A Japanese Black cow presented with anorexia. Exophthalmos, a subcutaneous mass, and astasia were noted on physical examination. Hematological examination revealed lymphocytosis (5544/μL). Serum biochemical findings included elevated activities of lactate dehydrogenase and thymidine kinase. Antibodies against bovine leukemia virus (BLV) were detected. The animal was euthanized and necroscopic evaluation was performed, and masses were found in both orbit and left pectoral region; white solid tissue growth in fatty tissue was observed throughout the body. Yellowish-white solid tissue was also observed around the right nerve roots from the 9th thoracic spinal nerves to the 4th lumbar spinal nerves. Immunohistochemical examination showed neoplastic B-cells (positive for BLA-36, CD79α, and PAX5, and negative for CD3) proliferation in the mass lesions and yellowish-white solid tissues. Two integration sites of BLV provirus in peripheral blood and tumor tissues were detected by inverse PCR. Based on these findings, the present case was diagnosed with enzootic bovine leukosis (EBL). The BLV provirus was found to have integrated into the introns of itchy E3 ubiquitin protein ligase (ITCH) and Selenoprotein I (SELENOI). ITCH is a key player of TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis, and SELENOI adjusts oxidative stress in tissues. Integration of BLV provirus into these genes might have contributed to the onset of EBL and influenced the distribution of neoplastic lesions.

A 9-month-old female mixed-breed dog weighing 3.25 kg was referred for elective ovariohysterectomy. A previous attempt had been aborted when the abdominal organs appeared to be enclosed within an abnormal membranous structure. At surgery, the abdominal viscera visible within the operative field were covered by a thin, translucent membrane that could be bluntly dissected from the organ surfaces without hemorrhage. The excised membrane was submitted for histopathological analysis. Postoperative non-contrast computed tomography did not identify abnormal soft-tissue densities or displacement of abdominal organs. Histopathological analysis revealed coarse, fibro-collagenous tissue composed of interspersed, flattened spindle cells without a mesothelial lining and without inflammation. These findings supported a presumptive diagnosis of congenital peritoneal encapsulation, an extremely rare developmental anomaly. This case highlights the need to recognize this condition as a potential incidental finding during routine abdominal procedures in dogs. Key clinical message: Congenital peritoneal encapsulation should be considered when an unexpected membranous covering of abdominal viscera is encountered during routine abdominal surgery in a young dog. Recognition of this rare developmental anomaly may prevent unnecessary surgical intervention or premature abandonment of the procedure.

Brachycephalic dogs, characterized by unique dome-shaped skulls and limited cerebral cortical volumes, are predisposed to brain tumors, particularly oligodendrogliomas. Canine oligodendrogliomasoften ariseadjacenttothecerebralventriclesandexpress several neural stem cell (NSC) markers, including sex-determining region Y-box transcription factor (SOX) 2, suggesting that NSCs are their origin. To investigate why oligodendrogliomas are more prevalent in brachycephalic dogs, the quantity, immunophenotypes, and proliferative activity of NSCs were examined and compared in the brains of adult brachycephalic and non-brachycephalic dogs. Histological examinations revealed clusters of two types of cells, small round cells and medium-sized spindle cells, in the subventricular zone and caudate nucleus in all samples. Immunohistochemically, small round cells were positive for SOX2 and doublecortin, corresponding to type A NSCs (neuroblasts). Medium-sized spindle cells were positive for SOX2, SOX9, and vimentin, corresponding to type B NSCs (multipotent astrocytes). The number of SOX2-positive and proliferating cell nuclear antigen-positive cells in the caudate nucleus was significantly higher in brachycephalic dogs than in non-brachycephalic dogs. We then examined canine oligodendroglioma tissues and found that tumor cells were immunopositive for SOX2, SOX9, and vimentin, similar to the immunophenotype of type B NSCs. These results indicate that brachycephalic adult dogs retain a higher number of NSCs with higher proliferative activity in the brain, which may create an environment prone to oligodendroglioma.

Hemangioblastomas are rare intramedullary vascular tumors. Their biological nature is considered benign, but there is little information in dogs. This report describes histopathological and immunohistochemical features and postoperative clinical courses of three dogs to expand the current knowledge of this tumor. Histopathological examination revealed the proliferation of neoplastic stromal cells with irregularly arranged blood vessels and clusters of lymphocytes. Immunohistochemically, neoplastic stromal cells were immunolabeled for glial fibrillary acidic protein (GFAP), neuron specific antigen (NSE), and vimentin, and capillary endothelia and vessel walls were immunolabeled for CD31 and smooth muscle actin (SMA). Postoperative follow-up revealed improvements in neurological symptoms and no evidence of tumor recurrence for 3 months to 3 years, suggesting that surgical excision is a beneficial treatment method.

