Prairie voles (Microtus ochrogaster) from 1 of the 3 laboratory animal facilities experienced increased unexpected deaths with no clinical signs. There was a total of 30 deaths in the affected facility and 16 deaths in the other 2 unaffected facilities in the same period. Significant gross findings included cardiomegaly (6/30, 20%) and pleural effusion (4/30, 13%). Heart weights (P = .0049) and widths (P = .0047) were significantly higher in M. ochrogaster from the affected facility than the other 2. Histology revealed cardiomyocytes with intracytoplasmic basophilic granular material in most M. ochrogaster from the affected facility (25/30, 83%). Of the affected animals, other changes included myocardial fibrosis (18/25, 72%), myocarditis (9/25, 36%), and atrial thrombosis (6/25, 24%). M. ochrogaster from the 2 other facilities, that died naturally or were euthanized for unrelated causes, did not reveal similar cardiac changes. Histochemical stains and immunohistochemical assays characterized the intracytoplasmic material as von Kossa negative and periodic acid-Schiff with diastase positive, that immunolabeled for myogenin and sarcomeric actin. Transmission electron microscopy showed the granular material as autolysosomes, with microtubular or filamentous dense aggregates, that were product of mitochondria and myofibrillar degradation. Affected and unaffected colonies are housed similarly, with identical husbandry except for water; reverse osmosis water was used in the affected facility and tap water in the unaffected. Water testing revealed significant differences in mineral content between reverse osmosis and tap water, with marked depletion in calcium, chloride, magnesium, potassium, sodium, zinc, sulfate, and orthophosphate. We speculate that the autolysosomal dysfunction is a result of mineral imbalance.

Infectious bursal disease (IBD) is an immunosuppressive disease caused by the IBD virus (IBDV), leading to substantial economic losses in the poultry industry. Recently, a novel antigenic variant IBDV (nvIBDV) has emerged in China and spread across Asia, including Japan. We previously isolated and characterized the nvIBDV strain, B2977CE2C3, by experimentally infecting specific pathogen-free chickens. Herein, we performed histological examinations of systemic organs using tissue samples from the infected chickens. At 3 days post-inoculation (dpi), lymphocyte depletion was observed in the bursa of Fabricius (BF), cecal tonsil, spleen, and thymic cortex. During the acute phase, the BF exhibited marked inflammation and accumulation of cell debris, likely apoptotic remnants. Immunohistochemistry and quantitative image analysis revealed significant B cell depletion in the BF and spleen, persisting for up to 21 dpi. In addition, structural destruction of the BF, including loss of follicles, epithelial infoldings, replacement by epithelial reticular cells, and stromal fibrosis, was observed. IBDV antigens were immunohistochemically detected in the BF and cecal tonsil during early infection. The bone marrow contained lymphoid cell aggregations, suggesting increased lymphopoiesis. These findings indicate that the pathogenicity of nvIBDV is comparable with that of classical IBDV (genogroup A1), although it belongs to genogroup A2. Notably, nvIBDV can induce chronic immunosuppression due to prolonged B cell depletion in the BF and spleen, thereby increasing the susceptibility to secondary infections and interfering with subsequent vaccinations. This study highlights the pathogenic potential of nvIBDV and provides valuable pathological insights for understanding its pathogenesis and evaluating preventive strategies.

Merino sheep exhibit a high follicular density, enhancing wool yield but predisposing them to inherited cutaneous disorders, such as breech wrinkle, which is characterized by the appearance of multiple skin folds in the breech area. This study provides the first clinicopathological description of the so-called body wrinkle, a congenital skin condition in Merino lambs where the folds affect the whole-body skin. Four affected lambs displayed generalized alopecia with excessive skin folds. Hematological analysis showed neutrophilia, lymphopenia, and eosinopenia. Histological examination revealed follicular dysplasia, follicular keratinization and keratosis, and degeneration of follicular epithelium, particularly in the outer root sheath. The information obtained from pedigree analysis suggested an autosomal recessive inheritance pattern. All affected lambs exhibited severe OrfV lesions in the oral cavity and muzzle, persisting from 2 weeks of age until death at 1 to 2 months. Our results suggest that body wrinkle condition might favor a more prolonged clinical course and more severe outcome of OrfV infection in lambs. Further genetic and immunopathological investigations are needed.

