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Sarcocystis spp. cause pigeon protozoan encephalitis, a neuronal disease. A female pigeon exhibiting torticollis had a necrotic area in the cerebral hemisphere surrounded by lesions with perivascular cuffing, gliosis, granulomatous foci, and meningitis. Non-necrotic lesions were also observed in the brainstem. Intact and degenerative schizonts were observed within the neuropils and neurons in the lesions. Deoxyribonucleic acid (DNA) was extracted from paraffin-embedded brain tissues and genetically analyzed after gel electrophoresis to determine Sarcocystis spp. using specific primer sets for 28S ribosomal ribonucleic acid and internal transcribed spacer region-1. DNA sequencing confirmed a significant homology with S. calchasi. This is the first report of meningoencephalitis with malacia caused by S. calchasi in a rock pigeon in Japan.

We encountered a case of cutaneous squamous cell carcinoma (SCC) in a 17-year-old female koala at a zoo. A fragile, papillary, elevated mass was found on the third digit of the right hind limb. SCC was identified histopathologically: squamous cell-like polygonal tumor cells showed a nest-like growth pattern with epidermal down growth, central keratinization and necrotic foci, and invaded dermal connective tissues. Metastatic lesions were observed in various organs, including the lung and axillary lymph node: in the lung, multiple metastatic foci similar to the primary lesion, and in the axillary lymph node, individual polygonal tumor cells infiltrated the sinusoids. Immunohistochemistry revealed that the tumor cells were positive for proliferating cell nuclear antigen, which exhibited 32-33% of labeling indices in the tumor cells. To our knowledge, this is the first report of a case of SCC in a digit of a koala.

A 25-month-old female crossbred cow presented with astasia, emaciation, and stunted growth. Macroscopic examination revealed a large mass in the abdominal cavity, approximately 100 × 30 × 30 cm. Microscopic examination revealed that the mass consisted of multilobular mature and immature cartilaginous matrices with chondrocytic cells, surrounded by spindle to pleomorphic mesenchymal tumor cells. The cartilaginous matrices consisted of hyaline and elastic cartilages, as confirmed with Azan stain, and Victoria Blue and Van Gieson stain. Immunohistochemistry revealed that the chondrocytic and mesenchymal cells both expressed S-100. The tumor was diagnosed as an extraskeletal chondrosarcoma in the abdominal cavity of this cow.

A female koala presented with hyperglycemia related to diabetes mellitus diagnosed at 9 years and treated with insulin. She presented with nasal hemorrhage, anemia, leukocytosis, and tachypnea at 10 years. A blood smear examination revealed scattered, atypical large myeloid cells and a clinical diagnosis of myelogenous leukemia was made. White blood cell count reached a maximum of 295 × 10 2 /µl, with evidence of severe regenerative anemia and thrombocytopenia. Grossly, systemic lymph node enlargement, fragile liver with hemorrhage, and bloody ascites were observed. Histopathologically, atypical myeloid cells, including myelocytic and metamyelocytic cells, were scattered in the vasculature and surrounding tissues throughout the organs. The patient was infected with a koala retrovirus, which might have caused the myelogenous leukemia.

We describe a case of choroid plexus carcinoma arising in the cerebrum of a 7-week-old male Sprague-Dawley rat. The tumor mass occupied the right lateral ventricle of the cerebrum. Histological analyses revealed that the epithelial tumor cells had proliferated in tubular, cribriform, papillary and solid growth patterns in the vicinity of the choroid plexus, with slight invasion into the cerebrum parenchyma. We divided the tumor cells into cuboidal, elongated and intermediate cells. Immunohistochemical studies showed that these tumor cells expressed relatively high levels of cytokeratin AE1/AE3, vimentin and glial fibrillary acidic proteins, and low levels of nestin, oligodendrocyte transcription factor and doublecortin proteins. The present case was diagnosed as a choroid plexus carcinoma with neuronal and glial differentiation.

