Nasopharyngeal cryptococcosis

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................................................................................................................................ 6. Mair TS , Brown PJ. Clinical and pathological features of thoracic neoplasia in the horse. Equine Vet J 1993;25:220-223. 7. Meagher DM, Wheat JD, Tennant B. Osburn BI. Squamous cell carcinoma of the equine stomach. J Am Vet Med Assoc 1974;164:81-84. 8. MacFadden KE. Pace LW. Clinical manifestations of squamous cell carcinoma in horses. Compend Contin Ed fract Vet 1991;13:669-676.

9. Olsen SN. Squamous cell carcinoma of the equine stomach: a report of five cases. Vet Rec 1992; 13 1:170-173. 10. Wrigley RH, Gay CC. Lording P, Haywood RN. Pleural effusion associated with squamous cell carcinoma of the stomach of a horse. Equine VetJ 1981;13:99-102. 1 1. Sweeney CR. Gilette DM. Thoracic neoplasia in equids: 35 cases (1967-1987). J Am Vet

Med Assoc 1989;195:374-377. 12. Zicker SC, Wilson WD, Medearis I. Differentiation between intra-abdominal neoplasms and abscesses in horses, using clinical and laboratory data: 40 cases (1973-1988). J Am Vet MedAssoc 1990;196:1130-1135. 13. Garma-Avina A. The cytology of squamous cell carcinomas in domestic animals. J Vet Diagn lnvest 1994;6:238-246. (Acceptedfor publicmion I0 jariunry 1997)

Nasopharyngeal cryptococcosis R MALIK2, P MARTINb, DI WIGNEyb, DB CHURCH', W BRADLEY', C R BELLENGER', WA LAMBd, VR BARRS3, S FOSTER', S HEMSLEyb, PJ CANFIELDb and D N LOVE" Naturally occurring cryptococcosis in five cats, a dog and a koala is described. Involvement of the nasopharynx was documented in all patients, and nasopharyngeal mass lesions accounted for the major presenting complaints in four. Signs referable to nasopharyngeal disease included snoring, stertor, inspiratory dyspnoea and aerophagia. Diagnoses were made by caudal rhinoscopy using a retroverted flexible endoscope, vigorous orthograde flushing with saline, or at necropsy. Concurrent cryptococcal rhinitis was present in all cases, although involvement appeared limited to the caudal nasal cavity in most cases. Typical signs of nasal cavity disease, such as sneezing and nasal discharge, were often absent. Treatment of nasopharyngeal cryptococcosis should include physical dislodgement or debulking of lesion(s) to provide immediate alleviation of upper airway obstruction, followed by systemic antifungal therapy to eliminate residual infection from the nasal cavity. Infections caused by Cryptococcus neoformans var gattii accounted for a disproportionately large number of these cases. Aust Vet J 1997; 75483-488 Key words: Cryptococcus neoformans. cryptococcosis, nasopharynx. dog, cat, koala.

DSH MIC LCAT

M

Domestic short-haired cat Minimum inhibitory concentration Latex cryptococcal antigen agglutination test

'ycotic rhinitis is usually a prominent feature of crypto.coccosis in the cat,'-3 d o g 4 horse,' goat6 and koala,' the animal species in which this mycosis has been best characterised. Accordingly, it is generally considered that naturally occurring cryptococcosis in animals begins as an upper respiratory tract infection.'-8 This is in contrast to the situation in people, in which nasal cavity involvement is believed to be extremely uncommon'1-" and the lung is considered the primary site from which infection disseminates. I? Physical manifestations of cryptococcal rhinitis in animals are often conspicuous. Typically there is sneezing and nasal discharge. Often there is thickening and inflammation of the visible nasal mucosa or protrusion of granulomatous tissue through one or

IV PO

SC

Intravenously Orally Subcutaneously

both nostrils. Infection may penetrate bones overlying the nasal cavity, causing swelling of subcutaneous tissues of the bridge or side of the nose.'-' The involvement of rostra1 structures within the nasal cavity facilitates diagnosis of infection because easily accessible tissues are available for cytology, histology and c ~ l t u r e . ' ~ ' ~ Less commonly, cryptococcal rhinitis arises more caudally within the nasal cavity, in which case signs of nasopharyngeal disease (stertor, inspiratory dyspnoea and upper airway o b s t r ~ c t i o n ) ' ~ may predominate, with signs typical of rhinitis (sneezing and nasal discharge) being subtle or a b ~ e n t In . ~ some cases caudal nasal cavity involvement may remain occult until infection spreads to the brain or skin, or penetrates overlying bones to involve the orbit or nasal bridge.' 4.x