A 1-year-3-month-old neutered female ferret presented with anorexia, weight loss, and increased liver enzymes and total bile acids. On day 49 of illness, neurologic signs appeared, necessitating humane euthanasia. Macroscopically, the liver was pale yellow with an irregular surface, and two tortuous shunt vessels from the cranial mesenteric vein to the caudal vena cava were observed cranial to the left kidney. Microscopically, single or a few hepatocytes were demarcated by reticular and collagen fibers with an extensive ductular reaction throughout all liver lobes. Bacterial chronic cholangitis was observed. Bilaterally symmetrical spongy degeneration was observed in the brain nuclei. Collectively, the present case showed lobular dissecting hepatitis-like chronic hepatitis with chronic cholangitis, accompanied by an acquired portosystemic shunt and hepatic encephalopathy.

Canine high-grade oligodendrogliomas (HGOGs) exhibit a high expression of platelet-derived growth factor receptor-α (PDGFRA). We examined PDGFRA mutations and gain of PDGFRA and their association with the PDGFRA expression and proliferation of tumor cells in canine HGOG cases and cell lines. Polymerase chain reaction and sequence analysis revealed expected pathogenic mutations in PDGFRA exons 7 and 8 in 16/34 (47%) cases. However, these mutations were not associated with PDGFRA expression, as examined by mRNA in situ hybridization (ISH) and immunohistochemistry, or proliferation activity, as examined by the Ki-67 labeling index (LI). Chromosomal ISH performed in 16 cases revealed PDGFRA and endoplasmic reticulum membrane protein complex subunit 2 ( EMC2) gains in 15 cases (94%). PDGFRA gain was moderately correlated with PDGFRA mRNA expression (ρ = 0.54, P = .04) and were moderately correlated with PDGFRA H-score, which is the score based on immunolabeling intensity (ρ = 0.44, P = .09). However, PDGFRA gain was not correlated with the Ki-67 LI (ρ = 0.23, P = .38). The canine HGOG cell line with PDGFRA gain showed higher PDGFRA mRNA expression ( P < .01), H-score ( P < .01), and Ki-67 LI ( P < .01) than the cell line without PDGFRA gain in vitro. The gain of PDGFRA and EMC2 suggests polysomy of canine chromosome 13, where both genes are located. The in vitro analysis results suggested that chromosome 13 polysomy is associated with increased PDGFRA expression and cell proliferation in canine HGOG. Chromosome 13 polysomy may be involved in canine gliomagenesis by increasing PDGFRA expression and inducing tumor cell proliferation.

Canine oligodendrogliomas express platelet-derived growth factor receptor alpha (PDGFRA), an oligodendrocyte precursor cell (OPC) marker. In this study, tumor cells derived from 3 French bulldogs with oligodendroglioma were cultured in conventional medium with 10% fetal bovine serum (FBS) and an OPC-tailored medium containing platelet-derived growth factor (PDGF)-AA and basic fibroblast growth factor (bFGF). Immunocytochemically, cells cultured with 10% FBS were negative for PDGFRA, but tended to express 2',3'-cyclicnucleotide 3'-phosphodiesterase (CNPase) and β3-tubulin. In contrast, the cells cultured with PDGF-AA and bFGF tended to express PDGFRA. These results suggest that canine oligodendroglioma cells cultured with PDGF-AA and bFGF exhibit OPC-like immunophenotype. Cells cultured with OPC-tailored medium may be useful for further in vitro research on canine oligodendrogliomas.

A 5-year-4-month-old neutered female French bulldog had a brain mass that was surgically excised. Histologically, the tumor consisted of neoplastic oligodendroglial and spindle-shaped cells, and chondroid tissues. Immunohistochemically, oligodendroglial cells were immunopositive for oligodendrocyte transcription factor 2 (OLIG2), 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), platelet-derived growth factor receptor alpha (PDGFRA), vimentin, cluster of differentiation 44 (CD44), and WW domain containing transcription regulator 1 (WWTR1). Spindle-shaped cells were immunopositive for OLIG2, vimentin, CD44, and WWTR1. In chondroid tissues, chondrocyte-like cells were immunopositive for OLIG2, PDGFRA, vimentin, and WWTR1. In the present case, the tumor had oligodendroglial features accompanied by mesenchymal and chondroid metaplasia. Based on these findings, the dog was diagnosed with an oligosarcoma with chondroid metaplasia.

