure 2—
Figure 2—

Gross photograph of the cat's brain prior to fixation. There is moderate bilateral enlargement of the trigeminal nerves and ganglia (white outlines). Bar = 10 mm.

Citation: Journal of the American Veterinary Medical Association 257, 10; 10.2460/javma.2020.257.10.1017

Histopathologic Findings

The brain, trigeminal nerves and ganglia, nasal turbinates, frontal sinus bones, and both eyes were fixed in neutral-buffered 10% formalin and processed routinely; sections were stained with H&E stain. The nasal turbinates were effaced and replaced by an unencapsulated, infiltrative, densely cellular neoplasm of stratified, cornifying squamous epithelial cells arranged in nests and islands and supported by a desmoplastic fibrous stroma (Figure 3). The neoplastic cells were polygonal with distinct cell borders, occasional intercellular bridges, and abundant eosinophilic and occasionally granular cytoplasm; nuclei were round with vesiculated chromatin and 1 distinct magenta nucleolus. Anisocytosis and anisokaryosis were moderate, and there were 32 mitotic figures/10 hpf (400X). The neoplastic cells also effaced and expanded the frontal bone and bilaterally infiltrated the epineurium and perineurium of the trigeminal nerves, leptomeninges and nerve fibers of the optic nerve, and leptomeninges and neuropil of the trigeminal ganglia (Figure 4). In these sections, as well as in the optic chiasm, there was mild to moderate, multifocal Wallerian-type degeneration with frequent dilated myelin sheaths, which either were empty or contained swollen, hypereosinophilic axon cylinders or gitter cells (digestion chambers). Neurons multifocally had acidophilic necrosis with shrunken, angular margins, hypereosinophilic cytoplasm, and pyknotic to lost nuclei. Additionally, in the optic chiasm, there was mild rarefaction (edema) and gliosis characterized by increased numbers of microglia. Extension into the brain parenchyma was not observed.

Figure 3—
Figure 3—

Photomicrograph of a section of the nasal turbinates. Neoplastic squamous epithelial cells form centrally stratifying and cornifying islands (arrowheads). H&E stain; bar = 200 μm. Inset—Intercellular bridges (arrows) and central regions of cornification (arrowheads) are visible. H&E stain; bar = 20 μm.

Citation: Journal of the American Veterinary Medical Association 257, 10; 10.2460/javma.2020.257.10.1017

Figure 4—
Figure 4—

Photomicrograph of a section of the right trigeminal nerve and ganglion. The nerve parenchyma is infiltrated and expanded by a similar neoplasm (black arrowhead). Multifocally captured are necrotic neurons (white arrowhead with black outline) and swollen axon cylinders (arrow). H&E stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 257, 10; 10.2460/javma.2020.257.10.1017

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: moderately well-differentiated squamous cell carcinoma (SCC) of the nasal turbinates with bilateral invasion of the optic nerves, trigeminal nerves, and frontal bones in an adult domestic shorthair cat that had a dropped jaw and fluctuating visual deficits and mentation.

Comments

For the cat of the present report, a multifocal lesion was suspected with involvement of the fore-brain or brainstem (abnormal mentation) and cranial nerves II (abnormal menace response and pupillary light reflexes in the left eye), III (mydriasis in the left eye), and V (bilaterally dropped jaw). Differential diagnoses included an inflammatory (infectious or noninfectious) or neoplastic disorder. Although the cat had no evidence of proprioceptive deficits or gait changes, a plaque-like lesion extending from the pituitary gland to the pons (possibly neoplastic disease [eg, lymphoma or meningioma] or infectious disease [eg, epidural abscess]) could not be fully excluded in light of the chronic nature of the clinical signs and absence of trauma.

The clinical finding of a dropped jaw is unusual in cats. A dropped jaw is a common finding in dogs with idiopathic bilateral trigeminal neuritis. However, any disease process that affects both trigeminal nerves would have the same clinical sign. In cats, nasal neoplasia is typically associated with chronic, progressive nasal discharge or epistaxis, often with facial deformity. To the authors’ knowledge, this is the first report of an SCC associated with a dropped jaw in a cat.

