Signalment: 9-year-old female Domestic Shorthair cat.
History: Within the last year, the cat had hematuria and eosinophilic gastroenteritis treated with 2.5 mg of prednisone ever other day for one year. Treatment was stopped 10 days before admission at which time the cat was vomiting, had diarrhea, and fever. Physical examination and ultrasonographic findings included thickened bowel loops and enlarged mesenteric lymph nodes. Multiple large areas of hyper-reflectivity were seen on ophthalmic examination. On day 12 of hospitalization, the cat died.
Gross Pathology: Only a cosmetic necropsy was permitted. The submucosa and tunica muscularis of the duodenum, jejunum and ileum are uniformly, markedly thickened, turgid, cream colored, and meaty to firm. Mesenteric lymph nodes are mildly enlarged, and mottled tan and dark brown on cut surface. The right and left renal pelves are moderately dilated and each contains a single, friable, black blood clot.
Laboratory Results: Leukopenic (1,600/ul), neutropenic, thrombocytopenic (90,000/ul) and borderline anemia (PCV=23) with no regeneration; total protein 7.4 g/dl, with globulins=5.0, albumin=2.4; mild azotemia (UN=65 mg/dl) and dehydration terminally. CSF: increased WBC from 1,600 to 4,400/ul.
Cytologic assessment of mesenteric lymph node = granulomatous inflammation, organisms compatible with Toxoplasma gondii. Laboratory tests for FIP, FIV, FeLV and Ehrlichia canis were negative. Titer for Toxoplasma gondii; IgM=negative; IgG=1:2,048.
In August of 1994 (on prednisone), the cat had a PCV and WBC in reference range. In July of 1995 (on prednisone) the cat was leukopenic (2,750 cells/ul) and neutropenic (1,375 cells/ul) with a PCV of 27%.
Contributor's Diagnosis and Comments: Jejunum, ileum, duodenum: Granulomatous enteritis and peritonitis, severe, with intralesional Toxoplasma gondiiorganisms.
Organisms compatible with T. gondii were identified in the small and large intestine, mesenteric lymph modes and liver. Organisms were not seen in lung, pancreas, kidney or adrenal glands; the brain and eyes were not examined (cosmetic necropsy). It is unusual to find intestinal lesions of this severity in the definitive host of T. gondii, especially considering the complete absence of organisms in more common sites of distribution, lungs and pancreas.3 Reports of relapsing toxoplasmosis in cats, caused by immunosuppression with corticosteroids (10-20 mg/kg/day), describe intestinal lesions ranging from mild mucosal inflammation, to severe myositis and necrosis, usually with intralesional Toxoplasma gondii tachyzoites and/or tissue cysts.4Presumably, the massive numbers of organisms in this cat are due to some degree of immunosuppression and the leukopenia (pancytopenia). A dose of 2.5 mg prednisone every other day is considered low and not immunosuppressive. There was no light microscopic evidence of adrenocortical atrophy. The leukopenia was probably the major factor that established the severe infection. A cause for the pancytopenia was not established, bone marrow was not examined.
Immunohistochemistry for T. gondii on the intestinal sections was strongly positive. Differentials include Neospora caninum tachyzoites, which are morphologically identical to tachyzoites of T. gondii by light microscopy but can be distinguished by ultrastructure and/or immunohistochemistry. There are no reports of naturally occurring neosporosis in cats. A toxoplasma-like organism has been described, 5 other differentials are Sarcocystis, Besnoitia and Hammondia hammondi.
Conference Note: Conference participants agreed with the contributor's diagnosis. Toxoplasma gondii is an obligate intracellular, cyst forming protozoan of the phylum Apicomplexa, capable of infecting a broad range of warm blooded intermediate hosts, including humans. Reptiles can be experimentally infected. Members of the family Felidae are the definitive host and the main reservoirs of infection.
There are two distinct phases of the life cycle, the enteroepithelial cycle which occurs only in felids (definitive host), and the extra-intestinal phase which occurs in both definitive and intermediate hosts. The enteroepithelial cycle usually begins following ingestion of tissue cysts and occasionally upon ingestion of sporulated oocysts; zoites are then released and penetrate into the epithelial cells of the small intestine. A series of genetically determined asexual generations (endodyogeny) takes place followed by a sexual cycle (gametogony). After a male gamete fertilizes a female gamete, a wall is formed around the fertilized female gamete forming an oocyst. Oocysts are shed in the feces, and after exposure to air, sporulate. Oocysts contain two sporocysts, each of which contains four sporozoites. Kittens are most likely to become infected and disseminate oocysts. Thereafter, most kittens develop protective immunity and do not shed oocysts with subsequent exposure. Sporulation of the oocyst takes between 1 and 5 days depending upon environmental conditions. The entire life cycle can be completed within three days after ingestion of tissue cysts; however, after ingestion of tachyzoites or sporulated oocysts by cats, the complete life cycle to oocyst formation is usually delayed for 3 weeks. Presumably, sporozoites and tachyzoites invade and multiply in intestinal and extraintestinal tissues forming bradyzoites. In tissues of cats, cysts rupture releasing bradyzoites that return to the intestine and continue the cycle as if tissue cysts had been ingested.
