Inter- and Intraobserver Agreement of Canine and Feline Nervous System Tumors.

In routine diagnostic activity, pathologists may be confronted with nervous system tumors. The lack of clinical information, economic restrictions for additional testing, and the lack of expertise in neuropathology may render the diagnosis challenging. The goals of this study were to assess the agreement in diagnosing nervous system tumors in domestic carnivores among 4 board-certified surgical pathologists without particular expertise in neuropathology and a neuropathologist expert, and to investigate the utility of special stains frequently used in routine diagnostic laboratories. Forty-six tumors (7 cats, 38 dogs, and 1 unknown carnivore) were retrieved and 1 hematoxylin and eosin-stained slide per tumor was selected. Diagnoses (tumor type and subtype) were formulated based on histological features and available clinical information. Confidence in the diagnosis was also scored. Subsequently, a panel of histochemical and immunohistochemical stains (Gordon Sweet silver stain and immunohistochemistry for AE1/AE3, vimentin, glial fibrillary acid protein, S100, neuron-specific enolase and neurofilament) was evaluated by the pathologists, who either confirmed or changed their original diagnoses. Intraobserver and interobserver agreement and confidence in relation to diagnosis before and after analysis of special stains were assessed. The use of special stains increased the complete agreement among surgical pathologists, with regard to tumor type, from 63% to 74%. Cases with a high confidence score had a higher interobserver agreement than cases with a low confidence score. These results suggest that pathologists without expertise in neuropathology agree in the diagnosis of most nervous system tumors, and special stains available in most laboratories only slightly increase this agreement.

Canine Nervous System Lymphoma Subtypes Display Characteristic Neuroanatomical Patterns.

Primary and secondary nervous system involvement occurs in 4% and 5%-12%, respectively, of all canine non-Hodgkin lymphomas. The recent new classification of canine malignant lymphomas, based on the human World Health Organization classification, has been endorsed with international acceptance. This histological and immunocytochemical classification provides a unique opportunity to study the histologic anatomic distribution patterns in the central and peripheral nervous system of these defined lymphoma subtypes. In this study, we studied a cohort of 37 dogs with lymphoma, which at necropsy had either primary (n = 1, 2.7%) or secondary (n = 36; 97.3%) neural involvement. These T- (n = 16; 43.2%) or B-cell (n = 21; 56.8%) lymphomas were further classified into 12 lymphoma subtypes, with predominant subtypes including peripheral T-cell lymphoma (PTCL) or diffuse large B-cell lymphoma (DLBCL), respectively. This systematic study identified 6 different anatomically based histologically defined patterns of lymphoma infiltration in the nervous system of dogs. Different and distinct combinations of anatomical patterns correlated with specific lymphoma subtypes. Lymphoma infiltration within the meningeal, perivascular, and periventricular compartments were characteristic of DLBCL, whereas peripheral nerve involvement was a frequent feature of PTCL. Similarly cell counts above 64 cells/µL in cerebrospinal samples correlated best with marked meningeal and periventricular lymphoma infiltration histologically. Prospective studies are needed in order to confirm the hypothesis that these combinations of histological neuroanatomic patterns reflect targeting of receptors specific for the lymphoma subtypes at these various sites.

Polyomavirus and Naturally Occuring Neuroglial Tumors in Raccoons (Procyon Lotor).

Polyomavirus (PyV) infections are widespread in human populations and, although generally associated with silent persistence, rarely cause severe disease. Among diseases convincingly associated with natural PyV infections of humans, there are remarkably different tissue tropisms and outcomes, including progressive multifocal leukoencephalopathy, transient or progressive nephropathy, and cancer. The variable character and unpredictable outcomes of infection attest to large gaps in our basic understanding of PyV biology. In particular, the rich history of research demonstrating the oncogenic potential of PyVs in laboratory animals begs the question of why cancer is not more often associated with infection. Raccoon polyomavirus (RacPyV), discovered in 2010, is consistently identified in neuroglial tumors in free-ranging raccoons in the western United States. Exposure to RacPyV is widespread, and RacPyV is detected in tissues of raccoons without tumors. Studying the relationship of RacPyV with its natural host is a unique opportunity to uncover cogent cellular targets and protein interactions between the virus and its host. Our hypothesis is that RacPyV, as an intact episome, alters cellular pathways within neural progenitor cells and drives oncogenesis.

