History
An 11-year-old 544-kg (1,197-lb) foreign warmblood gelding was examined because of an 8-week history of progressive ataxia, obtundation, and inappetence. The gelding was inferred to have serum antibodies against Sarcocystis neurona antigenic types by results of an ELISAa (requested by the referring veterinarian) and was subsequently treated for equine protozoal myeloencephalopathy (EPM) with compounded decoquinate-levamisole paste. No improvements were noted after 2 weeks of oral treatment for EPM, and the horse was referred for evaluation.
Clinical and Gross Findings
Neurologic examination revealed a wide range of both left- and right-sided neurologic signs, including hypermetria of the left forelimb, a tendency to lean to the left, subtle left-sided facial nerve paralysis, deviation of the muzzle to the right, erratic placement of the right hind limb, and intermittent circling to the right. The complexity of the clinical signs precluded specific localization of the neurologic lesion. Diagnostic tests performed included an unsuccessful attempt to collect a CSF sample from the lumbosacral portion of the vertebral column. Magnetic resonance imaging was recommended as a means to localize the neurologic lesion but was declined by the owners. In the absence of a definitive diagnosis, initial treatment included flunixin meglumine (1.1 mg/kg [0.5 mg/lb], IV), ponazuril (loading dose of 35 mg/kg [15.9 mg/lb], PO, once, followed by 5 mg/kg [2.3 mg/lb], PO, q 24 h), fenbendazole (10 mg/kg [4.5 mg/lb]), rifampin (10 mg/kg), and chloramphenicol (50 mg/kg [22.7 mg/lb]). After 4 days of treatment without clinical improvement, the owners elected euthanasia, and a postmortem examination was performed.
At necropsy, the brain was first removed for fluorescent antibody testing for rabies virus. Sagittal sectioning of the brain revealed a soft, round to oval, pale tan, 6 × 4-cm mass present within, but with no apparent attachment to, the right lateral ventricle (Figure 1). The surface of the mass was cerebriform and vascular, with multiple, variably sized, yellow foci that were also present on cut surfaces. There was marked dilation of the lateral ventricles, mesencephalic aqueduct, and fourth ventricle. The periventricular white matter was markedly atrophied. The result of fluorescent antibody testing for rabies virus was negative, and a complete necropsy was subsequently performed, with no other remarkable findings.
Photograph of a sagittal section of the brain in an 11-year-old foreign warmblood gelding with an 8-week history of progressive ataxia, obtundation, and inappetence. The markedly dilated right lateral ventricle contains a 6 × 4-cm cerebriform and vascular neoplasm with multifocal, variably sized, pale tan to yellow foci. The neoplasm has no apparent attachment to the ventricular wall. There is marked atrophy of the periventricular white matter.
Citation: Journal of the American Veterinary Medical Association 246, 10; 10.2460/javma.246.10.1067
Photograph of a sagittal section of the brain in an 11-year-old foreign warmblood gelding with an 8-week history of progressive ataxia, obtundation, and inappetence. The markedly dilated right lateral ventricle contains a 6 × 4-cm cerebriform and vascular neoplasm with multifocal, variably sized, pale tan to yellow foci. The neoplasm has no apparent attachment to the ventricular wall. There is marked atrophy of the periventricular white matter.
Citation: Journal of the American Veterinary Medical Association 246, 10; 10.2460/javma.246.10.1067
Photograph of a sagittal section of the brain in an 11-year-old foreign warmblood gelding with an 8-week history of progressive ataxia, obtundation, and inappetence. The markedly dilated right lateral ventricle contains a 6 × 4-cm cerebriform and vascular neoplasm with multifocal, variably sized, pale tan to yellow foci. The neoplasm has no apparent attachment to the ventricular wall. There is marked atrophy of the periventricular white matter.
