Insular dwarfism in horses from the Aegean Sea and the Japanese archipelago.

The horse (Equus caballus) varieties from Skyros and Rhodes islands (Greece) in the Aegean archipelago are extremely small, reaching shoulder heights of only about 1 m. Furthermore, the Japanese archipelago is home to eight small, native horse breeds. We investigated the evolutionary morphology and provided a review of historical documentations of these horses of cultural interest in Greece and Japan, thus providing a comparison of the independent evolution of small size in islands. We integrate cranial data from historical literature with data from newly gathered and curated skulls and analyse a measurement dataset featuring various domestic and mainland horse breeds and varieties. We use non-invasive imaging to study and measure 3D models of the bony labyrinth, housing the inner ear, and the braincase endocast. When considering the effects of allometry by regressing each PC1 scores (for each set of measurements) with the cranial geometric mean from linear measurements as a body size proxy, we show that size explains a large amount of the shape variation in horse crania, the bony labyrinths and brain endocasts. We found high intrabreed variation in all the analysed datasets. Globally, there are at least 30 distinct horse populations on islands, offering the chance to further study processes of convergence in morphological divergence and evaluate the effect of drift and the environment. Supplementary Information: The online version contains supplementary material available at 10.1007/s42991-024-00408-4.

A de novo nonsense variant in the DMD gene associated with X-linked dystrophin-deficient muscular dystrophy in a cat.

BACKGROUND: X-linked dystrophin-deficient muscular dystrophy (MD) is a form of MD caused by variants in the DMD gene. It is a fatal disease characterized by progressive weakness and degeneration of skeletal muscles. HYPOTHESIS/OBJECTIVES: Identify deleterious genetic variants in DMD by whole-genome sequencing (WGS) using a next-generation sequencer. ANIMALS: One MD-affected cat, its parents, and 354 cats from a breeding colony. METHODS: We compared the WGS data of the affected cat with data available in the National Center for Biotechnology Information database and searched for candidate high-impact variants by in silico analyses. Next, we confirmed the candidate variants by Sanger sequencing using samples from the parents and cats from the breeding colony. We used 2 genome assemblies, the standard felCat9 (from an Abyssinian cat) and the novel AnAms1.0 (from an American Shorthair cat), to evaluate genome assembly differences. RESULTS: We found 2 novel high-impact variants: a 1-bp deletion in felCat9 and an identical nonsense variant in felCat9 and AnAms1.0. Whole genome and Sanger sequencing validation showed that the deletion in felCat9 was a false positive because of misassembly. Among the 357 cats, the nonsense variant was only found in the affected cat, which indicated it was a de novo variant. CONCLUSION AND CLINICAL IMPORTANCE: We identified a de novo variant in the affected cat and next-generation sequencing-based genotyping of the whole DMD gene was determined to be necessary for affected cats because the parents of the affected cat did not have the risk variant.

Successful treatment of acute respiratory failure following hypertensive crisis in a dog with presumed pheochromocytoma or paraganglioma.

Background: Acute respiratory failure has been reported as one of the manifestations of hypertensive crisis in pheochromocytoma in human medicine. In dogs, no reports have been described as acute respiratory failure following hypertensive crisis. Here, we report the clinical presentation, course, and treatment of acute respiratory failure following the hypertensive crisis in a dog with presumed pheochromocytoma or paraganglioma. Case Description: A 12-year-old neutered male toy poodle was referred for the diagnostic evaluation of a right adrenal gland mass. The dog suddenly exhibited severe dyspnea with abnormal hypertension (systolic blood pressure >200 mmHg) 15 minutes after recovery from the anesthesia for the computed tomography (CT) examination. Pulmonary CT and ultrasonography findings suggested acute onset of severe pulmonary edema. Pulmonary edema was treated with mechanical ventilation (pressure-support ventilation with continuous positive airway pressure) and negative fluid balance after the administration of furosemide. Weaning from mechanical ventilation was successful 24 hours after the onset of respiratory failure. Finally, the dog was discharged 3 days after weaning from ventilation without complications. Conclusion: This report outlines a case of acute respiratory failure following a hypertensive crisis requiring mechanical ventilatory management in a dog. The onset and progression of pulmonary edema were extremely rapid. However, improvement in pulmonary edema was also rapid. Hemodynamic stability, in addition to prompt diagnosis and aggressive therapeutic intervention, including mechanical ventilation, may have contributed to the good prognosis of pulmonary edema following hypertensive crisis in a dog, which we attribute to a catecholamine storm.

