Cystic Nasal Adenocarcinoma in a Cat Treated With Piroxicam and Chemoembolization

Introduction

Nasal tumors of cats account for approximately 1% to 5.9% of all feline tumors.^1,2 Lymphosarcoma is the most common tumor affecting the nasal cavities of cats, with adenocarcinoma and squamous cell carcinoma as the most frequent epithelial tumors.^3,4

Radiation therapy is well tolerated and may prolong the survival of cats with nasal carcinomas and sarcomas, whereas surgery alone does not improve the prognosis.^2,5,6 This report describes a case of nasal adenocarcinoma in a cat that received alternative treatment consisting of piroxicam, carboplatin, and chemoembolization.

Case Report

A 13-year-old, 5.3-kg, castrated male Siamese cat was presented to the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania (VHUP); the cat had a 4-month history of recurrent seizures and bilateral conjunctivitis and rhinitis. Upon physical examination, dull mentation and bilateral mucopurulent ocular and nasal discharge were noted. The cat was thin but in good body condition. The neurological examination, besides the obtunded mental status, was unremarkable.

A complete blood cell count, biochemical analysis, resting ammonia level, and serum thyroxine (T4) were normal; however, there was a mild increase in serum creatinine (2.2 mg/dL; reference range 1.0 to 2.0 mg/dL). Serology for Toxoplasma gondii was negative. Thoracic radiography showed no significant abnormalities. Cerebrospinal fluid (CSF) was clear and colorless and had an elevated protein concentration (65 mg/dL, reference range <25 mg/dL) and cell count (43 white blood cells [WBCs]/μL, reference range <4WBCs/μL; 0 red blood cells [RBCs]/μL, reference range 0 RBCs/μL). The CSF differential cell count was 15% nondegenerate neutrophils, 2% small lymphocytes, and 83% mononuclear cells, with rare macrophages. Cytological interpretation of the CSF was mononuclear pleocytosis, with a suppurative component. Cryptococcus latex agglutination test result on CSF was negative.

Computed tomography (CT) examination of the brain and nose revealed a hypoattenuated mass in the right olfactory and frontal lobe of the brain [Figure 1A]. The mass extended into the right nasal cavity and eroded the cribriform plate. Density measurements revealed values of 15 Hounsfield units (HU) (range 11 to 19 HU) for the mass and 49 HU (range 46 to 55 HU) for the right frontal sinus, which were consistent with fluid and inspissated material, respectively. ⁷ After intravenous administration of iohexol^a contrast medium (3.4 mL/kg), marked turbinate enhancement in the nasal region and ring enhancement of the hypoattenuated mass were seen [Figure 1B]. Neural tissue adjacent to the mass also appeared hypoattenuated, with a mass effect on the left side (i.e., the falx cerebri shifted toward the left), which was consistent with peritumoral edema. A cystic neoplasm (e.g., carcinoma, meningioma) was considered most likely based on the homogenous appearance.

A nasal core biopsy obtained through the nostril indicated a chronic, active rhinitis; this was not believed to represent the disease process. Two days later, a surgical biopsy was performed using a bilateral, transfrontal approach.⁸ The right ethmoidal labyrinth and the inner table of frontal bone over the right frontal lobe were carefully removed to expose the most rostral part of the cystic mass. A 25-gauge needle was inserted in the cyst, and 0.4 mL of xanthochromic fluid was obtained that was characteristic of suppurative inflammation. Nondegenerate neutrophils comprised 90% of the nucleated cells and were accompanied by low numbers of large mononuclear cells, small lymphocytes, and plasma cells. Aerobic and anaerobic bacterial cultures of the fluid were negative.

The mass and the walls of the small cyst extending in the nasal cavity were excised and contained neoplastic glandular structures lined by cuboidal epithelium [Figure 2A]. The nuclei were ovoid and moderately hyperchromatic with central nucleoli [Figure 2B]. A fairly extensive amount of eosinophilic cytoplasm was present, and cell borders were distinct. There was little pleomorphism, and zero to one mitotic figure was found per 200× field. The final histopathological diagnosis was nasal adenocarcinoma.

