Cystic Nasal Adenocarcinoma in a Cat

Treated With Piroxicam and

Chemoembolization
A 13-year-old, castrated male Siamese cat was presented with a 4-month history of recurrent
seizures and bilateral conjunctivitis and rhinitis. Computed tomography of the brain and nose
revealed a cystic lesion in the cranial cavity that compressed the brain and invaded the nose.
Nasal biopsy revealed a nasal adenocarcinoma. The cat was treated with intermittent antibi-
otics, phenobarbital, piroxicam, and chemoembolization; it survived for 2 years after diagno-
sis. J Am Anim Hosp Assoc 2007;43:347-351.

Katia Marioni-Henry, DVM, PhD, Introduction

Diplomate ACVIM (Neurology) Nasal tumors of cats account for approximately 1% to 5.9% of all feline
Tobias Schwarz, MA, DrMedVet, tumors.1,2 Lymphosarcoma is the most common tumor affecting the nasal
DVR, Diplomate ECVDI, cavities of cats, with adenocarcinoma and squamous cell carcinoma as
Diplomate ACVR, the most frequent epithelial tumors.3,4
Diplomate MRCVS Radiation therapy is well tolerated and may prolong the survival of
cats with nasal carcinomas and sarcomas, whereas surgery alone does not
Chick Weisse, VMD, improve the prognosis.2,5,6 This report describes a case of nasal adeno-
Diplomate ACVS carcinoma in a cat that received alternative treatment consisting of pirox-
Kathleen B. Muravnick, DVM icam, carboplatin, and chemoembolization.

C A 13-year-old, 5.3-kg, castrated male Siamese cat was presented to the
From the Department of Small Animal
Clinical Sciences (Marioni-Henry),
Veterinary Teaching Hospital,
University of Tennessee,
Knoxville, Tennessee 37996-4544;
the Department of Surgical
Sciences (Schwarz),
School of Veterinary Medicine,
University of Wisconsin-Madison,
Madison, Wisconsin 53706-1102;
the Section of Small Animal
Surgery (Weisse, Muravnick),
Department of Clinical Studies,
School of Veterinary Medicine,
University of Pennsylvania,
Philadelphia, Pennsylvania 19104-6010.
Case Report
Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania
(VHUP); the cat had a 4-month history of recurrent seizures and bilater-
al 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 radiog-
raphy 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]/L, reference range <4 WBCs/L; 0 red blood cells [RBCs]/L,
reference range 0 RBCs/L). The CSF differential cell count was 15%
nondegenerate neutrophils, 2% small lymphocytes, and 83% mononu-
clear 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.

