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Intestinal lymphangiectasia (IL) is a common complication in dogs. This study analyzed intestinal microbiota using 16S rRNA amplicon analysis as candidate factors that strongly influence the small intestinal lymphatic vessels in dogs with and without IL. Twelve dogs were included, of which six were diagnosed with lymphoplasmacytic enteritis, four with small-cell lymphoma, and two with large-cell lymphoma. Seven of these dogs had IL, whereas five did not. First, the microbial diversity analyzed by Faith pd index was significantly decreased in dogs with IL compared to dogs without IL. Then, the relative amounts of each bacterial taxa were compared between dogs with and without IL using Linear discriminant analysis effect size analysis. At the genus level, the Ruminococcus gnavus groupsignificantly increased in dogs with IL compared to dogs without IL. A total of four genera, including Ruminococcus torques group and Faecalibacterium, which produce butyrate, significantly decreased in dogs with IL. This study showed decreased intestinal bacterial diversity and several alterations of intestinal microbiota, including a decrease in butyrate-producing bacteria in dogs with IL, compared to dogs without IL.

There is no nationwide necropsy database of animals in Japan, and most of the records are available from the postwar period. To clarify the chronological transition of animal necropsy cases in Tokyo, Japan, the records accumulated in the University of Tokyo from 1902 were investigated. Of necropsy records on paper or electronic from 1902 to 2021 kept at the Laboratory of Veterinary Pathology, the University of Tokyo, totally 3137 cases including 572 in 1903-1914 (the Meiji-Taisho period), 1258 in 1956-1969 (the Showa period) and 1307 in 2006-2020 (the Heisei-Reiwa period), respectively, were examined for species, breed, age and pathological diagnosis. Dogs (44.6%) and horses (34.8%) in the Meiji-Taisho period, dogs (62.9%) and cats (17.3%) in the Showa period, and dogs (46.0%), cats (26.1%) and exotic animals (20.5%) in the Heisei-Reiwa period were the most necropsied animal species. With the passage of time, the number of animal species increased, and the breeds of dogs and cats came to be more various. The median ages of death were 2 years, 3 years and 10 years old in dogs in the Meiji-Taisho, Showa and Heisei-Reiwa periods, respectively, and 2 years and 10 years old in cats in the Showa and Heisei-Reiwa periods, respectively. Viral, bacterial and parasitic infections were decreased, and inversely tumor cases increased due to the prolonged lifespan.

Cerebral amyloid β (Aβ) deposition is a pathological hallmark of Alzheimer's disease (AD). There are several molecular species of Aβ, including Aβ40, Aβ42, and Aβ43, and the pathological roles of Aβ43 have attracted particular attention in recent years. Aβ43 is mainly deposited as senile plaques (SPs) in AD brains, and is known to be more amyloidogenic and neurotoxic than Aβ42 and Aβ40. Aβ40 and Aβ42 deposition have been demonstrated in several animal species, while Aβ43 deposition has not been studied in animals. The brains of sea lions, dogs, and cats exhibit unique age-related Aβ pathologies. In the present study, the deposition patterns of Aβ40, Aβ42, and Aβ43 were examined immunohistochemically in the brains of aged dogs (n=52), sea lions (n=5), and cats (n=17). In dogs, most cerebral amyloid angiopathy (CAA) lesions and primitive SPs were positive for Aβ42, Aβ43, and Aβ40. However, diffuse SPs and capillary CAA lesions were negative for Aβ40. In sea lions, all SPs and most CAA lesions were positive for Aβ42, Aβ43, and Aβ40, while capillary CAA lesions were negative for Aβ40. In cats, Aβ42-immunopositive granular aggregates and arteriole and capillary CAA lesions were positive for Aβ43, but negative for Aβ40. Double-labelling immunohistochemistry revealed the co-localization of Aβ42 and Aβ43. These findings suggest that Aβ43 and Aβ42 are frequently deposited in the brains of Carnivora animals and may play an important role in Aβ pathology.

A captive male Linnaeus's two-toed sloth died without any obvious clinical signs. At necropsy, multifocal ulceration at the lumbar and perianal skin, mitral valve vegetation, and multifocal hemorrhage in the leptomeninges were observed. Histopathologically, suppurative meningo-ventriculitis, dermatitis, and endocarditis characterized by severe neutrophilic infiltration were observed. Gram-positive cocci arranged in pairs or chains were present in these inflammatory lesions. Streptococcus agalactiae gene was detected in the skin, heart, and brain tissues by PCR and sequence analysis. These findings may indicate that S. agalactiae primarily infected the skin and then caused septicemia resulting in endocarditis and meningo-ventriculitis. The present case suggests that S. agalactiae infection can cause severe meningo-ventriculitis in two-toed sloth without any specific clinical signs.

Hepatobiliary diseases of animals are frequently diagnosed by a combination of imaging, clinical pathology, and histopathology. A standardized surgical liver biopsy protocol, however, has not been established in veterinary medicine with regard to the selection of lobe and site of the liver to yield the most diagnostic information. To address this matter, we histologically examined 33 livers of autopsied dogs from which tissue samples of 4 different lobes as well as 4 different sites of each lobe were prepared. We measured the hepatic lobular diameter (HLD) as an objective variable to refer to the inter-lobar or inter-site difference among the biopsied samples. A measurement of 2,623 hepatic lobules resulted in 1.042 mm as the average of all the HLD values. Statistical analysis further revealed that the HLD tended to be small in a superficial 2 mm area of the liver parenchyma regardless of biopsy location, thus this area should be evaluated carefully by pathologists. The results also suggest that the HLD values of the quadrate lobe may measure smaller than those in the other lobes. Therefore, one would be able to obtain representative data of the entire liver by taking a sample from any single lobe except for the quadrate lobe. HLD measurements are needed in order to accumulate potentially useful information on the microanatomy and pathophysiology of the liver.