Reexamination of the brain and nasal cavities by CT, performed immediately after surgery to confirm decompression of the brain, showed a hypoattenuated area of probable edema in the right frontal lobe. The cystic lesion was no longer visible, and a bone defect was present in the right inner table of the frontal bone at the site of the craniectomy [Figure 3]. Postoperatively, the cat was started on phenobarbital^b (2 mg/kg per os [PO] q 12 hours), clindamycin^c (14 mg/kg PO q 12 hours), amoxicillin-clavulanic acid^d (18 mg/kg PO q 12 hours), and application of topical ophthalmic neomycin-polymyxin B-dexamethasone suspension^e in both eyes q 8 hours.

Eight months after initial presentation, clinical signs of sneezing, inspiratory stridor, and a clear nasal discharge from the right nostril developed. Piroxicam^f (0.3 mg/kg PO q 48 hours for 10 days, then q 24 hours) and misoprostol^g (4.7 mg/kg PO q 8 hours) were started, and the signs improved. During the following year, the cat had intermittent episodes of sneezing and nasal discharge that were treated with amoxicillin-clavulanic acid or clindamycin. Twenty-two months after the initial diagnosis, the cat was again presented to VHUP for swelling over the right nose and recurrence of bilateral nasal and ocular discharge. At this time the cat was still on phenobarbital (tapered by owner to 0.25 mg/kg PO q 12 hours), misoprostol, and piroxicam. Bilateral mucopurulent nasal discharge (more severe on the left side), bilateral epiphora, and inability to retropulse the right eye were found. Neurological examination, hematology, and serum biochemical analyses were normal. No evidence of metastatic disease was detected on thoracic radiography. Fine-needle aspirates of submandibular lymph nodes indicated lymphoid hyperplasia.

Repeat CT showed severe bony destruction of the nasal septum and right nasal, maxillary, palatine, cribriform, and frontal bones. Postcontrast images showed a contrast-enhancing mass associated with the sphenoid and frontal sinus that extended to the nasopharynx, oropharynx, right orbit, and nasal cavities. Hypoattenuating, nonenhancing material consistent with inspissated fluid was seen in both frontal sinuses. The owners declined all treatment except for amoxicillin-clavulanic acid (12 mg/kg PO q 12 hours).

Six weeks later, the cat was presented for recurrence of seizures, and the owners agreed to experimental treatment of the tumor with chemoembolization. The protocol required CT to be performed, which revealed a soft-tissue mass invading both nasal passages, extensive turbinate lysis, and destruction of the maxilla and nasal bone on the right side. The mass extended into the right orbital fossa displacing the globe, and through the right cribriform plate into the rostral portion of the brain [Figure 4A]. A midline shift to the level of the falx cerebri was seen, and the mass showed ring enhancement that was consistent with a necrotic or cystic lesion [Figure 4B]. A nonenhancing mass on the dorsal aspect of the nose appeared to be cystic. A fine-needle aspirate of the mass on the nose retrieved some fluid, which was compatible with suppurative inflammation. Culture of the fluid grew Staphylococcus warneri.

Chemoembolization was performed via intra-arterial injection of carboplatin^h (200 mg/m²) through a micro-catheter placed in the right superficial temporal artery. The injection was done under fluoroscopic guidance, via a left femoral artery approach.⁹ Subsequently, a polyvinyl alcohol particleⁱ and iohexol^a slurry was injected into the right superficial temporal artery under fluoroscopy until visibly slower arterial flow occurred in the vessel. Postoperatively, transient bilateral serosanguineous nasal discharge and epiphora occurred. At a recheck 10 days after chemoembolization, the cat was more alert, but a seizure episode had occurred the previous day. A serum phenobarbital level was 5.3 μg/mL (reference range 15 to 40 μg/mL), so the dose was increased to 1 mg/kg PO q 12 hours. Two months later and 744 days from the initial presentation, the cat died at home.

