Embedded Scribd iPaper - Requires Javascript and Flash Player

Israel Journal of Veterinary Medicine  Vol. 70 (3)  September 2015 Bouznach, A. 64
Systemic Toxoplasma gondii Infection in a Cat with
Incidental Cholangioma
Bouznach, A.,
1
Edery, N.,
1
Kelmer, E.,
2
Shicaht, N.,
1
Waner, T.
3
and Perl, S.
1
1
Department of Pathology, Kimron Veterinary Institute, Beit Dagan, Israel.
2
Koret School of Veterinary Medicine, Hebrew University, Rehovot, Israel.
3
Veterinary Clinic, 9 Meginay Hagalil Street, Rehovot, Israel.
*
Corresponding Author: Prof. S. Perl, Department of Pathology, Kimron Veterinary Institute, 50250 Bet Dagan, Israel. Email: perls@moag.gov.il
ABSTRACT
A ten year old castrated male domestic short haired cat was presented to the Veterinary teaching hospital of
the Koret School of Veterinary Medicine with a history of relapsing icterus, anemia, and lethargy. A diagnosis
of disseminated toxoplasmosis (Toxoplasma gondii) was made on histopathological examination and confrmed
by immunohistochemical studies. Te immune status of this cat was unknown and therefore it could not be
concluded that the disseminated infection was due to immunodefciency. Te presence of a cholangioma in
the liver of this cat was regarded as an incidental fnding.
Keywords: Feline; Toxoplasma gondii; Disseminated Toxoplasmosois; Cholangioma
INTRODUCTION
Tis case report describes a cat with a Toxoplasma gondii
infection and a hepatic tumor. Coincidences of this type are
usually unrelated and have no relationship to each other.
Toxoplasmosis is common in cats however the presence of a
cholangioma is relatively rare (1, 2). Te coincidence of both
a tumor and a T. gondii infection in this cat was considered of
interest in the light of other studies carried out in mice and
humans indicating that T. gondii may be a factor in suppress-
ing or slowing the development of various types of cancers
(3). Tis case represents a rare occurrence of two conditions
in the same cat, the incidence of which is rarely reported.
CASE REPORT
A ten year old castrated male domestic short haired cat was
presented to the Veterinary teaching hospital of the Koret
School of Veterinary Medicine with a history of relapsing
icterus, anemia, and lethargy. Te last episode was recorded
2 months prior to presentation.
On presentation the cat was mildly dehydrated (estimated
at 8%), with hypothermia (36.8°C), tachycardia (pulse 220
bests/minute) and a tachypnea (32 breaths/minute). On clini-
cal examination the abdomen was dilated and painful during
palpation. Hematology and blood chemistry demonstrated a
mild anemia (PCV/TS = 22/9). Serum albumin levels were
reduced and the concentration of total gamma globulins was
at the high end of the normal range.
Ultrasound examination revealed a splenomegaly with
suspicion of the presence of a splenic and hepatic infltration.
In addition two tumors were seen in the liver. Tese masses
were biopsied, examined cytologically and found to contain
cells representing a granulomatous reaction without the pres-
ence of neoplastic cells.
No free fuid was visualized in the abdominal cavity.
Te cat was treated with supportive care and showed
minor improvement. However, due to a relapse and deterio-
rating condition the cat was euthanized and submitted to the
Kimron Veterinary Hospital for a post mortem examination.
POST MORTEM
Gross pathology
Pale yellow mucous membranes and severe fea infestation
Israel Journal of Veterinary Medicine  Vol. 70 (3)  September 2015 65 Toxoplasmosis and Cholangioma in a Cat
was present. A small amount of transparent pericardial fuid
was noted. Te liver was difusely yellow with an irregular
rugged surface, multifocal nodules and a single 2 cm slightly
frm, roughly spherical mass in the right central lobe. Te
adrenal glands were bilaterally symmetrically enlarged. Te
mesenteric lymph nodes were moderately enlarged but ap-
peared to retain their normal form.
During the post mortem examination tissue samples
were taken and fxed in 10% neutral bufered formalin for
histopathology. Serum samples were sent for toxoplasma
antibody testing.
Toxoplasma antibody test
Indirect Immunofuorescence antibody (IFA) laboratory
results for Toxoplasma gondii antibodies revealed a strong
positive titer of 1:1024.
Histological description
Routine histopathological evaluation of formalin-fxed tissues
was carried out. In the liver a well demarcated unencapsulat-
ed, expansile neoplastic mass was seen. Te mass was formed
of cuboidal to polygonal cells closely packed supported by a
small amount of fbrous stroma resembling tubular structures
(Figure 1). Te neoplastic cells were cuboidal to polygonal
having variably distinct cell borders and small to moder-
ate amounts of eosinophilic cytoplasm. Te nuclei of the
neoplastic cells were intermediate to large in size, centrally
located with fnely stippled chromatin and 1-2 inconspicuous
nucleoli. Anisokaryosis and anisocytosis graded as mild to
moderate were present with a mitotic index of 10 at a high
power magnifcation.