A 13-year-old female Miniature Dachshund showed seizures and an intracranial mass was seen in the left temporal lobe. Three months after first surgical resection, a recurrence lesion was recognized. Histopathologically, proliferation of spindle cells with diffuse rosette-like eosinophilic deposits, which stained blue with Masson's trichrome stain, was observed. In electron microscopy, the rosette-like deposits were consisted of bundles of minute filaments which were assumed to be collagenous fibrils. Immunohistochemically, the neoplastic cells were positive for vimentin and cytokeratin, and negative for E-cadherin, S100, glial fibrillary acidic protein (GFAP), oligodendrocyte transcription factor (Olig2), and CD204. The rosette-like collagen deposits were positive for type 4 collagen and negative for type 1 collagen. In this report, we describe histopathological features of a canine meningioma with the rosette-like collagen deposits.

A two-months-old, male, mixed breed cat presented with epileptic seizures. The cat was diagnosed with drug-resistant epilepsy, and died at 3-years of age. No gross lesion was found at necropsy. Histopathologically, the dentate gyrus granule cell layer of the hippocampus was irregularly arranged. Granule cells were dispersed and ectopic cells were sporadically observed in the molecular layer. The granule cells had an enlarged cytoplasm and swollen nucleus. Immunohistochemistry for NeuN and GFAP confirmed severe neuronal loss and mild gliosis in CA1. Binucleation and ischemic change were observed in the remaining pyramidal cells. This report describes a case of feline temporal lobe epilepsy and hippocampal sclerosis associated with dentate gyrus malformation.

Intestinal lymphangiectasia (IL) is often observed in dogs with chronic small intestinal diseases. Hypoplasia of the lymphatic vessel due to decreased lymphangiogenesis, which has been suggested in human idiopathic IL, may contribute to the pathogenesis of canine IL. This study aimed to evaluate the diameter and number of lymphatic vessels in full-thickness small intestinal specimens of dogs with IL. Immunohistochemical labeling of lymphatic endothelial cell markers was performed on retrospectively retrieved full-thickness small intestinal specimens. Sixteen dogs with histologically confirmed IL were included, of which 10 had lymphoplasmacytic enteritis (LPE), and six had granulomatous lymphangitis (GL). Nine dogs that died from non-gastrointestinal disorders and with little or no abnormalities in the small intestine were used as controls. Lymphatic vessel diameters in dogs with IL were significantly increased in all layers of the small intestine, including the villus lacteal, lamina propria, submucosa, muscularis, and mesentery, compared with controls (all P0.01). There was no significant difference in the lymphatic vessel diameters between dogs with LPE and GL (all P0.05). There was no significant difference in the number of lymphatic vessels between dogs with IL and the controls in all layers of the small intestine (all P0.05). This study demonstrated that IL was observed in all layers of the small intestine, including the submucosa, muscularis, and mesentery, independent of the underlying disease. Factors other than reduced lymphatic vessels would contribute to the pathogenesis of IL in dogs.

A 10-month-old, intact male Toy Poodle was referred for a postural abnormality. Blood biochemical tests revealed a marked increase in plasma creatine phosphokinase (CPK) concentration. The isoenzyme test showed that 99% of serum CPK consisted of CPK-MM. Histopathological evaluation of muscle biopsy samples confirmed scattered degeneration and necrosis of myofibers. Immunohistochemistry for dystrophin showed an absence of staining in muscle cells. Based on these findings, the dog was diagnosed with dystrophin-deficient muscular dystrophy. Whole genome sequencing using genomic DNA extracted from blood revealed a single base pair insertion in exon 45 of the Duchenne muscular dystrophy (DMD) gene. This is the first report on muscular dystrophy in Toy Poodles and identified a novel mutation in the DMD gene.

An 8-year 8-month-old castrated male Munchkin presented with vomiting, anorexia and hypoactivity. Computed tomography revealed excessive gas accumulation within the intestinal lumen and gas bubbles in the liver, spleen, and portal venous system, indicating hepatic portal venous gas. The cat died without any significant improvement, and mild splenomegaly was found at necropsy. Histologically, multiple gas vacuoles were diffusely observed in the liver and spleen. In the stomach, multiple gas vacuoles and scattered focal ulcers were detected within the mucosa. Multifocal hemorrhage was noted in the small and large intestines, whereas gas vacuoles were not present. Based on these findings, a gastric ulcer under high gas pressure may have provided an entry point for gas into the portal venous system.

This report described the histopathological and immunohistochemical features of cutaneous mast cell tumor (MCT) in six hedgehogs. The hedgehogs presented single cutaneous mass with ulcer and crusting. Histologically, the neoplastic lesions were characterized by the proliferation of well-differentiated mast cells (3 cases), and atypical mast cells (3 cases) with one atypical histiocytic morphology. Immunohistochemically, tumor cells were positive for KIT and mast cell tryptase, and were negative for Iba-1. In well-differentiated MCT, all patients were clinically improved and survived more than 365 days after surgical excision, whereas an atypical histiocytic MCT showed aggressive behavior with re-recurrence, and the animal died 115 days after surgery. These findings suggest that, compatible with other animals, well-differentiated MCT has a better prognosis in hedgehogs.

A 5-day-old male crossbred beef calf presented with a well-coordinated bilateral hopping gait of the hind limbs. Postmortem CT showed a poorly defined oval-shaped region at the L3-L4 spinal segments, which had high signal intensity on T2 weighted postmortem MRI images. On pathological examination, we identified a large cystic cavity filled with a large amount of cerebrospinal fluid on the cut surface of the spinal region. Histopathological examination revealed that the spinal cord parenchyma was compressed by the cystic structure, and the cystic cavity was lined with a thin layer of discrete ependymal cells, indicating syringohydromyelia. This is the first reported case of a Holstein-Friesian × Japanese Black crossbred calf with solitary syringohydromyelia. Our findings suggest that myelodysplasia with cystic cavities can be suspected by CT, without the need for MRI.