An 18-year-old female black leopard (Panthera pardus) showed renal failure, leukocytosis and presence of subcutaneous masses in the lower abdominal region and right shoulder; she eventually died. Histopathological observations included a mammary gland carcinoma with comedo, solid and tubulopapillary patterns in subcutaneous tissue, and highly proliferated tumor cells in systemic organs. The tumor cells were positive for cytokeratin AE1/AE3. The mammary gland tumor was diagnosed as intermediate-grade adenocarcinoma, based on a previously reported histological grading system of feline mammary carcinomas. Chronic interstitial nephritis was estimated to have been ongoing for 5 years, whilst acute necrotic pancreatitis in relation to tumor metastasis could have been the cause of death.

A 9-year-old, spayed female Chihuahua was presented with a 1-week history of lethargy and anorexia. Abdominal ultrasonography and computed tomography found bilateral adrenal masses without metastasis. Serum cortisol levels that were sampled before and after an adrenocorticotropic hormone stimulation test were within reference ranges. Lethargy and anorexia completely resolved after short-term fluid therapy; the clinical signs did not occur for approximately 8 months until her sudden death. A postmortem examination revealed bilateral adrenocortical carcinomas and liver metastasis. Primary adrenocortical carcinomas developed in the dog met the definition of bilateral incidental adrenal gland masses (IAGMs). This is the first case report to demonstrate based on histological identification that adrenocortical carcinomas cause bilateral IAGMs in dogs.

An 11-year-old female goat had invasive and metastatic endometrial adenocarcinoma in the uterus. There was a notable proliferation of endometrial epithelial cells in a tubular growth pattern, with a desmoplastic response. The endometrial epithelial tumor cells metastasized to the kidney, liver and lung. In contrast to the primary and metastatic tumor cells, pleomorphic tumor cells with a choriocarcinoma-like growth pattern infiltrated the mesometrium. Cell proliferation activity was high in both types of tumor cells. Both types of tumor cells expressed cytokeratins AE1/AE3, 7 and CAM5.2; choriocarcinomatous cells also had positive immunoreactions to human chorionic gonadotropin, human placental alkaline phosphatase and α-inhibin. The present case was diagnosed as endometrial adenocarcinoma with choriocarcinomatous differentiation.

A 17-year-old female wolf (Canis lupus lupus) had a right lung mass that was adhered to the thoracic cavity. Histopathological examination revealed that the mass consisted of sheets, cord or ribbon-like structures of monotonous, small, cuboidal cells with round, oval or short-spindle nuclei and scant clear cytoplasm, demarcated by a fine fibrovascular stroma. Focal necrosis, congestion and thrombi were observed. Immunohistochemically, the tumor cells diffusely expressed cytokeratin AE1/AE3, and some expressed chromogranin A, neural cell adhesion molecule (CD56) and thyroid transcription factor-1. The number of proliferating cell nuclear antigen-positive tumor cells was low. A diagnosis of pulmonary neuroendocrine tumor was based on the resemblance to carcinoids.

Feline morbillivirus (FmoPV) is a new virus species and its detection is important, since correlation has been reported between FmoPV virus infection and tubulointerstitial nephritis in cats. Here, we report a real-time reverse transcription (RT)-PCR system that can detect the FmoPV L-gene sequence with more than 10-time higher sensitivity than a conventional PCR system, resulting in detection of less than 10 copies of the template DNA. The total FmoPV positive rate of urine samples from veterinary clinics and hospitals in Japan was 15.1% (25/166) using this system. This study demonstrates usefulness of the real-time RT-PCR system for detection of FmoPV for cat urine samples.

A rare case of complex apocrine carcinoma displaying dominant myoepithelial proliferation developed in the right leg subcutis of a 10-year-old male dog. The major cell population consisted of diffusely proliferating p63-expressing neoplastic cells that were largely myoepithelial in origin co-expressing α-smooth muscle actin. A small portion of the cell population consisted of concomitant basal epithelial cells lacking α-smooth muscle actin expression. The minor population consisted of p63-negative apocrine gland cells that expressed cytokeratin 8. The myoepithelial cell population showed a rather stronger proliferation activity than did the apocrine epithelial population. Thus, this tumor might have been derived from basal epithelial cells characterized by more predominant myoepithelial differentiation than luminal apocrine epithelial differentiation.

