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Gastric granulomatous cryptococcosis mimicking gastric carcinoma in a dog a

a

Ingrid van der Gaag , Marijke H.F. van Niel , B.E. b

Belshaw & W.Th.C. Wolvekamp

c

a

Institute of Veterinary Pathology , State University Utrecht , The Netherlands b

Clinic for Companion Animals , State University Utrecht , The Netherlands c

Department of Radiology , State University Utrecht , The Netherlands Published online: 01 Nov 2011.

To cite this article: Ingrid van der Gaag , Marijke H.F. van Niel , B.E. Belshaw & W.Th.C. Wolvekamp (1991) Gastric granulomatous cryptococcosis mimicking gastric carcinoma in a dog, Veterinary Quarterly, 13:4, 185-190, DOI: 10.1080/01652176.1991.9694307 To link to this article: http://dx.doi.org/10.1080/01652176.1991.9694307

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ORIGINAL PAPERS

Gastric granulomatous cryptococcosis mimicking gastric carcinoma in a dog Ingrid van der Gaagi, Marijke H.F.van Niel', B.E.Belshaw2, and W.Th.C.Wolvekamp3 SUMMARY. An ulcerated lesion resembling a tumour in the lesser curvature of the stomach

of a 3-year-old male Dobermann pinscher was found to be caused by Cryptococcus neoformans. The dog had been vomiting for two months and had slight leucocytosis and anaemia. Biopsies of the ulcerated lesion revealed granulomatous inflammation and many cryptococci, which were particularly prominent in PAS and mucicarmine stained sections. No

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other lesions were found at necropsy. INTRODUCTION

Cryptococcosis, Torulosis or European Blastomycosis is a subacute or chronic mycotic infection of man and animals. The disease has been reported in all parts of the world. In the United States it has been described in horses, cattle, sheep, goats, a pig, dogs, cats, foxes, minks, ferrets, koala bears, cheetahs, a civet cat, guinea pigs, monkeys and man (7) The organ systems most often affected by Cryptococcus in dogs are the central nervous system, the eyes and the respiratory system. The skin or subcutis is involved in approximately 25% of infected dogs (2, 7).

Clinical findings reported in 22 dogs with cryptococcosis included neurologic abnormalities, signs of ocular disease, anorexia or emaciation, skin lesions, fever, (39.4 to 40.5 C), peripheral lymphadenopathy, dry cough, vomiting, lytic bone lesions and nasal discharge (2). In this paper we present a 3-year-old male Dobermann pinscher with a tumourlike lesion in the stomach caused by Cryptococcus neoformans. A single cryptococcal lesion at this site has not previously been described. MATERIAL AND METHODS

Case Report

A three-year-old male Dobermann pinscher was referred to the Clinic for Companion Animals of the State University of Utrecht, with a history of vomiting every morning for the preceding two months. The dog had been treated with metoclopramide, sulphachlorpyrazine, ampicillin and cimetidine, but with no consistent improvement. The vomitus was described as containing bile and blood, and by the time of this examination the dog was refusing food. There had been no diarrhoea, nor any other notable clinical sign. There were no remarkable physical abnormalities except for a loss of weight (approximately

10 kg) and a slight elevation of rectal temperature (39.9° C). Plain radiographs of the epigastrium and mesogastrium revealed no abnormalities in the shape or size of the liver or stomach and no evidence of a gastric foreign body. Laboratory studies revealed a low packed cell volume (0.26 1/1), hypochromia, neutrophilia (18.1x109/1) with no left shift, and a decrease in serum albumin (21 g/l) together with an increase in beta globulin (27 g/l). I

Institute of Veterinary Pathology, 2 Clinic for Companion Animals and 3 Department of Radiology, State University Utrecht. The Netherlands. Requests reprints from Ingrid van der Gaag DVM,PhD, Institute of Veterinary Pathology, Faculty

of Veterinary Medicine, State University Utrecht, Yalelaan I, Postbus 80.158, 3508 TD, The Netherlands. THE VETERINARY QUARTERLY, VOL.