Within the neoplastic areas and the adjacent liver pa-
renchyma there were multiple randomly distributed foci of
coagulative necrosis, admixed with small numbers of neu-
trophils, macrophages, lymphocytes and plasma cells most
prominent at the periphery of the necrotic foci (Figure 2 and
3). Within the necrotic foci there were numerous 20-30 µm
in diameter, round to oval parasitic cysts, each one with a thin
0.5 µm basophilic cyst wall containing numerous 2-3 µm,
basophilic round to banana shaped bradyzoits. Occasional
tachyzoits could be visualized within macrophages and
hepatocytes.
Figure 2: Liver: Foci of coagulative necrosis admixed with a small
number of infammatory cells and parasitic cysts containing numerous
basophilic zoites. H&E. x10.
Figure 1: Liver – Neoplastic area adjacent to necrotic areas and
parasitic cysts are present H&E. x20. Figure 3: Liver: H&E x40 Enlargement of fgure 1.
Case Reports
Israel Journal of Veterinary Medicine  Vol. 70 (3)  September 2015 Bouznach, A. 66
Lesions in other organs include a severe necrotizing adre-
nalitis with the presence of protozoal cysts; mild lymphocytic
myocarditis; mild interstitial pneumonia with edema and
mild multifocal interstitial nephritis.
Parafn sections of liver, lung, kidney, intestine and mes-
enteric lymph node were sent for immunohistochemistry
using the avidin-biotin peroxidase technique of Haines
and Chelack using rabbit polyclonal antibodies (Novus
Biologicals, Littleton, CO., USA) (4). Immunohistochemistry
for Toxoplasma gondii showed strong positive staining in the
liver, lung, adrenal and mesenteric lymph nodes (Figure 4).
DISCUSSION
A morphologic diagnosis was made of hepatic cholangioma
and severe multifocal to coalescing acute necrotizing hepatitis
with the presence of myriad protozoal cysts and tachizoites
consistent in with Toxoplasma.
T. gondii is a zoonotic obligate intracellular protozoon.
Infection of cats is by ingesting of asexual stages in tissues or
by ingesting oocysts. Felidae the defnitive host of T. gondii
(1) can serve also as an intermediary host of the parasite. In
intermediate hosts asexual development with multiplication
of parasites occurs in various organs and tissues. T. gondii (and
Neospora caninum) has the ability to parasitize a wide range of
hosts. Natural infection occurs in birds, rodents, insectivores,
herbivores, carnivores and primates including humans.
Systemic toxoplasmosis occurs most often in immu-
nologically immature or immunocompromised animals
although cases of fatal disseminated toxoplasmosis has been
recorded in immunocompetent cats and humans (5). In the
cat, intestinal and systemic infection occurs almost simulta-
neously. It can spread via lymphocytes to the lymph nodes
and from there to the blood\lymph and portal circulation
to the liver. In the case of this cat feline immunodefciency
virus (FIV), status was not examined although there was no
history of pharmaceutical immunosuppression and therefore
there is a lack of information regarding the immune status
of the cat.
Te possibility of infection by a virulent strain of T. gondii
should be considered. In North America and Europe three
T. gondii clonal lineages of diferent levels of virulence des-
ignated I, II and III have been found based on polymerase
chain reaction-restriction fragment length polymorphism
(PCR-RFLP) (6, 7). Furthermore, the possibility of difering
feline genotypes of difering sensitive to Toxoplasma infection
has also been investigated and also remains an option for the
explanation for the reason for systemic severe toxoplasmosis
in immunocompetent cats (8).
Focal necrosis where tachyzoites are present is common
and appears to be related to the rapid replication of tachyzo-
ites. Immune animals develop a chronic or dormant form of
toxoplasma infection that is characterized by the formation
of cysts containing bradyzoites. In the liver irregular foci
of coagulative necrosis are usually scattered randomly and
there is usually only little infammation associated with the
necrotic area. Variable number of tachyzoites may be present
in hepatocytes and Kupfer cells usually at the periphery of
the lesions. In the adrenals vast area of necrosis are usually
seen in the adrenal cortex with minimal infammation.
Te adverse clinical signs which lead to the decision to
euthanize the cat were probably due to the disseminated
toxoplasmosis which resulted in severe liver disease and
hypoabluminemia. Te hypothermia present was indicative
of a poor prognosis. Te hepatic neoplasm in this case was
considered as an incidental fnding.
Tree diferential diagnoses that were considered re-
garding the liver tumor were: Cholangiocarcinoma, biliary
cystadenoma (congenital biliary cysts) and cholangioma.
Te small size, demarcation, low cellular pleomorphism, lack
of invasion or metastases, lack of substantial desmoplasia,
and lack of aggregates of hepatocytes between the neoplastic
tubules favored a diagnosis of cholangioma.
