Highly malignant endometrial stromal sarcoma in a cat.

An 11-year-old female Persian cat underwent ovariohysterectomy due to dilation of the uterine cavity with irregular thickening of the wall. Macroscopically, the middle and distal regions of the left uterine horn were swollen and the uterine wall was irregularly thickened due to the development of multiple coalescent, variably sized nodules. Microscopically, the nodules had originated in the endometrium and were composed of round to polygonal neoplastic cells arranged in dense sheets or ill-defined fascicles. The neoplastic cells had locally invaded the myometrium and reached the subserosa, with lymphovascular invasion. Immunohistochemically, the neoplastic cell population was partially positive for CD10, an established marker of endometrial stromal sarcoma (ESS) in humans, with focal and diffuse nuclear immunopositivity for oestrogen and progesterone receptors and immunonegativity for desmin and α-smooth muscle actin. Based on these findings, the uterine tumour was diagnosed as ESS and was considered to correspond morphologically to high-grade ESS in humans.

Uterine haemangiosarcoma in a Netherland Dwarf rabbit (Oryctolagus cuniculus Netherland dwarf).

A 7-year-old intact Netherlands Dwarf rabbit with bloody discharge from the vulva underwent ovariohysterectomy. Grossly, both sides of the uterus were enlarged. Histologically, the tumour had formed protruded from the myometrial wall toward the serosa and was composed of irregular small capillaries with irregularly shaped structures and bundled proliferation of spindle-shaped cells. No tumour cells infiltrated the endometrium. The tumour cells were positive for CD31, and histological and immunohistochemical staining confirmed the diagnosis of haemangiosarcoma. Vascular tumours in the uterus of animals are uncommon, and only one case has been reported in the uterus of rabbits.

Feline uterine carcinosarcoma infiltrated with osteoclast-like giant cells.

A 12-year-old female Himalayan cat underwent an ovariohysterectomy to remove an intra-abdominal mass. Histologic examination using immunohistochemical staining revealed that the mass was comprised of epithelial and mesenchymal components. Within the lesion, multinucleated giant cells (MGCs) were observed diffusely. MGCs were positive for vimentin and Iba-1 and negative for cytokeratin AE1/AE3 and CD204. In addition, MGCs were negative for Ki-67, indicating nonneoplastic cells. Osteoclast-like MGC (OLMGC) phenotype with tartrate-resistant acid phosphatase positivity was also seen. These findings suggested that the uterine tumor was carcinosarcoma with OLMGCs. Uterine tumors in humans, such as leiomyosarcoma and carcinosarcoma, with OLMGC infiltration, are well-known pathologic entities; however, they are rare in animals and to our knowledge, have not been previously reported in cats.

Benign Mixed Mammary Tumour with Hepatoid Gland Differentiation in a Dog.

A 10-year-old spayed female Shih Tzu underwent surgery to remove a tumour (8 mm diameter) in the right 4th mammary gland. Histopathologically, the tumour consisted of four different components: luminal epithelial cells, myoepithelial cells, cartilage and well-differentiated hepatoid gland-like cells. There were multiple nests composed predominantly of hepatoid gland-like tissue with a small number of tubules formed by luminal epithelial cells at the periphery, in which continuity between the two components was seen. Immunolabelling for cytokeratins (CK14, CK18 and CK19), p63 and α-smooth muscle actin clearly distinguished the neoplastic luminal epithelial, myoepithelial and hepatoid gland-like cells. The immunohistochemical phenotype of the hepatoid gland-like neoplastic cells was identical to that of normal hepatoid gland cells. Based on these findings, a diagnosis of benign mixed tumour of the mammary gland with differentiated hepatoid gland cells was made. To our knowledge, this is the first report of a canine mammary tumour with hepatoid gland differentiation.

Encapsulated gas accumulation in the spinal canal: Pneumorrhachis in two dogs.

A 17-year-old mongrel dog and 12-year-old Shiba Inu dog presented with ataxia and paresis of the pelvic limbs, respectively. Gas accumulation within the spinal canal adjacent to the herniated disc was suspected in both cases. Since the gas remained accumulated for a prolonged period, hemilaminectomy was performed to decompress the spinal cord. The bulged external lamina of the dura matter was removed and histopathologically examined. Granulomatous inflammation and hyperplasia of fibrous connective tissues was noted, suggesting that the gas was encapsulated and the fibrous nodules made reabsorption difficult. Clinical signs resolved post-surgery. This is the first report describing histopathological features of pneumorrhachis in dogs. The accumulated gas was successfully removed by surgery. Postoperative course remained uneventful in both cases.