Successful treatment of sclerosing encapsulating peritonitis in a cat using bioresorbable hyaluronate-carboxymethylcellulose membrane after surgical adhesiolysis and long-term prednisolone.

Case summary: An 8-year-old neutered male domestic shorthair indoor cat was presented with an 8-week history of intermittent vomiting, anorexia and weight loss that had been unresponsive to supportive treatment. Abdominal ultrasound revealed plication of the small intestine and fluid accumulation proximal to the lesion, and a linear foreign body was suspected. An exploratory celiotomy showed cocoon-like encapsulation of the entire intestine. Surgical adhesiolysis and full-thickness biopsy were performed, and histopathologic examination revealed mild thickening of the visceral peritoneum with fibrin deposition, as well as mild neutrophil and lymphocyte infiltration. These findings were compatible with sclerosing encapsulating peritonitis (SEP). The cat recovered well postoperatively and was discharged the next day. Prednisolone was administered for 7 weeks to prevent recurrence of SEP. Five months after surgery, the cat was re-presented with anorexia and chronic vomiting. Based on the clinical examination findings, recurrent SEP was suspected. At the second surgery, surgical adhesiolysis was repeated and a bioresorbable hyaluronate-carboxymethylcellulose membrane was used to cover the serosal surface and thus prevent adhesion formation. Histopathologic findings of the peritoneal biopsy specimen confirmed SEP. Long-term prednisolone treatment (1 mg/kg for the first dose and 0.5 mg/kg every 48 h for maintenance) was administered postoperatively. The cat survived for more than 1239 days without recurrence. Relevance and novel information: To our knowledge, this is the first report of SEP in a cat with long-term survival. The use of a bioresorbable hyaluronate-carboxymethylcellulose membrane and long-term prednisolone treatment may have prevented short-term and long-term recurrence, respectively, in this case.

Prognostic role of lymphocyte to monocyte ratio in feline high-grade lymphomas.

The lymphocyte to monocyte ratio (LMR) is a useful prognostic marker of various cancers in human and canine patients. This study aimed to determine whether this ratio could predict disease outcomes in cats with high-grade lymphoma. Medical records of 33 cats diagnosed with high-grade lymphoma were retrospectively analyzed. The prognostic influence of LMR and other clinicopathological data on the time to progression (TTP) and overall survival (OS) was studied using the Kaplan-Meier curves. The optimal cutoff value of this ratio was 3.4, which corresponded to the maximum sensitivity (1.000) and specificity (0.611) of the LMR for predicting median OS days, using receiver operating characteristic analysis. A univariate analysis demonstrated that cats with a low LMR had significant reductions in both TTP [hazard ration (HR) = 3.403, 95% confidence interval (CI): 1.502 to 8.720; P = 0.003] and OS (HR = 3.418, 95% CI: 1.433 to 9.449, P = 0.005). In multivariate analysis, independent predictors of OS included LMR (HR = 2.889, 95% CI: 1.048 to 8.843, P = 0.040), clinical stage (HR = 0.330, 95% CI: 0.118 to 0.960, P = 0.042), and age (HR = 4.151, 95% CI: 1.574 to 11.888, P = 0.004).

