Veterinary Pathology最新文献

Variation in nuclear size and shape is an important criterion of malignancy for many tumor types; however, categorical estimates by pathologists have poor reproducibility. Measurements of nuclear characteristics can improve reproducibility, but current manual methods are time-consuming. The aim of this study was to explore the limitations of estimates and develop alternative morphometric solutions for canine cutaneous mast cell tumors (ccMCTs). We assessed the following nuclear evaluation methods for accuracy, reproducibility, and prognostic utility: (1) anisokaryosis estimates by 11 pathologists; (2) gold standard manual morphometry of at least 100 nuclei; (3) practicable manual morphometry with stratified sampling of 12 nuclei by 9 pathologists; and (4) automated morphometry using deep learning-based segmentation. The study included 96 ccMCTs with available outcome information. Inter-rater reproducibility of anisokaryosis estimates was low (k = 0.226), whereas it was good (intraclass correlation = 0.654) for practicable morphometry of the standard deviation (SD) of nuclear size. As compared with gold standard manual morphometry (area under the ROC curve [AUC] = 0.839, 95% confidence interval [CI] = 0.701-0.977), the prognostic value (tumor-specific survival) of SDs of nuclear area for practicable manual morphometry and automated morphometry were high with an AUC of 0.868 (95% CI = 0.737-0.991) and 0.943 (95% CI = 0.889-0.996), respectively. This study supports the use of manual morphometry with stratified sampling of 12 nuclei and algorithmic morphometry to overcome the poor reproducibility of estimates. Further studies are needed to validate our findings, determine inter-algorithmic reproducibility and algorithmic robustness, and explore tumor heterogeneity of nuclear features in entire tumor sections.

Acute myeloid leukemia (AML) can infiltrate extramedullary tissues, such as the liver, spleen, and lymph nodes and can be difficult to differentiate from lymphoma in cytologic and histologic specimens. Our goal was to identify cytologic features that would support a diagnosis of AML in peripheral lymph node aspirates, for which we used the term extramedullary AML (eAML). Medical records of 23 dogs with a diagnosis of AML and archived lymph node aspirate smears from 2016 to 2024 were reviewed across 4 institutions. Inclusion criteria included ≥50% myeloid blasts plus differentiating myeloid cells in lymph node smears, confirmation of myeloid lineage by flow cytometric analysis, and complete medical records. Peripheral lymphadenopathy was the reason for presentation (9/23, 39%) or was found incidentally on physical examination (14/23, 61%). Most dogs were bi- or pancytopenic (18/23, 78%), with blasts identified in blood smears of 18 dogs (78%). Initial lymph node aspirate interpretations included hematopoietic neoplasia (8/21, 38%), AML (6/21, 29%), lymphoma (5/21, 24%), lymphoid hyperplasia (1/21, 5%), and granulocytic precursor infiltrates (1/21, 5%). On lymph node smear review, cytologic features supporting an eAML were differentiating granulocytes, blasts with myeloid features or promonocytes, dysplastic changes in myeloid cells, and retention of residual lymphocytes. The median survival was 22 days (range = 1-360 days), and 69% of 16 dogs given chemotherapy or glucocorticoids lived for 30 days or more. Our study highlights the importance of hemogram results and lymph node aspirate smear examination for morphologic features of myeloid differentiation to help diagnose eAML in lymph node smears.

Ankole-Watusi cattle, Bos taurus ankole, have a unique wide-based horn structure with a large communication to the frontal sinus compared to other cattle breeds. A total of 6 cases of cornual sinusitis presented at the Toronto Zoo and Disney's Animal Kingdom Lodge® and Disney's Animal Kingdom® Theme Park with a head tilt. Clinically, 4 of the 6 cases had concurrent otitis at the time of initial clinical observation. Medical management was the standard across all cases with limited surgical success in 2 cases. Due to intractable and progressive clinical signs despite treatment attempts, euthanasia and postmortem examinations were performed. All animals had gross and histologic evidence of cornual sinusitis with massive mucoid exudate in either 1 or both horns. Fluid accumulation and sinusitis within the cornual sinus should be considered a differential diagnosis in Ankole-Watusi cattle with a head tilt.