Aquaporin-2 (AQP2), a vasopressin-regulated water channel, plays an important role in renal water homeostasis. It has been reported that the level of AQP2 in human urine is altered during pregnancy. However, little is known about the level of urinary AQP2 in pregnant cattle. In this study, we examined the level of AQP2-bearing extracellular vesicles (uEV-AQP2), which account for most urinary AQP2, in both heifers and cows during the gestational and postpartum periods. The level of uEV-AQP2 was significantly decreased during gestation in comparison with the other cattle examined. Similarly, the levels of EV marker proteins in uEVs, including tumor susceptibility gene 101 (TSG101) protein and apoptosis-linked gene 2-interacting protein X (ALIX), were significantly decreased during gestation. There were significant correlations between the levels of uEV-AQP2 and uEV-TSG101, or uEV-ALIX. Immunohistochemistry data from pregnant and non-pregnant cattle supported the notion that the level of uEV-AQP2 was decreased during gestation. These data indicate that the level of uEV-AQP2 is decreased in pregnant cattle, possibly through a decrease in both the number of EVs released into the urine and renal AQP2 expression.

Meningioma is the most common primary brain tumor in cats, although there are few reports about their pathological features. To investigate the histopathological subtypes and immunohistochemical features including expression of cytokeratin and cell adhesion molecules, 45 cases of feline meningioma were examined. The mean age was 12.5 years (range 6-21 years). No statistically significant sex predilection was observed. Regarding the anatomical location of meningioma, tumors mostly developed in the cerebrum, followed by spinal cord and cerebellum, and multiple meningioma was observed in one cat. Microscopically, linear or focal mineralization was observed in 40 cases and cholesterol cleft was observed in 14 cases. Based on histopathological subtypes, there were 15 fibrous, 22 transitional, 2 meningothelial, 5 atypical, and 1 anaplastic meningiomas. These subtypes are classified into grade 1 (39 cases), grade 2 (5 cases), and grade 3 (1 case). There was no significant difference in the Ki-67 index among histological subtypes or grades. Immunohistochemically, the tumor cells were positive for cytokeratin in 5 cases (12.8%), vimentin in 17 cases (43.6%), E-cadherin in 36 cases (92.3%), β-catenin in 21 cases (53.8%), and N-cadherin in 1 case (2.6%), demonstrating the utility of E-cadherin-immunohistochemistry for the diagnosis of feline meningiomas.

A retrospective study involving eight African pygmy hedgehogs histopathologically diagnosed with granulosa cell tumors was conducted. The age at onset was 2.2–4.5 years, with a median age of 3.6 years. The most common clinical signs were hematuria and abdominal distension, which were observed in >50% cases. Exploratory laparotomy was performed in all cases, and ovariohysterectomy or excision of the abdominal mass was performed. Patients with only hematuria survived for >250 days after surgery, whereas those with initial ascites showed recurrence of ascites or tumor growth and survived for approximately 130 days after surgery. Intraperitoneal injection of carboplatin was performed in three recurrent cases. In one of these three cases, the tumor mass disappeared. Hence, carboplatin can be considered a potential antineoplastic drug for the treatment of granulosa cell tumors.

Copy number gain (CNG) and/or protein overexpression of ErbB2 have been observed in human breast cancer patients and are associated with poor prognosis. Similarly, ErbB2 overexpression has also been observed in canine mammary carcinoma; however, data on ErbB2 copy number is limited. The purposes of this study were to evaluate ErbB2 copy number in dogs with mammary carcinoma and to investigate associations of ErbB2 CNG with ErbB2 expression, histological and clinical characteristics, and survival. DNA samples were isolated from 59 formalin-fixed paraffin-embedded canine mammary gland tissues (34 carcinoma, 14 adenoma, and 11 normal). Using a digital PCR assay, the ErbB2 copy number in these samples was determined as compared to a reference gene on canine chromosome 8. ErbB2 CNG was detected in 14/34 (41%) carcinomas and 2/14 (14%) adenomas. ErbB2 overexpression was observed in 3/34 (9%) carcinomas but not in adenomas. Neither ErbB2 CNG nor ErbB2 overexpression were detected in the normal controls. There was no significant association of the ErbB2 CNG with histological and clinical characteristics such as age, neutered status, histological grade, tumor size, lymph node involvement, distant metastasis, and clinical stage in the dogs with mammary carcinoma. The presence of ErbB2 CNG, but not ErbB2 overexpression, was significantly related to the shorter overall survival. These findings suggest that ErbB2 CNG is a prognostic factor in dogs with mammary carcinoma.

Wnt/beta-catenin signaling, E-cadherin and p53 reportedly play important roles in the development and/or progression of human gastrointestinal cancer. The present study evaluated the roles of beta-catenin, E-cadherin and p53 in canine gastrointestinal tumors. Endoscopic biopsy or surgically resected samples, a total of 131, including 38 gastric, 13 small intestinal and 80 large intestinal tumors, were obtained from 95 dogs. Those specimens were examined pathologically. Immunohistochemically, nuclear beta-catenin expression was found in 88% (42/48) of polypoid type adenocarcinomas. Most cases of non-polypoid type adenocarcinomas lacked nuclear expression of beta-catenin with the exception of one case (6%, 1/17). Nuclear beta-catenin expression was not observed in signet ring cell carcinomas (0/15), mucinous adenocarcinomas (0/7) and undifferentiated carcinomas (0/4). The findings indicate that nuclear translocation of beta-catenin is closely related to the development of polypoid type adenocarcinomas but not that of non-polypoid type malignant tumors. The immunoreactivity of E-cadherin for tumor cells tended to decline overall in most of cases including benign tumors. Significant immunoreactivity for p53 was not found in 61% of tumors examined (80/131), including malignant tumors (63%, 57/91), while intense p53-immunoreactivity was rarely found in a few cases of malignant tumors (8%, 7/91). We could not conclude clearly significant correlations between histopathological tumor types and immunohistochemical results of E-cadherin or p53. This paper indicates the importance of the nuclear translocation of beta-catenin for the tumorigenesis of canine intestinal polypoid type adenocarcinomas, especially in the colorectum.