Rôle pronostique du rapport lymphocytes sur monocytes dans les lymphomes félins de grade élevé. Le rapport lymphocyte sur monocytes (LMR) est un marqueur pronostique utile de divers cancers chez les patients humains et canins. Cette étude visait à déterminer si ce rapport pouvait prédire l'issue de la maladie chez les chats atteints d'un lymphome de grade élevé. Les dossiers médicaux de 33 chats diagnostiqués avec un lymphome de grade élevé ont été analysés rétrospectivement. L'influence pronostique de la LMR et d'autres données clinicopathologiques sur le temps de progression (TTP) et la survie globale (OS) a été étudiée à l'aide des courbes de Kaplan-Meier. La valeur seuil optimale de ce rapport était de 3,4, ce qui correspondait à la sensibilité (1,000) et à la spécificité maximales (0,611) du LMR pour prédire les jours de OS médians, en utilisant l'analyse des caractéristiques de fonctionnement du récepteur. Une analyse univariée a démontré que les chats avec un faible LMR présentaient des réductions significatives du TTP [rapport de risque (HR) = 3,403, intervalle de confiance (IC) à 95 % : 1,502 à 8,720; P = 0,003] et de la OS (HR = 3,418, IC à 95 % : 1,433 à 9,449, P = 0,005). Dans l'analyse multivariée, les prédicteurs indépendants de la OS comprenaient le LMR (HR = 2,889, IC à 95 % : 1,048 à 8,843, P = 0,040), le stade clinique (HR = 0,330, IC à 95 % : 0,118 à 0,960, P = 0,042) et l'âge (HR = 4,151, IC à 95 % : 1,574 à 11,888, P = 0,004).(Traduit par Dr Serge Messier).

The use of 4-dimensional magnetic resonance angiography as a noninvasive procedure to diagnose subclavian steal syndrome in a dog.

CASE DESCRIPTION: A 5-year-old 4.1-kg (9.0-lb) spayed female Toy Poodle was referred because of a 6-month history of sporadic signs of neck pain. CLINICAL FINDINGS: Diagnostic imaging with MRI and CT revealed a dilated radicular artery connecting the right and left vertebral arteries and causing mild compression of the spinal cord. The left subclavian artery caudal to the origin of the left vertebral artery was absent. Subclavian steal syndrome (SSS) was suspected. TREATMENT AND OUTCOME: The owner declined surgical treatment; thus, the dog was treated conservatively with glucocorticoids and analgesics. Eight months later, the dog's clinical signs were unchanged but palliated with the administration of glucocorticoids and analgesics, and 4-dimensional (4-D) magnetic resonance angiography (MRA) revealed that the left vertebral artery received blood supply from the right vertebral artery through the dilated radicular artery and that the left vertebral artery caudal to this site had retrograde flow and drained into the left subclavian artery, confirming the diagnosis of SSS. The owner again declined surgery, and conservative treatment continued. The dog's condition was unchanged at the last follow-up communication 11 months after 4-D MRA. CLINICAL RELEVANCE: Subclavian steal syndrome is an extremely rare condition in dogs, and our findings suggested that 4-D MRA could be used to definitively diagnose SSS in dogs.

CT morphology of anomalous systemic arterial supply to normal lung in dogs.

Anomalous systemic arterial supply to the normal lung (ASANL) is a rare congenital anomaly in humans, in which the systemic arteries supply the basal segments of the lower lobe. It has a normal bronchial connection, but lacks a normal pulmonary artery. This anomaly has not been previously reported in the veterinary literature. The objectives of this retrospective descriptive study were to characterize the CT findings and clinical features of ASANL , and to determine the breed predisposition in a population of referral canine cases. Thoracic CT images, in which the caudal lung lobes were fully inflated and the pulmonary artery could be traced to the periphery, were reviewed. A total of 1,950 dogs were enrolled, and the aberrant vasculature equivalent to ASANL in humans was detected in 48 dogs. Shetland Sheepdogs (7/48, odds ratio [OR] = 8.0, P < 0.00001), Miniature Dachshunds (19/48, OR = 3.9, P < 0.00001), and Labrador Retrievers (6/48, OR = 4.5, P = 0.0009) were over-represented. The affected lung lobes were the right caudal lobe (24/48, 50%), the left caudal lobe (21/48, 43.8%), and bilateral caudal lobes (3/48, 6.3%). The aberrant vessels originated from the left gastric artery (14/48), descending thoracic aorta (8/48), celiac artery (6/48), and splenic artery (1/48). In the remaining 19 cases, the origin of the aberrant vessels could not be determined. Although the clinical significance of ASANL in dogs remains unclear, surgeons should be aware of this finding prior to lobectomy of the caudal lung lobes to avoid intraoperative systemic arterial bleeding.

