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Canine soft tissue sarcomas (STS) are common neoplasms and considered immune deserts. Tumour infiltrating lymphocytes are sparse in STS and, when present, tend to organize around blood vessels or at the periphery of the neoplasm. This pattern is associated with an immunosuppressive tumour microenvironment linked to overexpression of molecules of the PD-axis. PD-1, PD-L1 and PD-L2 expression correlates with malignancy and poor prognosis in other neoplasms in humans and dogs, but little is known about their role in canine STS, their relationship to tumour grade, and how different therapies affect expression. The objective of this study was to evaluate the expression of checkpoint molecules across STS tumour grades and after tumour ablation treatment. Gene expression analysis was performed by reverse-transcriptase real-time quantitative PCR in soft tissue sarcomas that underwent histotripsy and from histologic specimens of STS from the Virginia Tech Animal Laboratory Services archives. The expression of PD-1, PD-L1 and PD-L2 was detected in untreated STS tissue representing grades 1, 2, and 3. Numerically decreased expression of all markers was observed in tissue sampled from the treatment interface relative to untreated areas of the tumour. The relatively lower expression of these checkpoint molecules at the periphery of the treated area may be related to liquefactive necrosis induced by the histotripsy treatment, and would potentially allow TILs to infiltrate the tumour. Relative increases of these checkpoint molecules in tumours of a higher grade and alongside immune cell infiltration are consistent with previous reports that associate their expression with malignancy., (© 2023 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

A 6 yr old male castrated American Staffordshire terrier was referred for a nonhealing wound at the site of a previously incompletely excised, high-grade soft tissue sarcoma. Physical examination revealed right popliteal lymphadenopathy and a fungating mass of the right pelvic limb at the level of the hock. Thoracic and abdominal computed tomography revealed mild lymphadenopathy of multiple iliac and inguinal lymph nodes. Right pelvic limb amputation and inguinal lymphadenectomy were performed. Histopathology was consistent of a high-grade soft tissue sarcoma with diffuse spread through the lymphatic vessels of the right pelvic limb up to the right inguinal lymph node but not affecting the lymph node itself. Doxorubicin chemotherapy was elected postoperatively as adjuvant therapy. Approximately 4 mo following initiation of chemotherapy, the patient developed a firm, tubular subcutaneous mass starting near the previous amputation site with tracking toward the thorax. Fine needle aspiration of the new mass was consistent with atypical spindle cell proliferation. Palliative care was elected, and the patient was euthanized 3 mo later because of progressive disease. In-transit metastasis is a rare behavior for soft tissue sarcomas across all species, and this is the first report of such a presentation for canine soft tissue sarcoma., (© 2023 by American Animal Hospital Association.)

Melanoma in humans and dogs is considered highly immunogenic; however, the function of tumor-infiltrating lymphocytes (TILs) is often suppressed in the tumor microenvironment. In humans, current immunotherapies target checkpoint molecules (such as PD-L1, expressed by tumor cells), inhibiting their suppressive effect over TILs. The role of PD-L2, an alternative PD-1 ligand also overexpressed in malignant tumors and in patients with anti-PD-L1 resistance, remains poorly understood. In the current study, we evaluated the expression of checkpoint molecule mRNAs in canine melanoma and TILs. Analysis of checkpoint molecule gene expression was performed by RT-qPCR (real-time quantitative polymerase chain reaction) using total RNA isolated from formalin-fixed and paraffin-embedded melanomas ( n = 22) and melanocytomas ( n = 9) from the Virginia Tech Animal Laboratory Services archives. Analysis of checkpoint molecule expression revealed significantly higher levels of PDCD1 ( PD-1 ) and CD274 ( PD-L1 ) mRNAs and an upward trend in PDCD1LG2 ( PD-L2 ) mRNA in melanomas relative to melanocytomas. Immunohistochemistry revealed markedly increased numbers of CD3 + T cells in the highest PD-1 -expressing subgroup of melanomas compared to the lowest PD-1 expressors, whereas densities of IBA1 + cells (macrophages) were similar in both groups. CD79a + cell numbers were low for both groups. As in human melanoma, overexpression of the PD-1/PD-L1/PD-L2 axis is a common feature of canine melanoma. High expression of PD-1 and PD-L1 correlates with increased numbers of CD3 + cells. Additionally, the high level of IBA1 + cells in melanomas with low PD-1 expression and low CD3 + cells levels suggest that the expression of checkpoint molecules is modulated by interactions between T cells and cancer cells rather than histiocytes.

An 8-y-old Labrador Retriever was presented to a small animal practice in northern Virginia with a history of recent lethargy. Physical examination findings were unremarkable. Ultrasound revealed several large hepatic masses and multiple smaller masses involving the pancreas. Cytologic findings on fine-needle aspirates of the hepatic masses included inflammation and necrosis with eosinophilic, membranous oval structures consistent with cestode infection. Histopathologic findings for biopsies of these masses included extensive necrosis, inflammation, and PAS-positive hyaline-like membranous material interpreted as metacestode cyst wall. A PCR product was generated from aspirate material using primers specific for Echinococcus multilocularis . Subsequent sequence data were 100% homologous to E. multilocularis NADH dehydrogenase subunit I gene sequences. The dog received daily oral albendazole (10 mg/kg) treatment, but its condition deteriorated, and the dog was euthanized. The dog, born in Mississippi, was brought as a puppy to Virginia with no other travel history. To our knowledge, alveolar echinococcosis has not been reported previously in a dog in the United States; E. multilocularis infection was apparently acquired in the mid-Atlantic region of the United States.