Figure 4: Liver x40 – immunohistochemistry positive for
Toxoplasma gondi.
Case Reports
Israel Journal of Veterinary Medicine  Vol. 70 (3)  September 2015 67 Toxoplasmosis and Cholangioma in a Cat
Chloangiomas have been reported in dogs, cats, sheep,
cows and pigs (2). Tis benign tumor is uncommon and
there are a limited number of reports in the literature.
Cholangiomas are considered to be the most common hepa-
tobiliary neoplasm in cats in two studies (2, 8, 9). Clinical
signs in cats are non-specifc and the tumor may not be
detected at an early stage as they are clinically silent and
only detected when afected animals are examined for other
clinical conditions ( 9, 10, 11). Cholangiomas develop in cats
of 10-12 years of age and older, which was the case in this cat.
One survey found that males were overrepresented compared
to females with cholangiomas and that the results suggested
that domestic short haired cats may have a higher rate for
hepatic neoplasia than pure bred cats (12).
Te incidental fnding in this cat with an hepatic tumor
concomitantly with toxoplasmosis raises the question of the
relationship between these two events. Toxoplasma has been
demonstrated to have antitumor efects (3). Protein extracts
from Toxoplasma have shown quantifable efects in slowing
the development of various tumors such as fbrosarcoma,
melanoma, sarcoma and chemically induced tumors (3).
Most studies have been carried out in mice and humans.
No literature is available regarding cats. Whether there
was any interaction between the development of the chol-
angioma and the presence of a T. gondii infection remains
unknown.
Te diagnosis of toxoplasmosis (T. gondii) was made by
histopathological examination and confrmed by immu-
nohistochemical studies. Te immune status of this cat is
was unknown and therefore it cannot be concluded that the
disseminated infection was due to immunodefciency. Te
presence of a cholangioma in the liver of this cat is regarded
as an incidental fnding.
REFERENCES
1. Dubey, J.P., Lindsay, D.S. and Lappin, M.R.: Toxoplasmosis and
other intestinal coccidial infections in cats and dogs. Vet. Clin.
North Am. Small Anim. Pract. 39: 1009-1034, 2009.
2. Cullen, J.M. and Popp, J.A.: Tumors of the Liver and Gall Bladder:
Biliary Neoplasms, in Tumors in Domestic Animals, D.J. Meuten,
Ed., Iowa Sate Press: Ames, Iowa, USA. pp. 493-499, 2008.
3. Fox, B.A., Sanders, K.L., Chen, S. and Bzik, D.J.: Targeting tumors
with nonreplication Toxoplasma gondii uracil auxotroph vaccines.
Trends Pharmacol. 29: 431-437, 2013.
4. Haines, D.M. and Chelack, B.J.: Technical considerations for de-
veloping enzyme immunohistochemical staining procedures on
formalin-fxed parafn-embedded tissues for diagnostic pathology.
J. Vet. Diagn. Invest. 3: 101-112, 1991.
5. Nagel, S.S., Williams, J.H. and Schoeman, J.P.: Fatal disseminated
toxoplasmosis in an immunocompetent cat. J. S. Afr. Vet. Assoc.
84: E1-6, 2013.
6. Ajzenberg, D., Banuls, A.L., Tibayrenc, M. and Darde, M.L.:
Microsatellite analysis of Toxoplasma gondii shows considerable
polymorphism structured into two main clonal groups. Int. J.
Parasitol. 32: 27-38, 2002.
7. Howe, D.K. and Sibley, L.D.: Toxoplasma gondii comprises three
clonal lineages: correlation of parasite genotype with human dis-
ease. J. Infect. Dis. 172: 1561-1566, 1995.
8. Spycher, A., Geigy, C., Howard, J., Posthaus, H., Gendron, K.,
Gottstein, B., Debache, K., Herrmann, D.C., Schares, G. and Frey,
C.F.: Isolation and genotyping of Toxoplasma gondii causing fatal
systemic toxoplasmosis in an immunocompetent 10-year-old cat.
J. Vet. Diagn. Invest. 23: 104-108, 2011.
9. Mulligan, R.M.: Primary liver cell carcinoma (hepatoma) in the
dog. Cancer Res. 9: 76-81, 1949.
10. Blue, J.T., Frence, T.W. and Meyer, D.J.: Te Liver, in Diagnostic
Cytology and Hematology of the Dog and Cat, R. Cowell, R.L.
Tyler, and J.M. Meinkoth, Editors. 1999, Mosby: St. Louis, Mo.
pp. 183-194.
11. Hayashi, M.A., Tsuda, H. and Ito, N.: Histopathological clas-
sifcation of spontaneous hyperplastic liver nodules in slaughtered
swine. J. Comp. Pathol. 93: 603-612, 1983.
12. Post, G. and Patnaik, A.K.: Nonhematopoietic hepatic neoplasms
in cats: 21 cases (1983-1988). J. Am. Vet. Med. Assoc. 201: 1080-
1082, 1992.
Case Reports