Aortic body tumor in full-sibling English bulldogs.

A 10-year-old, neutered male English bulldog died acutely from respiratory distress after a short history of progressive dyspnea. Less than 2 months later, a spayed female full sibling of that dog died suddenly during a nail trim. An aortic body tumor was the cause of death in both dogs based on postmortem and histological examinations. A pheochromocytoma was also diagnosed in the neutered male. Neither dog had a history of brachycephalic airway syndrome, and the implication for a genetic predisposition toward the development of paraganglioma is discussed. This is the first case report of aortic body tumors in sibling dogs, although the condition may not be an uncommon phenomenon.

Suprasellar germ cell tumor in a dog

A case of suprasellar germ cell tumor is described in a 6-year -old Airedale Terrier bitch that presented behavioral changes and abrupt onset of blindness. The neoplasm compressed the ventral surface of the cerebrum from the level of basal ganglia to the mesencephalon. Histologically the neoplasm consisted of nests and trabeculae of round to polygonal cells that occasionally surround tubules and cysts formed by columnar cells. Neoplastic cells are immunopositive for cytokeratin and alpha-fetoprotein. The diagnosis was based on location, histological appearance and on the immunohistochemical staining.

É descrito um caso de tumor de células germinativas supra-selar em numa cadela Airedale Terrier de seis anos de idade, que apresentou transtornos do comportamento e aparecimento abrupto de cegueira. O neoplasma comprimia a superfície ventral do cérebro desde a altura dos núcleos basais até o mesencéfalo. Histologicamente, o neoplasma consistia de ninhos e trabéculas de células redondas ou poligonais que ocasionalmente arranjavam-se ao redor de túbulos e cistos formados por células colunares. As células neoplásicas foram positivas na imunoistoquímica para citoqueratina e a-fetoproteína. O diagnóstico foi feito com base na localização do tumor, no seu aspecto histológico e nos resultados da marcação imunoistoquímica.

Acute bilateral trigeminal neuropathy associated with nervous system lymphosarcoma in a dog.

A nine-year-old dog presented with clinical signs consistent with bilateral trigeminal neuropathy. Multicentric lymphoma was diagnosed, and neoplastic lymphocytes were identified in the cerebrospinal fluid. Electromyography revealed spontaneous activity in temporal and masseter muscles. Histopathological examination demonstrated neoplastic cell invasion of temporal and masseter myofibers and of multiple peripheral nerves, including the trigeminal nerve. Central nervous system pathology consisted primarily of spinal root and leptomeningeal lymphoid cell infiltration with relative sparing of spinal cord and brain parenchyma.

Multicentric schwannomas causing chronic ruminal tympany and forelimb paresis in a Holstein cow.

A nine-year-old Holstein cow that developed recurrent ruminal tympany and an abnormal forelimb gait and posture ultimately became recumbent and unable to rise, and was euthanased. A postmortem examination demonstrated numerous schwannomas affecting peripheral nerves and several thoracic and abdominal viscera.

Common neurologic diseases of older animals.

Of the various neurologic diseases that affect dogs and cats, some are more often encountered in older animals. Physical diagnosis may be challenging, as multiple disease processes that may minic neurologic disease can be present in the same animal. A diligent, complete neurologic examination should lend for an accurate neuroanatomical diagnosis. Once a level of involvement is determined, knowledge of diseases affecting the particular area of the nervous system will provide for appropriate diagnosis, treatment, and prognosis. Although neurologic diseases are still often devastating, successful management of many of these diseases will afford better quality of life during the geriatric years.

[Von Recklinghausen's disease: experimental models and comparative aspects]. / Bolezn' fon Reklinkgkhauzena: éksperimental'nye modeli i sravnitel'nye aspekty.