In the present study, histopathological and immunohistochemical findings of olfactory ganglioneuroblastoma in a dog were compared to those of canine olfactory neuroepithelia and neuroblastomas. Olfactory ganglioneuroblastoma consists of ganglion cell-like tumor cells with Schwannian stroma and neuroblast-like tumor cells. Immunohistochemically, ganglion cell-like tumor cells were immunopositive for synaptophysin, β3-tubulin, and tyrosine hydroxylase, Schwannian stroma was immunopositive for GFAP and SOX2, and neuroblast-like tumor cells were immunopositive for OLIG2, β3-tubulin, SOX2, cytokeratin AE1/AE3, and p63. The immunohistochemical results of olfactory neuroepithelia and olfactory neuroblastomas were similar to those of neuroblast-like tumor cells. These results suggest that the ganglion cell-like tumor cells in the present case have a sympathetic neuron immunophenotype, whereas neuroblast-like tumor cells have an olfactory neuroepithelial immunophenotype.

High-grade oligodendroglioma (HGOG) is the most common type of glioma in dogs and expresses platelet-derived growth factor receptor-α (PDGFR-α). Microvascular proliferation is often observed in HGOG. Therefore, the present study investigated the functional relationships between PDGFR-α, microvascular proliferation, and tumor cell proliferation in canine HGOG. The expression of PDGFR-α and PDGF-subunit A (PDGF-A) in tumor cells, as well as endothelial cells and pericytes of tumor-associated microvascular proliferations, in 45 canine HGOGs were examined immunohistochemically. Microvascular proliferation was observed in 24/45 cases (53%). PDGFR-α expression in tumor cells and microvascular proliferations was observed in 45/45 (100%) and 2/24 cases (8%), respectively. Furthermore, PDGF-A expression in tumor cells and microvascular proliferations was detected in 13/45 (29%) and 24/24 cases (100%), respectively. In vitro, stimulation of the canine HGOG cell line AOFB-01 with PDGF-A showed that the doubling time of AOFB-01 cells was significantly shorter with PDGF-A than without PDGF-A. Crenolanib (a PDGFR inhibitor) inhibited AOFB-01 cell proliferation. In vivo, the AOFB-01 xenograft mouse model was treated with crenolanib. Tumor xenografts were smaller in crenolanib-treated mice than in untreated control mice. PDGFR-α expression in tumor cells and PDGF-A expression in microvascular proliferations and tumor cells suggest autocrine and paracrine effects of PDGF-A in canine HGOG. The results of in vitro assays indicate that canine HGOG expresses functional PDGFR-α, which responds to PDGF-A. Therefore, PDGF-A produced by microvascular proliferations and tumor cells may promote the proliferation of PDGFR-α-expressing tumor cells in canine HGOG. PDGFR-α signaling has potential as a therapeutic target.

A 2-month-old Japanese Black calf exhibited mandibular and superficial cervical lymph node swelling. Fine needle aspiration cytology of the superficial cervical lymph node revealed large lymphoblast-like cells with mitoses. Hematological examination revealed remarkable lymphocytosis with atypical lymphocytes. Increased activities of serum total lactate dehydrogenase and thymidine kinase were detected. At necropsy, generalized swelling of lymph nodes was observed. Histopathological analysis revealed diffuse proliferation of medium-sized round centroblastic neoplastic cells that were positive for CD20, CD79α, PAX5, and BLA-36, and negative for CD3, CD5, CD10, and CD34. The calf was diagnosed with centroblastic diffuse large B-cell lymphoma (DLBCL) based on these findings. Analysis of DNA copy number variation revealed an increased copy number for the GIMAP family relative to that in healthy cattle. Moreover, decreases in copy numbers of GBP-1, MIR3141, OR5P1E, and PTPRG relative to those in healthy cattle were also observed. Because DNA copy number variation represent a major contribution to the somatic mutation landscapes in human tumors, these findings suggest that DNA copy number changes might have contributed to the onset of DLBCL in the present case.

Neural stem cell (NSC) lineage cells have not been fully identified in feline brains, and the NSC-like nature of feline glial tumors has not been determined. In this study, 6 normal cat brains (3 newborn and 3 older cats) and 13 feline glial tumors were analyzed using immunohistochemical NSC lineage markers. The feline glial tumors were subjected to immunohistochemical scoring followed by hierarchical cluster analysis. In newborn brains, glial acidic fibrillary protein (GFAP)/nestin/sex-determining region Y-box transcription factor 2 (SOX2)-immunopositive NSCs, SOX2-immunopositive intermediate progenitor cells, oligodendrocyte transcription factor 2 (OLIG2)/platelet-derived growth factor receptor-α (PDGFR-α)-immunopositive oligodendrocyte precursor cells (OPCs), OLIG2/GFAP-immunopositive immature astrocytes, and neuronal nuclear (NeuN)/β-3 tubulin-immunopositive mature neuronal cells were observed. The apical membrane of NSCs was also immunopositive for Na+/H+ exchanger regulatory factor 1 (NHERF1). In mature brains, the NSC lineage cells were similar to those of the newborn brains. A total of 13 glial tumors consisted of 2 oligodendrogliomas, 4 astrocytomas, 3 subependymomas, and 4 ependymomas. Astrocytomas, subependymomas, and ependymomas were immunopositive for GFAP, nestin, and SOX2. Subependymomas and ependymomas showed dot-like or apical membrane immunolabeling for NHERF1, respectively. Astrocytomas were immunopositive for OLIG2. Oligodendrogliomas and subependymomas were immunopositive for OLIG2 and PDGFR-α. Feline glial tumors also showed variable immunolabeling for β-3 tubulin, NeuN, and synaptophysin. Based on these results, feline astrocytomas, subependymomas, and ependymomas appear to have an NSC-like immunophenotype. In addition, astrocytomas, subependymomas, and ependymomas have the characteristics of glial, oligodendrocyte precursor, and ependymal cells, respectively. Feline oligodendrogliomas likely have an OPC-like immunophenotype. In addition, feline glial tumors may have multipotential stemness for differentiation into neuronal cells. These preliminary results should be validated by gene expression analyses in future studies with larger case numbers.

