Veterinary Pathology最新文献

The tumor-immune microenvironment (TIME) plays a pivotal role in cancer progression, yet its characterization in veterinary oncology remains limited. Eighty-five soft tissue sarcomas (STSs), comprising fibrosarcomas, leiomyosarcomas, liposarcomas, myxosarcomas, and perivascular wall tumors (PWTs), were immunohistochemically assessed for IBA-1 (total tumor-associated macrophages) and CD204 (M2-like macrophages) expression, scored by image analysis, and correlated with histological parameters. IBA-1 was higher in grade 3 STSs compared with grade 1 (W = 3.40, P = .043) and in PWTs compared with myxosarcomas (W = 6.037, P < .001). CD204 was lower in PWTs compared with fibrosarcomas (W = 5.152, P = .003), leiomyosarcomas (W = 4.394, P = .016), and myxosarcomas (W = 4.812, P = .006). Stratifying by STS type, IBA-1 was higher in grade 2 myxosarcomas compared with grade 1 (Mann U = 4, P = .018). IBA-1 and CD204 were higher in myxosarcomas with necrosis compared with those without (Mann U = 5, P = .026, and Mann U = 0, P = .001, respectively). In PWTs, the mitotic count was higher in cases with higher IBA-1 (Spearman's rho = 0.438, P = .041) and cases with lower CD204 (Spearman's rho = -0.459, P = .035). Considering all STSs, IBA-1 correlated with total tumor-infiltrating lymphocytes (TILs), T-cells, and regulatory T-cells (Tregs). In fibrosarcomas, IBA-1 and CD204 directly correlated with total TILs, T-cells, and Tregs. In myxosarcomas, CD204 correlated with Tregs. In leiomyosarcomas, IBA-1 scores correlated with Tregs and CD204 with T-cells and Tregs. In PWTs, B-cells correlated with IBA-1 and inversely correlated with CD204. These findings suggest the presence of a TIME favoring anti-tumor immunity in PWTs and a pro-tumoral TIME in myxosarcomas, reinforcing the concept that canine STS histotypes elicit distinct immune responses.

ΔNp63 is an isoform of p63 that plays an essential role in the development and growth of some epithelial tissues. In this study, we investigated the expression of ΔNp63 in normal and neoplastic tissues of cats and compared the results with the expression of pan-p63. Immunohistochemistry for ΔNp63 and pan-p63 was performed in normal tissues from 2 adult cats and in 10 cases each of 22 different types of feline neoplasms. In normal tissues, there was nuclear ΔNp63 immunolabeling in basal cells of stratified squamous, transitional, and pseudostratified columnar epithelia; basal cells of sebaceous glands; trophoblasts; and myoepithelial cells. Of the neoplasms, 10/10 apocrine ductal adenomas, 10/10 mammary ductal carcinomas, 10/10 pulmonary adenosquamous carcinomas, 10/10 squamous cell carcinomas, 10/10 trichoblastomas, and 10/10 urothelial carcinomas immunolabeled for ΔNp63. The ΔNp63 immunolabeling was diffuse in almost all neoplastic cells with squamous, basal, and urothelial origins. In the neoplasms with ductal differentiation, only the neoplastic suprabasal myoepithelial cells immunolabeled. Application of pan-p63 to the same set of neoplasms revealed positivity not only in the same neoplasms, but also in several unexpected tumor types (3/10 exocrine pancreatic carcinomas, 3/10 fibrosarcomas, 3/10 pulmonary adenocarcinomas, 2/10 lymphomas, 1/10 cholangiocarcinomas, 1/10 hemangiosarcomas, 1/10 mast cell tumors, and 1/10 meningiomas). Both ΔNp63 and pan-p63 antibodies demonstrated 100% diagnostic sensitivity and negative predictive value for diagnosing feline neoplasms with squamous, basal, and urothelial epithelia or myoepithelial cells. However, ΔNp63 showed higher diagnostic specificity (100% vs. 90.6%), positive predictive value (100% vs. 80%), and overall accuracy (100% vs. 93.1%) compared with pan-p63.

The histologic diagnosis of some cases of bovine dermatitis can be challenging. We investigated the predominant histologic patterns of dermatitis in cattle, to propose histologic pattern analysis as a diagnostic approach. Sixty-two cases of bovine dermatitis with confirmed etiologic diagnoses were selected in a 20-year retrospective study. The cases included 13 different primary and secondary diseases, ranging from infectious (48/62, 77%) to toxic/irritant-associated diseases (14/62, 23%). The cutaneous lesions were histologically classified into 11 dermatitis patterns, adapted from those described for small animals. Nodular to diffuse dermatitis (22/62, 34%), perivascular dermatitis (14/62, 23%), necrotizing dermatitis (11/62, 18%), and intraepidermal pustular dermatitis (10/62, 16%) were the most common patterns, followed by panniculitis (3/62, 5%); vasculitis (1/62, 2%); and perifolliculitis, folliculitis, or furunculosis (1/62, 2%). The nodular to diffuse, perivascular, necrotizing, and intraepidermal pustular dermatitis patterns included diseases with different etiologies, while the remaining patterns covered a smaller number of distinct cutaneous diseases in each classification. Our results highlighted the histologic analysis as an efficient tool for directing diagnoses, representing a starting point for the application of this technique in large animal dermatology.

