Intracranial medulloblastoma as the cause of progressive ataxia in a 6-month-old draft horse cross gelding.

We describe the unique clinical presentation of a central nervous system neoplasm in a 6-month-old draft horse cross gelding. Based on the neurologic examination at admission, neurolocalization was most consistent with a mildly asymmetric cervical, multifocal, or diffuse myelopathy. Mild vestibular involvement also was considered, but no cranial nerve deficits were observed. The gelding was negative for Sarcocystis neurona or Neospora hughesi based on paired serum and cerebrospinal fluid (CSF) samples analyzed, with no evidence of cervical compression based on contrast myelography. The horse was euthanized because of progression of clinical signs. At necropsy, a mass was identified associated with the cerebellum, and histopathology was consistent with medulloblastoma, which has not been reported previously in the horse.

A clinical case of presumed cerebellar medulloblastoma in a Japanese Black calf with increased neuron-specific enolase in cerebrospinal fluid.

A 2-day-old Japanese Black male calf that presented with opisthotonos with spastic extension of all four limbs and nystagmus was presented. Evaluation of cranial neurology revealed a horizontal slow nystagmus and absence of menace response in the left eye. Necropsy revealed a mass located between the posterior margin of the cerebrum and anterior margin of the cerebellum, and continuously with the cerebellar lesion. The brainstem was severely compressed by those lesions. Original structures of the cerebellum were mostly replaced by grayish-white and brownish tissues. Those lesions were diagnosed as presumed cerebellar medulloblastoma by histopathological and immunohistochemical examination. As neuron-specific enolase in the cerebrospinal fluid which is a biomarker for neuronal damage was increased compared with healthy calves.

MEDULLOBLASTOMA IN A GRIZZLY BEAR (URSUS ARCTOS HORRIBLIS).

A 3-yr-old female spayed grizzly bear (Ursus arctos horribilis) was evaluated for seizure activity along with lethargy, inappetence, dull mentation, and aggressive behavior. Magnetic resonance (MR) examination of the brain revealed a contrast-enhanced right cerebellar mass with multifocal smaller nodules located in the left cerebellum, thalamus, hippocampus, and cerebrum with resultant obstructive hydrocephalus. Cerebrospinal fluid analysis revealed mild mononuclear pleocytosis, with differentials including inflammatory versus neoplastic processes. Blood and cerebrospinal fluid were also submitted for polymerase chain reaction and agar gel immunodiffusion to rule out infectious causes of meningitis/encephalitis. While awaiting these results, the bear was placed on steroid and antibiotic therapy. Over the next week, the bear deteriorated; she died 1 wk after MR. A complete postmortem examination, including immunohistochemisty, revealed the cerebellar mass to be a medulloblastoma. This is the only case report, to the authors' knowledge, describing a medulloblastoma in a grizzly bear.

Magnetic resonance imaging features of cerebellar vermis medulloblastoma in an adult canine patient.

A seven-year-old, not-castrated male, Airedale Terrier presented with a history of ataxia and intention tremor of the head of three-week duration. Neurologic examination demonstrated severe hypermetria, intention tremor of the head and a bilateral menace response deficit. Magnetic resonance imaging revealed a well demarcated cerebellar vermis mass, hypointense on T1-weighted images, hyperintense on T2-weighted images, with multiple small foci of high signal similar to that of CSF. Foci dispersed in the mass creating a speckled appearance. Homogeneous faint, wispy post-contrast enhancement of the mass was noted; as a result the tumor became isointense to gray matter and was not clearly evident in post contrast images. The histopathological diagnosis of the excised tumor was cerebellar medulloblastoma.

Spontaneous cerebellar primitive neuroectodermal tumor in a juvenile cynomolgus monkey (Macaca fascicularis).