A subcutaneous tumor in the left inguinal region was present in an 11-year-old female bloodhound. Histopathologically, the tumor showed invasive growth and extensive necroses, and it was composed of spindle-shaped, elongated, and stellate neoplastic cells accompanied by occasional giant cells arranged in fascicular, herringbone, or irregular storiform patterns with abundant production of collagen fibers. The cytoplasm of most tumor cells was positive for vimentin, alpha-smooth muscle actin, and calponin, but was negative for desmin, smoothelin, and S-100. Furthermore, most of the tumor cells were negative for Iba1 while some tumor cells were weakly positive. Thus, this tumor was diagnosed as a high-grade myofibroblastic sarcoma according to the diagnostic criteria for human myofibroblastic sarcomas.

We have shown phosphoinositide 3-kinase (PI3K)/Akt signaling activation in thyroid capsular invasive carcinomas (CICs), which are highly induced by promotion with sulfadimethoxine (SDM) in a rat 2-stage thyroid carcinogenesis model. To examine the potency of calcitriol, a synthetic vitamin D3 analog, on the development or progression of CICs, male F344 rats were injected with calcitriol (0.1 µg/kg body weight) three times a week intraperitoneally, during an entire period of SDM-promotion for 13 weeks (Experiment 1) or during the last 2 weeks of a 15-week SDM-promotion (Experiment 2). Initiation with N-bis(2-hydroxypropyl)nitrosamine preceded all treatments. In Experiment 1, long-term calcitriol treatment reduced the multiplicity of CICs, while cell proliferation activity, estimated by Ki-67 cell index in the induced CICs, was unchanged with SDM-promotion alone. Considering the strong dependency of promotion with SDM during the early stages on thyroid-stimulating hormone, the reduced multiplicity in Experiment 1 may be due to the effect on an early stage of neoplastic proliferation. Although the magnitude was mild, cell proliferation activity was decreased in existing CICs after short-term calcitriol treatment in Experiment 2, which was associated with a mild decrease in cyclin-dependent kinase-2-positive cells, cytoplasmic immunolocalization of phosphorylated, inactive, Rb protein and a mild increase in nucleocytoplasmic expression of p27(kip1). Although the effect was mild at the late stage of SDM-promotion in this hypothyroidism-related thyroid carcinogenesis model, our results suggest that calcitriol targets cell proliferation via inhibition of a molecular cascade downstream of PI3K/Akt signaling, controlling G1/S transition.

In order to clarify whether cytokeratin (CK) 8/18 is a useful immunohistochemical marker for hepatocellular proliferative lesions in mice, partially hepatectomized male ICR mice were given 0.6% piperonyl butoxide (PBO) for 8 (Experiment I) or 25 weeks (Experiment II) after N-diethylnitrosamine (DEN) initiation treatment, and the livers were subjected to histological examinations on hematoxylin and eosin (HE) stained sections, CK8/18 immunohistochemistry and gamma-glutamyl transpeptidase (GGT) histochemistry. In Experiment I, the multiplicity of hepatocellular foci in paraffin-embedded sections which were observed in HE-stained sections and positive for CK8/18 was 10.17 and 18.50, respectively, while that of hepatocellular foci in frozen sections which were observed in HE-stained sections and positive/negative for GGT was 6.17 and 8.17, respectively. In Experiment II, the total multiplicity of hepatocellular foci in paraffin-embedded sections which were observed in HE-stained sections and positive/negative for CK8/18 was 4.47 and 23.17, respectively, while that of hepatocellular foci in frozen sections which were observed in HE-stained sections and positive/negative for GGT was 2.50 and 3.50, respectively. Most of the hepatocellular adenomas and carcinomas observed in HE-stained sections were positive for CK8/18, but some of the adenomas were negative for CK8/18. These findings indicate that more hepatocellular proliferative lesions can be detected in CK8/18 immunohistochemistry in addition to those observed in HE-stained sections, and suggest that CK8/18 may become a useful immunohistochemical marker for detecting hepatocellular proliferative lesions in mice.

