Veterinary Pathology最新文献

Feline diffuse iris melanoma (FDIM) is a common ocular neoplasm, typically affecting older cats, characterized by progressive hyperpigmentation and potential malignancy. This study evaluated the diagnostic value of iris biopsies in distinguishing FDIM from benign iris melanosis. Seventeen cases with suspected FDIM were analyzed through ex vivo iris biopsies and corresponding enucleated globes. Histological evaluation by 8 pathologists revealed an average concordance of 81.6% between biopsy and globe diagnoses. The reliability of biopsy samples was influenced by tissue quality, with 12/136 slides deemed non-diagnostic due to artifacts or insufficient tissue. While biopsy retrieval offers a less invasive alternative to enucleation, its effectiveness is limited by technical factors, including tissue handling and sampling techniques. The results suggest that iris biopsies can be valuable for diagnosing advanced FDIM but require skilled execution. Further studies should explore early-stage FDIM and melanosis to better assess the diagnostic potential of biopsies across various disease stages.

Lymphoma is a common neoplasm in cats, in which alimentary lymphoma is a common subtype, and it is usually diagnosed in elderly, feline leukemia virus (FeLV)-negative cats. This study aimed to describe the pathological features of lymphoma with involvement of the alimentary tract in FeLV-antigen-positive cats. In a 12-year retrospective study, 32 necropsied and FeLV-infected cats with lymphoma affecting the alimentary tract were identified. Twenty-one cases were multicentric lymphomas with secondary involvement of the alimentary tract, and the remaining 11 cats were considered to have primary alimentary lymphoma. The small intestine was the most common anatomic location (23/32; 72%), followed by the large intestine (19/32; 59%) and stomach (18/32; 56%). In 22/32 cases (69%), multiple organs within the alimentary tract were concomitantly affected. Thickening of the intestinal and gastric walls was the most common gross lesion (23/32; 72%), while mural nodules were observed in 16/32 cats (50%). The mesenteric lymph nodes were frequently affected (22/32; 69%). Most lymphomas were composed of large (17/32; 53%) and intermediate cells (14/32; 44%). B-cell lymphomas were more frequent (24/32; 75%), and diffuse large B-cell lymphoma was the most common diagnosis (15/32; 47%). In 31/32 (97%) cases, FeLV gp70 antigen was detected in neoplastic lymphocytes by immunohistochemistry. Lymphomas affecting the alimentary tract may be observed in FeLV-infected, young adult cats, in which large to intermediate cell and B-cell lymphomas are more frequently observed, and small cell T-cell intestinal lymphoma is unlikely to be diagnosed.

Eight rodents were submitted for necropsy after being found in soft drink beverages. To determine whether the postmortem changes in these mice were consistent with contamination at the time of bottling/canning or after the beverage was opened by the consumer, we conducted a study of the effects of prolonged rodent submersion in soft drinks. Thirty unmanipulated laboratory mice, euthanized for other reasons, were placed in bottled beverages (diet and regular cola, sweet and unsweetened tea, seltzer water, and water) for time intervals ranging from 3 days to 2 months. Starting at the 1-week time point, all rodents submerged in sealed carbonated beverages at room temperature showed severe, full-body gas distention. This change was not seen if the bottle was uncapped or if the beverage was refrigerated. Other significant changes included staining of the incisors starting at 1 week in the colored beverages (colas, teas), and erosion of the occlusal surface of the incisors starting at 2 weeks in the acidic beverages (colas, teas, seltzer). Visceral decomposition increased with time in all the beverages, but was most rapid in the regular cola. The mice submitted for necropsy showed no gas distention, no incisor erosion, and visceral decomposition similar to the experimental mice at the 1-week time point. As the interval between production and opening ranged from 3 weeks to 3 months, these results suggest that the rodents entered the beverage containers after they were opened by the consumer.