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Symptomatic treatment was prescribed for an additional two weeks (metoclopramide, bismuth subnitrate and small meals of soft food) but the dog continued to vomit, sometimes

more than once daily, and refused all solid food. There was occasionally blood in the vomitus. Gastroscopy performed with a fiberscope (Fujinon C0L-MP2) (9) revealed an ulcer along

the lesser curvature of the stomach, slightly proximal to the angulus. The ulcer was estimated to be about 1.5 cm in diameter and was surrounded by a raised rim of mucosa. The wall of the stomach was rigid over a large area surrounding the ulcer, as was the angulus

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and the wall of the lesser curvature of the pyloric antrum. The tip of the fiberscope could not be turned around the angulus to enter the antrum, nor could the antrum be insufflated sufficiently for examination. Five biopsies from the ulcer and six from the surrounding area were obtained via the fiberscope with standard endoscopic biopsy forceps and were fixed in Baker's fixative (13). The ulceration and the rigidity of the adjacent stomach wall were considered to be highly suggestive of gastric carcinoma, notwithstanding the dog's age. The owner's consent was obtained for euthanasia directly following gastroscopy. Necropsy was performed on the following day and tissues were fixed in neutral buffered 10% formalin. Biopsy and necropsy specimens were embedded in paraffin and sections were

cutt (6pm thick) and stained with haematoxylin and eosin (H&E), van Gieson, periodic acid-Schiff (PAS) and mucicarmine. Transmission electron microscopy was performed on 400A sections from formalin-fixed gastric biopsies. Unexpected microscopic findings, described below, led to a more detailed review of the

dog's history. When the dog was about 7 months old it required treatment for severe demodicosis. A few months later, due to an accident, it developed an abscess on the thorax.

The abscess was drained but did not heal and after excision the healing of the surgical wound was also prolonged and complicated by infection. It is of additional interest that the owner's hobby is breeding and raising tropical birds, that the dog usually accompanied the owner while he cared for the birds, and that a neighbour keeps pigeons. PATHOLOGICAL FINDINGS

At necropsy the mucous membranes were pale and black faeces stained the perineum. The lungs were oedematous and a few small nodules, less than 0.5 cm

in diameter, were found at the edge of one lobe. Examination of the stomach revealed the large tumour-like mass observed by endoscopy. It was located along

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186

THE VETERINARY QUARTERLY, VOL.

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the lesser curvature, partly in the corpus area partly in the pyloric antrum, together with an ulcer (6 cm in diameter). The wall of the stomach was thickened, white and firm. The regional lymph nodes were enlarged and contained gelatinous foci. The mesentery near the pancreas had an irregular surface. There were no lesions in the liver, kidneys, pancreas, adrenal glands, intestines, heart or brain. Histological examination of necropsy samples of the stomach revealed thickening

of the wall due to granulomatous inflammation, with many ovoid or spherical yeast-like bodies surrounded by a large, unstained space. The biopsy specimens

from the ulcer revealed fibrinous exudate and necrotic debris adjacent to granulation tissue infiltrated by neutrophils, macrophages and some lymphocytes. All five biopsies of the ulcer contained ovoid or spherical, thick-walled, yeastlike bodies surrounded by a large unstained capsule in H&E-stained sections (Fig 1). With van Gieson staining this capsule was sometimes slightly pink. With the PAS and mucicarmine methods many micro-organisms and budding forms were Downloaded by [Aston University] at 15:41 05 October 2014

visible. The cell-bodies stained PAS positive. The inner side of the halo, representing the capsule, was positive in the mucicarmine and showed 'spikes' due to shrinkage artifact (Fig 2). Based on their morphological and staining properties, the micro-organisms were identified as C. neoformans. Transmission electron microscopy showed that the micro-organisms were sometimes budding and were often surrounded by a thick layer of fine grey spots representing the capsule (Fig 3). Of the six biopsies from non-ulcerous tissue, only one contained cryptococci, in inflammatory and necrotic cells. The other biopsies consisted of corpus mucosa, with some superficial oedema and no inflammatory cells. There was massive infiltration of inflammatory tissue in the muscular layers and serosa. In the mesentery near the pancreas a similar inflammation with cryptococci was found. The regional lymph nodes were reactive, with secondary and tertiary follicles, but only a few micro-organisms could be found. The small nodules in the lung consisted of histiocytes, lymphocytes and plasma cells. No cryptococci were found.

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Gastric biopsy of the ulcer with ovoid or spherical bodies, sometimes with budding, and with a mucicarmine positive capsule and small spikes (arrows) surrounding the bodies (Mucicarmine 272x) THE VETERINARY QUARTERLY. VOL. 13, No. 4, OCTOBER 1991

187

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Transmission electron microscopy of gastric biopsy of the ulcur. Budding micro-organism with a lamellar cell wall and fine grey spots in the further unstained capsule (400 A) Fig.3.

