History
A 7-year-old 8.1-kg (17.8-lb) spayed female Cocker Spaniel–Poodle mix was evaluated because of lethargy, behavioral changes, and signs of pain that were difficult to localize. Four months prior, the dog started to have signs of pain and displayed aggressive behavior. One month later, the dog fell and subsequently developed intermittent ataxia of the pelvic limbs and a reluctance to bear weight on the right pelvic limb. The dog was treated for suspected intervertebral disk herniation, but its condition did not improve, and a referral examination was arranged. Additional history included enucleation of the right eye owing to a ruptured globe years earlier.
Photographs of portions of the brain and ventricular system of a dog that was evaluated because of lethargy, behavioral changes, and signs of pain that were difficult to localize. The dog was eventually euthanized. In a gross transverse section of the brain at the level of the rostral colliculi and medial geniculate nuclei (A), notice the pale gray mass that has expanded and filled the mesencephalic aqueduct. Gross invasion of the parenchyma is not visible. Small areas of cavitation (arrowhead) are present along with brown, stippled areas. Ventriculomegaly involving the lateral ventricles is evident. Contained within the ventricular system, the mass extends caudally through the midbrain (B) and pons (C) and into the rostral aspect of the fourth ventricle in the rostral portion of the medulla (D). Vertical and horizontal scale markings represent intervals of 1 mm.
Citation: Journal of the American Veterinary Medical Association 254, 6; 10.2460/javma.254.6.685
Clinical and Gross Findings
At the referral evaluation, results of diagnostic testing and physical examination findings were normal with the exception of prior right-sided globe enucleation. Neurologic examination revealed only a quiet mental state and aggression when handled, which the owner reported was not typical for the dog. Magnetic resonance imaging of the head revealed a mass measuring 1.2 × 1.4 × 1.9 cm, which effaced the mesencephalic aqueduct and extended into the rostral aspect of the fourth ventricle. The mass was primarily homogeneously hyperintense on T2-weighted images and hypointense on T1-weighted images; following contrast agent administration, the mass had slight, homogeneous contrast enhancement. The third and fourth ventricles were dilated; subjectively, there was less CSF overlying the gyri and within sulci of the cerebrum suggestive of partial ventricular outflow obstruction and obstructive hydrocephalus. Analysis of a CSF sample collected from the cisterna magna revealed a high WBC count (135 cells/μL; reference interval, 0 to 5 cells/μL) with mononuclear pleocytosis. Serum antibodies against Toxoplasma gondii and Neospora caninum and Cryptococcus neoformans antigen were not detected. The dog was treated with stereotactic radiation therapy and a 6-week course of prednisone (tapering dosage). Following treatment, the dog's mental state improved, and the aggression subsided. Approximately 2 months after completion of radiation therapy, the dog's mentation declined dramatically, and signs of aggression returned. Repeated MRI revealed that the size and signal characteristics of the mass had not changed. The owners elected euthanasia by means of IV injection of a barbiturate solution and permitted postmortem evaluation.
Externally, the brain appeared normal. It was preserved in neutral-buffered 10 % formalin and then sectioned transversely. On transverse section, the mesencephalic aqueduct through to the rostral aspect of the fourth ventricle was obliterated by a distinct, firm, pale gray to white mass that had a slightly rough texture on cut surface (Figure 1). Subjectively, the lateral and third ventricles were mildly dilated.
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic Findings
Sections of areas of the brain affected by the mass were routinely processed for histologic evaluation. Histologically, the mass was highly cellular and composed of a relatively monomorphic population of neoplastic cells. The cells had a moderate amount of eosinophilic cytoplasm and ill-defined cell borders (Figure 2). Cells were loosely arranged in sheets and interlacing streams. Interspersed throughout the mass were neoplastic cells with an anuclear clear zone that were circumferentially arranged around blood vessels consistent with pseudorosettes. Rare true rosettes that were characterized by a spoke-wheel arrangement of cells surrounding an empty area and that resembled the lumen of a tubule also were seen. Nuclei were round to ovoid with coarsely stippled chromatin. Anisocytosis and anisokaryosis were minimal. Mitotic features were not observed. Several areas of necrosis were present throughout the mass. The mass did not invade but compressed the neuroparenchyma. There was heterogeneous immunoreactivity to glial fibrillary acidic protein (GFAP); in some areas, no immunoreactivity was seen, whereas in other areas, there was strong positive immunoreactivity to GFAP (Figure 3). Immunoreactivity to cytokeratin was not observed.