A neoplastic mass compressing the left cerebellar hemisphere and hindbrain was observed at trimming in a 3½-year-old male cynomolgus monkey from a control dose group. Microscopically, the neoplastic mass was nonencapsulated, invasive, and showed two morphological patterns. The predominant area consisted of densely packed undifferentiated, polygonal to spindle cells arranged in vague sheets supported by a scant fibrovascular stroma. The other area was less cellular and composed of round neoplastic cells separated by eosinophilic fibrillar material. Immunohistochemical staining for vimentin, synaptophysin, glial fibrillary acidic protein, neuron-specific enolase, neurofilament, and S-100 confirmed the presence of primitive undifferentiated neuroectodermal cells and some cells with neuronal or glial differentiation. On the basis of histopathology and immunohistochemical findings, a diagnosis of cerebellar primitive neuroectodermal tumor with neuronal and glial differentiation was made. Primitive neuroectodermal tumors are rare in animals including nonhuman primates; this is the first published report in this species.

Immunohistochemical profiling and telomerase activity of a canine medulloblastoma.

A well-demarcated mass was found by computed tomography in the left cerebellar hemisphere of a 4-year-old male Boxer with acute onset of progressive central vestibular syndrome. At necropsy, the pink, gelatinous mass was in the flocculonodular lobe. Histologically, neoplastic tissue arose from the granular layer of the cerebellar cortex and consisted of sheets of oval to round hyperchromatic cells, consistent with the diagnosis of medulloblastoma. Synaptophysin and neuron-specific enolase immunoreactivity supported the neuronal origin of the neoplastic cells; furthermore, a weak to moderate c-kit expression was detected, as reported in pediatric medulloblastoma. Telomerase activity of tumor cells was demonstrated by immunohistochemistry and by the telomere repeat amplification protocol, suggesting involvement of this enzymatic pathway.

Magnetic resonance imaging findings of an intracranial medulloblastoma in a Polish Lowland Sheepdog.

Medullobastoma is an uncommon caudal fossa tumor. The imaging features of medullobastoma in the dog are poorly described. In this report, the magnetic resonance (MR) appearance of a cerebellar medullobastoma in a dog is described. The MR features were similar to medulloblastomas in adult humans, with the tumor arising laterally and extending to the surface of the cerebellar hemisphere. Correct localization of medulloblastoma may be difficult and it should be considered as a differential for both extra- and intra-axial caudal fossa masses.

Cerebrospinal fluid from a dog with neurologic collapse.

A 3-year-old Staffordshire Terrier was presented to the Texas Veterinary Medical Center with a short progressive history of anorexia, weight loss, and weakness that had progressed to ataxia and collapse with empirical treatment. The dog was tetraparetic and obtunded. Results of a complete neurologic evaluation were consistent with severe, multifocal to diffuse disease involving the forebrain, spinal cord, and brainstem. Cerebrospinal fluid, obtained via cerebellomedullary cisternal puncture, was highly cellular and contained large atypical round cells with small numbers of nondegenerate neutrophils and large mononuclear cells. Rare eosinophils and small lymphocytes were noted. The atypical round cells were approximately 15-25 micro m in diameter with a single nucleus set in a small amount of cytoplasm. The nuclei were typically round to slightly ovoid; however, occasional notched, lobulated, and reniform nuclei were observed. These cells were interpreted as malignant lymphocytes. Owing to a grave prognosis, the animal was euthanized and a necropsy was performed. No gross lesions were found in the central nervous system. Multiple sections of cerebellum, medulla, and spinal cord contained a diffuse neoplastic infiltrate that was predominantly meningeal with rare superficial neuropil invasion. The neoplastic cells were arranged in sheets, cords, and rosettes. Immunohistochemical staining for vimentin, pancytokeratin, CD3, CD79a, synaptophysin, S-100, and neuron-specific enolase was negative; glial fibrillary acidic protein (GFAP) staining was equivocal. Based on histologic findings, a diagnosis of medulloblastoma was made. This case documents the rare occurrence of a canine medulloblastoma and illustrates the difficulty in distinguishing between some embryonal brain tumors and lymphoma.