DISCUSSION

In all species the stomach is a rare site of involvement with C.neoformans and primary gastrointestinal infection is unlikely to occur (2). In the report by Gelatt et al. (6), duodenal ulcers in the dog were mentioned in the event of generalised cryptococcosis but not examined histologically, so it is uncertain whether they were caused by cryptococci. This report presents, as far as we know, the first case of cryptococci in the stomach

of a dog. The decision to destroy the dog was made on the assumption that the lesion was a gastric carcinoma based on its size, localisation and ulceration. Granulomatous lesions may bear symptomatic and even histologic resemblances to malignant neoplasms (5). Although the CNS, the eye, lung and kidney are the organs most frequently involved, Barsanti (2) reported that other sites of involvement,, in decreasing order

of frequency, are lymph nodes, spleen, liver, thyroid glands, adrenal glands, pancreas, bones, gastrointestinal tract, muscles, myocardium, prostate gland, heart valves and tonsils. Mastitis is also caused by Cryptococcus neoformans (1).

Drinking unpasteurised milk from cattle with cryptococcal mastitis does not induce the disease (2). However, Salkowsky et al. (15) have infected nude (nu/ nu) mice orally with C. neoformans showing that the parasite can cause primary lesions in the alimentary tract of immunodeficient animals. 188

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The most important mode of infection is thought to be inhalation of airborne micro-organisms, which enter via the nasopharynx (4, 19) and then spread haematogenously (6, 14). Another route of infection in the dog is by extension

from otitis externa (19) or otitis media (18) to the brain. In areas with asymptomatically infected pigeons, droppings are likely to be the source of infection (10). Swallows have also been described as a source of cryptococcal infection (8). Caged tropical birds (such as canaries and psittacines) can be carriers of C. neoformans (3). Lutsky and Brodis (11) were able to culture C. neoformans

from urine of experimentally infected dogs, but not from faeces, saliva or nasopharyngeal secretions. Soil has been suggested as possible source of infection (19), but since the micro-

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organism is an ubiquitous saprophyte, infection is thought to require an

underlying disorder in the host. As Lutsky and Brodish (11) stated 'The ubiquity of Cryptococcus neoformans in nature is not reflected by its incidence as a primary pathogen in routine canine necropsies'. Human patients in poor condition, especially with malignancies of the reticulo endothelial system (22), or with AIDS (21), are more susceptible to cryptococcosis. Scott (17) suggested a relationship between cryptococcosis in cats and infection with the feline leucosis virus. The experiments of Salkowski et al. (15) stress the importance of a functional lymphocytic system as a defence against C. neoformans. Long-term corticosteroid therapy can predispose man to cryptococcal infections (5). MacDonald and Stretch (12) reported a case of cryptococcosis in a dog after three weeks of corticosteroid therapy. The single gastric lesion in our patient suggests that the mode of infection was

oral. Whether the pigeons of the neighbour played a role in the infection is uncertain. The history of poor healing of wounds and a Demodex infection are suggestive of a defective T-Iymphocyte system (16). There has been no sex predisposition reported in dogs with C.neoformans. The average age of affected dogs is 3 years (range 1-7 years), and most reported cases have been in large breeds. The dog described here was a 3-year-old Dobermann pinscher. ACKNOWLEDGEMENTS

Thanks are due to Mr. Ronald Molenbeek and Mr. Ton Ultee for technical assistence. REFERENCES I. Barron CN. Cryptococcosis in animals. J Am Vet Med Assoc 1955; 127:125-32.

Barsanti JA. Cryptococcosis. In: Greene GE. Clinical Microbiology and Infectious Diseases of the dog and cat. WB Saunders, Philadelphia 1984; 700-9. 3. Branson WR, Dreesen DW. Avian zoonoses: proven and potential diseases. Part II: viral, fungal and miscellaneous disease. Comp Cont Ed 1988; 10:688-95. 2.

4.

Bristner S, de Lahunta A, Lorentz M. Generalized cryptococcosis in a dog. Cornell Vet 1971;61:440-56.

5. Emmons CW, Binford CH, Utz JP. Medical Mycology, Lea & Febiger, Philadelphia 2nd cd.1970; 186-206. 6.

Gelatt KN, McGill LD, Perman V. Ocular and systemic cryptococcosis in a dog. J Am Vet Med

7.