This report presents a series of cases in which cryptococcal rhinitis involved the caudal nasal cavity predominantly, and emphasises how clinical signs and diagnostic investigation may differ in cases with nasopharyngeal mass lesions. Case reports Case I A 3-year-old spayed DSH cat (4.3 kg) was referred because of a 'raspy' respiratory noise, which had been evident for 4 months and allegedly started suddenly after eating raw fish. T h e referring clinicians had been unable to diagnose the problem, despite inspection of the larynx and pharynx under general anaesthesia and radiographic examination of the nasal cavity. T h e cat failed to improve following treatment with antimicrobial drugs.

aDepartment of Veterinary Clinical Sciences, The University of Sydney, New South Wales 2006 bDepartment of Veterinary Pathology and Bacteriology, The University of Sydney, New South Wales 2006 CKu-ring-gaiVeterinary Hospital, Curagul Road, Turramurra North, New South Wales 2074 dPO Box 307, North Ryde, New South Wales 21 13

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Figure 1. A cat (case 1) positioned for nasopharyngeal investigation. Careful positioning of the cat in dorsal recumbency, fixation of the top jaw to the table top, retraction of the tongue using a Babcock tissue forceps and deflection of the endotracheal tube to one side facilitates systematic examination of the nasopharynx.

lnspiratory stridor was audible, emanating from the upper airways. T h e mandibular lymph nodes were enlarged, especially on the left. No other abnormalities were detected on physical examination. Disease of the caudal nasal cavity or nasopharynx was suspected, with a nasopharyngeal polyp considered likely. Anaesthesia was induced using IV ketamine (20 mg), midazolam (1 mg) and atropine (0.12 mg) and maintained using halothane in nitrous oxide and oxygen. T h e cat was positioned in dorsal recumbency with a cuffed endotracheal tube deflected to the side and the tongue retracted using a Babcock tissue forceps (Figure 1). No laryngeal o r pharyngeal lesions were evident, and rostral (anterior) rhinoscopy performed using an arthroscope" was unremarkable. Caudal (posterior) rhinoscopy was impossible because the available

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flexible videoendoscope was too large to be inserted retroflexed. The caudal nasopharynx was examined by retracting the soft palate rostrally using a spay hook, but no lesions were detected. A urinary catheter ( 3 French) could be passed without obstruction into the pharynx through the ventral nasal meatus on each side. When the left nasal cavity was flushed vigorously using 10 mL aliquots of sterile saline a mass was displaced and appeared as a swelling palpable through the soft palate. T h e mass, which was white and approximately 13 m m long was massaged caudally, removed (Figure 2) and submitted to the laboratory. Amoxycillin-clavulanate was adniinistered SC prophy-lactically. Stridor was much reduced after recovery from the anaesthesia, but some inspiratory noise persisted, suggesting concurrent mycotic rhinitis or residual mass. Cytology o f squash preparations of the lesion revealed numerous macrophages and neutrophils, scattered eosinophils, lymphocytes and plasma cells, and abundant spherical capsulate yeasts (Figure 3). T h e Cryptococcus neofrrnans var neofrrnans strain culturedl3,'"was sensitive to fluconazole (E-test MIC 0.047 mg/L). The mass was a cryptococcal granuloma, consisting of yeasts surrounded by a pyogranulomatous inflammatory response. Its surface was lined by ciliated columnar respiratory epithelium

Figure 2. Polypoid nasopharyngeal cryptococcoma removed from the cat (case 1). The lesion was first dlslodged from the nasopharynx by orthograde flushing, and subsequently massaged into the oral cavity by digital manipulation through the soft palate.

Figure 3. A squash preparation from the cryptococcoma shown in Figure 2. Several yeasts are present within the cytoplasm of a macrophage (on the right) adjacent to two columnar respiratory epithelial cells (on the left). Diff Quik. x 330.