Photomicrographs of sections of the mass within the mesencephalic aqueduct from the dog in Figure 1. A—Microscopically, the mass is composed of a densely cellular neoplasm; the cells are a relatively monomorphic population. Interposed between loosely arranged sheets of neoplastic cells are numerous perivascular pseudorosettes comprised of neoplastic cells arranged in a spoke-wheel pattern around a centrally placed vessel. Findings were consistent with an ependymoma. H&E stain; bar = 100 μm. B—Rare, true ependymal rosettes are present. H&E stain; bar = 20 μm. C—Perivascular pseudorosettes composed of palisading cells are arranged around a vessel. The slender, elongated neoplastic cells surrounding the vessel have an anuclear clear zone. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 254, 6; 10.2460/javma.254.6.685
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: ependymoma (cellular subtype) within the mesencephalic aqueduct in a dog.
Comments
For the dog of the present report, the neuroanatomic diagnosis was consistent with a lesion involving the prosencephalon or reticular activating system. Initially, the differential diagnoses included an extracranial cause (a metabolic disorder or toxin) or intracranial disorder, such as neoplasia; an inflammatory noninfectious or infectious process; or degenerative encephalopathy. In dogs, neoplasms involving the nervous system are relatively common with an estimated rate of 14.5 neoplasms/100,000 dogs.1 Meningioma and glial neoplasms are the most commonly reported primary brain neoplasms, whereas ependymomas are considered rare.2
Ependymomas in dogs, cats, and horses have been reported.3–6 Ependymomas are neoplasms that arise from the ependymal cell lining of the ventricles in the brain.3 They develop most commonly within the lateral ventricle but have been located in the third and fourth ventricles.4–6 Ependymomas also can develop in the spinal cord.4 Too few canine cases of ependymoma have been reported to determine a breed, sex, or age predilection; however, among cats, a bias toward females has been reported.6 Within the World Health Organization's classification of ependymal tumors in humans,7 there are several distinct histologic variants of ependymomas, namely papillary, tanycytic, cellular, and clear cell subtypes; other types of ependymoma include the classic grade II ependymoma, myxopapillary ependymoma, (grade II), anaplastic ependymoma (grade III), and subependymoma (grade I). Among the reported canine cases, cellular and papillary grade II ependymomas are the most common, although 1 case of clear cell ependymoma has been descibed.5 In the dog of the present report, the diagnosis of an ependymoma of the cellular subtype was based on the appearance of a densely cellular neoplasm composed of a relatively monomorphic cell population with elongate nuclei arranged in sheets with interspersed pseudorosettes and rare true rosettes. Moreover, the neoplasm lacked the papilliform structure characteristic of the papillary and myxopapillary subtypes. It lacked spindle-shaped cells that are observed in tanycytic ependymomas; also, a high mitotic index, microvascular proliferation, and necrosis, which are characteristic of an anaplastic ependymoma, were absent.
Photomicrographs of sections of the mass within the mesencephalic aqueduct from the dog in Figure 1 that underwent immunohistochemical analysis for glial fibrillary acidic protein or cytokeratin. A—Areas of affected tissue are devoid of glial fibrillary acidic protein immunoreactivity. Glial fibrillary acidic protein-specific immunohistochemical stain; bar = 20 μm. B—Areas of affected tissue have intracytoplasmic glial fibrillary acidic protein immunoreactivity. Glial fibrillary acidic protein-specific immunohistochemical stain; bar = 20 μm. Inset— Affected tissue lacks cytokeratin (AE1/AE3) immunoreactivity. Cytokeratin-specific immunohistochemical stain; bar = 20 μm. For all immunohistochemical staining, 3,3'diaminobenzidine, hematoxylin, and bluing reagent were applied.
