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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.

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.

A 10-year-old spayed female Shih Tzu underwent surgery to remove a tumour (8 mm diameter) in the right 4

This report documents the histopathological and immunohistochemical features of atypical epithelial tumours of the gland of the third eyelid (GTE) in seven dogs. Cases 1 and 2 were diagnosed as myoepithelioma, comprising of compressive proliferations of interlacing bundles of neoplastic spindle cells expressing cytokeratin 14, p63, calponin and α-smooth muscle actin. Cases 3, 4 and 5 were diagnosed as complex carcinomas comprising of atypical glandular cells expressing cytokeratin 8/18, together with spindle-shaped or round neoplastic cells expressing cytokeratin 14, p63, calponin and α-smooth muscle actin. Cases 6 and 7 were diagnosed as basal cell adenocarcinomas (BCACs) comprising of a mixed proliferation of glandular and basal-type cells expressing cytokeratin 14 and p63. Therefore, in addition to glandular components, these tumours may include neoplastic cells with a myoepithelial or basal cell phenotype. Hence, there is diversity in the features of epithelial neoplasia of the GTE in dogs, similar to tumours in human salivary and lacrimal glands.

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.

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.

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 (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.

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.

Expression of vascular endothelial growth factor (VEGF), its receptors (flt-1 and flk-1), and basic fibroblast growth factor (bFGF) in canine hemangiosarcoma (HSA) and hemangiomas was investigated by immunohistochemical analysis. In addition, expression of the mRNAs of VEGF, flt-1, flk-1, and flg-1 (a receptor for bFGF), was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) with cRNA probes. VEGF, bFGF, flt-1, and flk-1 were immunohistochemically detected in the neoplastic cells in HSAs; the staining intensity was stronger in HSAs than in hemangiomas. On the other hand, the neoplastic cells in hemangiomas exhibited very weak or no expression of VEGF, although they showed moderate expression of flt-1 and flk-1. The mRNAs of VEGF, flt-1, flk-1, and flg-1 were detected in the neoplastic cells in HSAs by ISH and RT-PCR. However, VEGF mRNA was not detectable in the neoplastic cells in hemangiomas by ISH, although it was detected in the inflammatory cells in the tumors by RT-PCR. Moreover, the HSAs that showed intense staining for flk-1 had a high proliferative activity, which was reflected as a high Ki-67 positive index. These results suggest that the expression of the growth factors and their receptors, especially flk-1, might be associated with the malignant proliferation of HSAs.

Light and electron microscopic features and immunohistochemical features of Cryptosporidium andersoni ( C. andersoni) and host reaction in the mucosa were studied. Although the affected cattle demonstrated no apparent clinical signs, a severe infection of C. andersoni was observed in the abomasum. C. andersoni were round in shape, measured 6-8 μm in size and were mainly observed to be freely located in the gastric pits, being attached in occasional cases to the surface of the abomasum epithelium. Frequent inflammatory cells had infiltrated the lamina propria of the affected mucosa, and frequent mitotic figures were observed in epithelial cells at the dilated isthmus. To access the cell kinetics, the number of epithelial cells infected with C. andersoni were counted and compared with noninfected cattle. The number of gastric pit cells in infected cattle was significantly higher than that in the controls. The number of proliferative cells determined by the Ki-67 antigen in C. andersoni infected cattle was also significantly higher than that in the controls. Transmission electron microscopy and scanning electron microscopy revealed that the morphology of the C. andersoni organism was common to those of other Cryptosporidium spp. immunohistochemically, several commercial antibodies against Cryptosporidium spp. showed positive reactions at the wall of these oocysts or parasitophorous vacuoles. This report is possibly the first to discuss the prominent hyperplasia of the abomasum mucosa, as well as morphologic features of C. andersoni in cattle.

The proliferative potential of 17 canine osteosarcomas (OSs) (13 osteoblastic, two anaplastic, one fibroblastic and one chondroblastic), 18 chondrosarcomas (CSs) (13 mesenchymal and five ordinary), three osteomas, and one chondroma was evaluated immunohistochemically by labelling Ki-67 antigen with MIB-1 antibody, and incorporated bromodeoxyuridine (BrdU) with anti-BrdU antibody. The location of BrdU-positive cells in OSs and CSs was similar to that of MIB-1 positive cells, and the mean value of the BrdU labelling index (BrdU LI) and the MIB-1 positive index (MIB-1 PI) in each case were significantly correlated (rs = 0.942, P0.05 with Spearman rank correlation coefficient; r = 0.779 P0.05 with linear regression analysis). The mean MIB-1 PI of OSs was 29.5%, which was approximately 2.5 times that of CSs, and the highest MIB-1 PI was 34.8% +/- 1.8 S.E.M. in areas without osteoid. In CS cases, the survival rate after 24 months was significantly higher than in OS cases. The high MIB-1 PI therefore supports the view that OSs are clinically more aggressive than CSs in dogs. On the other hand, the highest MIB-1 PI values of mesenchymal CS components occurred in transitional areas, which were composed of poorly differentiated cells embedded in a myxomatous matrix between the chondroidal and mesenchymal regions. The MIB-1 PI was 21.3% +/- 3.0 S.E.M. P0.001 in transitional areas. Proliferative markers may be useful in diagnosis and prognosis.

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.

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.

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.

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.