The present study describes the association between inflammatory cell types and feline infectious peritonitis virus (FIPV) antigen in the brain of 4 cats diagnosed as feline infectious peritonitis (FIP). Immunohistochemically, FIPV antigens were detected in the inflammatory foci of the leptomeninges, choroid plexus and ventricles in 3 of the 4 cats. In 3 cases, inflammatory foci mainly consisted of CD204- and Iba1-positive macrophages, and the FIPV antigens were found in the macrophages. In the other case which was negative for FIPV antigen, severe inflammation predominantly consisting of CD20-positive B lymphocytes was observed in the leptomeninges and subventricles, accompanied with diffuse proliferation of gemistocytic astrocytes. The difference in histopathology may reflect the inflammatory process or the strain variation of FIP virus.

A large abdominal mass was found in a dog. Histopathologically, the surface of the mass was covered with compressed adrenal gland tissue. The neoplastic cells showed typical features of malignant peripheral nerve sheath tumor (MPNST), including Antoni type A and type B pattern, and nuclear palisading. Immunohistochemically, these cells were positive for S100 protein, nerve growth factor receptor, nestin and claudin-1. The dog was euthanized because of the developing multiple metastatic lesions. The metastatic cells showed quite similar histopathological and immunohistochemical features as those in the original tumor. Although MPNST can develop at many body sites, this is the first report of MPNST originating from the adrenal gland in a dog.

Amyloid A (AA) amyloidosis, a fatal systemic amyloid disease, occurs secondary to chronic inflammatory conditions in humans. Although persistently elevated serum amyloid A (SAA) levels are required for its pathogenesis, not all individuals with chronic inflammation necessarily develop AA amyloidosis. Furthermore, many diseases in cats are associated with the elevated production of SAA, whereas only a small number actually develop AA amyloidosis. We hypothesized that a genetic mutation in the SAA gene may strongly contribute to the pathogenesis of feline AA amyloidosis. In the present study, genomic DNA from four Japanese domestic cats (JDCs) with AA amyloidosis and from five without amyloidosis was analyzed using polymerase chain reaction (PCR) amplification and direct sequencing. We identified the novel variation combination of 45R-51A in the deduced amino acid sequences of four JDCs with amyloidosis and five without. However, there was no relationship between amino acid variations and the distribution of AA amyloid deposits, indicating that differences in SAA sequences do not contribute to the pathogenesis of AA amyloidosis. Immunohistochemical analysis using antisera against the three different parts of the feline SAA protein-i.e., the N-terminal, central, and C-terminal regions-revealed that feline AA contained the C-terminus, unlike human AA. These results indicate that the cleavage and degradation of the C-terminus are not essential for amyloid fibril formation in JDCs.

Short chain fatty acids (SCFAs) play an important role in the maintenance of colonic homeostasis, and their depletion has been reported in various gastrointestinal disorders. Inflammatory colorectal polyps (ICRPs) are a recently recognized disease specific to miniature dachshunds (MDs), and fecal dysbiosis with a reduction of SCFA-producing bacteria has been reported with this disease. Therefore, this study was performed based on the hypothesis that a reduced SCFA concentration associates with the development of ICRPs. We recruited 11 ICRP-affected MDs and 25 control MDs. Their fecal SCFA concentrations and bacterial proportions were quantified using high performance liquid chromatography and quantitative real-time PCR, respectively. The feces of ICRP-affected MDs contained lower amounts of propionic acid and lower proportions of Bifidobacterium than the feces of control MDs. Furthermore, fecal proportions of Bifidobacterium, Firmicutes and Lactobacillus exhibited significant positive correlations with fecal concentrations of total SCFAs and/or propionic acid; fecal Escherichia coli proportions correlated negatively with fecal concentrations of total SCFAs, as well as acetic, propionic and butyric acid. This result indicates an association between fecal dysbiosis and fecal SCFA concentrations; these phenomena may contribute to ICRP pathogenesis in MDs. Potential therapeutic targeting of the reduced propionic acid concentration using probiotics, prebiotics or SCFA enemas merits further study.

Neuroaxonal dystrophy (NAD) is a neurodegenerative disease characterized by severe axonal swelling (spheroids) throughout the nervous system. In dogs, NAD has been reported in several breeds and a missense mutation in PLA2G6 gene has recently been identified in the Papillon dog NAD. Here we performed ultrastructural analysis to clarify the detailed ultrastructural features of the Papillon dog NAD. Dystrophic axons consisted of accumulation of filamentous materials, tubulovesicular structures, and swollen edematous mitochondria with degenerated inner membranes were often observed in the central nervous system. At axonal terminals, degeneration of presynaptic membrane was also detected. As reported in Pla2g6 knockout mice, mitochondrial and presynaptic degeneration may be related with the pathogenesis of NAD in Papillon dogs.

A 10-year-old mixed breed dog was presented with a 0.8 cm diameter mass below the left eye region. The mass was surgically removed and processed for histopathological examination. Microscopically, tumor cells proliferated in small lobules, nests and cords, and the tumor parenchyma was separated by desmoplastic stroma. Majority of the tumor cells were periodic acid-Schiff (PAS)-positive, and the desmoplastic stroma was densely collagenous and mucinous. Immunohistochemical results showed that the tumor cells were diffusely positive for cytokeratin 15, cytokeratin 19 and CD 34, while cytokeratin 8 reactivity was limited to the tumor cells proliferating in cords. Few tumor cells were positive for nestin. Based on the histopathological findings, the tumor was diagnosed as desmoplastic tricholemmoma.