Citation: Journal of the American Veterinary Medical Association 254, 6; 10.2460/javma.254.6.685
Histologic features of ependymomas typically include pseudorosettes, true rosettes, and ependymal canals.3,8 The diagnosis of an ependymoma is supported by results of immunohistochemical analysis and ultrastructure examination of the neoplastic cells. Positive GFAP immunoreactivity of neoplastic cells has been observed in ependymomas in dogs.5,9 However, for some ependymomas in dogs, there is no evidence of GFAP immunoreactivity.4,10 In the case described in the present report, the neoplasm had heterogeneous GFAP immunoreactivity. Ultrastructurally, ependymomas are characterized by microvilli, cilia, blepharoblasts, intercellular zonula adherens-type junctions, and dense whorls of intermediate filament.11
In people with ependymomas, treatment options include resection and radiation therapy, with resection having the greatest impact on survival time.12 People with infratentorial neoplasms have a higher survival rate than those with supratentorial neoplasms, which may reflect a more invasive phenotype of the latter.13 Reports of animals undergoing treatment are limited to case reports involving surgery in a cat14 and radiation therapy in a dog.5 Similar to the outcome for the dog of the present report, survival time of the dog that underwent radiation therapy in the previous report5 was 4 months, and euthanasia was deemed necessary because of poorly controlled signs despite reduction in the size of the neoplasm.
Although ependymoma is infrequently encountered in dogs, it should be included in the differential diagnosis list for dogs with intraventricular masses. Too few cases of ependymomas in dogs have been reported to define characteristic signalment or clinicopathologic and imaging features that would enable accurate presumptive diagnosis. Definitive diagnosis remains reliant on results of microscopic evaluation of affected tissue samples. With increasing experience in treatment of dogs with ependymomas, therapeutic and prognostic guidelines may emerge.
References
1. Vandevelde M. Brain tumors in domestic animals: an overview, in Proceedings. Conf Brain Tumor Man Anim 1984.
2. Hicks J, Platt S, Kent M, et al. Canine brain tumours: a model for the human disease? Vet Comp Oncol 2017;15:252–272.
3. Summers BA, Cummings JF, de Lahunta A. Tumors of the central nervous system. In: Veterinary neuropathology. St Louis: Mosby, 1995;351–401.
4. Michimae Y, Morita T, Sunagawa Y, et al. Anaplastic ependymoma in the cervical spinal cord of a Maltese dog. J Vet Med Sci 2004;66:1155–1158.
5. Traslavina RP, Kent MS, Mohr FC, et al. Clear cell ependymoma in a dog. J Comp Pathol 2013;149:53–56.
6. Woolford L, de Lahunta A, Baiker K, et al. Ventricular and extraventricular ependymal tumors in 18 cats. Vet Pathol 2013;50:243–251.
7. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumors of the central nervous system. Acta Neuropathol 2007;114:97–109.
8. Vandevelde M, Higgins RJ, Oevermann A. Neoplasia. In: Veterinary neuropathology: essentials of theory and practice. Chichester, England: Wiley-Blackwell, 2012;129–156.
9. Vural SA, Besalti O, Ilhan F, et al. Ventricular ependymoma in a German Shepherd Dog. Vet J 2006;172:185–187.
10. Vandevelde M, Fankhauser R, Luginbuhl H. Immunocytochemical studies in canine neuroectodermal brain tumors. Acta Neuropathol 1985;66:111–116.
11. Liberski PP, Kordek R. Ultrastructural pathology of glial brain tumors revisited: a review. Ultrastruct Pathol 1997;21:1–31.
12. Gramatzki D, Roth P, Felsberg J, et al. Chemotherapy for intracranial ependymoma in adults. BMC Cancer 2016;16:287.
13. McLaughlin MP, Marcus RB Jr, Buatti JM, et al. Ependymoma: results, prognostic factors and treatment recommendations. Int J Radiat Oncol Biol Phys 1998;40:845–850.
14. Simpson DJ, Hunt GB, Tisdall PL, et al. Surgical removal of an ependymoma from the third ventricle of a cat. Aust Vet J 1999;77:645–648.