JOURNAL of the American Animal Hospital Association 347

348 JOURNAL of the American Animal Hospital Association November/December 2007, Vol. 43

Computed tomography (CT) examination of the brain

and nose revealed a hypoattenuated mass in the right olfac-
tory and frontal lobe of the brain [Figure 1A]. The mass
extended into the right nasal cavity and eroded the cribri-
form 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, respec-
tively.7 After intravenous administration of iohexola 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 neo-
plasm (e.g., carcinoma, meningioma) was considered most
likely based on the homogenous appearance.
A nasal core biopsy obtained through the nostril indicat-
ed a chronic, active rhinitis; this was not believed to repre-
sent 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 inflam-
mation. 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 glandu-
lar structures lined by cuboidal epithelium [Figure 2A]. The
nuclei were ovoid and moderately hyperchromatic with cen-
tral 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
Figures 1A, 1BPre- and postcontrast, transverse com-
mitotic figure was found per 200 field. The final puted tomographic images of the brain at the level of the
histopathological diagnosis was nasal adenocarcinoma. frontal lobes of a 13-year-old, castrated male Siamese cat.
Reexamination of the brain and nasal cavities by CT, per- In the precontrast image (A), a hypoattenuated mass is
formed immediately after surgery to confirm decompression seen in the right frontal lobe (white arrow). In the postcon-
of the brain, showed a hypoattenuated area of probable trast image (B), the lesion is delineated by ring enhance-
ment (white arrow). In both images, the falx cerebri is
edema in the right frontal lobe. The cystic lesion was no shifted toward the left (white arrowhead), and inspissated
longer visible, and a bone defect was present in the right material is evident in the right frontal sinus (black arrow-
inner table of the frontal bone at the site of the craniectomy head). L=left, R=right.
[Figure 3]. Postoperatively, the cat was started on pheno-
barbitalb (2 mg/kg per os [PO] q 12 hours), clindamycinc
(14 mg/kg PO q 12 hours), amoxicillin-clavulanic acidd (18 improved. During the following year, the cat had intermit-
mg/kg PO q 12 hours), and application of topical oph- tent episodes of sneezing and nasal discharge that were
thalmic neomycin-polymyxin B-dexamethasone suspen- treated with amoxicillin-clavulanic acid or clindamycin.
sione in both eyes q 8 hours. Twenty-two months after the initial diagnosis, the cat was
Eight months after initial presentation, clinical signs of again presented to VHUP for swelling over the right nose
sneezing, inspiratory stridor, and a clear nasal discharge and recurrence of bilateral nasal and ocular discharge. At
from the right nostril developed. Piroxicamf (0.3 mg/kg PO this time the cat was still on phenobarbital (tapered by
q 48 hours for 10 days, then q 24 hours) and misoprostolg owner to 0.25 mg/kg PO q 12 hours), misoprostol, and
(4.7 mg/kg PO q 8 hours) were started, and the signs piroxicam. Bilateral mucopurulent nasal discharge (more
November/December 2007, Vol. 43
B
Figures 2A, 2BPhotomicrographs of the nasal adeno-
carcinoma from the cat in Figure 1. (A) The neoplastic cel-
lular proliferation is composed of glandular structures
formed by neoplastic epithelial cells (Hematoxylin and
eosin stain, 200; bar=50 ). (B) The neoplastic cells are
columnar with distinct cell borders, large amounts of
eosinophilic cytoplasm, and ovoid hyperchromatic nuclei
with central amphophilic nucleoli (black arrow)
(Hematoxylin and eosin stain, 400; bar=20 ).
severe on the left side), bilateral epiphora, and inability to
retropulse the right eye were found. Neurological examina-
tion, hematology, and serum biochemical analyses were
normal. No evidence of metastatic disease was detected on
thoracic radiography. Fine-needle aspirates of submandibu-
lar 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).
Cystic Nasal Adenocarcinoma in a Cat 349
Figure 3Precontrast, transverse computed tomographic
image of the brain at the level of frontal lobes obtained
