Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior.

Currently, prognostic and therapeutic determinations for canine cutaneous mast cell tumors (MCTs) are primarily based on histologic grade. However, the use of different grading systems by veterinary pathologists and institutional modifications make the prognostic value of histologic grading highly questionable. To evaluate the consistency of microscopic grading among veterinary pathologists and the prognostic significance of the Patnaik grading system, 95 cutaneous MCTs from 95 dogs were graded in a blinded study by 28 veterinary pathologists from 16 institutions. Concordance among veterinary pathologists was 75% for the diagnosis of grade 3 MCTs and less than 64% for the diagnosis of grade 1 and 2 MCTs. To improve concordance among pathologists and to provide better prognostic significance, a 2-tier histologic grading system was devised. The diagnosis of high-grade MCTs is based on the presence of any one of the following criteria: at least 7 mitotic figures in 10 high-power fields (hpf); at least 3 multinucleated (3 or more nuclei) cells in 10 hpf; at least 3 bizarre nuclei in 10 hpf; karyomegaly (ie, nuclear diameters of at least 10% of neoplastic cells vary by at least two-fold). Fields with the highest mitotic activity or with the highest degree of anisokaryosis were selected to assess the different parameters. According to the novel grading system, high-grade MCTs were significantly associated with shorter time to metastasis or new tumor development, and with shorter survival time. The median survival time was less than 4 months for high-grade MCTs but more than 2 years for low-grade MCTs.

Copper toxicosis in veal calves.

Copper toxicosis was diagnosed in 7 veal calves, 10-16 weeks old, from 5 separate farms. All calves died without specific clinical signs, although 4 of the calves were icteric. The calves' dietary rations had been supplemented with various copper-containing hematinics. Peritoneal hemorrhage was reported at post-mortem in 2 calves. Microscopic evidence of hepatopathy consisted of hepatocellular degeneration and necrosis, hemorrhage, and fibrosis. Concentrations of copper in livers from intoxicated calves ranged from 277 to 684 ppm and in kidneys from 1.1 to 82.0 ppm. The extent and severity of lesions in livers appeared to correlate with concentrations of copper. Nephrosis was minimal, without evidence of hemoglobinuria.

Clinical neosporosis in a 4-week-old Hereford calf.

Most reports of neosporosis associated with abortion in cattle are in dairy cattle and infected calves do not survive beyond 7 days of age. This paper reports neosporosis in a 4-week-old Hereford calf. The calf was full term and appeared clinically normal at birth. At 2 weeks of age, the calf had weakened and was unable to nurse unassisted. The calf was killed at 4 weeks because of paralysis. The primary lesions were in the brain and were associated with Neospora caninum tachyzoites. The diagnosis was confirmed by immunohistochemical staining with anti-Neospora rabbit serum.

Feline fibrosarcomas at vaccination sites and non-vaccination sites.

A retrospective study of 195 feline sarcomas diagnosed histologically between July 1988 and June 1994 showed that 170 (87.2%) were fibrosarcomas. Cats with vaccination site (VS) fibrosarcomas were younger (8.6 +/- 3.9 years; median = 8 years) than cats with non-vaccination site (NVS) fibrosarcomas (10.2 +/- 4.7 years; median = 11 years) (P = 0.03), but there was no such association with breed, sex, or "neuter status". Microscopical features more characteristic of VS fibrosarcomas than of NVS fibrosarcomas were (1) subcutaneous location (P < 0.001), (2) necrosis (P < 0.001), (3) inflammatory cell infiltration (P < 0.001), (4) increased mitotic activity (P < 0.02), (5) pleomorphism (P < 0.001), and (6) variability in the density of the extracellular matrix (P < 0.001). When these data were fitted to a logistic regression model, younger age (P = 0.003), subcutaneous location of the fibrosarcoma (P = 0.0002), and the presence of inflammation (P = 0.017) were more characteristic of VS fibrosarcomas than of NVS fibrosarcomas. The study showed that in the absence of any vaccination history, the age of a cat, coupled with certain histological characteristics (e.g., tumour location in skin, and inflammation), may help in distinguishing VS fibrosarcomas from NVS fibrosarcomas. The characteristic histological features of VS fibrosarcomas, such as necrosis, increased mitotic activity and pleomorphism, are those of aggressive tumours.

Oronasal squamous cell carcinoma in an African hedgehog (Erinaceidae albiventris).

Oronasal squamous cell carcinoma was diagnosed in an adult African hedgehog (Erinaceidae albiventris). Clinically, the carcinoma presented as a firm right maxillary swelling with deviation of the nose to the left. The carcinoma was attached to the hard palate and protruded into the oral cavity. At necropsy, the carcinoma appeared centered in the right maxillary sinus, and had replaced the maxilla and extended into the nasal cavity. Metastatic foci were not found.

Malignant mast cell tumor in an African hedgehog (Atelerix albiventris).

In November 1995, a malignant mast cell tumor (mastocytoma) was diagnosed in an adult African hedgehog (Atelerix albiventris) from a zoological park (West Lafayette, Indiana, USA). The primary mast cell tumor presented as a firm subcutaneous mass along the ventrum of the neck. Metastasis to the right submandibular lymph node occurred.

Pseudorabies in captive coyotes.

Pseudorabies (Aujeszky's disease) was diagnosed in three adult captive coyotes (Canis latrans) from southern Indiana (USA). The coyotes died in their outdoor enclosure within a 48 hr period. Histopathology revealed multifocal, nonsuppurative meningioencephalitis and eosinophilic intranuclear inclusion bodies within neurons. Samples of brain were positive for pseudorabies virus by fluorescent antibody testing and virus isolation. Source of infection was the probable consumption of pseudorabies virus-infected pig carcasses.