The term dropped jaw refers to an inability to close the mouth, which may be secondary to an orthopedic or neurologic problem. Orthopedically, a dropped jaw would have to be related to bilateral mechanical disruption of the temporomandibular joints. Neurologically, a dropped jaw is related to bilateral dysfunction of the trigeminal nerves, which innervate the masticatory muscles that function to close the mouth. In cats, this clinical sign may be secondary to bilateral luxation or fracture of the temporomandibular joints, bilateral caudal mandibular fracture, or bilateral impingement of the coronoid process of the mandible on the zygomatic arch or secondary to a mechanical obstruction.3 Bilateral trigeminal neuropathy has been suspected in cats with rabies, trauma,3 and idiopathic trigeminal neuritis4 and in a cat with neoplasia (lymphoma).5 An inflammatory cause of a dropped jaw in cats has not been reported, but is mentioned in some textbooks,4 whereas idiopathic trigeminal neuritis is a common cause of a dropped jaw in dogs. Importantly, rabies should also be considered in cases of dropped jaw, especially in animals with acute neurologic signs.6 In the case described in the present report, the cat's 2-month history of neurologic signs as well as its vaccination history made rabies an extremely unlikely differential diagnosis. Furthermore, that cat's lack of apparent signs of pain or resistance during manipulation of the mandible or the assessment of jaw function (opening and closing) and absence of a known traumatic event were not supportive of an orthopedic cause, which was confirmed on postmortem examination.

Neoplasia is often suspected in cats, particularly in elderly cats, with neurologic disorders localized to the brain. Intracranial neoplasms may extend outside of the calvaria or invade into the calvaria. In a retrospective study7 of 160 cats with intracranial neoplasia, dropped jaw was not reported as a clinical sign. Visual impairment was evident in 16 of those 160 (10%) cats, which included 5 of 14 cats with pituitary tumors, 1 of 8 cats with neuroepithelial tumors (the cat had a choroid plexus tumor), and 1 cat with SCC of the nasal cavity that had invaded the rostroventral meninges.7 An altered level of consciousness was reported for 42 of the 160 (26.3%) cats, which included 24 of 93 cats with meningioma, 2 of 6 cats with glioma, 4 of 23 cats with lymphoma, 4 of 14 cats with a pituitary tumor, and 4 of 7 cats with ependymoma.7

Extension of nasal tumors into the calvaria of cats has been described by Troxel et al.7 Of the 160 cats in that study, 3 had nasal tumors (2 with malignant nasal round-cell neoplasia and 1 with a nasal adenocarcinoma) that had extended into their calvariae; 2 of those 3 cats had neoplastic invasion of brain parenchyma. Of the 3 cats, 1 was evaluated because of neurologic signs (circling and signs of depression) and 2 were evaluated because of chronic upper respiratory tract signs. Lymphoma is a common neoplasm of cats; it is the second most common intracranial tumor after meningioma.7 Lymphoma was initially considered as a differential diagnosis for the cat of the present report given its clinical signs and gross postmortem findings. In the study7 of 160 cats, 23 (14.4%) had intracranial lymphoma. Analysis of a CSF sample from each of 6 cats was performed; 2 samples underwent cytologic examination, which revealed lymphoblasts in 1 sample. In a study8 of feline nasal and paranasal sinus tumors in 123 cats, lymphoma was found to be the most common type of neoplasia, representing 35 (28.5%) cases. Intracranial extension of a nasal lymphoma was not reported for any of the cats in that study.8 However, a case report9 of 2 cats with nasopharyngeal lymphoma and concurrent intracranial masses revealed MRI evidence consistent with direct communication of the masses. Upper respiratory tract signs and bilateral cranial nerve III deficits were noted in both cats, and 1 cat had bilateral cranial nerve II deficits. Cavernous sinus syndrome secondary to intracranial lymphoma in a cat has also been reported.10 Notably, although neoplasia was a top differential diagnosis for the cat of the present report, the nasopharynx of cats is also commonly affected by nonneoplastic, space-occupying lesions, such as nasopharyngeal polyps and cryptococcosis. Whereas there are no reports of nasopharyngeal polyps invading the calvaria, to the authors’ knowledge, cryptococcosis as a differential diagnosis is further supported by a report11 of extension of nasal cryptococcosis through the cribriform plate.

