Cristian de la Fuente

Presence of neural progenitors in spontaneous canine gliomas: A histopathological and immunohistochemical study of 20 cases.

Gliomas are the most common primary brain tumours in humans and are associated with a poor prognosis. An accurate animal model of human glioma tumorigenesis is needed to test new treatment strategies. Dogs represent a promising model because they develop spontaneous diffusely-infiltrating gliomas. This study investigated whether spontaneous canine gliomas contain cancer stem cells previously identified in all grades of human gliomas. Twenty spontaneous cases of canine gliomas were graded according to the human WHO classification. The expression of different markers of lineage differentiation was evaluated with immunohistochemistry as follows: nestin and CD133 for neural stem cells, doublecortin for neuronal progenitor cells, Olig2 for glial progenitor cells, glial fibrillary acidic protein, vimentin and S-100 for mature glial cells, and NeuN and βIII-tubulin for mature neurons. Gliomas were characterised as follows: five grade II (oligodendrogliomas); nine grade III (seven anaplastic oligodendrogliomas, one anaplastic astrocytoma, one anaplastic oligoastrocytoma); six grade IV (glioblastomas). Immunohistochemical evaluation revealed that (1) nestin and CD133 were expressed in all grades of gliomas with a higher proportion of positive cells in high-grade gliomas; (2) the expression of S-100 protein and Olig2 did not differ substantially between astrocytic and oligodendroglial tumours, and (3) all gliomas were negative for mature neuron markers. The results demonstrated the presence of undifferentiated neural progenitors in all grades of spontaneous canine gliomas, confirming the relevance of this animal model for further studies on cancer stem cells.

Immunohistochemical evaluation of tissue factor, fibrin/fibrinogen and D-dimers in canine gliomas

In human gliomas, tissue factor (TF) is overexpressed, associated with the grade of malignancy and influences tumour biology. Intra-tumoural fibrin/fibrinogen deposition and activation of the fibrinolytic system also play a role in tumour cell proliferation and angiogenesis. The first aim of the present study was to investigate TF expression and the presence of fibrin/fibrinogen and D-dimers in canine glioma biopsies, graded according to the World Health Organization (WHO) classification of tumours of the central nervous system. The second aim was to investigate the occurrence of intravascular thrombosis (IVT) in canine gliomas, as a potential histological marker of glioma type or grade of malignancy. An immunohistochemical study using antibodies against TF, fibrin/fibrinogen and D-dimers was performed with 24 glioma samples, including 15 oligodendrogliomas, 6 astrocytomas and 3 mixed gliomas. Immunohistochemical data were statistically analysed to determine whether there was any relationship between glioma type and grade of malignancy. All gliomas were moderate to strongly positive for TF and the staining score was significantly higher (P = 0.04) in high-grade (III or IV) than in low-grade (II) gliomas. Intra-tumoural fibrin/fibrinogen deposition was detected in all tumour biopsies assessed, and D-dimers were detected in 17/24 gliomas. IVT was a frequent finding, but was not linked to a specific glioma type or malignancy grade. TF expression, fibrin/fibrinogen deposition, extravascular fibrinolytic system activation and IVT occur in canine gliomas. Canine glioma might be a suitable model for studying coagulation and fibrinolysis as potential therapeutic targets for human gliomas.

IMAGING DIAGNOSIS—SPINAL EPIDURAL HEMANGIOSARCOMA IN A DOG

An 8-year-old, male Boxer was examined for an acute onset of ambulatory paraparesis. Neurologic examination was consistent with a T3-L3 myelopathy. Myelography revealed an extradural spinal cord compression in the region of the T10-T13 vertebrae. On magnetic resonance (MR) imaging, a well-defined epidural mass lesion was detected. The mass was mildly hyperintense on T1-weighted, hyperintense on T2-weighted and STIR images compared to normal spinal cord and enhanced strongly and homogenously. Postmortem examination confirmed a primary epidural hemangiosarcoma. Findings indicated that the MRI characteristics of spinal epidural hemangiosarcoma may mimic other lesions including meningioma and epidural hemorrhages/hematomas of non-neoplastic etiology.