(Figure 4). Presumably the granuloma had been attached to the mucosa of the caudal nasal cavity or rostral nasopharynx and was dislodged during the flushing process. The cat was treated with fluconazole (50 mg PO every 8 h for 6 months)!,'- to clear residual fungal infection from the caudal nasal cavity. Cure was suggested by resolution o f clinical signs and decline in the LCAT titre'" from 8192 (after removal o f the granuloma but before antifungal treatment) to 64 (after 5 months). Case 2

A spayed DSH cat (4.5 kg), about 3 years of age, was presented to Kuring-gai Veterinary Hospital for 'noisy breathing, which developed shortly after the cat stayed in a cattery. An inspiratory stridor and 'throaty rattle' were evident on physical examination. No significant lesions were noted in the larynx or pharynx under general anaesthesia. Radiographs of the chest were unremarkable, but skull radiographs demonstrated a soft tissue mass in the nasopharynx. Contrast rhinography did not define the lesion, but subsequent flushing dislodged a 1 cm dianieter soft tissue mass into the pharynx. Histologically, the lesion consisted o f solid sheets of yeasts, vacuolated macrophages, small amounts of fibrous tissue and perivascular accumulations of lymphocytes and plasma cells. Stridulous respiration persisted and the cat was referred for further treatment. Many budding, capsulate yeasts were observed in deep nasal washings, while sparse numbers o f yeasts were visible in

................................................................................................................................

Figure 4. Histological sections of the cryptococcoma from a cat (case 1). Yeasts, discernable because of their prominent capsule, are present in the upper lefl of the photomicrograph surrounded by pyogranulomatous inflammation. Note that the mass is covered by columnar respiratory epithelium. Haematoxylin and eosin, x 66.

smears made from pharyngeal and superficial rostral nasal swabs. A moderate to heavy growth of C neofrmans var gattii'3,16 was cultured from deep nasal washings and pharyngeal swabs, while fewer colonies grew from superficial rostral nasal swabs. T h e strain was resistant to fluconazole in vitro (E-test M I C > 32 mg/L) but susceptible to ketoconazole (disc diffusion method)' and the initial LCAT titre (determined retrospectively using stored serum) was 1024. Despite the susceptibility data, the cat was treated with fluconazole (50 mg PO every 12 h for 3 months), and subsequently with ketoconazole (50 mg PO every 12 h for 3 weeks, then daily for 5 months), and made a complete clinical recovery. Two years later, caudal nasal and nasopharyngeal cryptococcosis recurred. After dislodgement of the cryptococcoma the cat was treated with fluconazole (50 mg PO every 12 h for 6 months) then ketoconazole (50 mg PO daily for 18 months), and appeared cured, based on resolution of signs and decline of the LCAT titre to 8.

Cate 3 A 7-year-old castrated DSH cat (5.5 kg) was presented for loss of voice, inspiratory noise and reluctance to eat over a 2- to 3-week period during which it lost 0.5 kg in weight. Immediately before this the cat had been 'a bit snumy'. T h e cat was now refusing solid

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food, but could lap and swallow liquids. T h e referring clinician detected mild inspiratory dyspnoea with flaring of nostrils and exaggerated respiratory effort. T h e examination of the oral cavity revealed a mass that displaced the soft palate ventrally o n the right (Figure 5 ) . A neoplasm was suspected and the cat referred for diagnosis and treatment. T h e cat was sedated with ketamine (1 1 mg) and diazepam (1 mg), both SC, anaesthetised with propofol (30 mg IV), intubated and the anaesthesia maintained using halothane in nitrous oxide and oxygen. A fine needle aspirate of the lesion demonstrated numerous lymphoid cells, many large highly vacuolated macrophages, scattered neutrophils and moderate numbers of capsulated spherical yeasts. A moderate growth of C neofrmans var gattii was cultured, sensitive to fluconazole (Etest M I C 3 mg/L) and itraconazole (Etest M I C 0.047 mg/L).

Figure 5. Nasopharyngeal cryptococcoma causing ventral displacement of the right side of the sofl palate of a cat (case 3). The cat has been positioned in ventral recumbency with the upper canine teeth secured by tape to facilitate intra-oral photography.

