Veterinary Pathology最新文献

Ulcerative dermatitis is common in captive cephalopods and often results from trauma to their delicate epidermis with subsequent infection by opportunistic pathogens. We report 3 cases of fatal ulcerative dermatitis caused by a rare pathogen in a cohort of captive, adult, north Pacific big eye octopuses (Octopus californicus). Abundant, 5 to 8 µm diameter, roughly spherical organisms, often located in pairs or clusters, were infiltrating the ulcers in all 3 cases. Ultrastructurally, the organisms possessed multilamellated to scaley cell walls and were surrounded by empty, irregularly ovoid, 1 μm diameter, membrane-bound structures consistent with an ectoplasmic net. These features are consistent with thraustochytrid, a marine saprophyte. Previous reports of pathogenic thraustochytrid infections in cephalopods are rare, suggesting this is an uncommon albeit serious infection in captive cephalopod populations.

Mycobacteria (Mycobacteriaceae family) comprise five genera (Mycobacterium, Mycolicibacterium, Mycolicibacter, Mycolicibacillus, and Mycobacteroides), which include relevant animal and human pathogens. Histology is a rapid method for preemptively diagnosing mycobacteriosis, contributing to surveillance, control, and eradication. A constraint on histology is the limited sensitivity and specificity of acid-fast stains, as the number of detectable bacilli in formalin-fixed paraffin-embedded (FFPE) tissue varies and other microorganisms are acid-fast positive. Immunohistochemistry has low specificity and is cross-reactive with other bacteria. We developed an RNAscope probe-based in situ hybridization (ISH) assay, targeting a conserved sequence of 16S rRNA gene of Mycobacteriaceae, and tested it on archived FFPE tissues from 22 mammals, birds, amphibians, and fish, collected between 1999 and 2024, infected with 23 species of mycobacteria of veterinary importance, and tissue from 7 animals infected with other bacteria. Mycobacterium spp. (n = 17), Mycobacteroides spp. (n = 2), Mycolicibacter spp. (n = 1), and Mycolicibacterium spp. (n = 3) confirmed infected tissues were tested, and results were compared with 2 acid-fast stains, Ziehl-Neelsen and Fite-Faraco, and Mycobacterium spp. PCR from FFPE tissues. Hybridization signals were detected in all FFPE tissues, archived for up to 25 years, with confirmed Mycobacterium spp. (17/17; 100%), Mycobacteroides spp. (2/2), Mycolicibacter spp. (1/1), and Mycolicibacterium spp. (3/3), including cases with few or no acid-fast bacilli. Available FFPE tissues were positive by PCR (15/15, 100%). Hybridization signal was not identified in other bacterial infections. This ISH assay is a rapid screening and specific diagnostic tool for mycobacteria in FFPE tissues.

Hydrocephalus was first reported in Hereford cattle over 65 years ago; although no cause was identified in prior reports, it was suspected to be genetic. Advancements in reproductive technology and genomics have allowed for a determinative investigation of recent cases. Clinical and genomic data from 2 natural cases were followed by in vitro mating of a mother-son pair, each of which previously produced affected calves. Embryo transfer resulted in 7 calves, one of which had hydrocephalus, retinal dysplasia, and muscular dystrophy. Whole-genome sequencing of 2 affected calves, their sire, dams, and one related individual was supplemented with data from additional Hereford/Hereford cross cattle. Analyses identified a splice site variant in CRPPA (CDP-L-ribitol pyrophosphorylase A or ISPD) for which the affected calves were homozygous. This variant was not found in the homozygous state in any other individuals genotyped, in sequence data provided by the breed association, or in a public database query. The splice site mutation resulted in retention of intron 7, encompassing a stop codon predicted to truncate the protein. The transcript was expressed in the affected calf and the protein was detected in several tissues. Although translated into protein, immunohistochemistry demonstrated a lack of normal glycosylation of α-dystroglycan in the affected calf, which is necessary for a variety of processes including sarcolemma stability and neuronal migration. This phenotype is like Walker-Warburg syndrome in humans, some cases of which are attributed to mutations in CRPPA. This advancement allows for testing to eliminate carriers and potential for affected calves.

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-Prkdc^scid Il2rg^tm1Wjl/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.