IMAGING DIAGNOSIS: CRANIAL CERVICAL INTRASPINAL SCHWANNOMA IN A DOG

A 3-year-old, intact female Golden Retriever was presented with acute tetraplegia. Neurologic examination was consistent with a C1-C5 myelopathy. On magnetic resonance (MR) imaging a well-defined, extradural mass was detected within the spinal canal at the level of C1-C2. The mass was isointense to normal spinal cord gray matter on T1-weighted (T1W) images, hyperintense on T2-weighted (T2W), and gradient-echo (GE) images, and enhanced homogeneously after intravenous contrast administration. MR imaging features were mainly consistent with a meningioma. Surgical treatment was refused by the owners, and the dog was euthanized. Postmortem examination demonstrated that the intraspinal mass was a schwannoma.

Myelographic and low-field magnetic resonance imaging findings in dogs with presumptive acute hydrated non-compressive nucleus pulposus extrusion

MRI is considered gold standard for the diagnosis of presumptive acute hydrated non-compressive nucleus pulposus extrusions (AHNCNPE). This retrospective study describes the myelographic findings in dogs with AHNCNPE diagnosed by low-field MRI and their association with neurological grade, need of surgical decompression and outcome. Forty-two myelographies (21 dogs with presumptive AHNCNPE, 21 dogs with Hansen type I disc disease herniation) were blindly evaluated. Site of herniation, compression pattern, ratio of length of the lesion to length of the second lumbar vertebra (LL:L2) and degree of spinal cord compression (SCC) were measured on the myelographies of dogs with presumptive AHNCNPE and were compared with the corresponding MRI features. Percentage of extruded volume of nucleus pulposus (VNP) was calculated on MR images. Myelographic interobserver agreement for presumptive diagnosis of AHNCNPE was almost perfect (κ=0.8). Accuracy of myelography to detect site of herniation was 80.9 per cent and to identify extradural compression was 57.1 per cent. Mean SCC was 5.8±2.6 per cent for myelography and 6.6±3 per cent for MRI. Mean LL:L2 ratio was 1.7±0.9 for myelography and 1.2±0.8 for MRI. Mean percentage of extruded VNP was 40±14 per cent, and it was positively associated with neurological grade.

Imaging diagnosis-magnetic resonance imaging findings of an intracranial epidural tuberculoma in a dog.

Magnetic resonance (MR) imaging is highly sensitive for detecting tuberculomas in human patients but the specificity of the MR imaging features is low. Misdiagnosis with intracranial neoplasia is common, especially with dural-based lesions or lesions located in the epidural space. We describe the MR imaging characteristics of an intracranial epidural tuberculoma caused by Mycobacterium tuberculosis infection in a dog. The intracranial mass and skull flat bone lysis and erosion are similar to those described in human caseating tuberculomas and can mimic intracranial neoplastic disease.

Magnetic Resonance Imaging of Bacterial Meningoencephalitis in a Foal

Magnetic resonance imaging (MRI) in equidae suffering meningoencephalitis (ME) has not been described. The objective of this paper is to describe brain MRI findings in a foal with bacterial ME. A five-month-old, 200 kg bwt Arabian filly was referred with a history of abnormal mental status and locomotion. The filly was recumbent and obtunded, and pupillary light reflexes were sluggish, and oculocephalic movements were normally present. Ophthalmic examination revealed bilateral optic neuritis. Hematology revealed leukocytosis and neutrophilia. Cerebrospinal fluid analysis showed neutrophilic pleocytosis with intracellular bacteria. On brain MRI, there were multifocal cortical areas of mild hyperintensity on T2-weighted images (T2WI) affecting both hemispheres. The lesions had ill-delineated margins, and there was loss of differentiation between gray and white matter. Diffuse hyperintensity was also identified in the left cerebellar cortex on T2WI. Neither mass effect nor cerebral midline shift were identified. On FLAIR images, the lesions were also hyperintense and, in some areas, they seemed to coalescence to form diffuse cortical areas of hyperintensity. The MRI findings described were similar to the MRI features described in cases of humans and small animals with ME. Brain MRI can be a useful diagnostic tool in foals and small-sized equidae with intracranial disease.