Chicken lymphomas are generally classified into three virus-induced tumors: Marek's disease (MD), lymphoid leukosis, and reticuloendotheliosis, with MD being the most common T-cell lymphoma in commercial poultry. In this study, we describe 23 cases of a novel cytotoxic T-cell lymphoma affecting layer chickens aged >1 year in Japan that is distinct from previously known chicken lymphomas. These cases were initially misidentified as MD during routine poultry inspection but were later confirmed as a distinct and novel form of lymphoma. The average incidence of this lymphoma was 0.016%. Histological analysis revealed that the tumors comprised small uniformly round cells that were CD3+, CD4-, and CD8+, indicating a cytotoxic T-cell origin. Investigations using immunohistochemistry, in situ hybridization, and polymerase chain reaction ruled out the involvement of known tumor-inducing viruses in the development of these novel lymphomas. These findings confirm the existence of a novel lymphoma type in chickens and provide key histopathological and epidemiological data to aid in definitive diagnosis.

The PD-1 protein is an immune checkpoint present on T cells and, when bound to PD-L1, it inhibits the immune response. Tumor cells can exploit this mechanism to escape immune surveillance. In this study, we characterized the expression of PD-L1 and the infiltration of cytotoxic T lymphocytes (CTLs) and regulatory T lymphocytes (RTLs) in 92 mammary tumors of 92 female dogs to assess their prognostic value. Tumor samples were subjected to immunohistochemistry for PD-L1, FOXP3, and CD8. FOXP3- and CD8-positive and negative lymphocytes were counted to obtain the percentage of positive cells. PD-L1 expression was evaluated for protein localization (nuclear and/or cytoplasmic), percentage of positive cells, and labeling intensity. The majority of the tumors were positive for PD-L1 (72%). Dogs with PD-L1-negative tumors had shorter post-surgical survival (P = .0328; hazard ratio = 2.35). PD-L1-positive tumors had higher percentages of CTLs and were significantly associated with clinical stage I (P = .0046) and absence of lymph node metastasis (P = .0006). An increased percentage of RTLs was an indicator of shorter survival (P = .0084). Our results suggest that PD-L1 positivity indicates a better prognosis for dogs with mammary carcinomas, whereas the presence of intratumoral RTLs is an indicator of poor prognosis. These findings highlight prognostic biomarkers that may support personalized treatment approaches in veterinary oncology.

Low-salinity water exposure (freshwater exposure) is an emerging disease of cetaceans worldwide. The disease, termed "freshwater skin disease," causes gross skin lesions that appear as multifocal to coalescing, irregularly marginated targetoid patches that vary in color from pale gray to yellow to orange to green depending on the involvement of secondary bacterial and/or fungal/algal overgrowth. Histologically, these skin lesions range in severity from hydropic degeneration to widespread necrosis with associated bacterial and/or fungal/algal overgrowth. Currently, there is no histopathologic scoring system for freshwater skin disease lesions in any species. In this study, we created and validated a histopathologic scoring system for freshwater skin disease lesions in common bottlenose dolphins (Tursiops truncatus) compared with control bottlenose dolphins based on epidermal features, the presence/absence and location of suppurative inflammation, and the presence/absence of organisms. We also identified common histologic artifacts, such as postmortem epidermal changes, saprophytic bacterial overgrowth, vesiculation mimicking fungal organisms, and freshwater disease-associated eosinophilic inclusion-like bodies mimicking poxviral inclusions. In addition, salinity measurements taken from the stranding site were found to correlate with a diagnosis of freshwater skin disease in dolphins.

Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment for neoplasia and autoimmune diseases. Immunocompromised mice are a common model to test the efficacy and safety of CAR T cells of human origin. Preclinical toxicity associated with human CAR T-cell products encompasses a spectrum of morphologic changes, with currently limited documentation in the scientific literature. The purpose of this retrospective study was to characterize the histopathologic features associated with human CAR T-cell administration in immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice (n = 392) submitted to 3 different academic institutions in the United States between 2017 and 2024. Lesions were categorized into xenogeneic graft-versus-host disease (xGvHD) (n = 287), aberrant proliferation of human T cells (n = 188), vascular pathologies (n = 66), on-target/off-tumor (OTOT) toxicity (n = 44), immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) in mice previously humanized with human CD34+ hematopoietic stem cells (HSCs) (n = 21), and acute lysis syndrome (ALS) (n = 5). This study provides veterinary pathologists with descriptive guidance on the pathology associated with human CAR T-cell therapy in immunodeficient mice. Additional molecular data and detailed information related to each construct are necessary to further investigate the translatability of such liabilities to the clinical setting.