Citation: Journal of the American Veterinary Medical Association 246, 10; 10.2460/javma.246.10.1067
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histopathologic, Immunohistochemical, and Ultrastructural Findings
Various tissue samples, including the intraventricular mass, brain, choroid plexus, and spinal cord, were fixed in neutral-buffered 10% formalin and processed routinely for histologic evaluation. Histologic evaluation of the intraventricular mass revealed an unencapsulated, expansile, densely cellular neoplasm. The mass was composed of neoplastic spindle cells arranged in whorls or closely packed, interlacing streams, on a fine fibrovascular stroma, with often hyalinized and mineralized small- to medium-caliber blood vessels. Neoplastic spindle cells had variably distinct to indistinct cell borders and scant to moderate amounts of eosinophilic to amphophilic or vacuolated fibrillar cytoplasm. Nuclei were round, oval to elongate, with finely stippled chromatin and 1 variably distinct eosinophilic nucleolus. Moderate anisocytosis and anisokaryosis were noted. There was 1 mitotic figure/hpf. Neoplastic cells frequently formed perivascular pseudorosettes, characterized by a central blood vessel surrounded by an anuclear zone, with peripheral, palisading neoplastic cells extending radiating, tapering cytoplasmic processes (Figure 2). Throughout the neoplasm were several foci of necrosis with mineralization, with at least 1 focus containing necrotic metaplastic cartilage; foci of necrosis likely corresponded to the grossly evident pale yellow foci scattered throughout the mass. Within the neoplasm were several small to moderately sized aggregates of lymphocytes. The surrounding lateral ventricles were moderately dilated, with multifocal subependymal edema and neovascularization. Within the lateral ventricles, the choroid plexus was focally expanded by a loosely arranged connective tissue stroma intersected by mononuclear cells containing intracytoplasmic clear vacuoles or, occasionally, brown globular pigment (early cholesteatoma). Within the white matter of the proximal to midcervical spinal cord were rare spheroids, with occasional axonal loss, and mild multifocal astrogliosis.
Photomicrograph of a section of the intraventricular mass in the horse in Figure 1. Perivascular pseudorosettes composed of a central vessel surrounded by an anuclear zone formed by radially arranged tapering processes of neoplastic spindle cells are evident. H&E stain; bar = 50 μm. Inset—Neoplastic cells forming the perivascular pseudorosettes have strong intracytoplasmic immunoreactivity for glial fibrillary acidic protein. Immunohistochemical stain; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 246, 10; 10.2460/javma.246.10.1067
Photomicrograph of a section of the intraventricular mass in the horse in Figure 1. Perivascular pseudorosettes composed of a central vessel surrounded by an anuclear zone formed by radially arranged tapering processes of neoplastic spindle cells are evident. H&E stain; bar = 50 μm. Inset—Neoplastic cells forming the perivascular pseudorosettes have strong intracytoplasmic immunoreactivity for glial fibrillary acidic protein. Immunohistochemical stain; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 246, 10; 10.2460/javma.246.10.1067
Photomicrograph of a section of the intraventricular mass in the horse in Figure 1. Perivascular pseudorosettes composed of a central vessel surrounded by an anuclear zone formed by radially arranged tapering processes of neoplastic spindle cells are evident. H&E stain; bar = 50 μm. Inset—Neoplastic cells forming the perivascular pseudorosettes have strong intracytoplasmic immunoreactivity for glial fibrillary acidic protein. Immunohistochemical stain; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 246, 10; 10.2460/javma.246.10.1067
In addition to routine histologic evaluation, immunohistochemical analysis and transmission electron microscopyb (TEM) were performed on samples of the intraventricular mass. Immunohistochemical analysis revealed neoplastic cells to have diffuse, strong, intracytoplasmic immunoreactivity for glial fibrillary acidic protein (GFAP), S-100 protein, and vimentin but no immunoreactivity for cytokeratin and E-cadherin. Ultrastructurally, neoplastic cells contained numerous intracytoplasmic intermediate filaments and were interconnected by numerous prominent, intercellular junctions. Occasionally, neoplastic cells contained cilia, in longitudinal and cross section, composed of a central pair of microtubules and 9 surrounding peripheral doublet microtubules (9+2 microtubule structure; Figure 3).
Transmission electron micrograph of a section of the intraventricular mass in the horse in Figure 1. Neoplastic cells contain intercellular junctions (arrows), intracytoplasmic intermediate filaments (IF), and longitudinal and cross sections of cilia in the 9+2 microtubule arrangement (arrowheads). Lead citrate and uranyl acetate stain; bar = 500 μm.
Citation: Journal of the American Veterinary Medical Association 246, 10; 10.2460/javma.246.10.1067
Transmission electron micrograph of a section of the intraventricular mass in the horse in Figure 1. Neoplastic cells contain intercellular junctions (arrows), intracytoplasmic intermediate filaments (IF), and longitudinal and cross sections of cilia in the 9+2 microtubule arrangement (arrowheads). Lead citrate and uranyl acetate stain; bar = 500 μm.
Citation: Journal of the American Veterinary Medical Association 246, 10; 10.2460/javma.246.10.1067
Transmission electron micrograph of a section of the intraventricular mass in the horse in Figure 1. Neoplastic cells contain intercellular junctions (arrows), intracytoplasmic intermediate filaments (IF), and longitudinal and cross sections of cilia in the 9+2 microtubule arrangement (arrowheads). Lead citrate and uranyl acetate stain; bar = 500 μm.