T h e cat was positioned in dorsal recumbency with the mouth taped open, and a gag inserted. The soft palate was incised using diathermy, and the granuloma dorsal to it was debulked as much as possible. The dorsal extent of the lesion was curetted and lavaged with saline. T h e soft palate was closed in two layers using 2-0 polydioxanone. T h e cat was given fluconazole (200 mg IV) intraoperatively, and subsequently treated with itraconazole (100 mg PO daily with food)."' T h e cat's breathing and ability to eat improved immediately after surgery. Two weeks later there was still some swelling at the operative site. The dose of itraconazole was increased to 150 mg every 24 h, because C neofrmans var gattii infections tend to be refractory to rreatmenf.L.".?".?l This higher dose was well tolerated, and the LCAT titre fell from 4096 (before treatment) to 128 after 3 months. Itraconazole was continued at a lower dose (100 mg every 24 h) for 1 month and then changed to the less expensive ketoconazole (50 mg every 24 h), which was given for a further 3 months. T h e cat remains well 2 years after presentation.

Case 4 A 10-year-old castrated DSH cat (8.0 kg) was presented with a 4-week history of snoring and inappetence. A marked inspiratory stridor was detected and the cat referred to a specialist (WAL) for endoscopy. A rostral nasopharyngeal mass discovered during endoscopic evaluation of the respiratory tract was removed incompletely using artery forceps. T h e character of the cat's respiratory pattern improved, although some stridor persisted. Histologically, the mass consisted of budding capsulate yeasts surrounded by pyogranulomatous inflammation. Cytology of swabs from the rostral nasal cavity showed respiratory epithelial cells, scattered neutrophils and occasional spherical capsulate narrow necked budding yeasts. A light growth of C neofrmans var neofrmans susceptible to itraconazole (E-test M I C 0.064 mg/L) was cultured. The cat was treated successfully, with resolution of clinical signs and decline in the LCAT titre from 16 to 1 following 10 weeks of itraconazole (100 mg PO daily). T h e cat had no signs of cryptococcosis 3 months later. 485

................................................................................................................................ Case 5

A 6-year-old castrated Himalayan cat (4.2 kg) was presented for snuffling, stridor and coughing which progressed despite treatment with antibacterial drugs, a mucolytic and corticosteroids. The cat subsequently developed ataxia and vertical nystagmus, and was referred for evaluation 4 weeks after initial presentation. Physical examination revealed a cachectic cat with bilateral serous nasal discharge, increased upper airway sounds and inspiratory and expiratory dyspnoea. The cat was sedated with ketamine (15 mg SC), anaesthetised with propofol ( I 6 mg IV), and the anaesthesia was maintained using halothane in oxygen. Radiographs of the skull demonstrated loss of aeration of the left nasal cavity and frontal sinus; chest radiographs were unremarkable. Nasal swabs were obtained and material was collected with forceps from a nasopharyngeal mass seen when the soft palate was retracted using a spay hook. Cytological tests demonstrated mucus, numerous vacuolated macrophages, scattered neutrophils, large numbers of capsulated yeasts and ciliated columnar epithelial cells. C neofrmans var gattii sensitive to itraconazole (E-strip M I C 0.047 mg/L) was cultured. The cat deteriorated subsequently and, despite treatment with itraconazole (100 mg every 24 h), continued to have respiratory distress and neurological dysfunction. It died 2

Figure 6. Endoscopic appearance of nasopharyngeal cryptococcosis in the dog (case 6), after biopsy. The image Is oriented with the soft palate at the bottom of the photograph. Cryptococcomas partially obstruct both choanae. Note the haemorrhage and gelatlnous exudate. The latter is characteristlc of cryptococcal infection, reflecting the abundant polysaccharide capsular material present.