Avian pox in sanderlings from Florida.

Asian pox was diagnosed in three sanderlings (Calidris alba) on Sanibel Island, Florida (USA) in February 1997. All three cases had large tumor-like lesions which contributed significantly to their mortality. Poxvirus infection was confirmed by cytology, histopathology, and electron microscopy. This is the first report of poxvirus infection in sanderlings.

Lymphosarcoma with disseminated skeletal involvement in a pup.

Lymphoblastic lymphosarcoma with disseminated skeletal involvement was diagnosed in a 15-week-old Golden Retriever. The skeletal disease was characterized by diffuse, irregular areas of radiolucency most evident in the diaphyseal portion of long bones and was associated with gait abnormalities and signs of pain. Necropsy also revealed involvement of the spleen, liver, kidneys, and mesenteric lymph nodes.

Ependymoma of the neurohypophysis and hypernatremia in a horse.

A 2-year-old Standardbred gelding was examined because of prolapse of the third eyelid; myoclonus of the muscles of the head, neck, and forelimbs; and persistent tail swishing. The horse had a high plasma sodium concentration but was not drinking water. The hypernatremia could not be corrected by means of IV administration of fluids, and the horse became worse and, 6 days later, died. At necropsy, a tumor was found to be compressing the neurohypophysis and the area in the brain in which the thirst centers are believed to be located. It is believed that hypernatremia in this horse was a result of altered thirst.

Response to high-dose radioactive iodine administration in cats with thyroid carcinoma that had previously undergone surgery.

Seven cats with thyroid carcinomas that had previously undergone surgical removal of neoplastic tissue were treated with 30 mCi of radioactive iodine (131I). Six of the cats had clinical signs of hyperthyroidism; 1 did not. There were no complications associated with 131I treatment, and clinical signs resolved in all cats. Technetium scans of 4 cats made after treatment did not have evidence of isotope uptake. In the remaining 3 cats, small areas of isotope uptake, the intensity of which was equal to or less than the intensity of uptake in the salivary glands, were seen. All 7 cats became hypothyroid after treatment; 4 required L-thyroxine supplementation. One cat was alive 33 months after treatment. The other 6 cats were euthanatized because of unrelated diseases 10 to 41 months after treatment.

Unilateral cerebral necrosis resembling feline ischemic encephalopathy in an African lion (Panthera leo).

In November 1996, a 14-yr-old captive male African lion (Panthera leo) had sudden onset of left-sided hemiparesis and mydriasis of the left eye. After 24 hr of supportive care, the lion showed no improvement and was euthanized. At necropsy, the right cerebral hemisphere was diffusely and irregularly swollen and malacic. Histopathology revealed extensive acute necrosis and edema of the portion of the right cerebral hemisphere that received blood from the right middle cerebral artery. Gross and histopathologic cerebral findings resembled those of feline ischemic encephalopathy.

Fatal herpesvirus encephalitis in a reticulated giraffe (Giraffa camelopardalis reticulata).

Fatal meningoencephalitis caused by equine herpesvirus-1 (EHV-1) was diagnosed in a reticulated giraffe (Giraffa camelopardalis reticulate). The giraffe died following a history of stumbling, incoordination, and abdominal pain. Gross examination of the brain revealed asymmetric edema and red-brown discoloration, predominantly within the telencephalon. Microscopically, there was perivascular lymphohistiocytic cuffing, multifocal gliosis, and neuronal necrosis in the cerebrum. Necrotic neurons contained acidophilic intranuclear inclusions. EHV-1 was isolated from the brain of the giraffe, and polymerase chain reaction was positive on sections of the brain. Immunohistochemistry using an EHV-1-specific antibody identified positive staining in neurons, astrocytes, and endothelial cells. The giraffe had been housed with a group of zebras that were serologically positive for EHV-1 and suspected as the source of infection. This raises concerns for cross-species transmission of EHV-1 when housing equids together with other species in zoologic collections.

Spontaneous metastasis of PC-3 cells in athymic mice after implantation in orthotopic or ectopic microenvironments.

The ability of subcutaneous, prostatic, and nonprostatic intraabdominal organ microenvironments to influence local tumor growth and metastasis of PC-3 human prostate carcinoma cells in athymic mice was determined. Tumorigenesis and metastasis of PC-3 were evaluated 60 days after subcutaneous and intraprostatic (orthotopic) implantation of 5 x 10(5) PC-3 cells in 6-week-old, male athymic mice. Intraprostatic implantation of PC-3 cells resulted in paraaortic lymph node metastases in 10 of 10 (100%) mice with prostatic tumors, whereas metastases were present in only 2 of 9 (22%) mice after subcutaneous implantation. Next, we determined whether the urinary bladder (nonprostatic, urogenital microenvironment) or stomach (nonurogenital, intraabdominal microenvironment) would facilitate the metastasis of PC-3 cells in athymic mice. Tumorigenesis and metastasis were 100% after subserosal implantation of PC-3 cells within the wall of the urinary bladder (n = 6 mice). Subserosal implantation of PC-3 cells into the stomach wall (n = 7 mice) also resulted in tumor formation and metastasis to regional lymph nodes in 100% of mice. In all experiments, regional lymph nodes were the most frequent site of metastasis, regardless of implantation site. We conclude that tumor microenvironment factors responsible for the metastasis of PC-3 cells in athymic mice may not be organ-specific, since nonprostatic visceral microenvironments are sufficient for predictable metastasis. Use of these models may further our understanding of how tumor microenvironment modulates expression of the metastatic phenotype by human prostate carcinoma cells.