Hypertensive nonobstructive hydrocephalus as main magnetic resonance imaging feature in a dog with disseminated choroid plexus carcinomatosis.

Obstructive or nonobstructive hypertensive hydrocephalus is reported in choroid plexus tumors. Choroid plexus tumors typically present as T2-weighted hyperintense intraventricular masses with occasional cerebrospinal fluid-drop metastasis. Acquired neoplastic nonobstructive hydrocephalus without visible mass lesion in magnetic resonance imaging is not reported in dogs. A 4.5-year-old Rhodesian Ridgeback presented with reduced mental status, unilaterally absent pupillary light reflex, and neck pain. Magnetic resonance imaging revealed a nonobstructive hydrocephalus and widened lumbar subarachnoid space with no evidence of a primary mass lesion. Postmortem examination confirmed a disseminated choroid plexus tumor affecting the ependyma and choroid plexi of all ventricles and the cerebral and lumbar subarachnoid space. Disseminated choroid plexus carcinomatosis should be considered as a possible cause of hypertensive hydrocephalus even in absence of a primary mass.

Use of a telovelar approach for complete resection of a choroid plexus tumor in a dog.

OBJECTIVE: To describe a telovelar approach to the fourth ventricle for excision of a choroid plexus tumor within the ventricle. ANIMAL: A 3-year-old entire male Chihuahua. STUDY DESIGN: Case report METHODS: A 3-year-old dog with two-month history of progressive vestibular signs and subdued mentation was diagnosed with a fourth ventricle tumor. Gross total resection of the tumor was achieved through a telovelar approach to the fourth ventricle. RESULTS: Complete removal of the tumor was confirmed on immediate postoperative MRI. The dog recovered from the surgical procedure without complications, displaying some neurological deficits as preoperatively. His neurological examination was normal 2 weeks after surgery and remained so until the time of writing this case report (28 months) without additional treatment. CONCLUSION: The telovelar approach allowed complete excision of a choroid plexus tumor located in the fourth ventricle of the dog reported here.

Bovine intracranial neoplasia: A retrospective case series.

This case series describes the clinical and pathological findings of intracranial neoplasms in cattle, a rare entity. Data and archived tissues from 24 intracranial tumors were reviewed and investigated by immunohistochemistry for S100, glial fibrillary acidic protein, synaptophysin, pancytokeratin, vimentin, neuron-specific enolase, oligodendrocyte transcription factor 2, and isocitrate dehydrogenase 1. Ages of affected cattle ranged from 6 months to 14 years (5.7 ± 3.6 years; mean ± SD). Predominant clinical signs were altered mental state, central vestibular dysfunction, and cerebellar incoordination. Twelve gliomas, all high grade, were the most common tumors observed: oligodendrogliomas (n = 6), astrocytomas (n = 4), and undefined gliomas (n = 2). The oligodendrogliomas were located in the brainstem and extended into the ventricles, whereas all astrocytomas were located in the forebrain. Isocitrate dehydrogenase 1 gene mutation as described in humans was not detected. The 5 meningiomas exhibited microcystic, chordoid, atypical, papillary, and anaplastic subtypes. Metastatic carcinomas (n = 4) were the only secondary tumor type present, and these were located at the level of the medulla with infiltration of cranial nerves and in one case leptomeningeal carcinomatosis. In addition, 2 medulloblastomas and 1 choroid plexus carcinoma were diagnosed. Immunohistochemistry for vimentin and pancytokeratin was particularly useful to distinguish meningiomas and choroid plexus carcinoma (positive for vimentin only) from mestastatic carcinomas (positive for cytokeratin only) as all showed a papillary growth pattern. Overall, the morphological features were comparable with other species and the human and canine classifications could be applied.

Multimodality characteristics of multifocal choroid plexus carcinoma with bilateral calvarial defects in a dog.

An 8-year-old male intact miniature poodle presented for blindness, obtundation, tetraparesis, and vestibular signs. Magnetic resonance imaging, radiography, and ultrasound revealed a left piriform lobe lesion, right cerebellar and left brainstem lesions, and hydrocephalus and bilateral calvarial defects. Histopathology confirmed a choroid plexus carcinoma with meningeal and intraventricular metastases. The calvarial defect did not show evidence of necrosis, osteoclastic resorption, inflammation or neoplastic infiltration, reflecting a quiescent calvarial atrophy or dysplasia. These novel findings supported inclusion of bone atrophy secondary to chronic increased intracranial pressure as a differential diagnosis for large calvarial defects in dogs with choroid plexus carcinoma.

