Feline Meningiomas Research Articles

Subdural fluid accumulation with two meningiomas in a cat.

A case of two separate meningiomas with concurrent subdural fluid accumulation is presented. A 13-year-old, male neutered domestic shorthair cat presented with behavior change and progressive neurologic signs localizing to the forebrain. Two extra-axial masses were seen along with a large subdural fluid collection on advanced imaging of the brain. Histology of the lesions was consistent with multiple meningiomas, while analysis of the subdural fluid was consistent with cerebrospinal fluid. A case of multiple feline meningiomas with peritumoral subdural fluid accumulation has not previously been reported.

Expression of somatostatin receptors in canine and feline meningioma.

The standard treatment for canine and feline meningiomas includes radiotherapy, surgical excision or combined therapy. However, new therapeutic approaches are required due to the possible recurrence or progression of meningiomas despite initial therapy. Adjunctive therapy with synthetic long-acting somatostatin (SST) analogues has been described in humans with SST-expressing tumours. The expression of SST receptors (SSTRs) by feline meningiomas is currently unknown, and there are little data about canine meningiomas. We hypothesized that SSTR is expressed by canine and feline meningiomas (S1). Seven canines and 11 felines with histologically confirmed meningiomas underwent STTR screening. RNA expressions of SSTR1, SSTR2, SSTR3 and SSTR5 (canine) and SSTR1-SSTR 5 (feline) in fresh frozen and formalin-fixed and paraffin-embedded (FFPE) samples were investigated using real-time (RT)-qPCR. The expression of SSTR1 and SSTR2 in FFPE samples was evaluated using immunohistochemistry (IHC). The specificity of applied antibodies for canine and feline species was confirmed by western blotting. In canine meningiomas (n=7), RNA expression of SSTR1, SSTR2 and SSTR5 was detected in all samples; SSTR3 RNA expression was detected in only 33% of samples. In feline meningiomas (n=12), RNA expression of SSTR1, SSTR4, SSTR5 and SSTR2 was detected in 91%, 46%, 46% and 36% of samples, respectively; SSTR3 was not expressed. Overall, the detection rate was lower in FFPE samples. IHC revealed the expression of SSTR1 and SSTR2 in all samples from both species. However, it is important to exercise caution when interpreting IHC results due to the presence of diffuse background staining. SSTRs are widely expressed in canine and feline meningiomas, thereby encouraging further studies investigating SSTR expression to conduct trials about the effect of adjunctive therapy with long-acting SST-analogues.

Magnetic resonance and computed tomographic imaging characteristics and potential molecular mechanisms of feline meningioma associated calvarial hyperostosis.

Meningiomas are the most common feline primary brain tumours, and calvarial hyperostosis (CH) is frequently documented in association with this neoplastic entity. The clinical significance of and mechanisms driving the formation of CH in cats with meningiomas are poorly understood, although tumour invasion into the skull and tumour production of cytokines and enzymes have been implicated as causes of CH in humans. This retrospective study investigated relationships between signalment, MRI or CT imaging features, histopathologic tumour characteristics, alkaline phosphatase (ALP) isoenzyme concentrations, tumour expression of matrix metalloproteinases (MMP)-2, MMP-9, and interleukin-6 (IL-6), and progression free survival times (PFS) following surgical treatment in 27 cats with meningiomas with (n = 15) or without (n = 12) evidence of CH. No significant differences in breed, age, sex, body weight, tumour grade, tumour volume, peritumoral edema burden, ALP isoenzyme concentrations, tumour Ki-67 labelling indices or MMP-2 or MMP-9 expression and activity, or PFS were noted between cats with or without CH. There was a trend towards higher serum (p = .06) and intratumoral (p = .07) concentrations of IL-6 in cats with CH, but these comparisons were not statistically significant. Histologic evidence of tumour invasion into bone was observed in 5/12 (42%) with CH and in no (0/6) cats without CH, although this was not statistically significant (p = .07). Tumour invasion into bone and tumour production of IL-6 may contribute to the formation of meningioma associated CH in cats, although larger studies are required to further substantiate these findings and determine their clinical relevance.