Background: Stereotactic brain biopsy (SBB) is a technique that allows for definitive diagnosis of brain lesions. Little information is available regarding the diagnostic utility of SBB in dogs with intracranial diseases., Objective: To investigate the diagnostic accuracy (DA) of SBB in dogs with brain tumors., Animals: Thirty-one client-owned dogs that underwent SBB followed by surgical resection or necropsy examinations., Methods: Retrospective observational study. Two pathologists blinded to SBB and reference standard diagnoses reviewed histologic specimens and typed and graded tumors according to World Health Organization and revised canine glioma classification criteria. Agreement between tumor type and grade from SBB were compared to reference standards and assessed using kappa statistics. Patient and technical factors associated with agreement also were examined., Results: Stereotactic brain biopsy specimens were obtained from 24 dogs with gliomas and 7 with meningiomas. Tumor type agreement between SBB and the reference standard was observed in 30/31 cases (κ = 0.95). Diagnostic concordance was perfect for meningiomas. Grade agreement among gliomas was observed in 18/23 cases (κ = 0.47). Stereotactic brain biopsy underrepresented the reference standard glioma grade in cases with disagreement. The DA of SBB was 81%, with agreement noted in 56/69 biopsy samples. Smaller tumors and fewer SBB specimens obtained were significantly associated with diagnostic discordance., Conclusions and Clinical Importance: The DA of SBB readily allows for the diagnosis of common brain tumors in dogs. Although glioma grade discordance was frequent, diagnoses obtained from SBB are sufficient to currently inform therapeutic decisions. Multiple SBB specimens should be collected to maximize DA., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objective: To examine the concentrations of vascular endothelial growth factor (VEGF) in aqueous humor of dogs with intraocular disease and to evaluate the association of aqueous humor VEGF with pre-iridal fibrovascular membrane (PIFM) formation., Procedures: Two hundred and twenty six aqueous humor samples and 101 plasma samples were collected from 178 dogs with a variety of intraocular diseases (including cataract, primary glaucoma, uveitic glaucoma, aphakic/pseudophakic glaucoma, retinal detachment, lens luxation, and intraocular neoplasia), and aqueous humor was collected from 13 ophthalmically normal control dogs. Systemic disease status and administration of select medications were recorded. Aqueous and plasma VEGF was assayed via enzyme-linked immunosorbant assay validated for canine VEGF. Available histopathology samples were examined for the presence of PIFM. Where present, PIFMs were categorized as none, cellular, vascular or fibrous, and fibrovascular. Data were evaluated by mixed model anova, with application of Tukey-Kramer adjustment for multiple comparisons., Results: There was no association between aqueous humor and plasma VEGF levels. Compared with normal controls, aqueous humor VEGF was significantly elevated for all intraocular diseases (P < 0.05) except for primary and diabetic cataracts. Systemic disease and administered medications had no significant effect on aqueous humor VEGF concentration. Compared to dogs without PIFM, aqueous humor VEGF was significantly higher in dogs with fibrovascular PIFM (P = 0.001), but not cellular (P = 0.1704) or fibrous/vascular PIFM (P = 0.0667)., Conclusions: These findings confirm that VEGF is commonly elevated in aqueous humor of dogs with intraocular disease and likely plays a role in the causation or progression of a variety of intraocular disorders, including the development of PIFM., (© 2012 American College of Veterinary Ophthalmologists.)

The sensitivity of low-field magnetic resonance (MR) T2 images for predicting the presence of meniscal lesions was determined in 12 dogs with naturally-occurring cranial cruciate ligament rupture and three control dogs, using histopathology as the reference standard. Previously published grading systems were used to grade the severity of meniscal lesions on MR images, gross inspection and histopathology. Focal areas of increased signal intensity were detected in 11/12 symptomatic dogs and 3/3 control dogs. Lesions mimicking meniscal tears (pseudotears) were identified at junctions between meniscal margins and adjacent connective tissue in control dogs and dogs with naturally occurring disease. Histopathologic lesions were present in all menisci of both symptomatic and control dogs, including the menisci from two affected dogs that appeared grossly normal but were removed and submitted based on MR imaging findings. Histopathologic lesions identified included hyaline cartilage metaplasia and changes in the amount of ground substance and cellularity. The sensitivity of MR imaging for detecting the presence of meniscal histopathologic lesions was 90% in symptomatic dogs and 91% in control dogs. However, agreement between severity scores for the different tests was poor. Low-field MR imaging is a sensitive test for predicting the presence but not severity of meniscal histopathologic lesions in dogs with naturally-occurring cranial cruciate ligament rupture. Findings also supported previous studies indicating that histopathologic lesions can be present in dogs with grossly normal menisci. An improved grading system for comparing MR images and histopathologic severity of meniscal lesions in dogs is needed., (© 2011 Veterinary Radiology & Ultrasound.)

A 6-month-old, intact, male Weimaraner dog presented to the veterinary teaching hospital for bilateral mucopurulent ocular and nasal discharge that began at approximately 10 weeks of age. A computed tomography scan showed an expansile soft-tissue mass involving both frontal sinuses, the ethmoid regions, and nasal cavities with lysis of the maxillary turbinates and hyperostosis of the walls of the frontal sinus. The dog was euthanized after complications during a trephination and biopsy procedure. At necropsy, a large, tan, papillary, gelatinous mass filled the entire nasal cavity and frontal sinus. The mass was composed of large fronds of loose fibrovascular stroma covered by a single layer of pseudostratified, columnar, ciliated epithelium and intermixed goblet cells. The cells occasionally formed glandular structures that were continuous with the surface epithelium. The mass was diagnosed as a respiratory epithelial adenomatoid hamartoma based on the morphologic appearance.