Long-Term Outcome After Surgical Resection of a Spinal Choroid Plexus Tumor in a Dog.

A 6 yr old castrated male Clumber spaniel was referred for evaluation of acute paraplegia. MRI of the thoracolumbar spine demonstrated an intradural-extramedullary mass lesion at the level of T12 and extradural spinal cord compression at L1-L2. A hemilaminectomy was performed to achieve gross total resection of the mass lesion and removal of extruded disc material. A diagnosis of spinal choroid plexus tumor (CPT) and intervertebral disc extrusion was made. At 4 mo postoperatively, MRI demonstrated a mass lesion at the right lateral aperture of the fourth ventricle. Spinal drop metastasis from a primary intracranial CPT was suspected. The dog was ambulating independently and neurologically normal at that time. At 17 mo postoperatively, a third MRI was performed owing to decreased postural reactions in both hind limbs and vision loss in the right eye, and it demonstrated an increase in size of the intracranial mass lesion. These two additional MRI studies of the entire central nervous system showed no other metastatic lesions nor any evidence of local recurrence. At 25 mo postoperatively, the dog died at home. This is the first case report of surgical intervention and antemortem histopathological diagnosis of a spinal CPT in a dog.

Canine Ependymoma: Diagnostic Criteria and Common Pitfalls.

Reports of canine ependymoma are generally restricted to single case reports with tumor incidence estimated at 2% to 3% of primary central nervous system (CNS) tumors. While most commonly reported in the lateral ventricle, tumors can occur anywhere in the ventricular system and in extraventricular locations. Rosettes and pseudorosettes are a common histologic feature; however, these features can be mimicked by other CNS neoplasms. Thirty-seven potential ependymoma cases were identified in a retrospective database search of 8 institutions, and a histologic review of all cases was conducted. Of 37 cases, 22 candidate cases were further subjected to a consensus histologic and immunohistochemical review, and only 5 of 37 (13.5%) were conclusively identified as ependymoma. The neuroanatomic locations were the lateral ventricle (3/5), third ventricle (1/5), and mesencephalic aqueduct (1/5). Subtypes were papillary (4/5) and tanycytic (1/5). Histologic features included rosettes (5/5), pseudorosettes (5/5), ependymal canals (2/5), tanycytic differentiation (1/5), blepharoplasts (1/5), ciliated cells (1/5), and high nuclear to cytoplasmic ratio (5/5). Immunolabeling for GFAP (4/4) and CKAE1/3 (3/4) was found in pseudorosettes, rosettes, and scattered individual neoplastic cells. Diffuse but variably intense cytoplasmic S100 immunolabeling was detected in 3 of 4 cases. Olig2 intranuclear immunolabeling was observed in less than 1% of the neoplastic cells (3/3). Tumors that had pseudorosettes and mimicked ependymoma included oligodendroglioma, choroid plexus tumor, pituitary corticotroph adenoma, papillary meningioma, and suprasellar germ cell tumor. These findings indicate that canine ependymoma is an extremely rare neoplasm with histomorphologic features that overlap with other primary CNS neoplasms.

Comparative Cytogenetic Analysis of Dog and Human Choroid Plexus Tumors Defines Syntenic Regions of Genomic Loss.

Choroid plexus tumors (CPTs) occur spontaneously in humans and dogs providing an opportunity for comparative cross species analysis of common tumor mechanisms. Large scale chromosomal copy number alterations are the hallmark of human CPTs and identification of driver genes within these regions is problematic. Copy number alterations in 12 spontaneous dog CPTs were defined using an Illumina 170 K single nucleotide polymorphism array and were characterized by highly recurrent whole chromosomal losses in up to 100% of cases with few chromosome wide gains. Loss of canine chromosomes 2, 5, 8, and 20 were seen in 90%-100% of cases and included regions syntenic to loci within commonly reported whole chromosome losses in human choroid plexus tumors. These regions included previously defined tumor suppressor clusters on chromosome 3p and 17p as well as genes associated with chromosomal instability such as TP53 and VHL. This karyotypic signature is similar to a previously defined hypodiploid subgroup of human choroid plexus carcinomas. The nonrandom, highly recurrent alterations in dog CPTs suggest specific selection pressures and oncogenic mechanisms are present. More extensive analysis of this spontaneous tumor model is warranted and may provide key insights into driver mechanisms common to both species.

Choroid plexus carcinoma with neuronal and glial differentiation in a 7-week-old male Sprague-Dawley rat.