Von Recklinghausen's disease, or neurofibromatosis type 1 (NF-1), is an autosomal dominant syndrome with a highly variable tumorous (neurofibromas, gliomas, Wilms' tumors, leukemia, pheochromocytomas) and non-tumorous (cafe-au-lait skin spots, iris and ciliar hamartomas, osseous lesions) manifestations. NF-1 gene is mapped to chromosome 17. Central or bilateral acoustic neurofibromatosis (NF-2) has a gene mapped to chromosome 22. Hereditary and sporadic NF-1 are recognized. The most typical manifestation of NF-1-skin neurofibroma--has has a characteristic plexiform structure. Spectrum of tumors (schwannomas, gliomas, Wilms' tumors) produced by transplacental treatment with strong environmental mutagens-carcinogens-ethylnitroso- and methylnitrosourea (ENU and MNU, respectively) resembles on the whole that observed in human sporadic NF-1. Location of neurofibromas depends on the species: skin and subcutaneous tissue in humans, cattle and hamsters, trigeminal nerve, spinal roots in rats. Rat schwannomas differ from human neurofibromas by malignant structure, frequently with cystic component, but if induced by ENU treatment at day 15 of the pregnancy they resemble human plexiform neurofibromas with intraneural and extraneural growth of tumor cells. There were attempts to reproduce a transgenerational transmission of ENU carcinogenic effect, i.e. hereditary form of NF-1. In the experiments of this type the offsprings of rats prenatally treated with ENU remained untreated. The incidence of PNS, CNS and Wilms' tumors in these untreated offsprings in some experiments was significantly higher than in controls thus confirming the possibility, in principle, of hereditary NF-1 modelling. Only 10% of tumors developing in such untreated descendants of ENU treated parents contained a specific mutation of neu oncogene compared to 90-100% in tumors arising following direct treatment with ENU. The mechanisms of the transgenerational carcinogenesis are discussed. Lesions imitating NF-1 and in part NF-2 in transgenic mice with an HTLV-1-tax gene as well as in p-53 knockout mice are mentioned.

Metastatic multicentric neurofibrosarcoma of the lumbosacral plexus in a cow.

A metastatic multicentric neurofibrosarcoma of the lumbosacral plexus in an adult cow is described. The left lumbosacral plexus was obliterated by a mass which extended through the intervertebral foramen into the spinal canal and between the dorsal arches of the fifth and sixth lumbar vertebrae. A closely associated (possibly contiguous) mass extended into and separated the left sacroiliac joint. Multiple similar masses involved peripheral nerves and skeletal muscles of the pelvis, pelvic limbs, and abdominal wall. Metastatic lesions were scattered throughout the lungs. The lumbosacral lesion and all other masses consisted of interwoven bundles of loosely cohesive, elongated cells separated by variable collagenous matrix. Many neoplastic cells were positive for S-100 protein. Ultrastructurally, fibroblastic cells were mixed with scattered cells possessing schwannian characteristics.

An immunohistochemical study of peripheral neuroblastoma, ganglioneuroblastoma, anaplastic ganglioglioma, schwannoma and neurofibroma in cattle.

Immunohistochemical analysis of five paraffin wax-embedded neoplasms was performed to elucidate the characteristics of bovine nervous-tissue tumours. In case 1 (peripheral neuroblastoma), the neoplastic tissue was characterized by the formation of true and Homer-Wright rosettes and the existence of neuron-specific enolase. The neoplastic cells were possibly more immature than those of common neuroblastomas, because similar features are observed in human malignant neuroepitheliomas. The neoplastic cells in case 2 (ganglioneuroblastoma) ranged from large cells with abundant neurofilaments to immature small cells, rarely with neurofilaments or glial fibrillary acidic protein (GFAP). Such expression suggests the presence of pluripotential cells. The neoplastic tissue in case 3 (anaplastic ganglioglioma) was strikingly polymorphous, and had five elements; neuronal, astrocytic, oligodendrocytic, spindle cell and small oval cell. The neoplastic neurocytes and astrocytes were, respectively, characterized by neurofilament and GFAP positivity. The neoplastic oligodendrocytes made a honeycomb appearance, and the neoplastic spindle cells and small oval cells were considered to be less differentiated. The tumours of cases 2 and 3, which contained poorly differentiated cells and revealed both neuronal and glial differentiation, may be specific to calves. In case 4 (schwannoma), almost all the neoplastic cells were positive for S100 protein, while S100-negative fibroblasts were present in many areas of case 5 (neurofibroma). These two tumours were readily distinguished histologically and immunohistochemically.

