A comparison of clinical,magnetic resonance imaging and pathological findings in dogs with gliomatosis cerebri,focusing on cases with minimal magnetic resonance imaging changes‡

The primary study objective was to determine whether clinical examination and magnetic resonance imaging (MRI) can underestimate canine gliomatosis cerebri (GC); we also investigated immunohistochemical features. Seven dogs with GC were studied; four recruited specifically because of minimal MRI changes. Neuroanatomic localization and the distribution of MRI, gross and sub‐gross lesions were compared with the actual histological distribution of neoplastic cells. In six cases, clinical examination predicted focal disease and MRI demonstrated a single lesion or appeared normal. Neoplastic cells infiltrated many regions deemed normal by clinical examination and MRI, and were Olig2‐positive and glial fibrillary acid protein‐negative. Four dogs had concurrent gliomas. GC is a differential diagnosis for dogs with focal neurological deficits and a normal MRI or a focal MRI lesion. Canine GC is probably mainly oligodendrocytic. Type II GC, a solid glioma accompanying diffuse central nervous system neoplastic infiltration, occurs in dogs as in people.     

Magnetic resonance imaging features of canine gliomatosis cerebri

A retrospective, case series study was undertaken to identify magnetic resonance imaging (MRI) characteristics of gliomatosis cerebri in dogs. Fourteen dogs were included by review of histopathological records and contemporaneous MRI. On MRI, all lesions presented as ill‐defined, intraaxial lesions within the left and right forebrain hemispheres with involvement of white and gray matter. Lesions presented as hyperintense areas on T2‐weighted and FLAIR sequences and as hypointense or isointense areas on T1‐weighted images, with mild parenchymal contrast enhancement in three dogs. Signal changes were noted in three to 10 cerebral lobes. Other most commonly affected structures were the thalamus (13), caudate nucleus (13), interthalamic adhesion (11), hypothalamus (11), callosal commissure (10), hippocampus (9), and quadrigeminal plate (8). Abnormalities within the caudal fossa were noted in 10 dogs. Solid tumor portions were identified in five dogs. The histopathological examination demonstrated in all dogs a widespread diffuse infiltration with neoplastic glial cells in white and gray matter with meningeal infiltration. Comparison between MRI and histopathology showed that all areas with signal changes on MRI corresponded to diffuse and dense infiltration with neoplastic cells. The signal intensity on T2‐weighted and FLAIR images reflected the density of neoplastic cells. In all dogs, MRI underestimated lesion extent and meningeal infiltration. Involvement of the caudal fossa was not seen on MRI in three dogs. Despite this, MRI allowed identification of lesions extending into at least three cerebral lobes and therefore satisfying the criteria used for diagnosis of diffuse glioma with gliomatosis cerebri growth pattern in humans.     

Gliomatosis cerebri in two dogs

A 3.5 yr old Saint Bernard was evaluated for nonambulatory tetraparesis and cranial nerve dysfunction, and a 7 yr old rottweiler was evaluated for progressive paraparesis. Clinical signs of left-sided vestibular and general proprioceptive ataxia and cranial nerve VII dysfunction in the Saint Bernard suggested a lesion affecting the brain stem. Signs in the rottweiler consisted of general proprioceptive/upper motor neuron paraparesis, suggesting a lesion involving the third thoracic (T3) to third lumbar (L3) spinal cord segments. MRI was normal in the Saint Bernard, but an intra-axial lesion involving the T13-L2 spinal cord segments was observed in the rottweiler. In both dogs, the central nervous system (CNS) contained neoplastic cells with features consistent with gliomatosis cerebri (GC). In the Saint Bernard, neoplastic cells were present in the medulla oblongata and cranial cervical spinal cord. In the rottweiler, neoplastic cells were only present in the spinal cord. Immunohistochemistry disclosed two distinct patterns of CD18, nestin, and vimentin staining. GC is a rarely reported tumor of the CNS. Although GC typically involves the cerebrum, clinical signs in these two dogs reflected caudal brainstem and spinal cord involvement.     