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days later after an acute episode which could have been either a respiratory arrest or a seizure. Necropsy revealed cryptococcal rhinitis and a large cryptococcal granuloma obstructing the nasopharynx. T h e cryptococcoma could be readily separated from the nasopharynx by blunt dissection. It had occluded the opening of the right auditory tube and the ipsilateral osseous bulla was filled with serous fluid. Histological examination revealed pyogranulomatous cryptococcal rhinitis, with similar changes in the mass, and severe cryptococcal meningitis. T h e neurological signs were believed to have resulted from a combination of accumulation of fluid in the right middle ear cavity and the cryptococcal meningitis, and death was attributed to a seizure complicated by unrelieved obstruction of the nasopharynx. Case 6

An 18-month-old spayed Boxer dog

(23 kg) was referred because of chronic unilateral nasal discharge. T h e dog resided alternately in suburban and rural environments. It had been presented to a country practitioner 6 weeks earlier because of left-sided mucopurulent nasal discharge. This improved transiently during treatment with a tetracycline. T h e problem recurred 2 to 3 weeks before admission, and blood was then noted in the nasal exudate. T h e dog was otherwise well, though the nasal discharge was becoming more p r o f k e and accompanied by sneezing. A grass awn foreign body was suspected and the dog referred for rhinoscopy. Left-sided nasal discharge was confirmed on physical examination, but apart from mild left mandibular lymphadenomegaly there were no other significant findings. T h e diagnoses considered included nasal foreign body, mycotic rhinitis and sinonasal neoplasia. After sedation with morphine (1 1 mg SC), anaesthesia was induced with thiopentone (90 mg) and maintained using halothane in nitrous oxide and oxygen. Left rostral rhinoscopy using an arthroscope did not reveal discrete lesions, although the mucosa was hyperaemic. Caudal rhinoscopy using a retroverted flexible videoendoscope" revealed a mass obstructing the left choana and a smaller mass in the right

Figure 7. White translucent gelatinous mass protruding below the hard palate (corrugated) and obstructing the nasopharynx of the koala (case 7) at necropsy. The mass was easily dislodged by traction.

choana (Figure 6). T h e mass on the left oozed gelatinous material after it had been penetrated by the biopsy forceps. This material and deep nasal flushes were submitted for laboratory analysis. Cytological examination demonstrated numerous epithelial cells, moderate numbers of neutrophils, vacuolated macrophages and eosinophils, much mucoid material and scattered spherical yeasts with large capsules. A moderately heavy growth of C neoformtlns var gattii susceptible to amphotericin B (Etest M I C 0.25 mg/L) was cultured. T h e dog was treated using amphotericin B (1 1.5 mg in 700 mL 4% glucose and 0.18% NaCl S C twice a week).?" Despite this, the LCAT titre increased from 16 to 64 after 6 weeks of treatment. T h e dog developed neck pain and signs of vestibular dysfunction 13 weeks after commencing treatment and was euthanased.

Case 7 An 8-year-old female koala (6.7 kg) at Taronga Zoo was observed to have dyspnoea and wheezy respiration. It was treated with dexamethasone and improved transiently before deteriorating. Cryptococcal rhinitis was diagnosed on finding budding capsulate yeasts in samples of mucopurulent nasal discharge. T h e animal received two 100 mg doses of fluconazole IV, and one dose of amphotericin B ( 4 mg in 400 mL 0.45% NaCl and 2.5% dextrose SC), but succumbed. At necropsy, the stomach and small intestines were massively dilated with gas and fluid, and pulmonary emphy-

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................................................................................................................................ sema and congestion were present. A soft translucent white gelatinous mass completely obstructed the nasopharynx (Figure 7). This mass was easily dislodged by traction and histologically was composed almost entirely of masses of capsulate yeasts. The diagnosis was cryptococcal rhinitis and nasopharyngeal mass, causing upper airway obstruction, aerophagia, gastric dilatation and death. C neoformans var gattii was cultured from the nasopharyngeal lesion.