A necropsy was performed, and a severe, multifocal, suppurative bronchopneumonia was found in the lungs. The nasal cavities contained an adenocarcinoma; severe chronic, lymphoplasmacytic, suppurative rhinitis; and multifocal osteomyelitis. Intravascular foreign material (presumably the polyvinyl alcohol particles) was identified in the tumor. In the brain, the olfactory bulbs showed a severe, regionally extensive, chronic lymphoplasmacytic, neutrophilic meningoencephalitis with encephalomalacia; severe encephalomalacia that involved the right thalamus and midbrain was also seen. Carcinoma cells and particulate material were not observed histologically in the olfactory bulbs.

Discussion

The case reported here had unusual clinical and radiological features in that neurological signs are rarely associated with nasal tumors in cats.^3,4 In two recent retrospective studies of 153 cats with nasal and paranasal sinus tumors, the most common clinical signs were nasal discharge, dyspnea, and facial swelling.^3,4 In these studies, seizures were reported only in two cases of olfactory neuroblastoma.^3,4 Seizures and other neurological signs were also documented in another report of two cats with olfactory neuroblastomas.¹⁰

In the current case, the initial CT scan showed a predominantly intracranial cystic lesion that extended into the right nasal cavity. Brain tumors with macroscopic cysts have been described in dogs and cats, with meningiomas being the most common, followed by gliomas, nasal tumors, pituitary tumors, and ependymomas.^11–18 The two cystic nasal tumors in dogs were of epithelial origin.¹⁵ Cystic nasal adenocarcinomas have also been reported in cats, but the cysts have usually been incidental histopathological findings.³ Cystic meningiomas have been reported in cats, but the erosion of bone noted in the current case was not typical of feline meningiomas (which tend to cause hyperostosis of the overlying calvarium).¹⁸

Cats with nasal carcinomas typically do not survive >1 year without radiation therapy; it was remarkable that the cat reported here survived >800 days from the onset of clinical signs.^{2,4–6,19–21} Reports exist on the treatment of nasal carcinomas in cats using palliative therapy, surgery, radiation therapy, and chemotherapy.^{2,4–6,19–21} Mean survival time has varied from a few days up to 5 years.^{2,4,5,19–21} A possible explanation for the prolonged survival time of this cat is that the piroxicam, initially used with palliative intent, controlled the growth of the tumor. Piroxicam is a nonselective cyclooxygenase inhibitor that has antitumor activity against many canine malignancies.^22–25 The antitumor effect of piroxicam is unexplained, and the effects of piroxicam on feline tumors are unknown.

Chemoembolization involves the intra-arterial administration of chemotherapy in order to achieve extremely high concentrations within the tumor (when compared to concentrations achieved with traditional intravenous administration). In addition, particle embolization of the tumor capillary bed is performed to cause tumor ischemia, increase chemotherapy retention time, and minimize systemic toxicity from the chemotherapy.⁹ The chemoembolization treatment in this cat was performed 50 days before its death, so it probably did not contribute to the long survival time.

The tumor histologically had low pleomorphism and a low mitotic index, which was suggestive of a less aggressive tumor and may have explained the slow progression of the disease. The tumor did display malignant behavior, however, in its invasion of the cranial cavity and induction of neurological signs prior to initial presentation. The onset of seizures early in the clinical course may have led to an early diagnosis of the tumor compared to other nasal tumors that often are asymptomatic for a long period of time.

Conclusion

An intracranial, cystic lesion compressing the brain and invading the nose was detected by CT in a cat with seizures and bilateral conjunctivitis and rhinitis. A diagnosis of nasal adenocarcinoma was reached via a surgical excisional biopsy. The cat was treated with surgical drainage of the cyst; administration of piroxicam, phenobarbital, and intermittent antibiotics; and chemoembolization. The cat survived for >2 years. The possibility that the prolonged survival time was associated with piroxicam treatment warrants further investigation on the use of this drug in a larger number of cats.