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.

Metabolic dysfunction-associated steatohepatitis (MASH) is a global health care burden. Appropriate large animal models mimicking the main MASH characteristics of steatosis, inflammation, and hepatocyte damage alongside progression of fibrosis are imperative for robust preclinical studies, especially in the field of hepatobiliary surgery. The present study aimed to characterize a novel model of steatohepatitis in fumarylacetoacetate hydroxylase-deficient (FAH-/-) pigs. FAH-/- pigs were generated using a CRISPR/Cas9 system. The animals received a choline-deficient, L-amino acid-defined high-fat diet and subtherapeutic doses of nitisinone and were followed for 3 months. Liver biopsies were obtained at baseline and every month during treatment. Steatosis, inflammation, and fibrosis were assessed by conventional histological scoring systems and by an artificial intelligence (AI) model. Serum liver parameters were analyzed every 2 weeks. Steatosis increased significantly throughout the study, with severe steatosis observed as early as 2 months into treatment. The inflammation score was increased in all animals after 3 months of treatment, whereas the AI-based CD45+ cell count showed region-specific trends in the portal and lobular areas. Collagen content and the corresponding fibrosis stage showed an increase over the 3-month period; however, the difference was not significant. Serum liver parameters did not show any relevant elevations during the study. In summary, we successfully developed and characterized a novel model of steatohepatitis in the FAH-/- pig within 3 months. Further studies with prolonged observation time and/or cycling of nitisinone administration are needed to evaluate whether progressive fibrosis and cirrhosis could be achieved with this model.

Diagnosis and classification of ovarian epithelial neoplasms in guinea pigs (Cavia porcellus) are challenging due to inconsistent terminology and few available diagnostic criteria. This study evaluated 23 ovarian epithelial neoplasms in 15 guinea pigs with the objectives of (1) differentiating ovarian surface epithelial (OSE) neoplasms from rete ovarii neoplasms using immunohistochemistry, (2) describing salient histologic features, and (3) classifying neoplasms according to canine, human, and rodent classification schemes. PAX-8 immunohistochemistry separated immunoreactive rete neoplasms from nonreactive OSE neoplasms. OSE neoplasms (n = 12) were well-differentiated and arose directly from the ovarian surface, rather than the primarily cortical location of OSE neoplasms in other species. Focal OSE neoplasms with papillary projections on a fibrous core or tubules within a fibrous stroma were classified as surface papilloma and surface adenoma, respectively. Generalized OSE neoplasms with tubules, papillae, and fibrous stroma were classified as surface borderline tumors. Neoplasms with invasion, 2-4 mitotic figures per 2.37 mm2, and/or peritoneal implantation were classified as surface carcinoma. The only carcinoma with follow-up had resolution of clinical signs and no radiologic evidence of recurrence 6 months after ovariohysterectomy. Rete neoplasms (n = 11) included rete cystadenomas and rete adenomas, and consisted of epithelial cells arranged in papillae and tubules within a rete tubule, with or without cysts, respectively. Further investigation is needed to correlate diagnoses with neoplasms' biologic behavior. We propose using "surface" and "rete" in the diagnosis to denote location, rather than "papillary," "cystic," or "serous," which are variably used in other ovarian neoplasia classification schemes, to standardize terminology.