An 18-month-old female Holstein Friesian heifer presented with a history of stunted growth and a recent onset of anorexia; she presented with cyanosis and eventually died. A postmortem examination revealed obstruction of the right ventricular outflow tract, ventricular septal defect, overriding aortic root, right ventricular hypertrophy, and an atrial septal defect, indicating a pentalogy of Fallot (POF). In addition to POF, the heifer also had pulmonary artery dilatation, although she did not present with patent ductus arteriosus. This heifer had the longest lifespan among the Holstein cattle reported to have POF, which may be secondary to delayed pulmonary obstruction due to deformation of one of the pulmonary valves.

Pigmented viral plaque is most commonly seen in Pug dogs in association with canine papillomavirus (CPV). In the present study, nucleic acid sequence and localization of viral genes were examined in 4 cases of pigmented viral plaque in Pug dogs. The results of polymerase chain reaction and nucleic acid sequence analysis showed that the 3 cases with pigmented viral plaque were infected with CPV4, and 1 case with CPV18. In the case with CPV18-positive viral plaque, CPV18 gene was also detected in a lesion of cytokeratin-14- and P63-positive basal cell tumor that developed adjacent to a pigmented viral plaque. Moreover, CPV gene was detected in the squamous cells of pigmented viral plaques and the neoplastic cells of basal cell tumor by in situ hybridization. This is the first report of basal cell tumor associated with CPV18-infection in the dog. Infection of CPV18 may be associated with development of basal cell tumor.

Cutaneous tumors are commonly found in dogs. To date, few studies have investigated the epidemiology of canine cutaneous tumors in Asian countries. The present study aims to report the prevalence of canine cutaneous tumors in Japan, and assess the association of breed, age, sex, and anatomical locations with the development of common tumor types. A total of 1,435 cases of cutaneous tumors were examined, of which 813 (56.66%) cases were malignant, and 622 (43.34%) were benign. Soft tissue sarcomas (18.40%), mast cell tumor (16.24%), lipoma (9.69%), hair follicle tumors (9.34%), and benign sebaceous tumors (8.50%) outnumbered the other tumor types. Tumors were commonly found on the head (13.87%), hindlimb (10.52%), forelimb (8.01%), chest (5.78%), and neck (5.57%). The risk of developing cutaneous tumors increased significantly in dogs aged 11-year and above (P

Clinical and histopathological characteristics of 16 dogs with nodal paracortical (T-zone) lymphoma (TZL) were evaluated. At initial examination, generalized lymphadenopathy was found in all dogs, and peripheral lymphocytosis was found in 10 of the 16 dogs. At initial diagnosis or during the disease course, 8 dogs (50%) were affected with demodicosis. Immunohistochemical analysis for CD3, CD20 and CD25 was performed for 6 dogs with TZL; the tumor cells were positive for CD3 and CD25 and negative for CD20. Median overall survival time was 938 days. A watchful waiting approach was adopted for 6 cases (38%), and 5 of the 6 dogs were still alive at the end of follow-up. The clinical course of TZL in dogs is generally indolent; however, many cases develop a variety of infectious and other neoplastic diseases after the diagnosis of TZL.

A 2.5-year-old male French Bulldog was evaluated for seizures. Cranial magnetic resonance imaging (MRI) suggested a glioma in the left piriform area. Radiation therapy (RT) and continuous chemotherapy were administered. Although the lesion had regressed significantly 2 months after RT, a follow-up MRI revealed meningeal enhancement in the left piriform area, which expanded further, with hydrocephalus, by day 310 (8 months after RT). Because of the poor prognosis, the dog was euthanized on day 356 and necropsy was performed. Histopathological examination confirmed anaplastic oligodendroglioma with leptomeningeal dissemination. This case suggests that the possibility of leptomeningeal dissemination and hydrocephalus should be considered even after RT and chemotherapy for anaplastic oligodendroglioma.

A hard palate mass was surgically removed from an Australian green tree frog (Litoria caerulea) and examined pathologically. The tumor consisted of sheets of small cells arranged in a tubular structure and cords or rosettes with fibrovascular stroma. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin and neuron-specific enolase and partially positive for S-100 and doublecortin. These findings indicate that the tumor originated from the neuroectodermal tissue. Based on these findings, the tumor was classified as a neuromastoma (neuroepithelioma). Sensory cells located in the hard palate of the frog were considered to be the origin of the tumor. The frog died after going through 3 surgeries and experiencing difficulties closing its mouth.

Association of felis catus papillomaviruses (FcaPVs) with feline squamous cell carcinoma (SCC) has been reported worldwide, while there is limited information about FcaPVs in Asia. In this study, 21 feline SCC biopsy samples from cats in Japan were analyzed by PCR with PV consensus primers and type-specific primers for FcaPV type 2 (FcaPV-2), FcaPV-3 and FcaPV-4 designed in this study. Sequence analysis revealed that one sample was FcaPV-3, and two were FcaPV-4. In both FcaPV-4 positive samples, 334th tryptophan in L1 ORF was deleted compared with the reference sequence. Moreover, immunohistochemistry showed that p16 protein was positive in both FcaPV-4 detected samples. This study would contribute to the molecular epidemiological and pathological understanding of FcaPV in Japan.

A 6-year 5-month-old spayed female Scottish Fold cat presented with a one-month history of gait abnormalities, increased salivation, and decreased activity. A blood test showed hyperammonemia and increased serum bile acids. Imaging tests revealed multiple shunt vessels indicating acquired portosystemic shunt. Histopathologic analysis of liver biopsy showed features consistent with liver hypoperfusion, such as a barely recognizable portal vein, increased numbers of small arterioles, and diffuse vacuolar degeneration of hepatocytes. These findings supported the diagnosis of primary hypoplasia of the portal vein/microvascular dysplasia, (PHPV/MVD). To our knowledge, this is the first case of feline PHPV/MVD that developed multiple acquired portosystemic shunts and presented with hepatic encephalopathy.