Discussion ‘Classical’clinical features of cryptococcal rhinitis in the cat, dog, horse, goat and koala include nasal discharge and sneezing, often accompanied by mandibular lymph node enlargement, a proliferative lesion within the nostril($ and/or involvement of the subcutaneous tissues of the bridge or side of the nose, or the orbit.‘-H There is one report of a so called ‘atypical’ presentation of upper respiratory tract cryptococcosis in a cat that neither sneezed nor had nasal discharge, and in which a large ‘pseudomembranous mucoid membrane’ was expelled from the left nasal cavity during a diagnostic nasal flush.14 From this series of seven cases, it would seem that nasopharyngeal cryptococcosis may be more common than appreciated to date, perhaps because the nasopharynx is often neglected in clinical and necropsy investigations. The need for caudal rhinoscopy as an investigative procedure is suggested by physical findings such as snoring and snorting, and when signs are relieved by opening the mouth. Rhinoscopy should be considered also when upper respiratory tract noise is unexplained. Caudal rhinoscopy can be performed using a retroverted flexible endoscope, or using a heated dental mirror after retracting the soft palate using a spay hook. When the index of suspicion for nasopharyngeal disease is particularly high, access can also be justified through a midline incision through the soft palate. Vigorous orthograde flushing through each nostril, in turn, or passage of lubricated urinary catheters through the ventral nasal meatus may achieve the same end less invasively. A recent retrospective study of cryp-

tococcosis in dogs4 suggested preferential involvement of the caudal nasal cavity based on incomplete radiological data, and proposed that infections there may have been overlooked in dogs reported as having primary cryptococcal meningoencephalitis. Estimation of the prevalence of nasopharyngeal involvement in veterinary patients with cryptococcal rhinitis would require a systematic study of new cases to determine the proportion of those with straightforward (rostral) cryptococcal rhinitis and meningoencephalitis that have concurrent disease of the nasopharynx . There was some variation in the physical and histological structure of the nasopharyngeal masses, although in all patients the masses were clearly associated with cryptococcal rhinitis involving caudal nasal structures. In the koala, the mass consisted almost exclusively of aggregated fungal organisms loosely attached to the wall of the nasopharynx. However, in most other cases the mass was a cryptococcal granuloma, composed of organisms and inflammatory tissue. The degree of attachment of cryptococcomas to the caudal nasal cavity varied: they could sometimes be easily displaced by gentle (case 2) to vigorous (case 1 ) flushing, but others had invaded and become contiguous with the soft palate (case 3). If possible, treatment of nasopharyngeal cryptococcosis should include physical dislodgement or debulking of lesions to alleviate the upper airway obstruction and decrease residual infected tissue to be treated medically.15 T h e potential danger of complete upper airway obstruction in patients with nasopharyngeal cryptococcosis should not be underestimated, as some individuals and species are not readily able to convert to open mouth breathing. Structural obstruction of the upper airways contributed to the death of the koala and possibly one cat (case 5) in our series. We are aware of another similar infection in a koala (J McKee personal communication), and have seen similar signs in experimental cryptom ccosis in rats (CMen and R Malik, unpub lished observations). Tropism of C me j m m b r the nasal cavity has been reported in some experimental studies using laboratory rodent^.^*-*^

Variety gattii infections are over represented among this series of cases with nasopharyngeal cryptococcosis, accounting for 71% (five of seven) animals as compared to 28% of the 119 naturally occurring cases of cryptococcosis in cats (97 cases), dogs (19) and koalas (3) from which we have isolated C neofmans over the last 8 years (5/7 vs 33/112, P = 0.03; two-tailed Fischer‘s Exact test; R Malik, DI Wigney, P Martin, and DN Love, unpublished observations). The significance of this finding is not clear, although most infections in koalas are of this biotype’ presumably because of this species’ association with host eucalyptus trees.25.26If the data from koalas is excluded, the over representation of var gattii infections becomes marginal ( 4 / 6 vs 31/110; P = 0.07). The third case in this series emphasises the need to obtain a tissue diagnosis in cases with tumour-like lesions. The gross appearance of the lesion suggested a caudal nasal malignancy invading the soft palate, and a poorer prognosis may have been given had not appropriate samples been taken for cytological examination. Misdiagnosis has proved to be a problem in cryptococcal infections situated in other ‘atypical’ sites. For example a dog with cryptococcal gastritis was euthanased because endoscopic lesions strongly suggested gastric ~arcinoma.~’ Finally, this case series adds cryptococcosis to the list of disease conditions that can give rise to nasopharyngeal disease in cats and dogs. The causes of nasopharyngeal disease in small animals include nasopharyngeal polyps” (which tend to be situated more caudally), nasopharyngeal stenosis,2’cystic Rathke’s pouch,jOtenacious mucus (R Malik unpublished observations), foreign bodies (typically vomited up into the nasopharynx) including bones, tablets and blades of grass,.” and a variety of tumours (osteosarcoma, chondrosarcoma, lymphosarcoma). Computed tomography and magnetic resonance imaging have become methods of choice for viewing nasopharyngeal lesions in human patients,j2 although they have so far not been widely used for this purpose in veterinary practice.

