Concordance of the Histopathologic Diagnosis of Concurrent Duodenal and Ileal Biopsy Specimens in Dogs

Histopathologic discordance between gastrointestinal (GI) locations in canine chronic inflammatory enteropathy (CIE) has prompted recommendations to biopsy both the duodenum and ileum, while further evaluation is required for non-CIE. We aimed to determine the concordance of histopathologic diagnosis between duodenal and ileal endoscopic or full-thickness biopsy specimens for all dogs with CIE and GI neoplasia and to assess the association between histopathologic discordance between GI locations with clinicopathologic variables. Seventy-nine dogs were eligible, with endoscopic (74) or full-thickness (5) biopsy specimens. Clinicopathological data were recorded for all dogs. Concordance of histopathologic diagnosis was retrospectively assessed for concurrent duodenal and ileal biopsy specimens by a single board-certified veterinary pathologist using the modified World Small Animal Veterinary Association (WSAVA) Gastrointestinal Standardization Group guidelines. Sixty-seven dogs were diagnosed with CIE and 5 with enteric-associated T-cell lymphoma-2 (EATL-2). Concordance of histologic diagnosis between duodenal and ileal sites was similar between endoscopic (73.0%) and full-thickness (80.0%) biopsy groups. For the CIE cases, lymphoplasmacytic enteritis had the highest concordance (73.0%) and eosinophilic enteritis the least (16.7%). Of the 5 neoplastic cases, 5/5 (100%) were present at the duodenum but only 3/5 (60%) in the ileum. No clinicopathologic variables demonstrated a statistically significant association with discordance. We conclude that the level of discordance necessitates concurrent biopsy of both duodenum and ileum in all dogs with chronic GI signs. The rate of EATL-2 was lower than rates reported for cats.

Chemical-Induced Oral Squamous Cell Neoplasms in Rodents: An Overview of NTP 2-Year Cancer Studies

Oral cancer is the seventh most common malignancy worldwide, and lifestyle factors participate in its development. Rodent studies can help identify substances that contribute to its development and provide information on the early stages of carcinogenicity. The National Toxicology Program (NTP) has conducted more than 500 short-term and 2-year toxicology and carcinogenicity studies in rodents, and some of the tested compounds resulted in oral cancer. Our goal was to review the NTP carcinogenic studies to describe those chemicals that have oral carcinogenic outcome in rodents. For this project, we reviewed the results from all NTP carcinogenicity studies and a board-certified veterinary pathologist reviewed the slides from all neoplasms in the oral cavity that were considered treatment related. We have identified 26 chemicals with an adverse effect in the oral cavity. Fourteen chemicals demonstrated clear evidence of carcinogenicity in the oral cavity. We provide information on the carcinogenic findings in rodents together with a detailed description of the morphologic aspects of the oral cancers and speculate that the carcinogenic effects can be induced by different pathological modes of action. The findings reviewed here provide indicators for potential oral carcinogenesis processes in rodent models, which can be further investigated in future mechanistic studies.

Challenges and Opportunities for the Veterinary Pathologist in Biomedical Research

Animal models have critical roles in biomedical research in promoting understanding of human disease and facilitating development of new therapies and diagnostic techniques to improve human and animal health. In the study of myriad human conditions, each model requires in-depth characterization of its assets and limitations in order for it to be used to greatest advantage. Veterinary pathology expertise is critical in understanding the relevance and translational validity of animal models to conditions under study, assessing morbidity and mortality, and validating outcomes as relevant or not to the study interventions. Clear communication with investigators and education of research personnel on the use and interpretation of pathology endpoints in animal models are critical to the success of any research program. The veterinary pathologist is underutilized in biomedical research due to many factors including misconceptions about high fiscal costs, lack of perceived value, limited recognition of their expertise, and the generally low number of veterinary pathologists currently employed in biomedical research. As members of the multidisciplinary research team, veterinary pathologists have an important role to educate scientists, ensure accurate interpretation of pathology data, maximize rigor, and ensure reproducibility to provide the most reliable data for animal models in biomedical research.