The life cycle of T. gondii in extraintestinal tissues is the same for all intermediate hosts and cats. After ingestion of tissue cysts or oocysts, bradyzoites or sporozoites penetrate intestinal epithelial cells, multiply as tachyzoites, and then spread to other organs. Dissemination occurs within infected macrophages, lymphocytes, granulocytes, or as free forms in the blood. Tachyzoites multiply in almost any type of host cell until the cell is destroyed. The released tachyzoites repeat the cycle in new host cells and eventually encyst. Tissue cysts are formed in the brain, skeletal musculature, heart, and visceral organs, and probably persist for the life of the host. Parasitemia during pregnancy can cause placentitis resulting in congenital infection of the fetus. This results in a more severe infection if transmission occurs during the first half of gestation. Flies and cockroaches have been implicated as oocyst transport hosts.
Clinical feline toxoplasmosis usually develops in cats exposed
to large numbers of infective organisms, immunocompromised cats,
or by reactivation of a chronic infection. Clinical toxoplasmosis
is associated with FeLV, FIV, FIP, and Haemobartonellainfections,
or the administration of corticosteroids. In this case, the dose
of steroids was insufficient to cause immunosuppression and another
underlying immunosuppressive condition is suspected.
Contributor: North Carolina State University, College of Veterinary Medicine, Dept. of Microbiology, Pathology and Parasitology, 4700 Hillsborough St., Raleigh, NC 27606.
International Veterinary Pathology Slide Bank: Laser disc frame #4901, 7265, 11596, 12372.
Signalment: 9-year-old castrated male Domestic Shorthair cat.
History: The cat was presented to the referring veterinarian for annual vaccinations and a history of indiscriminate urination. It had lost three pounds over the past three years. Physical examination revealed an intermittent arrhythmia and gallop rhythm. Initial laboratory data included an absolute erythrocytosis (PCV = 65.7%, T.P. = 6.3 g/dl, RBC = 18.37 x 106/mm3, Hb = 19.1 g/dl and an elevated BUN (57 mg/dl), creatinine (2.7 mg/dl), and glucose (222 mg/dl). Urinalysis showed a protein of 4+, negative glucose and 10 WBC and 50 RBC per high power field and rare bacteria. The cat was hypertensive with a systolic blood pressure of 280 mmHg. Radiographs indicated an enlarged left kidney and enlarged cardiac silhouette. Abdominal ultrasound demonstrated an irregular spherical/oval mass on the dorsum of the left kidney. An echocardiogram indicated left ventricular hypertrophy with moderate left atrial enlargement and good contractility.
Gross Pathology: The surgical biopsy specimens consisted
of a 2.0 cm lymph node, a 5.0 cm segment of ureter, and a 6 cm
long intact kidney within which there was a 5.0 cm in maximum
dimension, discrete, circumscribed mass in one pole.
Laboratory Results: None.
Microscopic Findings: Left kidney: The specimen consists
of a wedge of renal tissue, within which there is an expansile,
circumscribed mass that is composed of a disorganized array of
back-to-back, narrow, irregularly branched, empty or proteinaceous
precipitate-filled tubules that are lined by a single layer of
relatively uniform orderly cuboidal epithelial cells. The latter
are characterized by a round, euchromatic nucleus, prominent nucleolus,
granular eosinophilic cytoplasm, and poorly defined cell boundaries.
There is less than one mitoses per ten high power fields.
Left ureter (not submitted): The specimen consists of a segment of ureter, the lumen of which is empty and slightly dilated. A sprinkling of lymphocytes and rare eosinophils, mast cells, and plasma cells characterizes the adventitia.
Mesenteric lymph node (not submitted): The specimen consists of a piece of nodal tissue, the architecture of which is altered by enlarged secondary lymphocytic follicles and expansion of the paracortex by densely packed, variably-sized lymphocytes.
Contributor's Diagnosis and Comments: Left Kidney: Adenocarcinoma
(renal cell carcinoma).