Morphometric evaluation of canine hepatocellular carcinoma using computed tomography: a promising tool for predicting malignancy.

The size of canine focal liver lesions (FLLs) is known to be one of the predicting criteria for malignancy. However, there are discrepancies for the measurement of maximum lesion size, resulting in contradicting results among studies and incidences of false positive outcomes. Thus far, the morphometric changes of FLLs for distinguishing malignancy from benignancy remains undocumented. This study aimed to investigate morphometric characteristics of FLLs using computed tomography (CT). CT images of 40 dogs with histopathological confirmation of 49 liver lesions, including 39 hepatocellular carcinomas and 10 nodular hyperplasias were retrospectively reviewed. The morphometric parameters including size (long and short axis diameters measured on transverse image), shape (measured by long to short axis (L/S) ratio), volume, and surface appearance of a liver lesion were evaluated using univariate and stepwise multivariate analyses, respectively. The results of univariate analysis showed that long and short axis diameters, L/S ratio, volume, and surface appearance of a lesion were significantly different between hepatocellular carcinomas and nodular hyperplasias. Multivariate analysis revealed that short axis diameter (>3.30 cm; odds ratio (OR): 36.1, 95% confidence interval (CI): 3.36-387.05, P=0.0031) and L/S ratio (>1.23; OR: 18.1, 95% CI: 1.61-205.12, P=0.0191) were independent predictors of malignancy, with the area under the curve of 0.9154. These results suggest that the combination of short axis diameter and L/S ratio is a promising tool for predicting liver malignancy with outstanding discriminating ability.

Cardiomyopathy in a dog with multicentric lymphoma following treatment with several anthracyclines.

Background: Canine lymphoma is one of the most frequently occurring malignant neoplasms in dogs. Anthracycline-based chemotherapy for the treatment of canine lymphoma is very effective; however, there is not enough evidence for the development of cardiac toxicity using several anthracyclines as chemotherapeutic agents. Case Description: An 8-year-old, castrated, mixed-breed dog was diagnosed with multicentric lymphoma and received multi-agent chemotherapy. Complete remission was achieved, but the patient had a relapse of lymphoma. After third-line chemotherapy with epirubicin, the patient was diagnosed with dilated cardiomyopathy. The total cumulative doses of doxorubicin, mitoxantrone, and epirubicin were 125, 8, and 125 mg/m2, respectively. Although the patient was treated with cardiac drugs and clinically stabilized, the patient had a relapse of lymphoma and died shortly after the diagnosis of cardiomyopathy. Conclusion: The patient was suspected to have anthracycline-induced cardiomyopathy. Further studies are required to establish prevention and management strategies for dogs receiving potentially cardiotoxic therapies, such as anthracyclines.

Intramedullary spinal nephroblastoma in a mixed breed dog.

A 1-year-old male mixed breed dog presented for the evaluation of progressive hindlimb paresis. Neurological examination indicated a spinal cord lesion between the 3rd thoracic and 3rd lumbar vertebrae. Magnetic resonance imaging (MRI) revealed an intramedullary spinal cord lesion located at the level of the 1st and 2nd lumbar vertebrae. Following cytoreductive surgery of the mass, palliative radiation therapy was administered. A diagnosis of nephroblastoma was made based on histological examination. After radiation therapy, the disappearance of the spinal lesion was confirmed by MRI. The dog was improved from gait abnormality and alive at 16 months postoperatively, with slight signs of neurological dysfunction.