The lymphatic system plays an essential role in the drainage of fluids, proteins, and cells from tissues. However, it facilitates the dissemination of cancer cells, favoring progression and the development of metastases. The present study aimed to characterize the intratumoral and peritumoral lymphatic vessel density and to evaluate their prognostic value in canine cutaneous mast cell tumors (MCTs). The lymphatic vessels from intratumoral and peritumoral areas were identified and quantified in 57 tumor samples from 51 dogs (28 low-grade and 29 high-grade MCTs), using immunohistochemistry with an anti-LYVE1 antibody. The results were compared with histological grades, mortality due to the disease, and post-surgical survival of the patients. The number of peritumoral lymphatic vessels was higher in high-grade MCTs (P = .0370) and in dogs that died due to the disease (P = .0215), while no statistically significant differences were found for intratumoral lymphatic vessel counts. Dogs that had MCTs with peritumoral lymphatic vessel counts higher than 113 had shorter post-surgical survival times, with a median survival of 122 days (P = .0080; hazard ratio = 4.886). No association was detected between lymphatic vessel counts and the presence of lymph node metastases. Our results suggest that peritumoral lymphatic vasculature is a prognostic indicator for post-surgical survival in cases of canine cutaneous MCTs.

Koala retrovirus (KoRV) is a significant infectious agent impacting the health of wild and captive koala populations worldwide. While previous studies have explored its association with neoplastic diseases such as leukemia and lymphoma, its potential involvement in primary bone tumors remains unclear. This study aimed to expand our understanding of KoRV's disease spectrum by examining its potential association with primary bone tumors in koalas. Koala retrovirus proviral DNA load was analyzed in neoplastic bone using real-time quantitative polymerase chain reaction (PCR) and compared to healthy bone samples across 4 different gene targets: KoRV pol, KoRV-A env, KoRV-B env, and KoRV-D env. The relative KoRV subtype A proviral load was significantly lower in bone tumor samples (n = 14) when compared to healthy bone samples (n = 11) (P = .025), while other subtype-specific proviral loads did not differ significantly between tumor and healthy controls. In addition, we developed a novel immunohistochemistry assay to detect the KoRV capsid protein. Immunolabeling revealed KoRV capsid protein expression in all bone tumor samples (14/14, 100%), with an overall mean positive immunolabeling of 50.4% of tumor cells. The bone tumor group had a higher median H-score compared to the control group (P < .001). Among tumor subtypes, the highest mean percentage of tumor cell labeling was observed in osteosarcomas (73.0%), followed by chondrosarcomas (51.6%) and osteochondromas (38.0%). Collectively, these findings suggest that KoRV may have an important role in koala bone tumor oncogenesis, warranting further investigation into its potential as a contributing factor in tumor development.

Understanding the origin, distribution, and biology of different cell populations in chimeric mice is critical for interpreting the pathological changes developed in these models. To this aim, the methodological work presented here illustrates the validation and application of a collection of labeling techniques to differentiate between specific mouse and human tissue/cell components in formalin-fixed paraffin-embedded samples from chimeric mice, especially those bearing human tumor and immune cells. First, broad approaches to identify cells of human origin using ubiquitous immunohistochemical targets such as HLA-A, Ku80, and human mitochondrial 60 kDa protein (hMito) were established using specimens from humanized mice and a human tissue microarray including both normal and neoplastic samples. Due to its crisp membranous immunoreactivity, HLA-A was the most useful marker for visual human cell identification; however, Ku80 and hMito may be suitable options when HLA-A is not expressed in the cells of interest. Importantly, using one or more of these markers provides a broad range of coverage for the vast majority of human-derived cells in chimeric mice. Second, tailored immunohistochemical or in situ hybridization methodologies to distinguish specific human or mouse cell subsets are presented, focusing on immune/inflammatory cells and human chimeric antigen receptor (CAR) T-cells. These diverse approaches are accompanied by descriptions of case examples highlighting practical diagnostic and experimental applications in the context of various humanized mouse models. While not comprehensive, this work represents a valuable starting reference for pathologists and investigators working with humanized mouse models and seeking to add spatial resolution to the complex landscape of chimeric tissues.