Multicentric nerve sheath fibrosarcomas of multiple cranial nerve roots in two dogs

Nerve sheath fibrosarcomas of the left 5th through 8th cranial nerve roots were diagnosed in 1 dog and of the left 4th through 8th cranial nerve roots in another dog. Clinical signs in both dogs included head tilt to the left, circling to the left, left hemiparesis and proprioception deficits, rotary nystagmus, left-sided atrophy of masticatory muscles, and cutaneous hypalgesia of the left side of the face. Cranial nerve roots from both dogs were incorporated in discrete, firm, encapsulated, lobulated, tan masses of various sizes that compressed adjacent brain stem and cranial nerves. There were no regional or distant metastases; however, there was enlargement of nerve roots adjacent to the masses. The masses were composed of bundles and sheets of anaplastic, polymorphic to spindle-shaped cells that infiltrated cranial nerves and ganglia and extended into the brain along nerve roots. Masses contained various amounts of collagen and reticulin fibers, but no mucopolysaccharide ground substance. There was no myelin or S-100 protein associated with neoplastic cells. The tumors appeared to have a multicentric origin from cranial nerve sheaths.     

A histologic and immunocytochemical study of choroid plexus tumors of the dog

Sixteen choroid plexus (CP) tumors in 12 male and four female adult dogs were analyzed microscopically. Tumors were in the lateral (six), third (six), and fourth (four) ventricles. The average age of the dogs was 6 years. Tumors were classified by the following criteria: 1) choroid plexus papilloma (CPP), which resembled normal choroid plexus and had low mitotic activity; 2) choroid plexus papilloma (CPP), which resembled normal choroid plexus and had low mitotic activity; 2) choroid plexus papilloma with atypical features (atypical CPP), which had increased cellular density, nuclear atypia, two to four mitoses per 40x microscopic field, necrosis, and infiltration of the brain parenchyma and/or leptomeninges; and 3) choroid plexus carcinoma (CPC), which had marked nuclear atypia, poorly formed papillae, greater than four mitoses per 40x microscopic field, abnormal mitotic figures, and/or extraneural metastasis. The 16 tumors were classified either as CPP or atypical CPP (none as CPC). Statistically significant associations between brain infiltration and necrosis and atypical CPP were identified. Immunohistochemical studies in 11 tumors demonstrated staining for keratin in three tumors, two of which also reacted with carcinoembryonic antigen (CEA). There was no immunoreactivity with glial fibrillary acidic protein or epithelial membrane antigen. Choroid plexus from one of three control dogs stained focally for cytokeratin only. It is concluded that normal choroid plexus and CP tumors in the dog express epithelial, but not glial differentiation.     

Insulinoma and Subclinical Peripheral Neuropathy in Two Dogs

Two dogs with diffuse, subclinical polyneuropathy associated with insulinoma are reported. Seizures were the dominant sign of central nervous system disease. One dog had clinical signs of facial nerve paralysis. Lesions in selected appendicular and cranial nerves included a mixture of demyelination, remyelination, and axonal degeneration. The incidence (range: 18-47%) of these changes far exceeded that of comparable nerves from six control dogs (range 0-11%). Myopathic and electrodiagnostic findings were compatible with the nerve changes.     

MR IMAGING OF HISTIOCYTIC SARCOMA OF THE CANINE BRAIN

Histiocytic sarcomas are characterized by proliferation and/or infiltration of neoplastic histiocytes localized to specific organs, unlike malignant histiocytosis which involves many organ systems. Only a few cranial histiocytic sarcomas have been reported. Here we describe four dogs that presented with neurological deficits referable to the forebrain, and were diagnosed histologically as having histiocytic sarcoma. Using magnetic resonance (MR) imaging, the tumors were characterized by a T2-hyperintense and T1-isointense mass in one dog, T2- and T1-isointense extraaxial masses in two dogs, and a diffuse T2-hyperintense lesion over the left cerebral cortex in one dog. All tumors had contrast enhancement. MRI features in three of the four dogs were similar to that of meningioma, supported by the observation of a dural tail in two of these three dogs, and a broad base of attachment in the other. In the other dog the imaging findings were similar to those of encephalitis. Intracranial histiocytic sarcoma does not appear to have specific MR imaging features and can be confused with meningioma or encephalitis.     