Lingual ganglioneuroma in a dog.

A mass was found at the base of the dorsum linguae of a male 11-year-old Labrador retriever. The tumor comprised of ganglion cells and Schwannian cells with Verocay bodies. The ganglion cells were positive for neuron-specific enolase, S-100, nerve growth factor receptor, and beta III tubulin. The Schwannian cells were positive for neuron-specific enolase, S-100, nerve growth factor receptor, and glial fibrillary acidic protein. The lingual mass was diagnosed as a ganglioneuroma. To our knowledge, there has been no previous report of a lingual ganglioneuroma in a dog.

Mixed germ cell-sex cord-stromal tumor with a concurrent interstitial cell tumor in a ferret.

A 5-year-old male ferret presented with an enlarged canalicular testis in the left inguinal region. Microscopically, the enlarged testis consisted of a diffuse intimately admixed proliferation of c-kit-positive germ cell-like and Wilms tumor-1 protein-positive Sertoli cell-like components, but no Call-Exner body was detected. In addition, the compact proliferation of steroidogenic acute regulatory protein-intense positive interstitial cells was identified in a separate peripheral area of the mass. Based on histopathological and immunohistochemical findings, the tumor was diagnosed as a mixed germ cell-sex cord-stromal tumor with a concurrent interstitial cell tumor.

Ganglioneuroma in the urinary bladder of a dog.

An 11-year-old male Labrador retriever presented with chronic oliguria. Ultrasonography findings revealed a protruding mass at the neck of the urinary bladder. A cystotomy was performed, and the mass was removed by ligation with surgical sutures. Histopathological examination revealed conspicuous foci with a variable number of ganglion cells in the tumor and abundant interwoven bundles of schwannian cells with fine fibers. The ganglion cells were positive for neuron-specific enolase and neurofilament. The schwannian cells were positive for vimentin, S-100 protein, and glial fibrillary acidic protein. Thus, according to the classification of tumor with neuronal cell differentiation, the urinary tumor was diagnosed as a ganglioneuroma.

Frequent development of inflammatory lesions and lymphoid foci in the kidneys of Japanese wild crows (Corvus macrorhynchos and Corvus corone) as a result of the entry of causal agents via the renal portal blood.

Although the increase in the number of wild crows is causing social problems in urban areas, crows play an increasingly important role in monitoring serious infectious diseases, such as highly pathogenic avian influenza and West Nile fever. To gain a better understanding of normal conditions and common disorders in crows, we conducted a retrospective study of wild crows captured in central Japan in the 1990s and examined the necropsy findings from 166 jungle crows (Corvus macrorhynchos) and 74 carrion crows (Corvus corone). We found frequent development of lymphoid foci and inflammatory lesions in the kidneys of both species of crows. These findings were unrelated to place or date of capture, indicating the universality of renal lesion developments in the Corvus species. In the kidneys, suppurative granulomas were concentrated in the renal cortex and the vein wall, indicating the haematoegenous spread of causal agents. However, the glomeruli remained intact, unlike the spreading of causal agents via arterial blood, which strongly suggested the renal portal blood as a possible entry route of causal agents. The renal lymphoid foci showed the same distribution as the granulomas, supporting the possibility of external agents entering through renal portal blood. We also identified types of parasites in Japanese wild crows by means of histopathological analysis. We hope that our data will contribute to the appropriate evaluation and a better understanding of pathological conditions in Japanese wild crows.

Mutations in the small heterodimer partner gene increase morbidity risk in Japanese type 2 diabetes patients.

Mutations in the small heterodimer partner gene (NR0B2; alias SHP) are associated with high birth weight and mild obesity in Japanese children. SHP mutations may also be associated with later obesity and insulin resistance syndrome that induces diabetes. To investigate this possibility, the prevalence of SHP mutations in Japanese with and without type 2 diabetes mellitus and the functional properties of the mutant proteins were evaluated. Direct sequencing of two exons and flanking sequences of SHP in 805 diabetic patients and 752 non-diabetic controls identified 15 different mutations in 44 subjects, including 6 novel mutations. Functional analyses of the mutant proteins revealed significantly reduced activity of nine of the mutations. Mutations with reduced activity were found in 19 patients (2.4%) in the diabetic group and in 6 subjects (0.8%) in the control group. The frequency difference between DM and control subjects adjusted for sex and age was statistically significant (P=0.029, odds ratio 2.67, 95% CI 1.05-6.81, 1-beta=0.91). We conclude that SHP mutations associated with mild obesity in childhood increase susceptibility to type 2 diabetes in later life in Japanese.