Primary renal neoplasms are uncommon in domestic animals and humans. These tumors represent 0.5 to 2.5 percent and 0.6 to 1.7 percent of all tumors in dogs and cats, respectively. Nephroblastoma is the most common primary renal tumor in swine and chickens. Metastasis to the kidney is more common and may occur through hematogenous or lymphatic routes or by direct extension from nearby structures.
In humans, primary renal tumors are subdivided by age of affected patient. In children, nephroblastoma is the most common and accounts for 80% of renal tumors in patients less than 15 years of age. In adults, primary renal neoplasms account for 3% of malignancies with renal cell carcinomas representing the majority of them at 85-90%. Renal cell carcinomas are further subdivided into the following histologic types: clear cell (70%), papillary (10-15%), granular cell (7%), sarcomatoid 1.5%), chromophobe cell (5%), and collecting duct (<1%). Epidemiologic studies show a greater frequency of renal cell carcinomas in cigarette, pipe, and cigar smokers. Men are affected twice as often as women. The incidence increases with advancing age, with a peak in the sixth decade of life. Genetic factors also play a role. Nearly 2/3 of patients with the von Hippel-Lindau syndrome (characterized by hemangioblastomas of the CNS and retina) develop bilateral, often multiple renal cell carcinomas.
Cytogenetic studies of renal cell carcinomas have shown that most tumors display consistent chromosomal abnormalities. A terminal deletion of the short arm of one of the two homologies of chromosome 3 is commonly observed. DNA sequence deletions have been found consistently on chromosome 3 mainly in clear and granular cell types of renal cell carcinomas.
Renal adenomas and carcinomas both arise from the epithelium of the proximal convoluted tubules. It can be difficult to distinguish a renal adenoma from a renal cell carcinoma. Ultrastructurally and immunohistochemically, there are not distinguishing differences. Small (less than 2.0 cm) discrete cortical adenomas are commonly found in 7-22 percent of human autopsies. There is controversy whether a benign epithelial neoplasm of the kidney can be defined and clearly distinguished from a renal cell carcinoma. All neoplasms, whether or not they have the capacity to invade and metastasize, are small at some point in development. Tumors smaller than 2-3 cm rarely metastasize, and those larger than 3 cm are more likely to metastasize. Renal tumors less than 3 cm have been documented to metastasize in humans.
Over 85% of primary renal tumors in the dog are epithelial in origin and over 90% are malignant. The reported mean age of dogs with epithelial and mesenchymal tumors ranges from 7-9 years. The male to female ratio is about 2 to 1 as in humans. Lymphoma is the most common renal tumor in the cat; however, controversy exists whether this represents a true primary renal tumor or renal involvement secondary to systemic disease present at the time of diagnosis. The average age of cats with renal lymphoma is 5-7 years of age. Excluding lymphoma, renal cell carcinoma accounts for 40% of feline renal tumors followed by nephroblastoma at 20%. The remainder is composed of mixture of epithelial and mesenchymal tumors.
Renal cell carcinomas may remain clinically occult for the majority of the natural course. Most tumors are confined to the kidneys for substantial periods and may cause no changes in renal structure or function that would result in clinical signs. In humans, hematuria is variable from 6-83% of patients with renal cell carcinoma. Most dogs do not present with clinical signs referable to the urinary tract, and the classic signs of abdominal mass, weight loss, pain, and hematuria are uncommonly observed. Hematuria is present in 0-33% of dogs.
Paraneoplastic syndromes that occur in dogs and cats with renal tumors include: hypertrophic osteopathy, polycythemia, leukemoid reaction, and cachexia. Erythrocytosis refers to an increase in the number of circulating red blood cells. Absolute erythrocytosis secondary to inappropriate secretion of erythropoietin or erythropoietin-like substances has been recognized in people in association with renal neoplasia and other visceral tumors and renal parenchymal disease. Renin producing renal cell carcinoma is an uncommon cause of renal hypertension in humans.
Initially, the cat did very well postoperatively. The cat's
systolic blood pressure dropped to 105-110 mm Hg and its PCV was
28%. One month later the cat presented to the referring veterinarian
with marked neutrophilic leukocytosis, severe hyperglycemia, and
marked glycosuria. Based on clinical signs, the cat was treated
for pancreatitis and diabetes mellitis. Over the following two
months, the cat's condition deteriorated, and the hyperglycemia
became refractory to insulin therapy. During the fourth postoperative
month the cat continued to deteriorate. Its blood pressure started
to increase, and the cat had seizures. The owner elected euthanasia,
and an autopsy was not performed.