Evaluation of serum MMP-2 and MMP-3, synovial fluid IL-8, MCP-1, and KC concentrations as biomarkers of stifle osteoarthritis associated with naturally occurring cranial cruciate ligament rupture in dogs

The purpose of this study was to evaluate matrix metalloproteinases (MMP) -2 and MMP-3 in serum, and keratinocyte-derived chemoattractant (KC), interleukin 8 (IL-8) and monocyte chemoattractant 1 (MCP-1) in synovial fluid (SF) as stifle osteoarthritis (OA) biomarkers in dogs. Dogs with naturally occurring cranial cruciate ligament (CrCL) rupture (OA group) and healthy controls were recruited. Stifles with CrCL deficiency were surgically stabilized. Serum, SF, and synovial biopsy samples were collected from the OA group preoperatively, whereas samples were collected once from control dogs. A blinded veterinary pathologist graded synovial biopsies. Serum and SF analyses were performed using xMAP technology. General linear regression was used for statistical comparisons of serum biomarkers, and mixed linear regression for SF biomarkers and temporal concentration changes. The overall discriminative ability was quantified using area under curve (AUC). Spearman’s correlation coefficient was used to assess correlations between synovial histology grades and the biomarkers. Samples from 62 dogs in the OA group and 50 controls were included. The MMP-2 and MMP-3 concentrations between the OA and control groups were not significantly different, and both with an AUC indicating a poor discriminative ability. All three SF biomarker concentrations were significantly different between the OA group and controls (P <0.05). The MCP-1 was the only biomarker showing an acceptable discriminative performance with an AUC of 0.91 (95% confidence interval: 0.83–0.98). The sum of the inflammatory infiltrate score was significantly correlated with all three SF biomarkers (P <0.01). Summed synovial stroma, and all scores combined were significantly correlated with IL-8 and MCP-1 concentrations (P <0.003), and the summed synoviocyte scores were significantly correlated with MCP-1 concentrations (P <0.001). Correlations between MCP-1 concentrations and synovial histopathologic grading and its discriminative ability suggest its potential as a synovitis biomarker in canine stifle OA associated with CrCL rupture.

A Comparative Neuro-Histological Assessment of Gluteal Skin Thickness and Cutaneous Nociceptor Distribution in Horses and Humans

The current project aims to build on knowledge of the nociceptive capability of equine skin to detect superficial acute pain, particularly in comparison to human skin. Post-mortem samples of gluteal skin were taken from men (n = 5) and women (n = 5), thoroughbreds and thoroughbred types (mares, n = 11; geldings, n = 9). Only sections that contained epidermis and dermis through to the hypodermis were analysed. Epidermal depth, dermal depth and epidermal nerve counts were conducted by a veterinary pathologist. The results revealed no significant difference between the epidermal nerve counts of humans and horses (t = 0.051, p = 0.960). There were no significant differences between epidermal thickness of humans (26.8 µm) and horses (31.6 µm) for reference (left side) samples (t = 0.117, p = 0.908). The human dermis was significantly thinner than the horse dermis (t = −2.946, p = 0.007). Epidermal samples were thicker on the right than on the left, but only significantly so for horses (t = 2.291, p = 0.023), not for humans (t = 0.694, p = 0.489). The thicker collagenous dermis of horse skin may afford some resilience versus external mechanical trauma, though as this is below the pain-detecting nerve endings, it is not considered protective from external cutaneous pain. The superficial pain-sensitive epidermal layer of horse skin is as richly innervated and is of equivalent thickness as human skin, demonstrating that humans and horses have the equivalent basic anatomic structures to detect cutaneous pain. This finding challenges assumptions about the physical capacity of horses to feel pain particularly in comparison to humans, and presents physical evidence to inform the discussion and debate regarding the ethics of whipping horses.