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................................................................................................................................ Acknowledgments The senior author acknowledges partial funding from the Valentine Charlton Bequest through the Postgraduate Foundation of Veterinary Science of The University of Sydney. Fluconazole was generously donated by Pfizer Australia. Biotyping and susceptibility testing was done by D Muir and DJ Gregory at the Australian Reference Laboratory in Medical Mycology at Royal North Shore Hospital.

References 1. Medleau L, Barsanti J. Cryptococcosis. In: Greene CE, editor. lnfectious diseases ofthe dog and cat. Saunders, Philadelphia, 1990:687-695. 2. Malik R. Wigney DI, Muir DB et al. Cryptococcosis in cats: clinical and mycological assessment of 29 cases and evaluation of treatment using orally administered fluconazole. J Med Vet Mycol 1992;30:133-144. 3. Wilkinson GT. Feline cryptococcosis: a review and seven case reports. J Small Animal Pract 1979;20:749-768. 4. Malik R, Dill-Macky E, Martin P et al. Cryptococcosis in dogs: a retrospective study of 20 consecutive cases. J Med Vet Mycol 1995;33:291-297. 5. Roberts MC, Sutton RH, Lovell DK. A protracted case of cryptococcal nasal granuloma in a stallion. Aust Vet J 1981;57:287-291. 6. Chapman HM. Robinson WF, Bolton JR, Robertson JP. Cryptococcus neoformans infection in goats. Aust VetJ 1990;67:263-265. 7. Spencer A, Ley C, Canfield PJ et al. Meningoencephalitis in a koala (Phascolarctos cinereus) due to Cryptococcus neoformans var gaffii infection. J Zoo Wildlife Med 1993;24:519522.

8 . Malik R, Wigney DI, Martin P et al. Veterinary aspects of cryptococcosis. 2nd lnternational Conference on Cryptococccus and Cryptococcosis: Programme and Abstracts L29, 1993:74. 9. Briggs DR, Barney PL, Bahu RM. Nasal cryptococcosis. Arch Otolaryngol1974;100:390-392. 10. Norris JC. Armstrong WB. Membranous cryptococcic nasopharyngitis (Cryptococcus neoformans) Arch Otolaryngol 1954;60:720-722. 11. Jones EL. Torula infection of the nasopharynx. South Med J 1927;20:120-126. 12. Diamond RD. Cryptococcus neoformans. In: Mandell GL. Douglas RG, Bennett JE, editors. Principles and practice of infectious diseases. 3rd edn. Churchill Livingstone. New York, 1990:1980-1989. 13. Dimech WJ. Diagnosis, identification and epidemiology of Cryptococcus neoformans infection. Aust J Med Lab Sci 1990;12:13-21. 14. Wiltnich C, Duder C, Belanger M, Renlund R. An atypical presentation of upper respiratory tract cryptococcosis in a cat. Can Vet J 1992;33:185-187. 15. McCarthy TC, McDermain SL. Rhinoscopy. Vet Clin N Am Small Anim Pract 1990;20:12651290. 16. Kwon-Chung KJ. Polacheck I, Bennett JE. Improved diagnostic medium for separation of Cryptococcus neoformans var neoformans (serotypes A & D) and Cryptococcus neoformans var gaffii (serotypes B & C). J Clin Microbiol 1982;15:535-537. 17. Craig AC, Ramzan I, Malik R. Pharmacokinetics of intravenous and oral fluconazole in cats. Res Vet Sci 1994;57:372-376. 18. Malik R, McPetrie R, Wigney DI, Love DN. A latex antigen agglutination test for diagnosis and monitoring of therapy for cryptococcosis. Aust Vet J 1996;74:358-364. 19. Medleau L, Jacobs GJ, Marks MA. ltraconazole for the treatment of cryplococcosis in cats. J Vet Int Med 1995;9:39-42. 20. Malik R , Craig AJ, Martin P et al. Combination chemotherapy of cryptococcosis