The use of intraneural doxorubicin in association with palmar digital neurectomy in 28 horses.

Painful neuroma formation after palmar digital neurectomy in the horse is common. Experimentally, injection of doxorubicin (Adriamycin) into the proximal transected nerve stump has been shown to prevent axon sprouting and neuroma formation for up to 5 months. This procedure was used in 28 horses with navicular disease, preexisting painful neuroma, or wing fractures of the distal phalanx. At 1 month, 16 horses had incisional complications. At 1 year, 15 horses were sound. Eight horses were lame, although three were improved. Three horses required a second surgical procedure, two of which became sound. Follow-up was not available in two horses. The technique used in this study has an unacceptable rate of wound complications and no benefit over other palmar digital neurectomy techniques currently in use.

Neurology of the geriatric patient.

Owing to improvements in health care, more animals are living to advanced ages. Many abnormal neurologic conditions can affect these patients, but those most commonly associated with advancing years include degenerative, neoplastic, and idiopathic processes. An understanding of the "normal" age-related changes seen on a neurologic examination must be kept in mind when evaluating geriatric patients. Special care and consideration of the patient and client are often required in managing these cases, especially because treatment protocols are often unsuccessful or do not exist, resulting in a prognosis that is often poor at best.

Craniolateral approach to the canine brachial plexus.

A craniolateral approach to the canine brachial plexus that provides good exposure by transection of the omotransversarius and, if necessary, the scalenus muscles is described. The technique facilitated diagnosis of brachial plexus tumors in three dogs and probable brachial plexus neuritis in a fourth dog.

Multiple organ metastasis of an aortic body tumor in a boxer.

A 9-year-old sexually intact male Boxer with a history of multiple episodes of syncope and various cardiac arrhythmias was determined radiographically to have a large mass in the heart-base region and was subsequently euthanatized upon worsening of clinical signs. Histologic and ultrastructural examination of tissue from the heart-base mass indicated that the tumor was most likely a chemodectoma derived from the aortic body (aortic body tumor, extra-adrenal paraganglioma). Macroscopic and/or microscopic evidence of metastasis of the tumor was seen in the lungs, myocardium, spleen, liver, kidneys, and dura mater over the cerebellum.

Spontaneous tumors of the nervous system and associated organs and/or tissues in rats.

Spontaneous tumors of the nervous system and associated organs and/or tissues in 346 male and 346 female F344/DuCrj rats and 200 male and 177 female Slc:Wistar rats were examined. The main neurogenic tumors observed were gliomas and neurinomas, which were detected in both strains of rats. Out of 7 gliomas, 6 were found in the brain and 1 in the spinal cord, and out of 4 neurinomas, 2 were in the trigeminal nerves and the other 2 were in the spinal nerves. In addition, other types of tumors (2 granular cell tumors in the brain, 1 pinealoma, 3 ganglioneuromas in the adrenal gland, 1 undifferentiated carcinoma in the nasal cavity and 1 chordoma in the posterior neck region) were observed.

Central nervous system lymphosarcoma in the dog.

Central nervous system lymphosarcoma was diagnosed in 8 dogs with seizures and clinical signs compatible with multifocal central nervous system involvement. Cerebrospinal fluid analysis showed high white cell counts with abnormal lymphoid cells in all dogs, and high protein concentration in 5 dogs. Two dogs were given systemic anticancer chemotherapy, and 4 dogs were given a combination of systemic chemotherapy, intrathecal cytosine arabinoside, and craniospinal irradiation, resulting in marked improvement of the clinical signs.