We describe a case of choroid plexus carcinoma arising in the cerebrum of a 7-week-old male Sprague-Dawley rat. The tumor mass occupied the right lateral ventricle of the cerebrum. Histological analyses revealed that the epithelial tumor cells had proliferated in tubular, cribriform, papillary and solid growth patterns in the vicinity of the choroid plexus, with slight invasion into the cerebrum parenchyma. We divided the tumor cells into cuboidal, elongated and intermediate cells. Immunohistochemical studies showed that these tumor cells expressed relatively high levels of cytokeratin AE1/AE3, vimentin and glial fibrillary acidic proteins, and low levels of nestin, oligodendrocyte transcription factor and doublecortin proteins. The present case was diagnosed as a choroid plexus carcinoma with neuronal and glial differentiation.

Glomeruloid Microvascular Proliferation, Desmoplasia, and High Proliferative Index as Potential Indicators of High Grade Canine Choroid Plexus Tumors.

Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade. In addition, the expression of angiogenic factors was assessed by immunohistochemistry in 25 tumors to investigate the pathogenesis of tumor-associated vascular hyperplasia. Based on the classical histological hallmarks, this study of 52 CPT identified 22 (42%) CPP (grade I) and 30 of (58%) CPC (grade III). GMVP was more prevalent in CPC (13/30; 43%) than CPP (1/22; 4%), whereas IVD occurred to a similar extent in CPP and CPC. Desmoplasia was more common in CPC (19/30; 63%) than CPP (2/22; 9%), and similarly, the proliferative index (PI) of neoplastic epithelium was significantly higher in CPC (5.14%) than CPP (0.94%). The majority of CPT expressed platelet-derived growth factor (PDGF), PDGFRα, PDGFRß, and vascular endothelial growth factor (VEGF) irrespective of tumor grade or tumor-associated vascular hyperplasia. These results suggest that tumor-associated GMVP, desmoplasia, and PI may serve as histological indicators of malignancy in CPT.

Concurrent Gliosarcoma and Choroid Plexus Carcinoma in a Cow.

Brain tumours in cattle are uncommon and the spontaneous development of primary brain tumours of different histological types is rare in both man and animals. In man, multiple concurrent primary tumours of different types are occasionally described. We report the rare simultaneous occurrence of two different primary brain tumours, gliosarcoma and choroid plexus carcinoma, diagnosed by microscopical and immunofluorescence evaluation in an 8-year-old cow with a 2-month history of neurological disease. Gliosarcoma is a rare variant of glioblastoma multiforme, characterized by the presence of malignant glial cells and mesenchymal tissue. This tumour has not been reported previously in animals.

Kir7.1 immunoreactivity in canine choroid plexus tumors.

Choroid plexus neoplasms are uncommon brain tumors in dogs. Choroid plexus carcinomas often spread diffusely throughout the ventricular system and subarachnoid space and, in aggressive forms, can mimic histologic patterns of other carcinomas, including being embedded in a desmoplastic reaction. Although choroid plexus tumors (CPTs) heterogeneously express pan-cytokeratin, little is known about other markers to identify choroid plexus and their associated tumors. Kir7.1, an inward-rectifier potassium channel, is reported to have high diagnostic utility in human neuropathology to distinguish CPTs from other primary brain tumors and cerebral metastases. To determine Kir7.1 expression in the dog brain, we analyzed the immunoreactivity of Kir7.1 in normal brain, gliomas, ependymomas, CPTs, meningiomas, and carcinomas. In normal brain tissue, the immunostaining was restricted to the choroid plexus where there was robust membrane immunoreactivity along the apical border of the cells with less intense cytoplasmic staining. Similar strong immunoreactivity was detected in 12 of 12 CPTs, whereas 5 of 5 gliomas, 4 of 5 ependymomas, 5 of 5 meningiomas, and 5 of 6 carcinomas had no immunoreactivity. One ependymoma and 1 nasal carcinoma with squamous metaplasia were up to 75% immunopositive, with moderate cytoplasmic and membranous immunoreactivity, but lacking the robust apical immunoreactivity pattern. Analysis for immunoreactivity in a tissue microarray failed to yield any other locations in which immunoreactivity was detected. These results, including the distinctive pattern of immunostaining in CPTs, suggest that Kir7.1 is an excellent marker for CPTs in the dog.

E-cadherin, N-cadherin Expression and Histologic Characterization of Canine Choroid Plexus Tumors.