Immunodeficient mice, particularly the NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ (NSG) strain and other non-obese diabetic (NOD)-derived lines are widely used in biomedical research due to their profound immunosuppression, which enables stable engraftment of human cells and tissues with minimal rejection. Despite their broad utility, these models exhibit unique immunologic and anatomic features and are predisposed to infectious and noninfectious diseases that may confound experimental outcomes and limit translational relevance. This review summarizes current knowledge on spontaneous, infectious, and experimentally induced lesions in NSG and related strains. These mice characteristically display hypoplastic lymphoid organs, including the spleen, thymus, and lymph nodes, due to a near-complete absence of lymphocytes. Spontaneous background lesions include splenic osseous metaplasia, neurodegeneration, pancreatic mastocytosis, cochlear degeneration, intervertebral disk disease, skull hyperostosis, and pancreatic duct cysts, among others. Common spontaneous neoplasms include lymphomas, osteosarcomas, and mammary gland tumors. Due to their immunodeficient status, NSG and NOD-derived mice are also highly susceptible to opportunistic infections, such as Corynebacterium bovis, Chlamydia muridarum, Clostridioides difficile, and mouse kidney parvovirus. In humanized models, engraftment of human immune cells can result in distinctive syndromes, including xenogeneic graft-versus-host disease, post-transplant lymphoproliferative disorders, and chimeric myeloid cell hyperactivation syndrome, which can impact study outcomes and lead to mortality and morbidity. This review is intended as a resource for comparative pathologists to become familiar with these widely used immunodeficient mice, so they can interpret strain-specific lesions and recognize experimental confounders in these mouse models.

Porcine circovirus 3 (PCV3) is a recently identified pathogen in swine populations. It is considered a ubiquitous virus and is frequently associated with subclinical infections throughout various stages of production. PCV3 is detectable in diverse tissues, blood, and secretions, indicating systemic dissemination and potential for both vertical and horizontal transmission. PCV3 has been implicated in reproductive and postnatal diseases collectively named as PCV3-associated diseases (PCV3-AD). Clinically, PCV3-AD encompasses reproductive disorders such as mummified fetuses, stillbirths, and weak neonates, alongside postnatal manifestations including anorexia, weight loss, and progressive wasting. Histopathologically, PCV3-AD is primarily defined by systemic nonsuppurative periarteritis and arteritis that are observed across multiple tissues, particularly within the heart, mesenteric arterial plexus, and kidneys. Despite the broad tissue tropism and frequent detection of viral nucleic acids within affected vascular and parenchymal structures, the precise mechanisms underpinning PCV3 pathogenesis remain poorly understood. Diagnosis of PCV3-AD relies on the confluence of characteristic clinical signs, compatible histopathological findings, and the in situ detection of the virus within lesions. However, the true prevalence of PCV3-AD under field conditions is likely underestimated due to the limited availability and high costs associated with laboratory techniques for definitive viral detection. This review seeks to consolidate and interpret clinical and pathological evidence indicative of PCV3-AD while addressing the critical diagnostic challenges faced by veterinary pathologists. Enhanced understanding of the disease's clinical-pathological correlations and diagnostic approaches is essential to accurately assess its impact on swine health and production.

To understand diseases of wild urban jackrabbits (Lepus townsendii), we autopsied 130 individuals that died near roadways in Calgary, Alberta, Canada. Renal hamartomas were present in 8 of 130 hares (6.2%; 95% confidence interval: 3.2%-11.7%). Most were unilateral (7/8); one case had bilateral lesions. Hamartomas are benign, tumor-like lesions comprised of normal tissue elements in abnormal amounts and arrangements. Macroscopically, hamartomas were white, tan, or pink-red, well-circumscribed, singular or multilobular, expansile nodules in the cortex or corticomedullary junction. Histologically, renal hamartomas consisted of well-demarcated mature stromal tissue with fibrous tissue and occasionally, adipocyte differentiation. These results represent a unique temporal and geographical cluster of a renal anomaly in an urban wildlife population. Renal hamartomas were not identified in other large studies of diseases in free-ranging leporids including hares. Contributing factors to this cluster remain unknown.