Citation: Journal of the American Veterinary Medical Association 246, 10; 10.2460/javma.246.10.1067
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: ependymoma of the right lateral ventricle with internal hydrocephalus in a horse.
Comments
Ependymomas are rare tumors of the CNS in domestic animals, with few reported cases of affected dogs, cats, and cattle and only 4 cases of affected horses.1–4 Ependymomas are derived from the lining epithelium of the cerebral ventricles and central canal of the spinal cord.5 Grossly, ependymomas may be infiltrative to destructive and can erupt from the neuroparenchyma into the ventricular space, with subsequent obstructive hydrocephalus and rare dissemination into the CSF.5,6 Histologically, ependymomas have a nodular architecture, are well demarcated from adjacent neural tissue, and are typified by perivascular pseudorosettes, with rare true rosette formation.3,5–7 Several distinct histologic variants in humans have been reported and include cellular, anaplastic, subependymoma, tanycytic, clear cell, and papillary or myxopapillary, the latter 2 having also been described in horses.2–5 The horse of the present report had an ependymoma with a morphology and distribution distinct from the currently characterized histologic subtypes.
Four equine cases of ependymomas have been reported.1–4 In 3 of those horses,2–4 the tumors were characterized as papillary and myxopapillary histologic subtypes and were composed of neoplastic columnar to fusiform cells, occasionally arranged in tubules or acini and forming perivascular pseudorosettes (the latter of which was a prominent feature in the present case). Additionally, 2 of the described ependymomas3,4 were immunohistochemically positive for GFAP and vimentin and negative for cytokeratin (similar to the findings for the horse of the present report).
The gross, histopathologic, immunohistochemical, and ultrastructural characteristics of the intraventricular ependymoma in the horse of the present report were similar to those described in the published case reports.1–4 However, the horse of this report had a highly cellular ependymoma originating from the right lateral ventricle. The neoplasm had a spindloid rather than papillary or myxopapillary morphology; the neoplastic cells formed streams, whorls, and numerous perivascular pseudorosettes. Although the presence of intratumoral cartilage in humans with ependymomas has been very rarely described,6 such a finding has not been previously documented for horses, to our knowledge. For the horse in the present report, the ultrastructural identification of cilia in samples of the neoplastic tissue, in conjunction with histologically evident perivascular pseudorosettes and immunohistochemically evident GFAP and vimentin expression, enabled the diagnosis of ependymoma to be confirmed.
On the basis of the clinical signs in the horse of the present report, initial clinical differential diagnoses were numerous and included EPM, trauma, aberrant parasite migration (eg, Halicephalobus gingivalis), viral encephalitides (eg, rabies, eastern equine encephalomyelitis, and equine herpesvirus-1 or West Nile virus infection), CNS or auditory tube diverticulum infections, and intracranial cholesterol granulomas, abscesses, or neoplasia. In addition to ependymomas, other rare intracranial neoplasms in horses include choroid plexus papillomas and meningiomas. Choroid plexus papillomas generally develop at the cerebellopontine angle and, unlike the intraventricular neoplasm in the case described in the present report, are characterized by cuboidal to columnar neoplastic cells.8 In horses, meningiomas only rarely involve the ventricular system9–12 and are histologically diverse, ranging from meningothelial to fibroblastic and transitional types, rendering differentiation from the neoplasm in the horse of this report difficult. For the horse of the present report, the expression of GFAP by neoplastic cells and ultrastructural evidence of cilia facilitated the differentiation between an intraventricular meningioma and ependymoma. Although not neoplastic, cholesterol granulomas represent the most common masses within the lateral ventricle of an aged horse. These mass-like enlargements of the choroid plexus are composed of acicular cholesterol clefts and granulomatous inflammation,13 all of which were not features of the intraventricular mass in the horse of this report.
In all reported equine cases of ependymomas, including the present case, a diagnosis of an intracranial neoplasm was made on the basis of postmortem findings. Advanced imaging methods such as CT and MRI can be instrumental in the antemortem diagnosis of intraventricular masses in anesthetized horses.9–11,14 Although the identification of an intraventricular mass in an aged horse would most likely suggest a cholesterol granuloma, ependymomas should also be considered as a possible but rare diagnosis.
SAG 1, 5, 6, Pathogenes Inc, Reddick, Fla.
JEM-1210 transmission electron microscope, Jeol Ltd, Tokyo, Japan.
References
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