Choroid plexus tumors (CPTs) are reported with an increasing incidence in dogs, and they call for a reexamination of histologic features and criteria of classification corresponding to their biological behavior. In this study, the human World Health Organization classification was applied to 16 canine CPTs, and the expression of molecules involved in neoplastic cell adhesion (E-cadherin, N-cadherin), invasion (doublecortin), and proliferation (Ki-67) was investigated. Mitotic index was found to be the main criterion for grading CPTs. Cell density and multilayering of papillae were also statistically associated with histologic grade. Intraventricular spread and parenchymal invasion was observed for tumors showing histologic benign features. E-cadherin was expressed in all CPT grades, independent of tumor invasion. N-cadherin immunolabeling was more expressed in grade I than high-grade CPTs, whereas doublecortin expression was not detected in CPTs. An increasing proliferative activity was observed in relation with histologic grade.

Expression of cell adhesion molecules in canine choroid plexus tumors.

Choroid plexus tumor (CPT) is a primary intracranial neoplasm of the choroid plexus epithelium in the central nervous system. In the current World Health Organization classification, CPT is classified into two categories; choroid plexus papilloma (CPP) and carcinoma (CPC). In the present study, we investigated immunohistochemical expressions of N-cadherin, E-cadherin and ß-catenin in 5 canine CPT cases (1 disseminated CPC, 2 CPCs and 2 CPPs). One CPP case was positive for N-cadherin and ß-catenin, but negative for E-cadherin. The disseminated CPC case was positive for E-cadherin and ß-catenin, but negative for N-cadherin. The other cases were positive for the three molecules examined. These results suggest that loss of the N-cadherin expression might associate with the spreading of CPC cells.

Aberrant E-cadherin, ß-catenin, and glial fibrillary acidic protein (GFAP) expression in canine choroid plexus tumors.

Expression of E-cadherin and ß-catenin has been widely studied in various human and canine epithelial tumors and has been correlated with dedifferentiation, invasiveness, and metastasis. Choroid plexus tumors (CPTs) are of epithelial origin, and the most important prognostic factor in human medicine is the tumor grade. Limited information is available regarding E-cadherin and ß-catenin expression in human CPTs, and no information is found in the veterinary literature. In the current study, 42 canine CPTs (19 choroid plexus papillomas and 23 choroid plexus carcinomas) were retrospectively reviewed, and the intensity and cellular staining pattern of E-cadherin and ß-catenin were correlated with histological features, paying special attention to grade, invasion, and metastasis. In addition, cytokeratin and glial fibrillary acidic protein (GFAP) antibodies were evaluated as markers for canine CPTs. It was found that loss of E-cadherin and ß-catenin expression was uncommon in canine CPTs. Rather, membranous expression of both molecules was increased in CPTs compared to normal choroid plexus (NCP), regardless of tumor grade. Additionally, aberrant cytoplasmic or nuclear expression of both E-cadherin and ß-catenin was often observed in CPTs. GFAP was frequently expressed in CPTs in contrast to NCP. None of these parameters were correlated with malignancy, and therefore, do not appear to be useful for prognostic information. Nevertheless, a panel of antibodies including E-cadherin and GFAP might be useful to support the diagnosis of CPTs and help to differentiate them from other tumors, such as ependymomas and metastatic epithelial tumors.

Choroid plexus carcinoma cells in the cerebrospinal fluid of a Staffordshire Bull Terrier.

An 11-year-old female intact Staffordshire Bull Terrier was referred to the Queen's Veterinary School Hospital at the University of Cambridge with sudden onset of episodic behavioral changes, a mammary mass, and papilledema in the right eye. On physical examination the dog appeared depressed and had a head tilt to the right with anisocoria. Using magnetic resonance imaging, a broad-based lesion that obliterated the fourth ventricle was detected in the right brainstem. There was no evidence of pulmonary metastasis. Cerebrospinal fluid (CSF) was then obtained; fluid analysis showed an increased cell count (165 cells/µL, reference interval 0-7 cells/µL) and total protein (0.30 g/L, reference value <0.25 g/L). Cytologic evaluation revealed a population of atypical epithelial cells arranged in cohesive rafts and characterized by moderate to occasionally marked anisocytosis and anisokaryosis. The appearance was highly suspicious of a malignant epithelial neoplasm. The dog was euthanized and on postmortem examination an asymmetrical nonencapsulated cerebellar mass was found within the choroid plexus of the fourth ventricle with local extension into the cerebellopontine angle. Histologic sections of the cerebellar mass contained arborizing papillary structures covered by a single layer of atypical epithelial cells that showed local infiltration into the adjacent neuropil. The diagnosis was choroid plexus carcinoma. The atypical epithelial cells were negative for pancytokeratin and strongly positive for vimentin. The finding of clusters of choroid plexus epithelial cells in the CSF demonstrates the value of utilizing a relatively noninvasive diagnostic technique for diagnosis of choroid plexus tumors.