Even though some renal tubular epithelial cell tumors possess characteristics associated with benignancy, the aggressiveness of these neoplasms cannot be underestimated. Thirty percent of dogs with renal cell carcinoma have pulmonary metastasis at presentation. There is a high pre-operative mortality rate in dogs, presumed to be a result of associated paraneoplastic syndromes. For dogs surviving longer than 21 postoperative days, the median survival is 8 months.
AFIP Diagnosis: Kidney: Renal cell carcinoma, Domestic Shorthair cat, feline.
Conference Note: The conference participants agreed with the contributor's diagnosis. The histology of renal cell carcinoma is highly variable. The cells are usually cuboidal and may have "clear", eosinophilic or basophilic cytoplasm. They may be arranged in solid sheets, papillary projections or tubules, and may line cystic spaces. All of these patterns may occur in a single tumor. No prognostic value is associated with any pattern. The stroma is usually scant but highly vascularized and predisposed to extensive necrosis. Renal carcinomas tend to grow expansively and often invade the renal vein. Peritoneal implantation sometimes occurs. Widespread metastasis is common, especially to the lung and liver.
Middle aged to older German Shepherd Dogs with generalized nodular dermatofibrosis often have concurrent renal cystadenocarcinoma, usually bilaterally. Affected bitches also often have multiple uterine leiomyomas. These renal cystadenocarcinomas have been shown to be inherited as an autosomal dominant trait and to secrete growth factors which stimulate accumulation of fibrous tissue in various sites.
Contributor: Angell Memorial Animal Hospital - Pathology, 350 South Huntington Ave., Boston, MA 02130.
International Veterinary Pathology Slide Bank:
Laser disc frame #361, 362, 20674.
Signalment: A young male owl.
History: This owl presented with corneal ulceration and ocular hemorrhage. The veterinarian treated the animal with corticosteroids and neomycin. It died a few days later, was kept frozen and was necropsied. We received samples of pleura, lung, liver, kidney and spleen.
Gross Pathology: None.
Laboratory Results: None.
Contributor's Diagnosis and Comments: Severe fibrino-necrotic bronchopneumonia due to Aspergillus sp. Severe infestation of leukocytes with gametocytes of Leucocytozoon sp.
The Aspergillus infection was restricted to the respiratory system. Respiratory aspergillosis is one of the common fungal infections of birds. Since no supplementary laboratory examination was done, the species of Aspergillus was not determined.
Leucocytozoon infestation was observed in the circulating leukocytes of all organs examined. The life cycle of these parasites is discussed by Levine (1985). The parasite is transmitted by black flies (Simulium spp.).Sporogony takes place in these flies and the infective sporozoites invade parenchymal organs of birds and undergo schizogony. The schizonts infect leukocytes or, in certain species of Leucocytozoon, red blood cells, and develop to gametocytes. The gametocytes in leukocytes have elongate or round forms or both, depending on the species. These parasites occupy almost all the cytoplasm pushing the nucleus aside. The nucleus remains as an elongate basophilic structure on the side of the cell.
Leucocytozoonosis is one of the most frequently encountered blood parasite of birds (Bennet, et al, 1992; Forrester, et al 1994). According to Bennet, et al (1992) most Leucocytozoon species produce a short term infection of high intensity which drops rapidly to chronic disease. However, some species of Leucocytozoon may produce high mortalities in domestic birds. In owls, the most cited species of Leucocytozoon is L. ziemanni (Bennet et al. 1992).
This is not the first observation of simultaneous leucocytozoonosis and aspergillosis in birds. Miller, et al (1983) have observed similar cases in European and American eiders. These authors observed essentially schizogonic stages. In this case of owl leucocytozoonosis, we observed gametogenic stages in leukocytes in the organs examined and very few megaloschizonts in the liver. From histopathological examination, it was difficult to determine the primary infection and if one of these infections is secondary to the other.
Conference Note: Some of the sections examined by the conference participants did not contain air sac.
Aspergillosis is most often a respiratory infection caused by inhalation of spores. Aspergillus fumigatus is responsible for most infections in birds, mammals, and humans. Other species, including A. flavus, A. niger, A. nidulans, and A. terius, occasionally act as pathogens.
Infections with Leucocytozoon have been described in numerous avian species and at least one reptile. Infections in European and American Eider ducks mentioned by the contributor involved L. simondi. Like this owl, most birds were young and had massive pulmonary and airsac aspergillosis. Leucocytozoon in blood cells can readily be differentiated from other common avian hemoparasites, but in tissue sections, schizonts of Leucocytozoon must be differentiated from Haemoproteus and Plasmodium.