Epithelial membrane antigen-reactive feline chordoid meningioma in a European wildcat (Felis silvestris)

Meningioma is the most frequent intracranial neoplasm in cats. Here we describe the first case of chordoid meningioma (CM), a rare grade II meningioma subtype, in a 5.5-year-old European wildcat (Felis silvestris) from a Swiss zoo. The wildcat was found dead after a clinical history of neurological signs and clinical suspicion of a carcinoma in the right external ear canal with concurrent chronic otitis. Post-mortem examination revealed a large intracranial, extra-axial and intradural neoplasm that invaded into the right ear canal and had histological features compatible with CM, which has been only reported in humans and dogs. Neoplastic cells expressed vimentin but were negative for glial fibrillary acidic protein, S100 and pancytokeratin. Immunohistochemistry revealed epithelial membrane antigen (EMA) expression in neoplastic cells. To the best of our knowledge, we provide the first evidence of EMA expression in feline meningioma.

The expression of platelet-derived growth factor and its receptor in canine and feline meningiomas.

Feline meningiomas usually have benign biological behavior, while canine and human meningiomas are often classified as grade 2 or 3. Activation of the platelet-derived growth factor (PDGF) and its receptor signal pathway through PDGFβ/Rβ autocrine and paracrine is considered to play an important role in the tumor proliferation and malignant transformation of human meningiomas. However, there have been few studies about the expression of these molecules in canine meningiomas and no studies about their expression in feline meningiomas. We analyzed the PDGFα/Rα and PDGFβ/Rβ expression in canine and feline meningiomas by immunohistochemistry and western blotting. Immunohistochemically, most canine meningiomas showed the expression of PDGFα (42/44; 95.5%), PDGFRα (44/44; 100%) and PDGFRβ (35/44; 79.5%), and a few showed the expression of PDGFβ (8/44; 18.2%). In contrast, feline meningiomas were immunopositive for PDGFRα and PDGFRβ in all cases (14/14; 100%), while no or a few cases expressed PDGFα (0/14; 0%) and PDGFβ (2/14; 14.3%). Western blotting revealed specific bands for PDGFα, PDGFRα and PDGFRβ, but not for PDGFβ in a canine meningioma. In a feline meningioma, specific bands for PDGFRα and PDGFRβ were detected, but not for PDGFα and PDGFβ. These results suggested that canine meningiomas commonly express PDGFα/Rα, and thus autocrine or paracrine PDGFα/Rα signaling may be involved in their initiation and progression. Moreover, PDGF negativity may be related to benign biological behavior and a low histopathological grade in feline meningioma.

Case Report: Long-Term Chemotherapy With Hydroxyurea and Prednisolone in a Cat With a Meningioma: Correlation of FDG Uptake and Tumor Grade Assessed by Histopathology and Expression of Ki-67 and p53

A 15.5-year-old, neutered, male, domestic shorthair cat was presented with neurologic dysfunctions. At presentation, an obtunded mental status and vestibular ataxia were identified. On neurologic examination, postural reactions were decreased-to-absent in all four limbs, and pupillary light reflexes showed bilaterally delayed results. Magnetic resonance imaging was performed, and a demarcated lesion was identified in the third ventricle. The cat was tentatively diagnosed with a brain tumor, which was suspected to be a meningioma. The cat was treated with hydroxyurea and prednisolone. Mental status was considered more alert, and ataxia improved following treatment. On the 106th day after the commencement of treatment, a 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan was performed. On the PET images, a hypermetabolic region was found in the lesion. The average standardized uptake value of FDG was 2.47, and the tumor-to-normal-tissue ratio was 1.25. The cat died 408 days following the commencement of treatment, and a grade 1 meningioma was confirmed by postmortem histopathology. Immunohistochemistry for Ki-67 and p53 was performed. The labeling indices of Ki-67 and p53 were 2.56 and 0%, respectively. This case shows that chemotherapy with hydroxyurea and prednisolone may be considered in the treatment of feline meningiomas. Furthermore, this is the first case describing the application of FDG-PET to visualize a naturally occurring meningioma in a cat.