In a single case report,12 SCC was found to cause unilateral ophthalmoplegia and blindness in a cat. The tumor was primarily associated with the right side of the skull (affecting the tympanic bulla, temporal bone, and mandible); radiography, CT, necropsy, and histologic examination of tissue specimens revealed that the SCC had surrounded the cranial nerves in the cavernous sinus on the right side by invasion through the sphenoid bone. It had also invaded through the lamina cribrosa into the right globe. This yielded unilateral functional deficits of cranial nerves II, III, IV, and VI and of the sympathetic nerve supply. However, the present report appears to be the first report of bilateral invasion of cranial nerves II and V secondary to local invasion from a nasal SCC (resulting in dropped jaw) in a cat. The muscles of mastication include the masseter; temporal, lateral, and medial pterygoid; and digastricus muscles. The function of these muscles is to close the jaw, with the exception of the digastricus muscle, which opens the jaw. All those muscles are innervated by the mandibular nerve from the trigeminal nerve except the caudal portion of the digastricus muscle, which is innervated by the facial nerve.13 Therefore, the cat's dropped jaw was a result of bilateral invasion of the trigeminal nerve, affecting all of the muscles responsible for closing the jaw. Although the cat of the present report was suspected to have had a flare-up of herpesvirus infection because of recent episodes of sneezing in combination with a lifelong history of upper respiratory tract signs, the reported upper respiratory signs were likely largely attributable to the nasal turbinate SCC. Therefore, in cats with a dropped jaw (solely or in addition to other cranial nerve or neurologic signs) and especially in cats with concomitant upper respiratory tract signs, invasion of the calvaria by a nasal tumor (such as SCC) should be included as a differential diagnosis. For such cats, advanced diagnostic imaging of the head and analysis of a CSF sample should be considered. As neither the cat of the present report nor the previously described cat with SCC that invaded the calvaria12 was treated, treatment recommendations and prognosis with treatment are unknown.

Acknowledgments

No third-party funding or support was received in connection with this study or the writing or publication of the manuscript. The authors declare that there were no conflicts of interest.

References

  • 1. Smith B. Respiratory system. In: Atlas of feline anatomy for veterinarians. 2nd ed. Jackson, Wyo: Teton NewMedia, 2010;138–139, 142143.

    • Search Google Scholar
    • Export Citation
  • 2. Hudson L, Hamilton W. Musculoskeletal system. In: Atlas of feline anatomy for veterinarians. 2nd ed. Jackson, Wyo: Teton NewMedia, 2010;2829.

    • Search Google Scholar
    • Export Citation
  • 3. Constantaras ME, Charlier CJ. Maxillofacial injuries and diseases that cause an open mouth in cats. J Vet Dent 2014;31:168176.

  • 4. Dewey CW, Talarico LR. Disorders of the peripheral nervous system: mononeuropathies and polyneuropathies. In: Dewey CW, da Costa RC, eds. Practical guide to canine and feline neurology. 3rd ed. Ames, Iowa: Wiley-Blackwell, 2016;445480.

    • Search Google Scholar
    • Export Citation
  • 5. de Lahunta A. Lower motor neuron: general somatic efferent, cranial nerve. In: de Lahunta A, Glass E, eds. Veterinary neuroanatomy and clinical neurology. 3rd ed. St Louis: Saunders Elsevier, 2009;134167.

    • Search Google Scholar
    • Export Citation
  • 6. Dewey CW. Encephalopathies: disorders of the brain. In: Dewey CW, da Costa RC, eds. Practical guide to canine and feline neurology. 3rd ed. Ames, Iowa: Wiley-Blackwell, 2016;141236.

    • Search Google Scholar
    • Export Citation
  • 7. Troxel MT, Vite CH, Van Winkle TJ, et al. Feline intracranial neoplasia: retrospective review of 160 cases (1985–2001). J Vet Intern Med 2003;17:850859.

    • Search Google Scholar
    • Export Citation
  • 8. Mukaratirwa S, van der Linde-Sipman JS, Gruys E. Feline nasal and paranasal sinus tumours: clinicopathological study, histomorphological description and diagnostic immunohistochemistry of 123 cases. J Feline Med Surg 2001;3:235245.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Chang Y, Thompson H, Reed N, et al. Clinical and magnetic resonance imaging features of nasopharyngeal lymphoma in two cats with concurrent intracranial mass. J Small Anim Pract 2006;47:678681.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Guevar J, Gutierrez-Quintana R, Peplinski G, et al. Cavernous sinus syndrome secondary to intracranial lymphoma in a cat. J Feline Med Surg 2014;16:513516.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Sykes JE, Sturges BK, Cannon MS, et al. Clinical signs, imaging features, neuropathology, and outcome in cats and dogs with central nervous system cryptococcosis from California. J Vet Intern Med 2010;24:14271438.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Murphy CJ, Koblik P, Bellhorn RW, et al. Squamous cell carcinoma causing blindness and ophthalmoplegia in a cat. J Am Vet Med Assoc 1989;195:965968.

    • Search Google Scholar
    • Export Citation
  • 13. Evans HE, de Lahunta A, eds. The muscular system. In: Miller's anatomy of the dog. 4th ed. St Louis: Elsevier Saunders, 2013;185280.