Chronic inflammatory rhinitis (CIR) is among the most common causes of chronic nasal signs in dogs. Despite research efforts, the etiology of CIR remains mostly undiscovered. The aim of our study was to describe the histological findings in nasal biopsies of control dogs without signs of nasal disease compared to dogs with CIR. The study groups were control dogs euthanized for reasons unrelated to this study (n = 20) and previously collected, archived nasal biopsies from dogs diagnosed with CIR (n = 20). A CIR diagnosis was based on clinical presentation, computed tomography, rhinoscopy, and histopathological findings indicative of CIR. Inflammatory cell counts and changes in the mucosal epithelium and associated lamina propria were evaluated from nasal biopsy specimens. The numbers of lymphocytes and plasma cells (P < .0001), neutrophils (P < .0001), and eosinophils (P = .0016) in the lamina propria, and mucosal intraepithelial leukocytes (P < .0001) were significantly higher in dogs with CIR compared to control dogs. A small population of leukocytes was also observed in control dogs, likely representing a physiological immune cell population. The type of inflammation in CIR is not purely lymphoplasmacytic, as both neutrophils and eosinophils were also detected in CIR dogs. The mucosal epithelium was thicker (P = .006), and visible goblet cells (P < .001) were decreased, in dogs with CIR, with a multifocal loss of cilia in some dogs, which may represent a form of respiratory epithelial metaplasia. Epithelial alterations likely play a role in the pathophysiology of CIR and contribute to the clinical signs.

Diagnosing early nodal metastases in canine malignant melanoma is challenging due to the morphological similarities between nodal melanophages and neoplastic melanocytes, and the limitations of conventional immunohistochemical markers like melan-A, which only labels a subset of tumor cells and requires tissue bleaching. This retrospective study investigated the utility of the immunohistochemical marker SOX-10, a nuclear transcription factor, in identifying metastatic cells in lymph nodes (LNs) from dogs with oral, labial, or digital malignant melanoma undergoing regional or sentinel lymphadenectomy. The analysis included 49 LNs from 27 dogs with oral (n = 10), labial (n = 9), and digital (n = 8) melanoma. Primary tumors were highly melanotic in 7 (26%) dogs, sparsely melanotic in 15 (56%), and amelanotic in 5 (19%). SOX-10 immunohistochemistry increased the detection rate of nodal metastasis from 29% (14/49 nodes) with hematoxylin and eosin staining alone and 31% (15/49 nodes) with melan-A immunohistochemistry to 33% (16/49 nodes), allowing the identification of 12 LNs with macrometastases, 2 with micrometastases, and 2 with isolated tumor cells. Compared with melan-A, SOX-10 exhibited a more uniform labeling pattern, enhancing the identification of micrometastases and isolated tumor cells. It also facilitated the distinction between neoplastic cells and melanophages, even in heavily pigmented samples, without the need for bleaching, thereby preserving tissue integrity. These findings suggest that SOX-10 is a promising diagnostic marker for canine melanoma, offering improved detection of early melanocytic metastatic lesions.

Here we assess the diagnostic features of 73 canine extramedullary plasmacytomas (EMPs) and their differentiation from canine cutaneous histiocytomas (CHs) using histology and immunohistochemistry for MUM1, CD3, CD79a, immunoglobulin (Ig) light chains (λ and κ), and IBA1. Most EMPs were classified as cleaved and mature subtypes. Almost 92% of EMPs were positive for MUM1, whereas 77% were positive for CD79a and 74% for Ig light chains λ and κ. The use of MUM1 and Ig light chains resulted in a sensitivity of 100% in diagnosing EMPs, surpassing the combination of MUM1 and CD79a (94%). In 8% of the EMPs, there was pseudofollicular arrangement of neoplastic cells, whereas 7% had amyloid deposition and 3% had mineralization. CHs were positive for IBA1 but negative for all other IHCs.

Intracellular inclusions are singular structures that may occur secondary to viral infection, cytoplasmic invagination, and organelle entrapment, or due to abnormal accumulation of biological material, such as proteins. Determining the exact nature of an inclusion is crucial in diagnostic pathology, especially in the context of colony management and toxicity studies. In this case series, we identified pancreatic islet intranuclear (IN) and intracytoplasmic (IC) eosinophilic inclusions in 13 out of 21 southern giant pouched rats (Cricetomys ansorgei), a species studied for its outstanding olfactory capacities. Intranuclear inclusions were smooth, globular, and marginated the chromatin. Intracytoplasmic inclusions were either single or multiple, and polygonal to globular. Females and males were both affected, regardless of their wild-caught or inhouse-bred status. Immunohistochemistry labeling for p62 in some IN inclusions suggested a correlation with autophagy. Okajima's stain for hemoglobin positively stained all inclusions. Periodic acid-Schiff reaction, Masson's trichrome, Congo red, and Prussian blue were all negative, ruling out polysaccharides, β-pleated sheets, fibrin, and free iron. Ultrastructural evaluation further revealed that IN inclusions consisted of aggregated fibrillar to microtubular material and excluded a viral infection. By contrast, IC inclusions were identified as giant mitochondria with crystalline deposits and abnormal cristae. In conclusion, the frequent occurrence of either type of inclusion, irrespective of clinical health status, suggests that they are likely incidental although possibly related to autophagy. Importantly, the natural occurrence of giant mitochondria in seemingly healthy individuals is unusual. Giant pouched rats may thus represent a suitable species to deepen our understanding of these peculiar organelles.