using subcutaneously administered amphotericin B. Aust Vet J 1996;73:124-128. 21. Malik R, Martin P, Wigney DI, Love DN. Diagnosis and treatment of cryptococcosis in cats. In: Feline practice. University of Sydney Post Graduate Committee in Veterinary Science, Proceedings 1995;(243):49-54. 22. Dixon DM. Polak A. In vivo and in vitro studies with an atypical rhinotropic isolate of Cryptococcus neoformans. Mycopathologia 1986;96:33-40. 23. Kuttin ES, Feldman M, Nyska A et al. Cryptococcosis of the nasopharynx in mice and rats. Mycopathologia 1988;101:99-104. 24. Bodenhoff J. Chronic cryptococcosis in the mouse. Acta Path Microbiol Scand 1969;75:169176. 25. Ellis DH. Pfeiffer TJ. Natural habitat of Cryptococcus neoformans var. gaffii. J Clin Microbiol 1990;228:1642-1644. 26. Ellis DH, Pfeiffer TJ. Ecology, life cycle and infectious propagule of Cryptococcus neoformans. Lancet 1990;336:923-925. 27. van der Gaag I, van Niel HF, Belshaw BE, Wolvekamp WTC. Gastric granulomatous cryptococcosis mimicking gastric carcinoma in a dog. Vet Quarterly 1991;13:185-190. 28. Lane JG, Orr CM. Lucke VM. Gruffyd-Jones TJ. Nasopharyngeal polyps arising from the middle ear of the cat. J Small Anim Pract 1981;22:511-22. 29. Mitten RW. Nasopharyngeal stenosis in four cats. J Small Anim Pract 1988;29:341-345. 30. Slatter DH. Surgical correction of cystic Rathke's cleft in a dog. J Am Anim Hosp Assoc 1976;12:641-643. 31. Riley P. Nasopharyngeal grass foreign body in eight cats. J Am Vet Med Assoc 1993;202:299-300. 32. Ruprecht A, Dolan KD. The nasopharynx in oral and maxillofacial radiology. Oral Surg Oral Med Oral Pathol1991;72:484-491. (Accepted,firpublication 4 Mm.h 1997)

Squamous cell carcinoma of the lung in a dog Y AYDIN3a N TOPLUa and Z ALKANb Departments of Patholo&'

A

and Radiolo$,

lthough metastatic tumours of the lung are relatively common, rimary lung tumours are rare in domestic animals.',? Reported incidence for the dog is approximately 4 to 5 per 100,000 animals in the population per year.! The frequency based on necropsy findings varies with the population sampled, but as many as 1 Yo of dogs necropsied have been recorded as having primary lung tumours.ZThere are only a few comprehensive papers on primary lung tumours in dogs, and they indicate that squamous cell carcinoma is This rarity is in marked contrast to the high frequency in man and, therefore, this type of tumour is less well defined in dogs and other domestic specie^.'^?^^ 488

Faculty of Veterinary Medicine, Ankara University, 061 10, Diskapi, Ankara, Turkey In Europe and North America, lung carcinoma occurs in approximately 0.5% of dogs that die from all causes and are examined at necropsy. T h e overall frequency of lung tumours among dogs examined at necropsy in various veterinary facilities throughout the world from 1928 to 1984 was 1.24%.' During subsequent years this prevalence has changed very little. T h e most common primary tumour of the canine lung is adenocarcinoma, which accounts for about three quarters of all such t u m o u r ~Squamous .~ cell carcinomas are occasionally found. Affected animals are usually middle aged or older (average age 10 years) and the

disease is rare in those younger than 7 year^.^,^ There are no sex or definite breed predispositions, although a higher incidence has been reported in Boxer and Beagle Cough and changes in breathing pattern signs that occur late in the course of disease. Radiographic findings provide the most reliable clinical evidence of primary tumour of the lung in the intact Confirmatory findings may be obtained by diagnostic procedures such as cytological examination of fine needle aspirates and transtracheal washes, surgical biopsy, bronchoscopic biopsy and closed core biopsy. T h e purpose of this study is to describe gross and histopathologic Aust Vet/ Vol 75, NO 7, July 1997

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