Slaughterhouse inspections play a crucial role in the sanitary control of zoonoses and foodborne diseases. This study aimed to identify and analyze the frequencies of lymph node diseases in cattle slaughtered for human consumption, using the samples sent to the anatomic pathology service of the Federal Laboratory for Agricultural Defense (Laboratório Federal de Defesa Agropecuária), Minas Gerais, Brazil, from January 2015 to September 2022. In total, 2000 lymph node samples were analyzed, and additional information was individually retrieved. Lesions were most frequently identified in thoracic lymph nodes. Bacterial isolation and quantitative polymerase chain reaction (qPCR) were performed using samples suspected of tuberculosis. Tuberculosis cases accounted for 89.3% of the samples. Histopathology was more sensitive than other ancillary tests for diagnosing tuberculosis. Paraffin-embedded tissues from lymphoma cases were subjected to immunophenotyping using anti-CD3 and anti-CD79a immunohistochemistry. Frozen and/or paraffin-embedded tissues from lymphoma cases were used to identify the enzootic bovine leukosis (EBL) retrovirus through qPCR. Other diagnoses included primary (T- and B-cell lymphoma) and metastatic neoplasms (squamous cell carcinoma, pulmonary adenocarcinoma, undifferentiated carcinoma, undifferentiated adenocarcinoma, undifferentiated sarcoma, undifferentiated round cell tumor, mesothelioma, hepatic carcinoid, meningioma, and seminoma), actinogranulomas (pyogranulomatous lymphadenitis [actinobacillosis and actinomycosis]), idiopathic lymphadenitis (neutrophilic and/or histiocytic, granulomatous, and suppurative), and miscellaneous nonspecific lymphadenopathies (depletion/lymphoid atrophy, lymphangiectasia, erythrocyte drainage, parasitic eosinophilic lymphadenitis, follicular hyperplasia, and toxic granulomatous lymphadenitis). The combination of histopathology with complementary techniques is important for successful diagnosis, especially in complex cases of high epidemiological, economic, and zoosanitary importance, such as tuberculosis and EBL.

Although neoplasia has been documented in invertebrates, it has not been reported in scorpions. This report describes presumed hemocytic neoplasia in 2 scorpions: a >3-year-old, female emperor scorpion (Pandinus imperator) and a >4-year-old, male, Asian forest scorpion (Heterometrus sp.). The emperor scorpion had a 1-month history of body wall swelling separating the exoskeleton of the caudal opisthosoma. At necropsy, this corresponded to a white mass in the caudal coelom. The forest scorpion was found dead and processed whole for histology, at which point multiple masses were identified in the coelom and invading skeletal muscle. Histologically, both masses were composed of sheets of hemocytes with round to oval nuclei; eosinophilic, periodic acid Schiff-positive, cytoplasmic granules; mild cellular atypia; and low mitotic rates. Features of inflammation (e.g., melanization and nodulation) were not observed. These masses were diagnosed as a hemocytoma (emperor scorpion) and a hemocytic sarcoma (forest scorpion), possibly of plasmatocyte origin.

Cutaneous plaques and squamous cell carcinoma (SCC) are common in captive North American snow leopards (SLs) (Panthera uncia). Our objective was to determine whether these lesions are potentially associated with papillomavirus(es). Polymerase chain reaction (PCR) was performed on 3 cutaneous plaques using degenerate primers for papillomaviruses. A putatively novel papillomavirus was identified that shared 76% sequence identity to Felis catus papillomavirus 2. Specific PCR for this virus was performed on 5 cutaneous SCC samples and 7 normal skin samples, which were all positive. In situ hybridization for this putatively novel virus was performed, which revealed strong hybridization signals within hyperplastic cells in cutaneous plaques (n = 3) and within neoplastic cells in cutaneous SCC samples (n = 5). No hybridization signals were identified within normal skin. Ultimately, identification of a causal viral agent in the development of plaques and SCC in SLs will help guide therapeutic intervention and lay the foundation for development of prophylactic vaccines.