The significance of p53 and retinoblastoma pathways in canine hemangiosarcoma.

To investigate whether inactivation of the p53 and retinoblastoma (Rb) protein pathways contributes to the development of canine hemangiosarcoma (HSA), we examined immunohistochemically the expression of p53, Rb, phosphorylated Rb (phospho-Rb), p16, and cyclin D1 in 39 spontaneous canine HSAs and 10 hemangiomas. In addition, mutations in the p53 gene were analyzed by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and PCR direct sequencing; furthermore, we quantified cyclin D1 mRNA by semiquantitative real-time reverse transcription-PCR. Positive immunoreactivity for p53 was observed in 17.9% of HSAs. However, mutations were not detected in these cases. The labeling indices for Rb, phospho-Rb, and cyclin D1 were markedly higher in all HSAs than in hemangiomas. Of the 7 cases with cyclin D1-positive immunoreactivity, 4 overexpressed cyclin D1 mRNA (to a level more than 10-fold higher than that of GAPDH mRNA). The p16 protein was clearly detected in all hemangiomas; however, 82% of the neoplastic cells in HSA showed a loss of or low immunoreactivity. These results suggest that alteration of the p16-cyclin D1-Rb pathway, rather than the p53 pathway, may be associated with the pathogenesis of canine HSA.

Rhabdomyosarcoma in a ferret (Mustela putorius furo).

A 5-year-old spayed male ferret showed a subcutaneous mass in the right lateral thoracic wall. Microscopic examination revealed that the neoplasm had proliferated in the subcutis with infiltration into the surrounding tissues. A packed bundle of large polymorphic neoplastic cells, containing abundant eosinophilic cytoplasm and a round to ovoid, occasionally bizarre nucleus, were arranged interwoven. The neoplasm had metastasized to the right axillary lymph node. The neoplastic cells were intensively positive for vimentin, desmin and myoglobin. Skeletal muscle type creatine phosphokinase-positive granules were detected in the cytoplasm. Ultrastructurally, various amounts of disorganized myofibrils with focal density resembling the Z-band were shown in the cytoplasm of the neoplastic cells. The neoplasia was diagnosed as rhabdomyosarcoma.

Proventricular adenocarcinoma in a Humboldt penguin (Spheniscus humboldti) and a great horned owl (Bubo virginianus); identification of origin by mucin histochemistry.

Cases of proventricular neoplasm in a Humboldt penguin (Spheniscus humboldti) and a great horned owl (Bubo virginianus) were observed. Microscopically, the neoplastic cells formed branching tubules or acini in both cases. Galactose oxidase-Schiff (GOS) staining revealed that the cytoplasm of the normal surface epithelium and surface mucosubstances of the proventriculus adjacent to the neoplasm were positive in both cases. The neoplastic cells in both cases were also classified as GOS-positive. Therefore, the two proventricular neoplasms in this report were diagnosed as proventricular adenocarcinoma that arose from the proventricular surface epithelium. This study suggests that the mucosubstances, which the neoplastic cells produced, were a useful index for identifying the origin of the neoplastic cells in the birds.

Gallbladder adenocarcinomas in two captive African lions (Panthera leo).

Gallbladder adenocarcinomas in two captive African lions (Panthera leo), an 18-yr-old male and a 17-yr-old female, are described in this report. Grossly, both lions had hemoperitoneum with thickened and sclerotic gallbladder walls. Histopathologically, the male's tumor was well differentiated and the female's was poorly differentiated with multinucleate giant cells. Both tumors were highly invasive and involved the gallbladder serosa. The male also had a tumor in the liver, and the female's tumor had disseminated to the serosal surfaces of abdominal organs. In both cases, neoplastic cell cytoplasm stained diffusely for cytokeratin AE-1/AE-3 and cytokeratin 7 and granularly for lysozyme on immunohistochemical staining.

Establishment of a new canine cell line (CCT) originated from a cutaneous malignant histiocytosis.

A new canine cell line, named CCT, was established from the cutaneous malignant histiocytosis in a 4-year-old male Borzoi. CCT proliferated with loose adherence and doubling time was approximately 30 hr. When co-cultured with latex beads, CCT phagocytized beads vigorously. Lysozyme and vimentin were positive by immunostaining, and non-specific esterase and acid phosphatase were positive by cytochemical staining. These features indicated the cells had a histiocytic nature. Furthermore, by subcutaneous injection to nude mice CCT could successfully form tumors with the morphological and immunohistochemical features similar to the original tumor.