from the cat in Figure 1, after surgery. A hypoattenuated
area is present in the right frontal lobe (black arrowhead),
and a bony defect is seen in the right inner table of the
frontal bone (white arrowhead). L=left, R=right.
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 displac-
ing 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 cys-
tic lesion [Figure 4B]. A nonenhancing mass on the dorsal
aspect of the nose appeared to be cystic. A fine-needle aspi-
rate 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 carboplatinh (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 iohexola 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 chemoem-
bolization, the cat was more alert, but a seizure episode had
occurred the previous day. A serum phenobarbital level was
5.3 g/mL (reference range 15 to 40 g/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.
350 JOURNAL of the American Animal Hospital Association
Figures 4A, 4BPostcontrast, transverse computed tomo-
graphic (CT) images of the head of the cat in Figures 1
through 3 that were obtained almost 2 years after the initial
images. The CT image of the head at the level of the cribri-
form plate (A) shows erosion of the right cribriform plate
(white arrow) and presphenoid bone (black arrow). A con-
trast-enhanced mass (black arrowhead) is invading the
cranial cavity, nasopharynx, and right periocular tissues
and is displacing the globe (white asterisk). A fluid-filled
mass (white arrowhead) is also seen dorsal to the frontal
bone. The CT image of the brain at the level of the olfacto-
ry lobes (B) shows a ring-enhanced mass (black arrow-
head) consistent with a cystic lesion in the right olfactory
lobe. L=left, R=right.
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
November/December 2007, Vol. 43
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 menin-
goencephalitis with encephalomalacia; severe encephalo-
malacia 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 anoth-
er report of two cats with olfactory neuroblastomas.10
In the current case, the initial CT scan showed a pre-
dominantly 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 hyper-
ostosis 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 clin-
ical signs.2,4-6,19-21 Reports exist on the treatment of nasal
carcinomas in cats using palliative therapy, surgery, radia-
tion 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 nonse-
lective cyclooxygenase inhibitor that has antitumor activity
against many canine malignancies.22-25 The antitumor
effect of piroxicam is unexplained, and the effects of pirox-
icam on feline tumors are unknown.
Chemoembolization involves the intra-arterial adminis-
tration of chemotherapy in order to achieve extremely high
concentrations within the tumor (when compared to con-
centrations achieved with traditional intravenous adminis-
tration). In addition, particle embolization of the tumor
capillary bed is performed to cause tumor ischemia,
increase chemotherapy retention time, and minimize sys-
temic toxicity from the chemotherapy.9 The chemoem-
bolization treatment in this cat was performed 50 days
before its death, so it probably did not contribute to the long
survival time.
November/December 2007, Vol. 43
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, howev-
er, in its invasion of the cranial cavity and induction of neu-
rological 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 biop-
sy. 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 inves-
tigation on the use of this drug in a larger number of cats.
Footnotes
a Omnipaque; Nycomed, Inc., Princeton, NJ 08540
b Phenobarbital; Roxane Laboratories, Columbus, OH 43216
c Antirobe; Pharmacia & Upjohn Company, Kalamazoo, MI 49001
d Clavamox; Pfizer Animal Health, Exton, PA 19341
e Neomycin-Polymyxin B-Dexamethasone Ophthalmic Suspension;
Steris, Phoenix, AZ 85043
f Feldene; Pfizer, New York, NY 10017
g Cytotec; GD Searle & Co., Skokie, IL 60077
h Paraplatin; Bristol-Myers Squibb Oncology, Princeton, NJ 08543
i Contour emboli; Target Therapeutics, Fremont, CA 94538
References
11. Legendre AM, Krahwinkel DJ, Spaulding KA. Feline nasal and
paranasal sinus tumors. J Am Anim Hosp Assoc 1981;17:1038-1039.