High survivin expression has been correlated with poor outcomes in several canine tumors but not in soft tissue tumors (STTs). Survivin is a target gene of the Wnt/β-catenin pathway, which is involved in human STT oncogenesis. Immunohistochemistry for survivin, β-catenin, and Ki-67 was performed on 41 canine perivascular wall tumors (cPWTs), and statistical associations of protein expression and histopathologic and clinical variables with clinical outcomes were investigated. Immunohistochemically, there was nuclear positivity (0.9%-12.2% of tumor cells) for survivin in 41/41 (100%), cytoplasmic positivity (0 to > 75% of tumor cells) for survivin in 31/41 (76%), nuclear positivity (2.9%-67.2% of tumor cells) for β-catenin in 24/41 (59%), and cytoplasmic positivity (0% to > 75% of tumor cells) for β-catenin in 23/41 (56%) of cPWTs. All tumors expressed nuclear Ki-67 (2.2%-23.5%). In univariate analysis and multivariate analysis (UA and MA, respectively), every 1% increase of nuclear survivin was associated with an increase of the instantaneous death risk by a factor of 1.15 [hazard ratio (HR) = 1.15; P = .007]. Higher nuclear survivin was associated with grade II/III neoplasms (P = .043). Expression of cytoplasmic survivin, nuclear and cytoplasmic β-catenin, and nuclear Ki-67 were not significantly associated with prognosis in UA nor MA. Tumor size was a significant prognostic factor for local recurrence in UA [subdistribution HR (SDHR) = 1.19; P = .02] and for reduced overall survival time in MA. According to UA and MA, a unitary increase of mitotic count was associated with an increase of the instantaneous death risk by a factor of 1.05 (HR = 1.05; P = .014). Nuclear survivin, mitotic count, and tumor size seem to be potential prognostic factors for cPWTs. In addition, survivin and β-catenin may represent promising therapeutic targets for cPWTs.

The Cd40l^-/- mouse is a well-established model of X-linked hyper-immunoglobulin M (IgM) syndrome, an immunodeficiency disorder of human beings characterized by the lack of expression of the CD40 ligand (CD40L) on activated T-cells, predisposing to infections with opportunistic pathogens like Pneumocystis jirovecii. The aim of our study was to describe the pulmonary lesions in Cd40l^-/- mice experimentally infected with Pneumocystis murina, in comparison with naturally infected severe combined immunodeficient (SCID) mice. Formalin-fixed paraffin-embedded lungs from 26 Cd40l^-/-, 11 SCID, and 5 uninfected Cd40l^-/- mice were examined by histology and immunohistochemistry for the presence of the pathogen and for leukocyte populations (CD3, CD4, CD45R/B220, CD8a, Iba-1, Ly-6G, CD206, MHC II, and NKp46/NCR1). Infection was confirmed by immunohistochemistry in 18/26 (69%) Cd40l^-/- mice and in 11/11 (100%) SCID mice. Fourteen out of 26 (54%) Cd40l^-/- mice had interstitial pneumonia. Twenty-three out of 26 (88%) Cd40l^-/- mice had peribronchiolar/perivascular lymphoplasmacytic infiltrates, rich in B-cells and Mott cells. Acidophilic macrophage pneumonia was additionally found in 20/26 (77%) Cd40l^-/- mice. Only 4/11 (36%) SCID mice had interstitial pneumonia, but no peribronchiolar/perivascular infiltrates or acidophilic macrophage pneumonia were observed in this strain. This study represents the first description of pulmonary histopathological lesions in Cd40l^-/- mice infected with P. murina. We speculate that the singular characteristics of the inflammatory infiltrates observed in Cd40l^-/- mice could be explained by the specific immune phenotype of the model.

Melanoma is the most common malignant oral tumor in dogs. It frequently presents a diagnostic challenge as many melanomas lack or contain scant melanin and may have a variable microscopic phenotype. Previous studies evaluating immunohistochemical markers for diagnosing melanoma have shown limited sensitivity and/or specificity for S-100, PNL2, melan A, TRP-1, TRP-2, and HMB-45. Sry-related HMG-box gene 10 (SOX-10) is a transcription factor associated with melanocytic, peripheral neural crest, and peripheral nervous system development. In humans, SOX-10 expression has been demonstrated in melanoma, breast carcinoma, glioma, and schwannoma, but has only recently been explored in veterinary species. In this study, 198 tumors comprised of 147 melanocytic neoplasms and 51 non-melanocytic neoplasms were evaluated by immunohistochemistry using a tissue microarray for SOX-10, PNL2, melan A, TRP-1, and TRP-2 expressions. The SOX-10 had the highest diagnostic sensitivity (96.7%) in melanomas. In addition, SOX-10 had the highest percentage (91.5%; 130/142) of melanomas label at least 75% of neoplastic cells. Of the 51 selected non-melanocytic tumors examined, SOX-10 labeling was observed in mammary carcinomas (6/6), gliomas (4/4), and oral soft tissue sarcomas (4/18). Of the 41 non-melanocytic oral neoplasms evaluated, SOX-10 had a specificity of 92.7%. Therefore, SOX-10 represents a useful immunohistochemical screening marker for the diagnosis of canine melanoma given its extremely high sensitivity and robust labeling intensity. The SOX-10 may have utility in diagnosing some non-melanocytic neoplasms in the dog, although this requires further investigation.