Canine cognitive dysfunction (CCD) is a syndrome that manifests itself in abnormal behaviors, such as disorientation and wandering. β-amyloid deposition in the brain, including the senile plaque (SP) and cerebral amyloid angiopathy (CAA), has been suggested as a major cause of the syndrome. However, the pathological significance of β-amyloid deposition in CCD dogs remains unclear. The present study was conducted using 16 dogs aged 10 years or older to clarify the relationship between the age-related histopathological lesions, such as β-amyloid deposition, in the brain and the clinical symptoms of CCD as evaluated in a questionnaire previously established in a large survey. In addition, age-related brain lesions were assessed in 37 dogs. The pathological lesions were evaluated by the severity of β-amyloid deposition (SP and CAA), the amount of ubiquitin-positive granules (UBQ), GFAP-positive astrocytes, Iba-1-positive microglia and Nissle stain-positive nerve cells. The results revealed that there was no significant correlation between the severities of canine SP and CCD. The SP increased until 14 years old, but decreased thereafter, although the incidence of CCD is high at these ages. The CAA consistently increased with age, but did not correlate greatly with the CCD score. In contrast, the increases of UBQ, astrocytes and microglia were significantly correlated with CCD. Thus, the impairment in the synapse and/or myelin suggested by increased UBQ and glial activation might be involved in CCD pathogenesis, but β-amyloid deposition, especially SP, is not a direct pathogenic factor of CCD.

Canine squamous cell carcinoma (SCC) shows highly invasive and locally destructive growth. In animal models and human cancer cases, periostin plays a critical role in the enhancement of cancer growth; however, the mechanism of involvement in canine cancers remains unknown. The aim of this study was to examine the involvement of periostin in the pathophysiology of SCC in dogs. We examined the localization of periostin and periostin-producing cells in 20 SCC and three squamous papilloma specimens. Furthermore, we focused on transforming growth factor (TGF)-β1, which was assumed to be an inducing factor of periostin, using culture cells. By immunohistochemistry, limited periostin expression in the stroma was observed in all squamous papillomas. In SCC, periostin protein diffusely expressed at the tumor invasion front of cancer growth. In situ hybridization revealed that periostin mRNA was expressed in the stromal fibroblasts in SCC. In vitro analysis determined that canine SCC cells expressed significantly higher levels of TGF-β1 mRNA compared with canine keratinocytes. In addition, recombinant TGF-β1 induced secretion of periostin from cultured dermal fibroblasts. These data suggest that periostin produced by stromal fibroblasts may be involved in the pathophysiology of canine SCC. TGF-β1 derived from SCC cells may stimulate fibroblasts to produce periostin.

Canine histiocytic sarcoma (HS) is a malignancy originating from the histiocytic cell lineage and characterized by poor response to chemotherapy and short survival time. Mutation of the TP53 gene and its association with poor prognosis has been reported in several canine tumors. However, the mutation of this gene has not been investigated in canine HS. The aim of this study was to examine a TP53 gene mutation in dogs with HS. Aberrations of the TP53 gene were examined by polymerase chain reaction-single strand conformational polymorphism analysis and DNA sequence analysis, revealing mutations of the TP53 gene in 12 (46%) of 26 dogs affected by HS. The incidence of the TP53 gene mutation was relatively high in canine HS compared with other canine tumors. Among these mutations, 10 of 12 dogs (83%) with a TP53 gene mutation harbored the same mutation: a 2-base (AT) insertion in exon 5, resulting in the introduction of a stop codon (c.446_447insAT, p.Tyr150SerfsX8). Further studies are needed to examine the functional change due to the mutation and its association with the pathogenesis of canine HS.

A 7-year-old castrated male ferret developed unilateral cervical lymphadenomegaly over a 1-month period. Histological examination revealed proliferation of tumor cells in a diffuse and partially nodular pattern. The tumor cells were predominantly Hodgkin cells and binucleated Reed-Sternberg cells, characterized by abundant, clear, vacuolated cytoplasm, pleomorphic, ovoid nuclei with thick nuclear membranes and distinct nucleoli. Multinucleated cells, resembling lymphocytic and histiocytic (L&H) cells, were also observed. Immunohistochemically, the tumor cells expressed Pax-5, BLA-36 and vimentin. A small population of the tumor cells expressed CD20. This case showed proliferation of Hodgkin/Reed-Sternberg cells in conjunction with L&H cells that were histologically analogous to feline Hodgkin’s-like lymphoma. However, Pax-5 and BLA-36 expression along with rare CD20 expression were consistent with classical Hodgkin’s lymphoma in humans.

An 8-year-old spayed female Netherland Dwarf rabbit presented with a two-month history of dyspnea and snoring. A computed tomography (CT) scan of the head revealed mass lesions in the right nasal cavity. Surgical exenteration of the lesions was performed, and the histopathological diagnosis was an intranasal adenocarcinoma. On the basis of this diagnosis, radiotherapy was planned and consisted of eight fractions of 6 Gy administered once a week. After the completion of radiation therapy, the soft tissue density in the right nasal cavity, as detected by CT, significantly decreased. The prognosis has remained good for over 3 years after treatment. This paper is the first to describe the clinical and pathological features of an intranasal tumor in a rabbit.

Histiocytic sarcoma is a progressive and fatal malignant neoplasm that mainly occurs in middle- to old-aged dogs. This study describes clinicopathological, histological and immunohistochemical characteristics of intracranial histiocytic sarcomas in 23 dogs. Magnetic resonance imaging and/or computed tomography of the brains revealed that the tumors mainly located in the cerebrum, particularly the frontal lobe. Seizure was a predominant clinical sign in most of the cases. Histologically, the tumor cells were morphologically classified into round/polygonal- and spindle-shaped cell types. There was a significant association between tumor cell types and hemophagocytic activity (P

A 12-year-old spayed female Labrador retriever was presented with forebrain signs. Brain MRI revealed a huge cystic lesion with the thickened falx in the frontal region. The brain parenchyma surrounding the lesion showed significant signs of a mass effect and also increased intracranial pressure. However, the dog suddenly became lucid after about two weeks, and an MRI scan one month after the initial study revealed a dramatically shrunken cystic lesion. The dog survived for over a year until it was euthanized for other reasons, and the brain lesion was diagnosed as a cystic meningioma histologically. To the authors' knowledge, this is the first report that described the reduction of the cystic lesion of a cystic meningioma in dogs.