Primary malignant peripheral nerve sheath tumor with eosinophilic cytoplasmic globules arising from the greater omentum in a dog

A 10-year-old Golden Retriever dog had a solitary tumor mass arising from the greater omentum. Histologically, the tumor showed varying cellularity and patterns of cellular arrangement. In dense cellular areas, spindle-shaped cells were arranged in interlacing bundles. The sparse cellular area was characterized by loosely arranged fusiform cells. The neoplastic cells frequently contained PAS-positive eosinophilic globules in the cytoplasm, and mitotic figures were frequently observed. The tumor cells were positive to vimentin, S-100 protein, glial fibrillary acidic protein, myelin basic protein, neuron-specific enolase and myoglobin. The present tumor was diagnosed as a malignant peripheral nerve sheath tumor (MPNST) with eosinophilic cytoplasmic globules arising from the greater omentum. To our knowledge, this may be the first case of primary omental MPNST in domestic animals.     

RESULTS OF MYELOGRAPHY IN SEVEN DOGS WITH MYELOMALACIA

Myelomalacia is a hemorrhagic infarction of the spinal cord that can occur as a sequel to acute spinal cord injury. Myelomalacia may be focal or diffuse; the diffuse form is typically associated with cranial migration of neurologic signs ("ascending syndrome") and is often fatal. In a retrospective study of seven affected dogs, diffuse myelomalacia was associated with intervertebral disc extrusion in five dogs, focal myelomalacia was associated with fibrocartilagenous embolus in one dog, and had no apparent cause in one dog. The myelographic signs included a variable degree of contrast medium infiltration into the spinal cord in six dogs (86%) and/or spinal cord swelling in six dogs (86%). In one dog with focal myelomalacia, the only myelographic sign was spinal cord swelling.     

Pulmonary Lymphomatoid Granulomatosis in Seven Dogs (1976–1987)

Seven dogs with pulmonary lymphomatoid granulomatosis were reviewed. The disease occurred in six large-breed and one small-breed dogs. The dogs were five to 14 years old (mean, 8.4; median, 7), and four of seven dogs were males. Three dogs had been previously treated with adulticide therapy for canine dirofilariasis. Clinical histories included a progressive respiratory disease characterized by varying degrees of cough, dyspnea, exercise intolerance, and weight loss. Thoracic radiographic features included hilar lymphadenopathy, pulmonary masses of varying sizes, and mixed pulmonary patterns of lobar consolidation with ill-defined interstitial and alveolar pulmonary infiltrates. Cardiovascular changes compatible with chronic dirofilariasis were present in three dogs. The clinical course was usually progressive and fatal. The survival time ranged from six days to four years (mean, 12.5 mos; median, 3 mos). Gross and histologic features included mass lesions with areas of necrosis that replaced normal pulmonary architecture. Cytologically, these lesions were characterized by infiltration with pleomorphic, angioinvasive mononuclear cells that often resulted in vascular obliteration. The infiltrating cells resembled large lymphoid cells that possessed large hyperchromatic nuclei and small amounts of cytoplasm. Systemic lymphoid neoplasia with peripheral lymphadenopathy was diagnosed in two dogs. In both cases, lymph-node cytology was similar to the cellular infiltrates found in the lungs and consistent with a diagnosis of lymphomatoid granulomatosis. These features are compared with previously reported cases of canine lymphomatoid granulomatosis and those features identified in a similar disease described in man.     