Choroid plexus tumors in 56 dogs (1985-2007).

BACKGROUND: Choroid plexus tumors (CPTs) comprise approximately 10% of all primary brain tumors in dogs. The clinical utility of magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, or both in the presumptive diagnosis of CPTs has not been determined. OBJECTIVES: To report MRI and CSF findings in dogs with CPT and determine if there are distinguishing features that allow clinical discrimination between the tumor grades. ANIMALS: Fifty-six client-owned dogs with naturally occurring CPT. METHODS: Retrospective case series. The inclusion criterion was histologically confirmed CPT. Blinded review of cranial MRI and cisternal CSF analysis was performed. RESULTS: Thirty-six of 56 dogs had a choroid plexus carcinoma (CPC) and 20 had a choroid plexus papilloma (CPP). Golden Retrievers were overrepresented compared with the hospital population (frequency 3.7 times that expected, confidence interval 95%= 2.0-6.7, P< .0002). Median CSF protein concentration in CPCs (108 mg/dL, range 27-380 mg/dL) was significantly higher than in CPPs (34 mg/dL, range 32-80 mg/dL) (P= .002). Only dogs with CPCs had a CSF protein concentration >80 mg/dL. Cytological evidence of malignancy in CSF was seen in 7 of 15 CPCs. Only CPCs had evidence of intraventricular or subarachnoid metastases on MRI. CONCLUSIONS AND CLINICAL IMPORTANCE: MRI, CSF analysis or both can help to differentiate between CPPs and CPCs, and may provide valuable prognostic and pretreatment information.

Choroid plexus papilloma in a Scottish highland cow.

Choroid plexus papilloma, a rare tumour in bovids, arising from the roof of the third ventricle was diagnosed at necropsy in a 4-year-old Scottish Highland cow. The animal presented with a 2-month history of progressive ataxia, ventromedial strabismus, and hyperaesthesia. Neoplastic epithelial cells were positive immunohistochemically for pancytokeratin and S-100, and negative for GFAP. Ultrastructurally, epithelial cells were characterized by intercellular junctions, zonulae adherens, and zonulae occludens. Neither cilia nor basal bodies were identified. The gross, microscopical, immunohistochemical and ultrastructural findings were consistent with those of a choroid plexus papilloma.

Choroid plexus carcinoma in a goat.

A 15-year-old female goat suddenly developed right-sided head tilting with anorexia and depression. Post-mortem examination of the brain revealed a large, unilateral, well-demarcated, intraventricular neoplasm which was diagnosed as a choroid plexus carcinoma. The neoplasm, which occupied about 75% of the left lateral ventricle, led to unilateral obstructive hydrocephalus and invaded the white and grey matter of the left piriform lobe, with focal subarachnoid spread and meningeal implantation. Histopathological examination revealed loss of branching papillary architecture, invasive growth, a high mitotic index and marked necrosis in the undifferentiated areas of the tumour. Neoplastic cells expressed vimentin and, multifocally, broad spectrum cytokeratins, but were negative for GFAP, NSE and Sl00 antigen. This is the first report of a choroid plexus carcinoma in a goat.

Canine intracranial primary neoplasia: 173 cases (1986-2003).

This study investigates the clinical and pathologic findings associated with 173 primary brain tumors in our hospital population of dogs that presented between the years 1986 and 2002. Of the 173 primary brain tumors, 78 (45%) were meningiomas, 29 (17%) were astrocytomas, 25 (14%) were oligodendrogliomas, 12 (7%) were choroid plexus tumors, and 7 (4%) were primary central nervous system lymphomas. Smaller numbers of glioblastomas (n = 5), primitive neuroectodermal tumors (n = 5), histiocytic sarcomas (n = 5), vascular hamartomas (n = 4), and unclassified gliomas (n = 3) were identified. One dog had both a meningioma and an astrocytoma. Most tumors were located within the telencephalon, and seizures were the most common clinical presenting complaint. Of 168 tumors for which a location in the brain was recorded at postmortem examination, 79 were found to involve more than 1 brain division. Other neoplasms unrelated to the primary brain tumor were identified on postmortem examination in 39 dogs (23%). Intrathoracic and intraabdominal neoplasms were present at necropsy in 13 and 24 cases, respectively. Based on the results of this study, thoracic radiographs and abdominal ultrasonography may be indicated to look for extracranial neoplasia prior to advanced imaging of the brain or intracranial surgery.