Neural stem cells (NSCs) produce neuron intermediate progenitor cells (nIPC), oligodendrocyte precursor cells (OPCs), and immature astrocytes. To confirm NSC lineages in the normal canine brain and the association of these cells with gliomas, an immunohistochemical study was conducted on fetal and adult canine brains, gliomas, and a glioma cell line. In fetal brains, glial fibrillary acidic protein (GFAP)- and nestin-immunolabeled NSC were observed in the ventricular zone, β-3 tubulin- and/or neuronal nuclei (NeuN)-immunolabeled nIPC in the subventricular zone (SVZ), and platelet-derived growth factor receptor-α (PDGFR-α)- and OLIG2-immunolabeled OPC and GFAP- and OLIG2-immunolabeled immature astrocytes in the SVZ and intermediate zone. Ki-67 immunohistochemistry revealed that nIPC exhibited high proliferative activity. Quiescent nIPC and OPC were observed in adult brains. Among 58 glioma cases including 4 low-grade oligodendrogliomas (LGOGs), 48 high-grade oligodendrogliomas (HGOGs), 1 low-grade astrocytoma, and 5 high-grade astrocytomas (HGACs), immunohistochemical analyses revealed that oligodendrogliomas expressed PDGFR-α and OLIG2, whereas astrocytomas expressed GFAP and OLIG2. HGOG showed significantly higher immunohistochemical scores for NeuN and β-3 tubulin than LGOG. The Ki-67 labeling index was high in PDGFR-α and NeuN-immunolabeled tumor cells, and low in β-3 tubulin- and synaptophysin-immunolabeled cells. A HGOG cell line possessed the same immunohistochemical characteristics as HGOG. In this study, glioma cells with the OPC and IPC immunophenotypes had a higher Ki-67 labeling index, indicating their high proliferative activity. Furthermore, high-grade gliomas showed the characteristics of nIPC and neurons, which may suggest the pluripotent NSC lineage nature of these tumors.

We investigated the pathological characteristics of renal dysplasia with hydronephrosis and congenital ureteral stricture in two calves. Macroscopically, the affected kidneys were enlarged and the renal calyces were dilated and associated with ureteral strictures. Histopathologically, multifocal regions of mesenchyme were observed in the renal medulla. This mesenchyme was weakly eosinophilic with haematoxylin and eosin, blue with Alcian blue and pale blue with Masson's trichrome, and was immunopositive for vimentin and smooth muscle actin, consistent with persistent mesenchyme. There was asynchronous differentiation of the renal cortex characterized by immature glomeruli, immature tubules and arteriolar proliferation. Similar persistent mesenchyme was observed in the ureteral walls with ureteral stricture, and the ureteral musculature or smooth muscle bundles had a disorganized arrangement. Congenital ureteral stricture appeared to have caused ureteral obstruction and hydronephrosis. The lesions may represent a new phenotype of renal dysplasia with concomitant congenital ureteral stricture in Holstein-Friesian calves.

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.

放牧されていた9カ月齢，雌のホルスタイン種育成牛が，後躯蹌踉を呈した．投薬による治療を行うも改善せず，起立不能となった．身体検査では，前肢は突球様を呈し，後肢は脱力し，尾力は減弱していた．神経学的検査では，両後肢の膝蓋腱反射と屈曲反射の低下及び交叉伸展反射の亢進が認められた．病理解剖では，明らかな異常は認められなかった．病理組織学的検査により，脊髄全長の白質と脳幹の一部に軸索変性が認められた．また，脊髄近位端と遠位端，及び脳幹の病変分布と質から中枢性遠位性の脊髄軸索変性症と考えられた．本症例の病理像と一致する報告は過去に存在しなかった．本研究では原因は明らかでなかったが，病理組織学的所見と病変分布はマレーグレイ種の遺伝性進行性脊髄症と類似していた．