Acute monoblastic leukemia in a feline leukemia virus-negative cat.

A 12-year-old female domestic short-haired cat was presented due to weight loss, anorexia, and tachypnea. Complete blood count revealed severe anemia, leukocytosis with massive undifferentiated blast cells, and thrombocytopenia. Bone marrow aspiration showed acute myeloid leukemia, subclassified as monoblastic leukemia (M5a) based on the outcomes of the cytochemistry examinations. The SNAP feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) test using whole blood was negative. In addition, FeLV/FIV proviral polymerase chain reaction test using bone marrow aspirate was also negative. Although the cat was treated with doxorubicin, cytosine arabinoside, and prednisolone, anemia did not improve without blood transfusion. The owner declined further treatment after 2 months, and the cat died a few days later.

Computed tomographic features for differentiating benign from malignant liver lesions in dogs.

Thus far, there are few computed tomography (CT) characteristics that can distinguish benign and malignant etiologies. The criteria are complex, subjective, and difficult to use in clinical applications due to the high level of experience needed. This study aimed to identify practical CT variables and their clinical relevance for broadly classifying histopathological diagnoses as benign or malignant. In this prospective study, all dogs with liver nodules or masses that underwent CT examination and subsequent histopathological diagnosis were included. Signalments, CT findings and histopathological diagnoses were recorded. Seventy liver nodules or masses in 57 dogs were diagnosed, comprising 18 benign and 52 malignant lesions. Twenty-three qualitative and quantitative CT variables were evaluated using univariate and stepwise multivariate analyses, respectively. Two variables, namely, the postcontrast enhancement pattern of the lesion in the delayed phase (heterogeneous; odds ratio (OR): 14.7, 95% confidence interval (CI): 0.82-262.03, P=0.0429) and the maximal transverse diameter of the lesion (>4.5 cm; OR: 33.3, 95% CI: 2.29-484.18, P=0.0006), were significantly related to the differentiation of benign from malignant liver lesions, with an area under the curve of 0.8910, representing an accuracy of 88.6%. These findings indicate that features from triple-phase CT can provide information for distinguishing pathological varieties of focal liver lesions and for clinical decision making. Evaluations of the maximal transverse diameter and postcontrast enhancement pattern of the lesion included simple CT features for predicting liver malignancy with high accuracy in clinical settings.

Quantification of plasma cell-free DNA levels in dogs with various tumors.

Circulating cell-free DNA (cfDNA) is extracellular DNA released into the bloodstream by apoptotic or necrotic tumor cells, with cfDNA determination proposed as a noninvasive, sensitive marker for the diagnosis of human cancer. We evaluated cfDNA quantification as a diagnostic and prognostic tool in dogs with various tumors. We quantified plasma cfDNA concentration by absolute real-time PCR of long interspersed nuclear elements in 50 dogs with malignant tumors, 13 dogs with benign tumors or nodules, and 11 healthy controls. Six patients with malignant tumors were followed-up, and plasma cfDNA was quantified throughout disease progression. We found that plasma cfDNA concentrations were significantly elevated in dogs with malignant tumors compared with dogs with benign nodules or healthy controls. The DNA integrity index (the ratio between long and short cfDNA fragments) was significantly lower in dogs with malignant tumors compared to healthy controls. Significantly higher cfDNA levels and a lower DNA integrity index were observed in dogs with lymphoma or leukemia, hemangiosarcoma, and distant metastasis; cfDNA levels correlated well with clinical stage and tended to increase during or before periods of disease progression, suggesting potential efficacy of cfDNA for the detection of distant metastasis and to monitor the clinical stage of neoplasia.

Usefulness of noninvasive shear wave elastography for the assessment of hepatic fibrosis in dogs with hepatic disease.