Magnetic resonance imaging and computed tomographic characteristics of a glioma causing calvarial erosion in a dog

An 8-year-old female Boxer was examined for acute onset of seizures. On magnetic resonance imaging (MRI), an intra-axial mass with imaging features consistent with glioma was observed in the right cerebral hemisphere. A defect in the temporal bone adjacent to the mass was observed. Postmortem computed tomography (CT) confirmed temporal bone osteolysis and necropsy demonstrated a glioblastoma with associated calvarial erosion. Although occasionally described in human medicine, to our knowledge, this is the first description of a brain glioma causing calvarial erosion in a dog. Glioma should be included as a differential diagnosis for intracranial lesions that could cause bony changes in the skull.

Canine intracranial meningiomas: Immunohistochemical evaluation of tissue factor, fibrin/fibrinogen and D-dimers.

The haemostatic system influences angiogenesis, cell growth and metastasis in solid tumours. The aim of this study was to investigate tissue factor (TF) expression, fibrin/fibrinogen and D-dimer deposition, as well as the occurrence of intravascular thrombosis (IVT) in canine intracranial meningiomas using immunohistochemistry. All but three (26/29) meningiomas expressed TF. TF immunolabelling was significantly higher in high-grade (grades II and III) than in low-grade (grade I) meningiomas. Fibrin/fibrinogen and D-dimer deposits were detected in all meningiomas and staining scores were statistically different between different meningioma grades. IVT was detected in 19/29 specimens, but no statistical differences were observed between different malignancy grades. In conclusion, the haemostatic system may be involved in meningioma pathobiology and may be a potential therapeutic target for canine meningiomas, as also suggested for human meningiomas.

A case of spongiform polioencephalomyelopathy in a cat with a history of behavioural problems

A 7-month-old, entire female, domestic shorthair cat was referred to our behavioural service owing to soiling in the house and a play-related problem. The owners’ complaints were that the cat had never used the litter tray, and it did not know how to play. After reviewing the behavioural history, a problem of substrate preferences acquisition was suspected with regard to the elimination problem. During the consultation, the physical examination was unremarkable, but the neurological examination revealed a moderate and hypermetric ataxic gait, and a bilateral lack of menace response. Some degree of visual impairment was suspected. The problem was located in the central nervous system (CNS); specifically, an intracranial and multifocal problem was diagnosed. After a complete work-up (complete ophthalmological examination, complete blood count and a complete biochemistry panel, feline immunodeficiency virus/feline leukaemia virus test, thorax radiographs, abdominal ultrasound, brain magnetic resonance imaging [0.2 T], cerebrospinal fluid analysis and a urinary metabolic screen test), a degenerative CNS problem was suspected. No treatment was prescribed for the neurological problem. Regarding the problem of soiling in the house, reward-based training with a clicker was used, and the cat partially improved in a few weeks. Three months later, the cat was referred to the neurology service in status epilepticus. A symptomatic treatment was prescribed, with a mild response. After 2 years of treatment and a progressive worsening, the cat was euthanased. Necropsy revealed spongiform polioencephalomyelopathy. In order to rule out prion aetiology a PrPsc inmunohistochemistry assay was performed, and the results were negative. Congenital spongiform polioencephalomyelopathy (CSP) was diagnosed. We strongly suggest that the cat’s behavioural clinical signs were caused by the CSP, causing learning impairment. To the best of our knowledge, this would be the first case in which a congenital degenerative disease affected a cat’s capability to learn, leading to behavioural signs as the main complaint of the owners, even before neurological signs are detected by the owners.