Contributor: Ecole Veterinaire d'Alfort, Laboratoire d'Anatomie Pathologique, 7 Avenue du General de Gaulle, 94704 MAISONS ALFORT - FRANCE.
International Veterinary Pathology Slide Bank:
Laser disc frame #09291, 19495, 19496, 19497, 7220, 7221, 10128, 20202.
Signalment: 1-year-old female ovine.
History: Last summer, after a long rainy period, the lambs from a children's park were housed in a barn, and fed with a commercial rabbit ration for two weeks. Suddenly, they presented with apathy, fever, dark urine and mild icterus. The clinician suspected leptospirosis. Two lambs died.
Gross Pathology: At necropsy, the lambs presented with icterus; the liver was yellowish and friable, and had a "nutmeg" mottling. The urine was markedly yellow- brown, and the kidneys were enlarged and dark brown.
Laboratory Results: Red blood cell counts revealed anemia (2,200,000 cells/ml) with a PCV of 18%. Blood urea nitrogen was 762 mg%. Creatinine was 21 mg%. TGO was above 200 IU, and TGP was 31 IU. Serologic test for leptospirosis and a leptospira culture from the kidney were negative. Liver copper level was 440 ppm (wet weight).
Contributor's Diagnosis and Comments: Copper intoxication causing periportal and centrilobular inflammation and fibrosis, with fibrotic bridges, bile casts, liver, 1 year old lamb.
Copper intoxication in Brazil has been reported in ovines mostly in the southern region of this country, where sheep are raised extensively, probably due to contamination of the pasture. In the present case, the lambs were housed, as is most frequently observed in this kind of intoxication. The intoxication occurred because the lambs were fed with a diet specifically balanced to another species, which contained inappropriate copper levels. Sheep are more susceptible to copper intoxication than other species because their hepatocyte lysosomes are sensitive to copper uptake and biliary excretion is limited. It is reported that by the time liver copper concentration increases, there is also an increase in hepatocyte turnover enhancing both the mitotic and the apoptotic rates. Sheep with high blood copper concentrations can show no symptoms until the rate of hepatocyte loss exceeds the replacement rate, and the blood copper level increases. In this case, the lamb presented a liver with histological evidence of a chronic process with extensive fibrotic areas. It is probable that this already compromised liver was unable to replace the lost hepatocytes, so the blood copper level increased vastly. The blood copper concentration in this case seemed to be high enough to damage the circulating erythrocytes causing intravascular hemolysis and subsequent anemia. The hemolysis accelerates the rate of hepatocellular necrosis, accelerating liver failure. Therefore, death occurred suddenly.
The picrosirius method was applied in this case to stain specifically the liver collagen, and the rhodanine stain was used to detect copper deposits in the liver and kidneys.
AFIP Diagnosis: Fibrosis, bridging, portal to portal and portal to central, diffuse, severe, with multifocal chronic hepatitis, biliary hyperplasia, and marked canalicular cholestasis, breed not specified, ovine.
Conference Note: There is some minor variation in the histologic sections. In some, small foci of nodular hyperplasia are evident.
This is a classic example of chronic hepatotoxicity and could be the result of a number of different toxins. Primary ruleouts should include: copper, aflatoxins, pyrrolizidine alkaloids, nitrosamines, sporodesmin, phomopsin, Alsike clover, and the triterpines of Lantana sp.
Of the heavy metals, copper alone seems to have a selective toxic effect on the liver with a significant variation among species. Sheep and dogs, particularly Bedlington and West Highland white terriers are the most susceptible. Chronic copper toxicity usually occurs in one of three ways: (1) excessive copper intake as a result of contamination of pasture or prepared feed. (2) increased availability of dietary copper, particularly when dietary molybdenum levels are low. In the presence of sulfate, molybdenum forms insoluble complexes with copper in the gut and liver rendering copper biologically inert and (3) the action of other hepatotoxins, particularly phomopsin and pyrrolizidine alkaloids which can interfere with hepatocellular mitosis and provoke a hemolytic crisis. The histologic and hematologic changes associated with chronic copper toxicity have been described.
Contributor: Department of Pathology, Faculty of Veterinary Medicine and Zootechny - University of São Paulo. São Paulo. Brazil.
International Veterinary Pathology Slide Bank:
Laser disc frame #13923, 13924, 18270, 18942-3, 20738-9, 21342-3, 24076.
Captain, VC, USA
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202)782-2615; DSN: 662-2615
* The American Veterinary Medical Association and the American College of Veterinary Pathologists are co-sponsors of the Registry of Veterinary Pathology. The C.L. Davis Foundation also provides substantial support for the Registry.