Little information is available regarding triple-phase computed tomography (CT) of canine pancreatic insulinoma. A few case reports with small numbers of cases have indicated that hyper-attenuation in the arterial phase was a common finding on multi-phasic CT in dogs with insulinoma. Our purpose was to clarify the characteristic findings of dogs with insulinoma on triple-phase CT. Nine dogs with insulinoma that underwent triple-phase CT were included in the present study. Attenuation patterns in the arterial phase indicated hypo-attenuation in 4 cases and hyper-attenuation in 2 cases. In the remaining 3 cases, 1 case showed hypo-attenuation and 1 case showed hyper-attenuation in the pancreatic phase, and 1 case presented hyper-attenuation in the later phase. Altogether, 5 cases showed hypo and 4 cases showed hyper-attenuation in at least one phase. The enhancement pattern was homogenous in 7 cases and heterogeneous in 2 cases. Tumor margins were well-defined in 5 cases and ill-defined in 4 cases. Capsule formation was present in 5 cases and absent in 4 cases. In conclusion, it is important to note that hypo-attenuation was as common as hyper-attenuation in dogs with insulinoma in triple-phase CT in at least one phase. Additionally, mass lesions were most conspicuous not only in the arterial phase but in the pancreatic and later phases in some cases. Therefore, it is important to perform triple-phase CT and notice about variable findings for the detection of canine pancreatic insulinoma.

Ollulanus tricuspis is a small nematode parasite of the stomach, and its infection has been reported worldwide in cats but only one report in dogs as post-mortem diagnosis. Two dogs, kept in the Tokyo area, were presented for chronic vomiting. Chronic gastritis was diagnosed histologically, and many nematodes were detected in endoscopically-biopsied gastric samples and in the mucus of vomitus in both dogs. The parasites were small (

A 10-year-old castrated male mixed-breed dog exhibited vomiting, lethargy and anorexia. An abdominal ultrasound examination revealed a focal dilation of the abdominal aorta. The dog died 2 days after examination, and necropsy revealed a ruptured aneurysm at the abdominal aorta between the kidneys. Histological examination revealed severe granulomatous and necrotizing pan-arteritis with fungal organisms. Graphium species was identified through DNA sequence analysis of the PCR product from formalin-fixed paraffin-embedded samples. To our knowledge, this is the first report of aortic aneurysm caused by Graphium species in a dog. Sequence was submitted to the DNA Data Bank of Japan with the accession number LC007972.

A 6-year-old female rabbit was presented to a veterinary clinic, and the result of ultrasound examination suggested a tumor in the uterine tube. Subsequently, both ovaries and uterus were surgically removed. In gross, a single large cyst in the right ovary and enlargement of the left uterine tube were observed. Histological examination revealed that the cyst had developed in the hilus of the ovary and was lined by single-layered cuboidal cells. In the left uterine tube, a tumor composed of epithelial cells arranged in tubular structures and pleomorphic cells between the tubular structures was observed. Immunohistochemically, the epithelial cells of the cyst were positive for pan-cytokeratin, cytokeratin 18, CD10, E-cadherin, calretinin and estrogen receptor; the tumor cells of the left uterine tube were positive for pan-cytokeratin, cytokeratin 18, E-cadherin, vimentin, calretinin and estrogen receptor. From these results, the cyst was diagnosed as cystic rete ovarii, and the tumor was diagnosed as adenoma of the uterine tube. This case is the first to demonstrate cystic rete ovarii and uterine tube adenoma in rabbits.

It is known that Helicobacter hepaticus or Helicobacter bilis infection causes chronic inflammation of the colon and liver. Chronic active hepatitis was found in radiation exposure experiments using male C3H/HeNrs mice at our institute. Histopathologically, 103 cases among 978 mice (64-91 weeks of age at autopsy) had hepatic lesions regardless of irradiation exposure. Mild lesions showed only focal necrosis and focal inflammation in the liver. Severe cases were accompanied by hepatocytomegaly, bile duct hyperplasia, hypertrophy and activation of Kupffer cells, cholangitis, pleomorphic hepatocytes and/or tumor. Helical-shaped bacteria were detected between hepatocytes by Warthin-Starry silver stain and immunohistochemistry (IHC) with an antibody against Helicobacter pylori. It was suggested that these cases of chronic hepatitis were caused by Helicobacter spp. Although chronic hepatitis occurred frequently in mice exposed high-dose irradiation compared with nonirradiated mice in one lot, it was not concluded that radiation might influence the incidence or degree of hepatitis. Our report suggested that natural Helicobacter spp. infection in mice can occur in an experimental animal facility. Therefore, it is suggested that monitoring of Helicobacter infection is very important for quality control of animal experiments.