Safety and Feasibility of a Novel Esophageal Balloon for Circumferential Cytologic Sampling

Objectives: A prior publication introduced the Strome-Blitzer balloon’s ability to obtain circumferential esophageal cytologic sampling. This GLP study was requisite for FDA approval to determine if equivalent cell capture and cellularity was observed with the balloon compared to surface sampling brushes and to determine the balloon’s usability for naive otolaryngologists. Methods: Three naïve users tested the Hobbs brush and Strome-Blitzer balloon on 4 Yorkshire swine. Four anatomical sites were sampled, beginning distally and ending proximally. In 2 animals, the balloon was used first distally and in the remaining 2, 4 new Hobbs brushes were used distally first. Moving proximally, the balloon and brushes were sequentially alternated. In follow-the-leader fashion, the balloon was introduced trans-orally followed by an endoscope to the desired site. The balloon was inflated exposing the abrasive strips to contact the esophageal mucosa. Moving the balloon 1 to 2 cm superiorly and inferiorly effected circumferential cell capture. The balloon was collapsed and removed, preserving the cellularity. The Hobbs brush was passed through the scope’s channel. Four brushes, 1 per quadrant, obtained the samples at an anatomical site. The balloon was rated as pass/fail on the following: delivery, kinking, usability, and malfunction. A blinded veterinary pathologist evaluated the cytology. Results: There was no device malfunction, mucosal trauma, or difficulty with device use. Balloon cytologic samples were comparable in cellularity and quality to the brush. Conclusion: A single balloon sampling was comparable to 4 brushes in capturing diagnostically relevant cellular volumes and architecture. Naïve users easily performed the procedures after reading the guidelines. Level of Evidence: 3

Practical Strategies for Navigating Toxicologic Pathology in One’s Early Career…and Beyond!

The toxicologic pathologist plays a vital role in the scientific community, using their unique blend of diagnostic and investigative skills to advance biomedical research, public health, drug discovery, or regulatory practices. But what exactly do toxicologic pathologists contribute? Where do these specialized professionals work? How can toxicologic pathologists maximize their efficiency and potential? To enlighten students and trainees, as well as early- or mid-career toxicologic pathologists, or even those approaching retirement, the Career Development and Outreach Committee of the Society of Toxicologic Pathology (STP) sponsored a career development workshop entitled “Practical Strategies for Navigating Toxicologic Pathology in One’s Early Career…and Beyond!” in conjunction with the STP 37th annual symposium. The workshop featured toxicologic pathologists from contract research organizations and the pharmaceutical industry, who provided their perspectives on career preparation, evolving veterinary pathologist roles within various sectors of toxicologic pathology, the fundamentals of safety assessment, logistics of projects involving good laboratory practices, tools for effective interpretation and communication of anatomic and clinical pathology results, and a recap of scientific resources available to support the toxicologic pathologist in his or her journey. This article provides brief summaries of the talks presented during this career development workshop.

Hugh Munro Pirie

A world-renowned investigative veterinary pathologist who made an outstanding contribution to education and research.

The Role of the Veterinary Pathologist in Voice Research

Veterinary pathologists fill many vital roles in a multidisciplinary biomedical research team. They can serve as diagnosticians, basic medical scientists, or liaisons between investigative work and clinical medicine. Advanced education in veterinary pathology can provide expertise in the biology of the whole animal, spontaneous disease manifestations in both human and non-human animals, and experimental disease models. Veterinary pathologists have a unique standpoint in understanding the pathophysiology of disease from a One Health perspective in which human, animal, and environmental health are linked. By collaborating with a veterinary pathologist, voice and voice disorder research can reach new, innovative success and exploration.

From the working group "Experimental Pathology" to the department "Pathology Unit" – historical development in retrospect

The Pathology Unit of the German Primate Center started as the working group of Experimental Pathology in 1992. This small group with one veterinary pathologist and a technician was founded based on an idea of Prof. Dr. Kuhn, who wanted to strengthen the pathology research activities and to establish a centralized electron microscopy laboratory. Later on, experimental pathology, veterinary services and primate husbandry were integrated as the Department of Veterinary Medicine and Primate Husbandry but subsequently again separated. Prof. Dr. Franz-Josef Kaup, the head of the previously integrated department, remained in his capacity as the leader of the different units. Over the years, the research activities have changed from SIV-associated pathology to other infectious diseases. Today, the main research focus is on the pathogenesis of orthopoxvirus infection, primate pathology, neglected tropical diseases and nonhuman primates as models for chronic respiratory diseases. This paper gives an overview of the historical development and aspects of research activities.