The emergence of cell and gene therapies has transformed the therapeutic landscape, offering curative potential for a range of previously intractable diseases. However, their biological complexity and patient-specific mechanisms of action present significant challenges for preclinical evaluation, particularly in modeling human responses and predicting safety outcomes. Traditional animal models often lack translational fidelity, prompting the adoption of humanized immunodeficient mice, including those engrafted with human immune cells, as more predictive in vivo platforms. These models enable the assessment of pharmacodynamics, biodistribution, and immunotoxicity in a human-relevant context. This review critically explores the integration of humanized mice into regulatory submissions for cell and gene therapy products, highlighting their utility across proof-of-concept, pharmacokinetic, toxicology, and tumorigenicity studies. We also address key limitations of the different models, including variability in engraftment efficiency, immune reconstitution, and lifespan, as well as challenges in standardization and regulatory acceptance. Future directions include refining humanized mouse models to better mimic human physiology, incorporating pathological endpoints, and aligning with 3R principles and new methodological approaches. By enhancing the translational relevance of nonclinical data, humanized mice are poised to play an increasingly strategic role in early safety assessment and successful development of advanced therapies.

Companion animal cancer diagnostic reports are text-based documents containing essential information on tumor classification and diagnosis. Establishing an animal cancer registry requires integrating and extracting structured data from diverse report formats across multiple providers. This study presents the development of an object-oriented programming approach to standardize and automate cancer data collection for canine and feline patients, enabling the creation of the Australian Companion Animal Registry of Cancers (ACARCinom); Australia's first national registry of cat and dog cancers. An object-oriented programming approach was developed using the C# language for data processing, tested on sample data from 6 data providers. The initial programming phase focused on designing a parser that identified report sections using regular expressions based on standardized headings. The text was then cleaned to remove unnecessary formatting and HTML tags. Data dictionaries containing preferred terms and synonyms were used to extract key information such as diagnosis, topography, grade, and metastasis, improving consistency and accuracy. A coordinate map of extracted terms was generated to analyze spatial relationships within the report, allowing prioritization of diagnoses. The system also logged parsing decisions and potential issues for expert review. Markup using HTML tags enabled clear visualization of parsed content within the original reports. Extracted data and patient metadata were stored in an intermediary database table, allowing veterinary pathology experts to review and refine entries before final import. This automated solution streamlines data extraction and standardization from diverse sources, enabling the efficient analysis of cancer records and enhancing research and surveillance capacity in veterinary oncology.

Cutaneous malignant melanomas from 81 rabbits were retrospectively evaluated, and 51 cases were re-examined to elucidate their histopathological and immunohistochemical characteristics and to identify potential associated prognostic factors. The mean age of rabbits at tumor incidence was 6 years, 9 months (median age: 7 years; range: 2 years, 1 month to 12 years, 4 months). Netherland dwarfs and intact males were more prevalent in terms of breed and sex, respectively. The most common tumor location was the scrotum, followed by the head, including the eyelids and pinna, and trunk. The tumors were composed of 3 cell types: epithelioid, spindle, and mixed. Histopathological parameters examined included mitotic counts, nuclear atypia, multinucleated giant cells, degree of pigmentation, local invasion, tissue margins, presence of satellite nodules, vascular invasion, intralesional necrosis, and intralesional inflammation. In this study, most histopathological parameters were not associated with a shorter survival time. Maximum tumor diameter and mitotic counts were associated with a poor prognosis, with cutoffs of 2.0 cm and 10 mitoses per 2.37 mm2, respectively. Immunohistochemically, 51 of 51 cases (100%), 50 of 51 cases (98%), and 49 of 51 cases (96%) were positive for PNL2, melan-A, and HMB-45, respectively. No apparent differences in positivity were observed among the cell types of the neoplasms. This study provides several new insights into malignant melanomas of rabbits, such as breed, anatomical site, and sex predilections, and detailed histopathology, including useful cutoff values of associated prognostic factors.