Urea breath test (UBT) using an infrared spectral analyzer is widely used for non-invasive and rapid detection of gastric Helicobacter spp. in human, but not veterinary medicine. The main purposes of this study were to determine the reference range of the UBT in dogs and to evaluate its clinical usefulness. To address the first aim, 6 healthy laboratory beagles were subjected to UBT and upper gastrointestinal endoscopy. Gastric endoscopic biopsy samples from the antrum, corpus and fundus were examined for Helicobacter spp. by polymerase chain reaction (PCR) testing, rapid urease test (RUT), histology and cytology. Amoxicillin, metronidazole and omeprazole were given to infected dogs for 14 days, and dogs that became Helicobacter-negative were used to determine the reference range for UBT. To address the second aim, 32 canine patients underwent UBT before upper gastrointestinal endoscopy, and the sensitivity and specificity of UBT were calculated based on our newly determined reference range using PCR as the gold standard for detection of Helicobacter spp. Initially, all 6 laboratory beagles were infected in all gastric regions and became uninfected after eradication. The mean ± 2 SD UBT value after eradication was 0.6 ± 1.8‰, and the reference range for UBT was determined to be less than 2.5‰. UBT was completed successfully in 27 patients. Using our reference range, UBT displayed 89% (16/18) sensitivity and 89% (8/9) specificity, indicating that UBT was quite useful for the detection of gastric Helicobacter spp. infection in dogs.

A new-born (8-day-old) male marmoset (Callithrix jacchus) was found dead in a zoo. The littermate and parents had no clinical abnormalities. By gross observations at necropsy, there were moderate to severe multiple necrotic foci in the liver and heart. Histopathological examinations also revealed mild focal necrosis with neutrophilic infiltration in the cerebral cortex. By Giemsa stained sections, intracytoplasmic bundles of large bacilli were observed in the hepatocytes, intestinal epithelial cells, cardiac myocytes and neuronal cells around the necrotic lesions. Immunohistochemically, these bacilli were intensely positive for rabbit sera against Clostridium piliforme, RT and MSK strains. Although Tyzzer's disease has been rarely reported in primates, the central nervous system (CNS) lesions by Clostridium piliforme infections are very unusual.

Canine polyneuropathy is a neurological disorder characterized by a dysfunction of multiple peripheral nerves. The etiology of the disease is diverse; it may occur in cases of infectious, immune-mediated, or hereditary conditions or in association with endocrinopathy, neoplasm, or chemical intoxication. It is often difficult to determine the etiology through clinical symptoms. The aim of this study is to investigate pathological differences among three canine polyneuropathy cases with each presumably having a different etiology. Cases included a 13-month-old female border collie (Dog No.1), a 21-month-old male chihuahua (Dog No.2) and an 11-year-old male beagle (Dog No.3). Clinical examinations revealed hindlimb ataxia and sensory loss in Dog No.1, forelimb paralysis and vertebral pain in Dog No.2, and paddling-gait and hypothyroidism in Dog No.3. Histopathologically, axonal swelling and pale myelin were observed in Dog No.1. Giant axons mimicking giant axonal neuropathy were obvious in Dog No.2. Dog No.3 showed atrophic axons and severe interstitial edema. Distributions of peripheral nerve lesions coincided with respective clinical symptoms. According to their clinical and pathological features, Dogs No.1 and No.2 were suspected of hereditary polyneuropathy, while Dog No.3 seemed to have hypothyroidism-associated polyneuropathy. As each case demonstrated unique pathological features, different pathogeneses of peripheral nerve dysfunction were suggested.

A 9 year-old, neutered, male French Bulldog showing cluster seizures was diagnosed with a glioma in the right piriform cortex by MRI. Hypofractionated radiation therapy (RT) was performed using a linear accelerator. Although the lesion had involuted significantly at 2 months after RT, recurrence was observed at 4 months after RT. Chemotherapy was started using CCNU (60 mg/m(2) every 6-9 weeks) and was continued for one year. Follow-up MRI revealed involution of the lesion and the intervals of CCNU were increased to every 9-14 weeks. Two years after the first presentation, the dog suffered status epilepticus, followed by deficits of left sided postural reaction with cognitive dysfunction. The dog died on day 910, and histopathological diagnosis confirmed anaplastic oligodendroglioma.

A Japanese domestic long-hair cat of about 8 years of age was presented with vomiting and hematochezia and was found to have significant hypereosinophilia. Bone marrow aspiration revealed moderate increases of eosinophilic lineages. Histopathological examination revealed mild eosinophilic and epitheliotropic T-lymphocytic infiltrations in the duodenum. Although the cat remained asymptomatic with only prednisolone administration, the cat presented with hematemesis, weight loss, and severe anorexia 512 days after the initial presentation. Subsequently, gastrointestinal perforation developed, and the cat died on Day 536. Histopathological examination of autopsy specimens revealed mixed cellular infiltration including eosinophils and neoplastic lymphocytes in the intestinal lymph nodes, intestine, liver, spleen, and pancreas. Immunohistochemical examination supports a diagnosis of intestinal T-cell lymphoma with severe hypereosinophilic syndrome.

Curcumin is a constituent phenol compound of turmeric, and has been used as a dietary spice and Indian medicine. Curcumin has been reported to inhibit the formation of amyloid β fibrils and aggregation. In this study, the binding activity of curcumin to various types of canine amyloid was examined. Tissue samples used were lesions of AA, AL, amyloid of canine amyloid-producing odontogenic tumor (Aapot), and senile cardiovascular amyloid (ScA). Curcumin stained all types of amyloid. The binding of curcumin to AA, ScA, and AL was lost by the KMnO(4) treatment, but Aapot maintained the binding. These findings indicate that curcumin binds several types of amyloid, while the binding sites of amyloid molecules might be different from that of Congo red.

Medical records of dogs with colorectal polyps were retrospectively reviewed, and clinical presentation of inflammatory colorectal polyps in miniature dachshunds was evaluated. Of 33 dogs found to have colorectal polyps, miniature dachshunds were markedly over-represented with 16 dogs (48%), of which 12 (75%) were found to have inflammatory polyps. Multiple polyps localized between the rectum and the descending colon was the most common finding in miniature dachshunds with inflammatory polyps. Twenty dogs (80%) out of 25 miniature dachshunds with inflammatory colorectal polyps responded to immunosuppressive therapy using prednisolone and cyclosporine. The results of this study indicate that miniature dachshunds are predisposed to develop inflammatory colorectal multiple polyps, for which immunosuppressive therapy may be a treatment option.