12. Cox NR, Brawner WR, Powers RD, et al. Tumors of the nose and
paranasal sinuses: 32 cases with comparison to a national database
(1977 through 1987). J Am Anim Hosp Assoc 1991;27:339-347.
13. Mukaratirwa S, van der Linde-Sipman JS, Gruys E. Feline nasal and
paranasal sinus tumours: clinicopathological study, histomorphologi-
cal description and diagnostic immunohistochemistry of 123 cases. J
Feline Med Surg 2001;3:235-245.
14. Henderson SM, Bradley K, Day MJ, et al. Investigation of nasal dis-
ease in the cata retrospective study of 77 cases. J Feline Med Surg
2004;6:245-257.
15. Evans SM, Hendrick M. Radiotherapy of feline nasal tumors. A ret-
rospective study of nine cases. Vet Radiol Ultrasound 1989;30:
128-132.
16. Theon AP, Peaston AE, Madewell BR, et al. Irradiation of nonlym-
phoproliferative neoplasms of the nasal cavity and paranasal sinuses
in 16 cats. J Am Vet Med Assoc 1994;204:78-83.
17. Fike JR, LeCouteur RA, Cann CE. Anatomy of the canine brain
using high resolution computed tomography. Vet Radiol
1981;22:236-243.
18. Glass EN, Kapatkin A, Vite C, et al. A modified bilateral transfrontal
approach to the canine frontal lobe and olfactory bulb: surgical tech-
nique and five cases. J Am Anim Hosp Assoc 2000;36:43-50.
19. Weisse C, Clifford CA, Holt D, et al. Percutaneous arterial emboliza-
tion and chemoembolization for treatment of benign and malignant
tumors in three dogs and a goat. J Am Vet Med Assoc
2002;221:1430-1436.
Cystic Nasal Adenocarcinoma in a Cat 351
10. Smith MO, Turrel JM, Bailey C, et al. Neurologic abnormalities as
the predominant signs of neoplasia of the nasal cavity in dogs and
cats: seven cases (1973-1986). J Am Vet Med Assoc 1989;195:
242-245.
11. Zaki F, Harris J, Budzilovich G. Cystic pituicytoma of the neurohy-
pophysis in a Siamese cat. J Comp Pathol 1975;85:467-471.
12. Schulman FY, Carpenter JL, Ribas JL, et al. Cystic papillary menin-
gioma in the sella turcica of a dog. J Am Vet Med Assoc
1992;200:67-69.
13. Bagley RS, Kornegay JN, Lane SB, et al. Cystic meningiomas in 2
dogs. J Vet Intern Med 1996;10:72-75.
14. Thomas WB, Wheeler SJ, Kramer R, et al. Magnetic resonance
imaging features of primary brain tumors in dogs. Vet Radiol
Ultrasound 1996;37:20-27.
15. Kraft SL, Gavin PR, DeHaan C, et al. Retrospective review of 50
canine intracranial tumors evaluated by magnetic resonance imaging.
J Vet Intern Med 1997;11:218-225.
16. Bagley RS, Silver GM, Gavin PR. Cerebellar cystic meningioma in a
dog. J Am Anim Hosp Assoc 2000;36:413-415.
17. Lipsitz D, Higgins RJ, Kortz GD, et al. Glioblastoma multiforme:
clinical findings, magnetic resonance imaging, and pathology in five
dogs. Vet Pathol 2003;40:659-669.
18. Troxel MT, Vite CH, Massicotte C, et al. Magnetic resonance imag-
ing features of feline intracranial neoplasia: retrospective analysis of
46 cats. J Vet Intern Med 2004;18:176-189.
19. Theon AP, VanVechten MK, Madewell BR. Intratumoral administra-
tion of carboplatin for treatment of squamous cell carcinomas of the
nasal plane in cats. Am J Vet Res 1996;57:205-210.
20. Straw RC, Withrow SJ, Gillette E, et al. Use of radiotherapy for the
treatment of intranasal tumors in cats: six cases (1980-1985). J Am
Vet Med Assoc 1986;189:927-929.
21. Moore A, Ogilvie G. Tumors of the respiratory tract. In: Ogilvie G,
Moore A, eds. Feline Oncology. A Comprehensive Guide to
Compassionate Care. Trenton NJ: Veterinary Learning Systems,
2001:368-384.
22. Knapp DW, Richardson RC, Bottoms GD, et al. Phase-I trial of
piroxicam in 62 dogs bearing naturally-occurring tumors. Cancer
Chemother Pharmacol 1992;29:214-218.
23. Knapp DW, Richardson RC, Chan TC, et al. Piroxicam therapy in 34
dogs with transitional cell carcinoma of the urinary bladder. J Vet
Intern Med 1994;8:273-278.
24. Boria PA, Murry DJ, Bennett PF, et al. Evaluation of cisplatin com-
bined with piroxicam for the treatment of oral malignant melanoma
and oral squamous cell carcinoma in dogs. J Am Vet Med Assoc
2004;224:388-394.
25. Langova V, Mutsaers AJ, Phillips B, et al. Treatment of eight dogs
with nasal tumours with alternating doses of doxorubicin and carbo-
platin in conjunction with oral piroxicam. Aust Vet J 2004:676-680.