Canine orbital meningiomas: a review of 22 cases

Clinical and pathologic features of primary orbital meningiomas in the dog were reviewed. Twenty-two meningiomas, confined to the orbit, were identified from the Comparative Ophthalmic Pathology Laboratory of Wisconsin from 1981 to 1997. The dogs ranged in age from 3 to 17 years (mean = 9.2 years). The clinical presentation, reported in 20 cases, was indicative of a retrobulbar mass and included exophthalmos and orbital swelling (18/20), and papilledema or abnormalities of the posterior segment (7/20). Visual acuity was reported in 15 cases; of those, 12 dogs were blind in the affected eye. Follow-up information was obtained on 17 cases; six dogs developed local recurrence of the neoplasm. Two dogs with recurrent neoplasms simultaneously developed blindness in the opposite eye. Extension along the optic nerve to the optic chiasm was suspected. No metastasis was found at the time of the study. Enucleation with excisional biopsy was effective therapy to date in 11 cases (0.2–4.5 years follow-up time). All neoplasms were located within the vicinity of the optic nerve and, when sectioned through the optic nerve head, appeared to completely envelope the nerve. The neoplastic cells were arranged in tight whorls and bundles characteristic of meningiomas. Most tumors had islands of chondroid and osseous metaplasia (17/22). Ocular invasion was limited to small foci in the posterior choroid or optic nerve head of six dogs. Immunoperoxidase stains on 10 cases were positive for vimentin and S-100, but negative for cytokeratin. Electron microscopy revealed complex interdigitations between cell membranes and few desmosomal intercellular attachments. Primary orbital meningiomas have a characteristic histologic appearance and may recur locally after surgical excision.     

Diffuse leptomeningeal histiocytic sarcoma in the cerebrospinal fluid of 2 dogs

Two adult male castrated dogs were evaluated for progressive paraparesis and ataxia. Neurologic examination showed severe ataxia, delayed proprioceptive placement in the pelvic limbs, pain upon palpation of the lumbar spine as well as facial paresis in one dog, and decreased withdrawal reflex of the pelvic limbs in the other dog. Magnetic resonance imaging (MRI) in both dogs showed diffuse meningeal and intramedullary lesions. However, no evidence of a mass was found. Biopsies could not be performed safely due to the location of the lesions. Cerebrospinal fluid (CSF) examination revealed an inflammatory pleocytosis associated with increased protein concentration and numerous large atypical round cells, often multinucleated. Nuclear fragmentation, micronuclei, and rare atypical mitoses were observed. Immunocytochemistry revealed CD1⁺ and CD11c⁺ staining, which, in concert with the morphology confirmed the diagnosis of histiocytic sarcoma (HS). Euthanasia was elected due to poor prognosis. Histopathologic examination showed diffuse spinal and meningeal infiltration with CD18⁺ neoplastic cells, without any evidence of mass formation, which completed the diagnosis of diffuse leptomeningeal HS involving the brain and the spinal cord. Canine central nervous system (CNS) HS has been seldom reported in the literature, with only isolated cases identified on CSF cytology. The cases reported here are remarkable in describing a diffuse CNS leptomeningeal HS associated with neoplastic cells in the CSF of dogs without a tumor mass. These cases emphasize the potential critical importance of CSF analysis in providing an antemortem diagnosis of neoplasia in neurologic patients.     

Cutaneous plasmacytomas with amyloid in six dogs.

Cutaneous plasmacytomas associated with local deposition of amyloid were diagnosed by light microscopy in a series of six older dogs (mean age 10.7 years) consisting of two Cocker Spaniels, a Poodle, a Weimeraner, and two mixed-breed dogs. The neoplasms occurred on the digits (2 dogs), forelimb (2 dogs), lip (1 dog), and ear (1 dog). In most cases, groups of neoplastic plasma cells were widely separated by large homogeneous islands of amyloid. The neoplastic cells had characteristic plasmacytoid features, but the degree of pleomorphism varied greatly between different neoplasms. In four of the six tumors, the diagnosis of plasmacytoma was confirmed by the demonstration of a monoclonal plasma cell population using immunofluorescent staining for anti-canine immunoglobulins. In these tumors, the neoplastic cells reacted with only one class of immunoglobulins (IgG). The amyloid did not react with any of the reagents used. The suspicion that the amyloid was of immunoglobulin origin (primary amyloid) was supported by its retention of birefringence under polarized light after treatment with potassium permanganate and staining with Congo red.     