In vivo antitumor activity of S16020, a topoisomerase II inhibitor, and doxorubicin against human brain tumor xenografts.

New active drugs are needed for the treatment of primary brain tumors in both children and adults. S16020 is a cytotoxic olivacine derivative that inhibits topoisomerase II. The aim of the study was to determine its antitumor activity in athymic mice bearing subcutaneous medulloblastoma (IGRM33, 34, 57) and glioblastoma (IGRG88, 93, 121) xenografts treated at an advanced stage of tumor growth in comparison with that of doxorubicin. Animals were randomly assigned to receive i.v. S16020 or doxorubicin weekly for three consecutive weeks. The optimal dose was 80 mg/kg per week. S16020 demonstrated a significant antitumor activity in two out of three medulloblastoma xenografts. IGRM57 xenografts were highly sensitive with 100% tumor regressions and a tumor growth delay (TGD) of 102 days, while one of eight IGRM34 xenografts showed a partial regression with a TGD of 16 days. Doxorubicin was significantly more active than S16020 in these two models. IGRM33, a model established from a tumor in relapse after chemotherapy and radiotherapy, was refractory to both drugs. S16020 demonstrated a significant antitumor activity in the three glioblastoma xenografts evaluated. The wild-type p53 IGRG93 xenograft was highly sensitive with 100% tumor regressions and a TGD of 54 days. IGRG121 (wt p53) and IGRG88 (mutant p53) were moderately sensitive with TGDs of 33 and 23 days, respectively. Doxorubicin showed greater activity in two of these models. All six xenografts exhibited low expression of mdr1 as quantitated by RT-PCR, and no correlation was found with the activity of either drug. Conversely, a low activity of the two drugs was significantly associated with a high expression of MRP1 in medulloblastomas. Finally, no relationship was observed between drug sensitivity to either drug and expression of their target, topoisomerase IIalpha. In conclusion, S16020 and doxorubicin showed significant antitumor activity in brain tumor xenografts treated at an advanced stage of tumor growth. Their activity was related to MRP1 expression in medulloblastomas.

Medulloblastoma in a cat: clinical and MRI findings.

A two-year-old, castrated crossbred cat presented with loss of balance and anorexia. A mass of the caudal aspect of the cerebellum was revealed by magnetic resonance imaging (MRI). The mass was hypointense on T1-weighted images, iso- and hyperintense on T2-weighted images and was enhanced by intravenous gadolinium contrast medium. The MRI characteristics of this case were similar to those of medulloblastoma of the cerebellar vermis in humans. The authors were able to remove almost all of the tumour. The cat was discharged from hospital on day 22 after surgery, but died on day 45. The excised tissue was histologically diagnosed as medulloblastoma.

Cerebellar medulloblastoma with multiple differentiation in a dog.

A 4-year-old female, spayed Border Collie Dog was brought to the Veterinary Medical Teaching Hospital for evaluation of a progressive head tilt and ataxia that were unresponsive to therapy. Neurologic examination localized a right-sided lesion. The owner refused additional diagnostic tests, and necropsy was performed after euthanasia. Gross findings included atrophy of the temporal muscles and a moderately well delineated, 2.5- x 1.5- x 1.0-cm, gray soft-tissue mass compressing the right cerebellar hemisphere and dorsal hindbrain, resulting in massive dilatation of the lateral, third, and fourth ventricles and hydrocephalus. Histologic examination revealed two distinct features: undifferentiated, primitive, polygonal to fusiform cells with typical morphologic characteristics of medulloblastoma and interspersed areas containing myelinated axons and cells with glial and neuronal differentiation. Immunohistochemical examination confirmed the presence of primitive neuroepithelium and cells with glial and neuronal differentiation.

A medulloblastoma in a baboon (Papio papio).

A transitional medulloblastoma was found in the cerebellum of a young female baboon. The primary lesion that permitted its discovery was papillary and retinal edema in the peripapillary zone.