BACKGROUND: Two-dimensional shear wave elastography (2D-SWE) can noninvasively evaluate hepatic elastic modulus as shear wave velocity (SWV). Additionally, it may predict the presence of clinical relevant hepatic fibrosis (≥F2) in dogs with hepatic disease. OBJECTIVES: To investigate whether SWV measured by 2D-SWE can differentiate between dogs with (≥F2) and without (F0-1) clinically relevant hepatic fibrosis. ANIMALS: Twenty-eight client-owned dogs with hepatic disease and 8 normal healthy Beagle dogs were enrolled. METHODS: In this cross-sectional prospective study, SWVs were measured using 2D-SWE in all dogs. Hepatic fibrosis stages and necroinflammatory activity grades were histopathologically evaluated using a histological scoring scheme that was adapted from the Ishak schema used in human medicine. RESULTS: Median SWVs were significantly higher in dogs with clinically relevant hepatic fibrosis (2.04 m/s; range, 1.81-2.26 m/s) than in healthy dogs (1.51 m/s; range, 1.44-1.66 m/s; P = .007), and dogs without clinically relevant hepatic fibrosis (1.56 m/s; range, 1.37-1.67 m/s; P < .001). However, no significant difference was found in the SWVs between dogs without clinically relevant hepatic fibrosis and healthy dogs (P = .99). Furthermore, median SWVs were not significantly different among dogs with necroinflammatory activity, those without necroinflammatory activity, and healthy dogs (Kruskal-Wallis test, P = .12). CONCLUSIONS AND CLINICAL IMPORTANCE: The 2D-SWE may be useful for predicting the presence of hepatic fibrosis in dogs with hepatic disease.

Findings of contrast-enhanced ultrasonography with Sonazoid for cholangiocellular adenoma in three dogs.

Contrast-enhanced ultrasonography (CEUS) is useful to distinguish benign and malignant focal liver lesions in dogs. Cholangiocellular adenoma is an extremely rare benign tumor in dogs and has not been examined using CEUS with Sonazoid. The aim of this study was to describe findings of CEUS with Sonazoid in three dogs with cholangiocellular adenoma. All three dogs showed contrast defects in the Kupffer phase and these findings mimicked malignant neoplasia during the Kupffer phase. Moreover, all dogs showed early washout and hypoechoic lesions relative to the surrounding normal liver parenchyma in the portal phase. To our knowledge, this is the first study to report that CEUS findings of cholangiocellular adenoma with Sonazoid mimicked malignancy in three dogs.

Three-legged radiographic view for evaluating cranioventral lung region in standing calves with bovine respiratory disease.

This study proposed a novel radiographic positioning in order to image the cranioventral lung region using a portable X-ray unit and digital radiography system. In the novel position, calves were restrained in a chute and a unilateral forelimb was pulled cranially with the contralateral forelimb tied to the chute; the forelimbs were then spread cranio-caudally as in a scissor position (Three-legged view: TL view). In a preliminary study, we applied the TL view for imaging of 14 clinically healthy calves. In a clinical study, accuracy in detecting cranioventral lung lesions was compared between the standard standing view and the TL view for 19 calves, which were culled from herd; the results of postmortem examination were used as gold standard. Seven evaluators independently interpreted the images. The median (range) number of trials and the time for obtaining optimal position were 2 (1-7) and 263 sec (105-488), respectively in 14 healthy calves. Calves thicker than approximately 40 cm were not considered candidates for TL view in this setting because of difficulty in restraint and the low output of the portable X-ray unit. The TL view improved the detection of consolidation in the cranioventral lung region, compared with the standard view. The TL view was considered an optional view when the cranioventral lung region was an area of interest, because this view was relatively easy to perform and required a small number of personnel, even for large calves.

MRI of lobar holoprosencephaly in a cat with hypodipsic hypernatraemia.

CASE SUMMARY: A 2-year-old neutered female domestic shorthair cat presented with a history of hypodipsia, recurrent hypernatraemia, pelvic limb ataxia and tremor. The serum arginine vasopressin level was low for the serum osmolality. MRI of the brain revealed a failure of separation of the cerebrum, which manifested as absence of the rostral part of the corpus callosum, fornix and septum pellucidum, thus resulting in a single fused ventricle. The diagnosis was lobar holoprosencephaly with hypodipsic hypernatraemia. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first description of the MRI characteristics of lobar holoprosencephaly in a cat. This report suggests that MRI examination should be considered for precise diagnosis of hypodipsic hypernatraemia in young cats.