Bilateral cavernous sinus syndrome in dogs: 6 cases (1999-2004)

OBJECTIVE: To determine clinical features, diagnostic imaging abnormalities, underlying disease, disease progression, and outcome in dogs with bilateral cavernous sinus syndrome. DESIGN: Retrospective study. ANIMALS: 6 dogs. PROCEDURE: Dogs were included if clinical signs consistent with bilateral cavernous sinus syndrome (i.e., deficits of the third, fourth, and sixth cranial nerves and at least 1 of the first 2 branches of the fifth cranial nerve) were present and a lesion of the cavernous sinus was identified by means of diagnostic imaging or postmortem examination. RESULTS: 5 dogs were evaluated because of problems referable to abnormal ocular motility or pupillomotor dysfunction, and 1 dog was evaluated because of partial motor seizures involving the face and bilateral mydriasis. Four dogs had neurologic signs referable to an extrasinusoidal lesion at the time of initial examination, and the remaining 2 dogs eventually developed extrasinusoidal signs. Besides neuroanatomic location, the only consistent neuroimaging feature was variably intense, heterogeneous enhancement of cavernous sinus lesions. Neoplasia was histologically confirmed as the underlying cause in 5 of the dogs and was suspected in the remaining dog. Median survival time for the 4 dogs that were treated was 199 days (range, 16 to 392 days). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that bilateral cavernous sinus syndrome is rare in dogs but should be suspected in dogs with compatible clinical signs. Affected dogs have a poor prognosis, and dogs with clinical signs of bilateral cavernous sinus syndrome should be systematically evaluated for neoplastic disease.     

Spontaneous listeric encephalitis and neuritis in sheep. Light microscopic studies

Sixteen of 17 sheep with spontaneous listeric encephalitis had neuritis characterized by diffuse and focal intrafascicular and perineural accumulations of lymphocytes, plasma cells, macrophages and neutrophils in one or more cranial nerves. Nine sheep had extensive trigeminal neuritis which was usually unilateral. Brain lesions were mainly in the stem and were foci of macrophages or neutrophils or both, malacia, neutrophilic neuronophagia, vascular cuffing, and meningitis. Lesions in the brain and trigeminal ganglia were most severe on the same side as the affected trigeminal nerve. Gram-positive bacilli were in proximal parts of cranial nerves in foci of inflammatory cells and occasionally in morphologically intact nerve fibers. Organisms in the brain were in phagocytes in areas of inflammation and in scattered neurons and axons. The results were consistent with centripetal migration of the infectious agent along one or more branches of the trigeminal nerve to the brain and dissemination in the brain stem occurring, at least partly, along fiber tracts. Intraaxonal movement of bacteria probably is a mechanism involved in the pathogenesis of this disease.     

Macro and microstructural organization of the dog's caudal mesenteric ganglion complex (Canis familiaris-Linnaeus, 1758)

The caudal mesenteric ganglion (CMG) is located ventral to the abdominal aorta involving the initial portion of the caudal mesenteric artery. Its macro and microstructural organization was studied in 40 domestic dogs. From the CMG, there were three nerves: the main hypogastric, the left hypogastric and the right hypogastric. The main hypogastric nerve emits two branches: the left colonic nerve and the cranial rectal nerve. Afterwards they give rise to branches to the descending colon (colonic nerves) and rectum (rectal nerves). The cranial rectal nerve, and left and right hypogastric nerves were directed to the pelvic ganglia. The microscopic study permitted the observation of the histological organization of the CMG, which is a ganglionic complex composed of an agglomeration of ganglionic units. Each ganglionic unit is composed of three major cell types: principal ganglion neurones (PGNs), glial cells and small intensely fluorescent (SIF) cells, and they were separated by nerve fibres, septa of connective tissue (types 1 and 3 collagen fibres), fibroblasts and intraganglionic capillaries. Hence, the ganglionic unit is the morphological support for the microstructural organization of the CMG complex. Further, each ganglionic unit is constituted by a cellular triad (SIF cells, PGN and glial cells), which is the cytological basis for each ganglionic unit.     

RETROSPECTIVE ANALYSIS OF BRAIN SCINTIGRAPHY IN 116 DOGS AND CATS

We performed a retrospective study of 100 dogs and 16 cats with planar brain scintigraphy and histopathologically established diagnoses from a total of 485 studies performed from 1976 to 1992. Necropsy (112) or surgical biopsies (4) diagnoses were categorized in two ways: first as focal brain disease, diffuse brain disease or normal; second as either neoplastic, non-neoplastic or normal. A radiologist reviewed brain scintigrams and categorized the studies as focal areas of increased accumulation, diffuse or poorly localized areas of increased accumulation, or normal. We calculated for this population of 116 animals that focal brain scintigrams had 75% sensitivity and 90% specificity for any focal brain disease. The sensitivity and specificity of a focal scintigraphic lesion for a brain tumor was 72% and 82% respectively. The sensitivity and specificity of a diffuse or poorly localized scintigraphic lesion as a test for diffuse brain disease was 40% and 88% respectively.     