Comparison of Canine and Feline Meningiomas Using the Apparent Diffusion Coefficient and Fractional Anisotropy.

Meningiomas are the most common intracranial tumor in dogs and cats, and their surgical resection is often performed because they are present on the brain surface. Typical meningiomas show comparatively characteristic magnetic resonance imaging findings that lead to clinical diagnosis; however, it is necessary to capture not only macroscopic changes but also microstructural changes to devise a strategy for surgical resection and/or quality of removal. To visualize such microstructural changes, diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) have been used in human medicine. The aim of this retrospective study was to investigate the different characteristics of the apparent diffusion coefficient (ADC) from DWI and fractional anisotropy (FA) from DTI of meningioma between dogs and cats. Statistical analyses were performed to compare ADC and FA values between the intratumoral or peritumoral regions and normal-appearing white matter (NAWM) among 13 dogs (13 lesions, but 12 each in ADC and FA analysis) and six cats (seven lesions). The NAWM of cats had a significantly lower ADC and higher FA compared to dogs. Therefore, for a comparison between dogs and cats, we used ADC and FA ratios that were calculated by dividing the subject (intra- or peritumoral) ADC and FA values by those of NAWM on the contralateral side. Regarding the intratumoral region, feline meningiomas showed a significantly lower ADC ratio and higher FA ratio than canine meningiomas. This study suggested that ADC and FA may be able to distinguish a meningioma that is solid and easy to detach, like as typical feline meningiomas.

Pathological and immunohistochemical features of 45 cases of feline meningioma.

Meningioma is the most common primary brain tumor in cats, although there are few reports about their pathological features. To investigate the histopathological subtypes and immunohistochemical features including expression of cytokeratin and cell adhesion molecules, 45 cases of feline meningioma were examined. The mean age was 12.5 years (range 6–21 years). No statistically significant sex predilection was observed. Regarding the anatomical location of meningioma, tumors mostly developed in the cerebrum, followed by spinal cord and cerebellum, and multiple meningioma was observed in one cat. Microscopically, linear or focal mineralization was observed in 40 cases and cholesterol cleft was observed in 14 cases. Based on histopathological subtypes, there were 15 fibrous, 22 transitional, 2 meningothelial, 5 atypical, and 1 anaplastic meningiomas. These subtypes are classified into grade 1 (39 cases), grade 2 (5 cases), and grade 3 (1 case). There was no significant difference in the Ki-67 index among histological subtypes or grades. Immunohistochemically, the tumor cells were positive for cytokeratin in 5 cases (12.8%), vimentin in 17 cases (43.6%), E-cadherin in 36 cases (92.3%), β-catenin in 21 cases (53.8%), and N-cadherin in 1 case (2.6%), demonstrating the utility of E-cadherin-immunohistochemistry for the diagnosis of feline meningiomas.

Immunohistochemical expression of cyclooxygenase-2 (COX-2) is not associated with tumor grade in feline meningiomas

Meningioma is the most common primary brain tumor in cats and occurs less frequently in the spinal cord. This study aimed to investigate cyclooxygenase-2 (COX-2) expression in feline meningiomas, and the possible association between COX-2 immunoreactivity and tumor grade using eight low-grade and seven high-grade meningiomas. All tumors (n=15/15) were immunoreactive to COX-2. The expression of COX-2 was not significantly correlated with tumor grade (P=0.22 and 0.34 for staining and intensity, respectively) but was significantly associated with necrosis (P=0.04 and 0.01 for staining and intensity, respectively). The findings in this study suggest that feline meningiomas express COX-2, but there were no differences in COX-2 immunoreactivity patterns between low- and high-grade meningiomas. However, the association between COX-2 expression and the presence of necrosis indicates a potential area for therapeutic intervention with selective COX-2 inhibitors.