To determine whether developmental hypothyroidism causes permanent disruption of neuronal development, we first performed a global gene expression profiling study targeting hippocampal CA1 neurons in male rats at the end of maternal exposure to anti-thyroid agents on weaning (postnatal day 20). As a result, genes associated with nervous system development, zinc ion binding, apoptosis and cell adhesion were commonly up- or down-regulated. Genes related to calcium ion binding were up-regulated and those for myelination were often down-regulated. We, then, examined immunohistochemical cellular distribution of Ephrin type A receptor 5 (EphA5) and Tachykinin receptor (Tacr)-3, those selected based on the gene expression profiles, in the hippocampal formation at the adult stage (11-week-old) as well as at the end of exposure. At weaning, both EphA5- and Tacr3-immunoreactive cells with strong intensities appeared in the pyramidal cell layer or stratum oriens of the hippocampal CA1 region. Although the magnitude of the change was decreased at the adult stage, Tacr3 in the CA1 region showed a sustained increase in expressing cells until the adult stage after developmental hypothyroidism. On the other hand, EphA5-expressing cells did not show sustained increase at the adult stage. The results suggest that developmental hypothyroidism caused sustained neuronal expression of Tacr3 in the hippocampal CA1 region, probably reflecting a neuroprotective mechanism for mismigration.

We report a rare case of benign sex cord-stromal tumor consisted largely of luteoma with minor portion of Sertoli cell tumor located at the position of the left ovary excision in an 11-year-old ovariectomized bitch. Granulosa cell component was lacking, and both luteal and Sertoli cell portions were entirely positive for inhibin alpha and neuron-specific enolase, whereas luteoma portion alone was positive for Wilms' tumor-1 (WT1), immunohistochemically. The results suggest that this tumor is a possible complication of incomplete ovarian excision at the time of ovariectomy and consisted of uncommon hybrid of luteal and Sertoli cells to be diagnosed as an unclassified sex cord-stromal tumor if applied in human cases. WT1-expression pattern suggested the signature of the difference in the phenotype of these cell types.

We report a case of cerebellar neuroblastoma in a 19-week-old p53 null mutation mouse. A white and soft mass was observed at the cerebellar vermis. Histologically, the tumor consisted of solid growth of round to oval pleomorphic cells with frequent mitotic figures. While there were no typical cellular arrangements of embryonic neurogenic tumors, such as Homer-Wright rosette, perivascular pseudorosette, or streaming of neoplastic neurocytes, small populations of the neoplastic cells were immunohistochemically positive for synaptophysin, microtubule-associated protein 2, S-100 and nestin. Both glial fibrillary acidic protein and vimentin were entirely negative in the neoplastic cells. Based on the biological characteristics of neoplastic cells, this tumor was diagnosed as neuroblastoma of the cerebellar origin.

We report a case of mixed epithelial and stromal tumor of the kidney (MESTK) in a 32-week-old heterozygous sphingosine 1-phosphate-2 (S1P2) receptor deficient female mouse. A white solid mass replacing the left kidney was observed at the left retroperitoneal wall. Histologically, the tumor mass consisted of dimorphic cellular components of epithelial and stromal cells. Epithelial cells formed various sized irregular-shaped tubular structures resembling renal tubules surrounded by stromal cells. Immunohistochemically, epithelial cells were positive for cytokeratin, while stromal cells showed positive immunoreactivity with alpha-smooth muscle actin as well as vimentin. Based on the morphological and immunohistochemical findings, this tumor was diagnosed as a MESTK.