Detection of an autoantibody from Pug dogs with necrotizing encephalitis (Pug dog encephalitis).

An autoantibody against canine brain tissue was detected in the cerebrospinal fluid (CSF) and serum of two Pug dogs (Nos. 1 and 2) by indirect immunofluorescence assay (IFA). Dog No. 1, a 2-year-old male, exhibited severe depression, ataxia, and generalized seizures and died 2 months after the onset of symptoms. Dog No. 2, a 9-month-old male, exhibited severe generalized seizures and died 17 months after the onset of symptoms. Histopathologic examination revealed a moderate to severe multifocal accumulation of lymphocytes, plasma cells, and a few neutrophils in both the gray and white matter of the cerebrum in dog No. 1. In dog No. 2, the cellular infiltrates were mild, but there was a severe, diffuse, and multifocal necrosis in the cerebral cortex with prominent astrocytosis. With the aid of IFA using fluorescein isothiocyanate-labeled antidog IgG goat serum and a confocal imaging system, specific reactions for glial cells were detected in the CSF of these Pug dogs but not in six canine control CSF samples. Double-labeling IFA using CSF from these Pug dogs and a rabbit antiserum against glial fibrillary acidic protein (GFAP) revealed that the autoantibody recognized GFAP-positive astrocytes and their cytoplasmic projections. By immunoblot analysis, the autoantibody from CSF of these Pug dogs recognized two common positive bands at 58 and 54 kd, which corresponded to the molecular mass of human GFAP. The role of this autoantibody for astrocytes is not yet clear. However, if the presence of the autoantibody is a specific feature of Pug dog encephalitis, it will be a useful clinical diagnostic marker and a key to the pathogenesis of this unique canine neurologic disease.     

Gliomatosis cerebri in a dog

Gliomatosis cerebri is a rare tumourous disease of the central nervous system consisting of glial cells characterized by diffuse widespread infiltration and preservation of preformed brain structures. This report describes a case of gliomatosis cerebri in a 9-year-old, male, flat-coated retriever dog with central nervous symptoms. Magnetic resonance imaging of the brain demonstrated ill-defined hyperintense zones of paramedian white matter within the right cerebral hemisphere, brainstem and cerebellum. Histological examination showed a proliferation of tumour cells in the brain structures mentioned. Glial fibrillary acidic protein-immunohistochemistry revealed a lot of fibres positively stained. Based on these findings, the alteration was diagnosed as gliomatosis cerebri.     

Pathological features of ganglioradiculitis (sensory neuropathy) in two dogs

Canine ganglioradiculitis (sensory neuropathy) was examined pathologically in two dogs (dog Nos. 1 and 2). The affected dogs had 1 and 2 years clinical courses from the onset, respectively. As common clinical signs, both cases showed progressive ataxia, difficulty in prehending food, visual deficit, and several sensory abnormalities. Gross observation after tissue fixation revealed whitish discoloration in the dorsal column of the spinal cords. The histological lesions were mainly distributed in the spinal dorsal roots, ganglions, and dorsal columns. In the spinal dorsal roots and ganglions, there were striking myelin loss, mild infiltration of mononuclear cells, and proliferation of small spindle cells. In the dorsal funiculus, there were moderate to severe diffuse myelin-loss and axonal degeneration. Immunohistochemistry for substance P (SP) revealed marked reduction of SP-immunopositive granules in the spinal substantia gelatinosa of affected dogs. By immunohistochemistry, CD3-positive cells were observed in the dorsal roots of dog No. 2, while CD3-positive cells were rare in those of dog No. 1. In the spinal ganglion of dog No. 1 there were many CD3- and MHC class II-positive cells. By indirect immunofluorescence assay using sera from affected dogs, no autoantibodies against canine nerve tissues were detected. The clinicopathological features of the present cases are almost consistent with those in previous reports of canine sensory neuropathies, while the etiology remains unclear.