Chimeric antigen receptor (CAR) T cells are revolutionary cancer therapies that are Food and Drug Administration-approved for hematologic malignancies and under investigation for solid tumors. The use of allogeneic over autologous CAR T cells offers advantages, including broader availability and reduced costs. However, allogeneic CAR T cells frequently trigger graft versus host disease (GvHD), a complication observed in patients and experimental models where human CAR T cells are delivered into immunocompromised mice. To understand the contribution of the mouse immune response to human CAR T cell-mediated xenogeneic GvHD, we analyzed GvHD lesions in a human xenograft tumor model in NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ (NSG) mice. The animals were treated with second-generation CAR T cells targeting a human tumor-specific antigen without a murine homolog. Mice treated with CAR T cells had more severe GvHD lesions than control mice receiving nontransduced (NT) T cells. Also, tumor burden was negatively correlated with GvHD lesion severity. Immunohistochemical characterization of the GvHD lesions showed that approximately 45% of the immune cell infiltrate consisted of murine cells, most of which were IBA1+ histiocytes, with a small population of CD11c+ dendritic cells. The murine histiocytes expressed activation/antigen presentation markers, including high levels of the costimulatory molecule CD86. Analysis of macrophage polarization indicated an M2-like phenotype. These findings demonstrate a significant contribution of the mouse histiocytic compartment to lesions of human CAR T cell-mediated xenogeneic GvHD. Our results suggest that CD86+ murine antigen-presenting cells help trigger and sustain the xenoreactive CAR T cell response. Furthermore, xenogeneic GvHD exhibits a shift toward M2 polarization in murine macrophages.

Yersinia pseudotuberculosis (Yptb) is a gram-negative bacterium that can cause sporadic fatal infections in humans, domestic animals, and wildlife. We describe an outbreak of Yptb in a captive collection of 222 Seba's short-tailed bats (Carollia perspicillata), 50 of which died of confirmed (39 of 222, 17.6%) or suspected (11 of 222; 5.0%) Yptb infection. Females were more likely to be infected than males (odds ratio: 3.4), and non-pregnant females were more likely to be infected than pregnant females (odds ratio: 13.6). The most common gross lesions were multifocal cream/white discolorations and/or nodules (30 of 39, 77%) in the liver, followed by splenomegaly (23 of 39, 59%) and mesenteric lymphadenomegaly (9 of 39, 23%); 5 of 39 (13%) animals had no gross lesions. Histology was performed on the livers of 33 confirmed Yptb-positive animals, with the most common findings being extramedullary hematopoiesis (27 of 33, 82%) and pyogranulomatous or suppurative hepatitis (20 of 33, 61%). Hemosiderosis was observed in 32 of 33 (97%) cases and in 27 of 27 (100%) control animals that were not infected with Yptb. Solution inductively coupled mass spectrometry showed that infected bats had an average of 1.7× more hepatic iron than uninfected bats (P = .0067); this was corroborated by image analysis of Perl's stained sections (P < .0001), but laser ablation on a subset of cases was not significant (P = .1051). We hypothesize that hemosiderosis favors the systemic spread of Yptb by limiting the efficacy of hepcidin-mediated iron depletion, and that limiting dietary iron may protect captive wildlife from bacterial infections.

Axolotls (Ambystoma mexicanum) are critically endangered paedomorphic salamanders with remarkable regenerative capacity. While nearly extinct in the wild, they are commonly maintained in captivity as companion animals, zoological display animals, and biomedical research colonies, where they serve as an animal model for genetics, developmental biology, and regenerative medicine. This report documents a case series of spontaneous myeloid leukemia in genetically related, co-housed adult axolotls in a zoological collection that resulted in 50% overall mortality over 38 months. Affected axolotls exhibited a range of signs, including generalized edema, hydrocoelom, long-term wasting, and sudden death. The most common gross lesions were splenomegaly (5/10) and hepatomegaly (4/10). Microscopically, widespread intravascular neoplasia, consisting of large round cells, was consistently observed (10/10). Neoplastic cells infiltrated and effaced the parenchyma of numerous visceral organs, particularly the spleen and liver. Cytochemical staining of neoplastic cells in blood smears showed strong positive cytoplasmic reactivity for α-naphthyl butyrate esterase and α-chloroacetate esterase and weak staining with periodic-acid Schiff. In tissues, neoplastic cells did not react with Sudan black B and did not express CD3 or ionized calcium-binding adaptor molecule 1 (IBA-1). The morphologic features of the cells and phenotyping tests supported acute myeloid leukemia. This report represents the first documentation of acute myeloid leukemia in caudates.