CD3 and CD20 co-expression in a case of canine peripheral T-cell lymphoma with prominent cardiac and peripheral nerve involvement.

An 8-y 9-mo-old male Pug dog was presented because of anorexia, hindlimb ataxia, vomiting, and progressive weight loss. Clinical examinations revealed atrophic hindlimb muscles with decreased postural reaction, enlargement of the cardiac silhouette and megaesophagus on radiograph, and reduced cardiac contractility on ultrasonography. The dog died 10 d after the initial examination, and an autopsy was performed. Grossly, the heart was enlarged, with multifocal-to-coalescing extensive plaque-like areas of discoloration on the epicardial surface. On cross-section, the ventricles were moderately dilated, and discoloration extended into the myocardium. Peripheral lymph nodes were of normal size. Histologically, atypical lymphoid cells replaced the myocardium and also extensively infiltrated peripheral nerve bundles in various organs. With immunohistochemistry, the neoplastic cells exhibited strong immunoreactivity for CD3 and CD20, and were negative for CD8, granzyme B, CD79α, and Pax5. Double-label immunofluorescence confirmed co-expression of CD3 and CD20 by the neoplastic cells. Molecular clonality analysis presented a clonal T-cell receptor gamma gene rearrangement. The case was diagnosed as a CD3+/CD20+ peripheral T-cell lymphoma with prominent cardiac and peripheral nerve involvement, indicating neurolymphomatosis.

Evaluation of costimulatory molecules in dogs with B cell high grade lymphoma.

B cell high grade lymphoma is the most common hematopoietic malignancy in dogs. Although the immune checkpoint molecules, programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and immune checkpoint inhibitors have been evaluated for the treatment of various human lymphoid malignancies, the expression of those molecules and their relationship with prognosis remain unknown in canine lymphoma. The objective of this study was to evaluate the expression of costimulatory molecules on peripheral blood lymphocytes and tumor infiltrating lymphocytes, in addition to associated ligand expression in the lymph nodes of patients with B cell multicentric high grade lymphoma. Eighteen patients diagnosed with B cell high grade lymphoma and nine healthy control dogs were enrolled. Flow cytometric analysis revealed that the expression of PD-1 on CD4+ peripheral and tumor infiltrating lymphocytes and CTLA-4 on CD4+ peripheral lymphocytes was significantly higher in the lymphoma group than in the control group. The expression level of CD80 mRNA was significantly lower in the lymphoma group than in the control group. In contrast, there were no significant differences in PD-L1, PD-L2, and CD86 expression between the groups. Dogs with CTLA-4 levels below the cutoff values, which were determined based on receiver operating characteristic curves, on peripheral CD4+, CD8+, and tumor infiltrating CD4+ lymphocytes had significantly longer survival than dogs with values above the cutoff. Although it is uncertain whether the expression of immune checkpoint molecules affect the biological behavior of canine lymphoma, one possible explanation is that PD-1 and CTLA-4 might be associated with the suppression of antitumor immunity in dogs with B cell high grade lymphoma, particularly through CD4+ T cells.

Lissencephaly in a Pekingese.

A 1-year-old neutered male Pekingese was presented for evaluation and further treatment of cluster seizures. The dog had behavioral abnormalities, and a prosencephalic lesion was suspected following neurological examination. The dog showed signs of learning difficulty. Magnetic resonance imaging of the brain revealed a remarkably smooth cerebral cortex with a reduced number of gyri, as well as a cystic lesion associated with the quadrigeminal cistern. A diagnosis of lissencephaly, concurrent with a quadrigeminal cisternal cyst, was made. High-dose and multiple anticonvulsants were necessary to control the seizures. This is the first report of lissencephaly in a Pekingese.