Alice Reginato

A Retrospective Investigation on Canine Papillomavirus 1 (CPV1) in Oral Oncogenesis Reveals Dogs Are Not a Suitable Animal Model for High-Risk HPV-Induced Oral Cancer

CPV1 (also called COPV) is a papillomavirus responsible for oral papillomatosis in young dogs. The involvement of this viral type in oral oncogenesis has been hypothesized in oral squamous cell carcinomas (SCCs), but has never been investigated in other neoplastic and hyperplastic oral lesions of dogs. Aim of this study was to investigate the presence of CPV1 in different neoplastic and hyperplastic lesions in order to assess its role in canine oral oncogenesis; according to the results obtained, a second aim of the study was to define if the dog can be considered a valid animal model for oral high risk HPV-induced tumors. Eighty-eight formalin-fixed, paraffin-embedded (FFPE) canine oral lesions including 78 oral tumors (papillomas, SCCs, melanomas, ameloblastomas, oral adenocarcinomas) and 10 hyperplastic lesions (gingival hyperplasia) were investigated with immunohistochemistry for the presence of papillomavirus L1 protein and with Real-Time PCR for CPV1 DNA. RT-PCR for RNA was performed on selected samples. All viral papillomas tested were positive for immunohistochemistry and Real-time PCR. In 3/33 (10%) SCCs, viral DNA was demonstrated but no viral RNA could be found. No positivity was observed both with immunohistochemistry and Real-Time PCR in the other hyperplastic and neoplastic lesions of the oral cavity of dogs. Even though the finding of CPV1 DNA in few SCCs in face of a negative immunohistochemistry could support the hypothesis of an abortive infection in the development of these lesions, the absence of viral RNA points out that CPV1 more likely represents an innocent bystander in SCC oncogenesis. The study demonstrates a strong association between CPV1 and oral viral papillomas whereas viral contribution to the pathogenesis of other oral lesions seems unlikely. Moreover, it suggests that a canine model of CPV1 infection for HPV-induced oncogenesis could be inappropriate.

Feline Injection-Site Sarcoma

Feline injection-site sarcoma (FISS) is an aggressive tumor believed to arise from the proliferation of fibroblasts and myofibroblasts in areas of chronic inflammation, particularly at sites of injection. Local recurrence is frequent after surgical excision. Gelatinases (MMP-2 and MMP-9) and their inhibitor (TIMP-2) are endopeptidases pivotal in extracellular matrix remodeling and therefore in tumor invasiveness. The aim of this study was to investigate the immunohistochemical expression of MMP-2, MMP-9, and TIMP-2 in FISS to assess their usefulness as prognostic factors. Size, soft tissue sarcoma (STS) grading system, depth of infiltration, surgical margins, and Ki-67 index were evaluated as additional prognostic markers. Twenty-four cases of primary FISS were classified according to clinical follow-up as nonrecurrent (NR, n = 14; 58.3%) and recurrent (R, n = 10; 41.7%). MMP-2, MMP-9, and TIMP-2 were variably expressed in the FISS examined, confirming their role in tumor invasiveness, yet they did not show significant differences between the R and NR groups. These results could be due to different tumor stages or to the multiple activities of these enzymes, not limited to ECM remodeling. The immunohistochemical expression of these enzymes considered alone does not seem to be useful as a prognostic marker. STS grading system, depth of infiltration, surgical margins, and Ki-67 index did not relate to recurrence. Instead, the size of the tumor, measured after formalin fixation, with an optimal cutoff of 3.75 cm (accuracy = 86%; P < .05), and the mitotic count, with an optimal cutoff of 20 mitoses/10 HPF (accuracy = 80%; P < .05), could be evaluated as useful prognostic markers.

E-cadherin, N-cadherin Expression and Histologic Characterization of Canine Choroid Plexus Tumors.

Choroid plexus tumors (CPTs) are reported with an increasing incidence in dogs, and they call for a reexamination of histologic features and criteria of classification corresponding to their biological behavior. In this study, the human World Health Organization classification was applied to 16 canine CPTs, and the expression of molecules involved in neoplastic cell adhesion (E-cadherin, N-cadherin), invasion (doublecortin), and proliferation (Ki-67) was investigated. Mitotic index was found to be the main criterion for grading CPTs. Cell density and multilayering of papillae were also statistically associated with histologic grade. Intraventricular spread and parenchymal invasion was observed for tumors showing histologic benign features. E-cadherin was expressed in all CPT grades, independent of tumor invasion. N-cadherin immunolabeling was more expressed in grade I than high-grade CPTs, whereas doublecortin expression was not detected in CPTs. An increasing proliferative activity was observed in relation with histologic grade.

Papillary meningioma in the dog: A clinicopathological case series study.

Papillary meningioma (PM) is one of the most aggressive variants of meningioma in humans and classified as grade III by WHO system. To date, the biological behavior of PM is still not clear in dogs. This study investigated the correlation between histopathological findings of 16 canine PMs and follow up data. Moreover, the expression of doublecortin, E-cadherin, and N-cadherin was investigated by immunohistochemistry. The supratentorial compartment resulted the most common involved. Despite the low grade of histological malignancy, 87.5% of dogs that underwent surgery experienced tumor recurrence. Intratumoral necrosis was observed in a strict correlation with malignancy histological parameter and tumor recurrence. The post-surgery mean survival time was much lower than thus observed in the most common histological subtypes. This data were also confirmed in dogs that received a conservative treatment alone. Tumors with a severe clinical behavior showed a high N-cadherin expression versus a low or absent E-cadherin expression.

A leukomyeloencephalopathy of unknown origin in an Azawakh dog

A diffuse bilaterally symmetrical leukomyeloencephalopathy was observed in a 6-year-old male Azawakh dog showing a slowly progressive ataxia of six months duration associated with sensory disorders. Severe bilaterally symmetrical demyelination and vacuolisation were confined to the dorsal columns along the entire spinal cord with a minor axonal degeneration. The main changes of myelin sheaths consisted in splitting and intramyelin vacuolization. Naked axons were scattered in a network of astrocytic processes and collagen fibres. Few reactive macrophages exhibiting a foamy pattern were observed adjacent to the small vessels. In the brain, cuneatus nuclei showed a number of atrophic neurons. A spongy change was observed in the raphe nuclei, spinal tract and nuclei of trigeminal nerve, and caudal cerebellar peduncles. Lesions there were neither in the spinal and trigeminal nerves, nor in the spinal ganglia. Although in the absence of a pedigree analysis support an inherited cause cannot be completely excluded.

Bilateral Telencephalic Gliomatosis Cerebri in a Dog

An 8-year-old intact male Lagotto Romagnolo was presented with forebrain signs. Neuroanatomic localization was diffuse prosencephalon. MRI revealed diffuse, bilateral, and symmetric T2 and FLAIR hyperintensities in the parieto-occipital white matter and corpus callosum. No mass effect or contrast enhancement was noted. Analysis of cerebrospinal fluid revealed normal protein content and mild mononuclear pleocytosis. Atypical cells were not identified. 15 days later because of the worsening of clinical condition the patient was euthanized upon owner’s request. Neuropathological investigations were consistent with gliomatosis cerebri (GC). Such an unusual imaging pattern appeared similar to some cases of human GC and to a previous reported case in a dog, suggesting a possible repeatable imaging findings for this rare brain neoplasm. GC should be included in the MRI differentials for diffuse bilateral white matter signal changes and specific MRI findings described in this report may help in reaching a presumptive diagnosis of this tumor.