Gillespie JH, Timoney JF. Hagan, and Brunner's Infectious Diseases of Domestic Animals.

Assoc 1973; 162:370-5.

8. 9.

Comstock Publ Assoc. Cornell Univ Press 7th ed.1981. Glasziou D, McAleer R. Cryptococcosis: an unusual avian source. Med J Austr 1984;140:447.

Happé RP, van der Gaag I. Endoscopic examination of oesophagus, stomach and duodenum

in the dog. J Am Anim Hosp Assoc 1983;19:197-206. 10. Khan ZU, Pal M, Randhawn HS et a/. Carriage of Cryptococcus neoformans in the crop of pigeons. J Med Microbiol 1978;11:125-218. Cited in: Green GE. Clinical Microbiology and Infectious Diseases of the dog and cat. Saunders, Philadelphia 1984: 700. 11. Lutsky I, Brodis I. Experimental canine cryptococcosis. J Inf Dis 1964;114:273-6. THE VETERINARY QUARTERLY. VOL.

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12. MacDonald DW, Stretch HC. Canine Cryptococcosis Associated with Prolonged Corticosteroid Therapy. Case Report. Can Vet J 1982;23:200-2. 13. Pearse AGE. Histochemistry, and A Churchill, London 3rd ed.1968; 601. 14. Rubin LF, Craig PH. Intraocular cryptococcosis in a dog. J Am Vet Med Assoc 1965; 147:27-

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15. Salkowski CA, Bartizal KF, Balish MJ, Balish E. Colonization and pathogenesis of Cryprococcus neoformans in gnotobiotic mice. Infect Immun 1987;55:2000-2005. 16. Scott DW, Schultz RD, Baker E. Further studies on the therapeutic and immunologic aspects of generalized demodectic mange in the dog. J Am Anim Hosp Assoc 1976;12:203-13. 17. Scott DW, Feline Dermatology. J Am Anim Hosp Assoc 1980;16:349-365. 18. Seibold HR, Roberts CS, Jordan EM. Cryptococcois in a dog. J Am Vet Med Assoc 1953;122:213-5. 5.

19. Wagner JL, James RP, Krigman MR. Cryptococcus neoformans infection in a dog. J Am Vet Med Assoc 1968;153:945-9.

20. Wilkinson GT. Feline cryptococcosis: a review and seven case reports. J small Anim Pract

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1979;20:749-68.

21. Young LS. Management of opportunistic infections complicating the acquired immunodeficiency syndrome. Med Clin North Am 1986;70:677-92. 22. Zimmerman LE, Rappaport H. Occurrence of cryptococcosis in patients with malignant disease of the reticulo endothelial system. Am J Clin Path 1954;24:1050.

Investigations with enzyme-linked immunosorbent assays for Trichinella spiralis and Toxoplasma gondii in the

Dutch 'Integrated Quality Control for finishing pigs' research project B.R. Berendsl, J.F.M. Smeetsl, A.H.M. Harbersl, F. van Knapen2, J.M.A. Snijdersl SUMMARY. In the framework of the Dutch field trial 'Integrated Quality Control (IQC) for finishivg pigs' ELISA (screening) techniques were used to detect animals seropositive for Toxoplasma gondii and/or Trichinella spiralis. The aim was to determine whether farms which consistently delivered seropositive pigs could be detected and monitored (defined as 'problem farms'). The investigation involved 120 farms and three slaughterhouses, and a total of 23,348 serum samples were examined. In addition, all pigs were also screened for the presence ofTrichinella spiralis with the digestion method (pooled samples). The prevalence of seropositivity for Trichinella spiralis and Toxoplasma gondii was 0.3% and 2.1% respectively. Parasitological examinations concerning T. spiralis were negative. Considering the characteristics of the used methodology, the conclusion was drawn that there were no parasitologicalor serological indicationsfor T. spiralis infections, and that with respect to T. gondii the infection rate seemed to be equally low for all farms involved. In addition, a longitudinal pilot study during a whole finishing period was undertaken at two finishing farms. Animals seropositive for Toxoplasma gondii were fOund from the earliest days of the finishing period. Housing and management may (still) play an important role in the prevention of contact with this parasite. 1

2

Department of the Science of Food of Animal Origin, Faculty of Veterinary Medicine, P.O. Box 80175, 3508 TD Utrecht, The Netherlands National Institute for Public Health and Environmental Protection, (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands Correspondence to the first author. THE VFTFPINARY QUARTERLY, VOL

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