    • Search Google Scholar
    • Export Citation
  • Figure 1—

    Photograph of an indoor 10-year-old domestic shorthair cat that was presented for evaluation of chronic weight loss; dysphagia, anorexia, and impaired vision of 2 months’ duration; and recent episodes of sneezing. A sudden onset of additional clinical signs (dropped jaw, ptyalism, and blepharospasm of the left eye) was reported 2 months prior to the evaluation. Notice mydriasis of the left eye; the dropped jaw allows protrusion of the tongue.

  • Figure 2—

    Gross photograph of the cat's brain prior to fixation. There is moderate bilateral enlargement of the trigeminal nerves and ganglia (white outlines). Bar = 10 mm.

  • Figure 3—

    Photomicrograph of a section of the nasal turbinates. Neoplastic squamous epithelial cells form centrally stratifying and cornifying islands (arrowheads). H&E stain; bar = 200 μm. Inset—Intercellular bridges (arrows) and central regions of cornification (arrowheads) are visible. H&E stain; bar = 20 μm.

  • Figure 4—

    Photomicrograph of a section of the right trigeminal nerve and ganglion. The nerve parenchyma is infiltrated and expanded by a similar neoplasm (black arrowhead). Multifocally captured are necrotic neurons (white arrowhead with black outline) and swollen axon cylinders (arrow). H&E stain; bar = 50 μm.

  • 1. Smith B. Respiratory system. In: Atlas of feline anatomy for veterinarians. 2nd ed. Jackson, Wyo: Teton NewMedia, 2010;138–139, 142143.

    • Search Google Scholar
    • Export Citation
  • 2. Hudson L, Hamilton W. Musculoskeletal system. In: Atlas of feline anatomy for veterinarians. 2nd ed. Jackson, Wyo: Teton NewMedia, 2010;2829.

    • Search Google Scholar
    • Export Citation
  • 3. Constantaras ME, Charlier CJ. Maxillofacial injuries and diseases that cause an open mouth in cats. J Vet Dent 2014;31:168176.

  • 4. Dewey CW, Talarico LR. Disorders of the peripheral nervous system: mononeuropathies and polyneuropathies. In: Dewey CW, da Costa RC, eds. Practical guide to canine and feline neurology. 3rd ed. Ames, Iowa: Wiley-Blackwell, 2016;445480.

    • Search Google Scholar
    • Export Citation
  • 5. de Lahunta A. Lower motor neuron: general somatic efferent, cranial nerve. In: de Lahunta A, Glass E, eds. Veterinary neuroanatomy and clinical neurology. 3rd ed. St Louis: Saunders Elsevier, 2009;134167.

    • Search Google Scholar
    • Export Citation
  • 6. Dewey CW. Encephalopathies: disorders of the brain. In: Dewey CW, da Costa RC, eds. Practical guide to canine and feline neurology. 3rd ed. Ames, Iowa: Wiley-Blackwell, 2016;141236.

    • Search Google Scholar
    • Export Citation
  • 7. Troxel MT, Vite CH, Van Winkle TJ, et al. Feline intracranial neoplasia: retrospective review of 160 cases (1985–2001). J Vet Intern Med 2003;17:850859.

    • Search Google Scholar
    • Export Citation
  • 8. Mukaratirwa S, van der Linde-Sipman JS, Gruys E. Feline nasal and paranasal sinus tumours: clinicopathological study, histomorphological description and diagnostic immunohistochemistry of 123 cases. J Feline Med Surg 2001;3:235245.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Chang Y, Thompson H, Reed N, et al. Clinical and magnetic resonance imaging features of nasopharyngeal lymphoma in two cats with concurrent intracranial mass. J Small Anim Pract 2006;47:678681.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Guevar J, Gutierrez-Quintana R, Peplinski G, et al. Cavernous sinus syndrome secondary to intracranial lymphoma in a cat. J Feline Med Surg 2014;16:513516.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Sykes JE, Sturges BK, Cannon MS, et al. Clinical signs, imaging features, neuropathology, and outcome in cats and dogs with central nervous system cryptococcosis from California. J Vet Intern Med 2010;24:14271438.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Murphy CJ, Koblik P, Bellhorn RW, et al. Squamous cell carcinoma causing blindness and ophthalmoplegia in a cat. J Am Vet Med Assoc 1989;195:965968.

    • Search Google Scholar
    • Export Citation
  • 13. Evans HE, de Lahunta A, eds. The muscular system. In: Miller's anatomy of the dog. 4th ed. St Louis: Elsevier Saunders, 2013;185280.

    • Search Google Scholar
    • Export Citation

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