Iatrogenic Spread of Tumour Cells Due To Subcutaneous Surgical Seeding of a Feline Meningioma

Iatrogenic Spread of Tumour Cells Due To Subcutaneous Surgical Seeding of a Feline Meningioma

Immune Cell Infiltration in Feline Meningioma

Meningioma is the most common primary brain tumour in the cat. Although most of these tumours are considered to be benign based on histological characteristics, little is known regarding microenvironmental changes associated with the tumour. The characterization of the immune-cell infiltrate in human and canine meningiomas has been described; however, there are no data regarding the cat equivalent. Seventeen formalin-fixed, paraffin wax-embedded samples of feline meningioma were evaluated by light microscopy and immunohistochemistry (IHC) for expression of CD3, Pax5, Iba-1, HLA-DR, MAC387, CD163 and Ki67. Variable immune cell infiltrates were seen in every case. All tumours had moderate numbers of infiltrating CD3+ T lymphocytes. Seven of 17 tumours (41%) had infiltrating PAX5+ B lymphocytes that were often dispersed randomly throughout the neoplasm. Macrophage infiltration was abundant in all tumours with widespread immunoreactivity for Iba-1 and HLA-DR. Most tumours (15/17; 88%) had infiltration by MAC387+ macrophages; however, the number of infiltrating cells per ×400 field varied widely (from 0 to 57). Thirteen of 17 tumours (76%) had infiltration by CD163+ macrophages; however (similar to the MAC387 IHC), several tumours had numerous infiltrating cells. There was a potential weak negative rank correlation between the counts of CD3 and Ki67+ cells (rSp=-0.57; P=0.018); however, no other rank correlations could be established between types of infiltrating immune cells (all other P≥0.10). This study establishes evidence for a robust population of immune cells in feline meningioma and indicates that further study is needed to better understand the role of these cells with respect to tumour progression and post-surgical outcome.

Immunohistochemical Detection of CD34, E-cadherin, Claudin-1, Glucose Transporter 1, Laminin, and Protein Gene Product 9.5 in 28 Canine and 8 Feline Meningiomas

The variation in histologic pattern of meningiomas can make their diagnosis challenging. The immunohistochemical profile of 28 canine and 8 feline meningiomas was examined. Tumor types included anaplastic (6 dogs), angiomatoid (1 cat), fibroblastic (3 dogs, 1 cat), meningothelial (1 dog), microcystic (2 dogs), myxoid (3 dogs), psammomatous (4 cats), and transitional (13 dogs, 2 cats). The authors compared the expression of novel markers (CD34, E-cadherin, claudin-1, glucose transporter 1 [GLUT-1], laminin, and protein gene product [PGP] 9.5) with published markers (cytokeratins, glial fibrillary acidic protein [GFAP], progesterone receptor, S100, and vimentin). Neoplastic cells were immunohistochemically positive for vimentin in 100% of the meningiomas; CD34, 94%; GLUT-1, 86%; E-cadherin, 81%; S100, 75%; laminin, 72%; claudin-1, 60%; PGP 9.5, 55%; progesterone receptor, 44%; pancytokeratins, 39%; cytokeratins 8/18, 17%, and GFAP in 9%. Ki67 index did not correlate well with mitotic index. Based on these results and those in the human literature, immunohistochemistry for vimentin, CD34, and E-cadherin is proposed to support a diagnosis of meningioma. Immunohistochemistry for claudin-1, albeit of only moderate to low sensitivity in canine and feline meningiomas, may help to distinguish meningioma from some mesenchymal neoplasms involving the brain and associated structures, such as schwannomas, which in humans express claudin-1 poorly or not at all. Further studies with CD34, E-cadherin, and claudin-1 in canine and feline tumors that may mimic meningiomas are needed to determine the adequacy of this approach.

Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Expression in Canine and Feline Meningioma

Fifty-one meningiomas obtained from 28 dogs and 23 cats were selected for this study to investigate the immunohistochemical expression of matrix metalloproteinase (MMP)-2 and MMP-9 and to compare it to the reverse transcriptase subunit of human-telomerase, progesterone receptor expression, and the proliferative index of the tumors, expressed by Ki67 and proliferating cellular nuclear antigen. Paraffin-embedded tumor tissue was obtained from biopsy samples (28 cases) and at necropsy (23 cases). The most common histotype was malignant in dogs (12/28) and transitional in cats (12/23). Slides immunolabelled for MMPs showed a diffuse cytoplasmic pattern. Twenty-one cases (19 dogs and 2 cats) did not express MMP-2, while only 2 cases were completely negative for MMP-9. The highest values of MMP-2 and MMP-9 were observed in a psammomatous and meningothelial tumor, respectively. On statistical analysis, MMP-2 expression did not show a significant correlation with MMP-9. Moreover, both MMP expressions failed to show significant variance among histologic patterns of the tumor and correlation with the proliferative index. MMP immunolabeling showed an inconstant correlation with progesterone receptor expression. No significant correlation was found between MMP and reverse transcriptase subunit of human-telomerase expression. In feline meningiomas, the MMP-2 value was significantly higher than in canine tumors and the MMP-9 value tended to be low for meningiomas with a follow-up duration from the 23(rd) month to the 44(th) month. In cats, the longer the time from surgery, the lower the proliferative index seemed to be. In dogs, we failed to find a correlation between MMP expression and the follow-up duration.

IMAGING DIAGNOSIS—HYPEROSTOSIS ASSOCIATED WITH MENINGIOMA IN A DOG

A 5-year-old neutered male Beagle mix dog had a 5-day history of generalized tonic-clonic seizures. Before the seizures, the dog had a 1-2-month history of progressive right hemiparesis. In computed tomography images, a presumed extraaxial mass with hyperostosis and destruction of the skull covering the mass were identified. Surgical excision was performed and the histopathologic diagnosis was meningioma. Hyperostosis is frequently associated with feline meningioma, but this report documents that hyperostosis may also occur secondary to meningioma in the dog.

Immunohistochemical expression of h-telomerase reverse transcriptase in canine and feline meningiomas

Telomere length maintenance is regarded as a fundamental step in tumorigenesis, as most human brain tumors, including meningiomas, stabilize the ends of their chromosomes using telomerase. This investigation represents an introduction to telomerase expression in canine and feline meningiomas. Twenty-five archived cases (14 dogs and 11 cats) were immunohistochemically tested for human-telomerase reverse transcriptase (h-TERT), scored, and quantified; furthermore, mitoses were counted on sections stained with a modified toluidine blue. The h-TERT antibody immunolabelled the nucleus and nucleolus of meningeal neoplastic cells, with an intensity ranging from mild to strong and a speckled distribution; a significantly higher expression in cats was noted, while no significant association between h-TERT immunolabelling and sex or histotype was evident in dogs or cats. The telomerase enzyme represents a fundamental parameter of potential malignant transformation, which may occur independently of the signal to proliferate, thereby supplying the cells with unlimited growth capabilities. Telomerase expression could be a prognostic indicator independent of the kinetic parameters, although this should be evaluated using a larger dataset with available clinical information.

Immunohistochemical Identification and Image Analysis Quantification of Oestrogen and Progesterone Receptors in Canine and Feline Meningioma

Oestrogen and progesterone receptor expression has been detected in human meningioma; in canine and feline meningiomas, however, the identification of steroid receptors requires further investigation. Fourteen meningiomas obtained from nine dogs and five cats were examined immunohistochemically for oestrogen receptors (ORs) and progesterone receptors (PRs). The immunolabelling reaction was quantified by light microscopy and image analysis. ORs were expressed in low numbers in two feline meningiomas and in one canine meningioma. PRs were more numerous, with more extensive tissue labelling. Conventional linear regression analysis showed that OR expression was not significant as compared with PR expression. PR expression was lowest in meningiomas with a high proliferation index, as determined by Ki67 expression. Conventional linear regression analysis between PR and Ki67 concentration confirmed a significant indirect relationship. All rights reserved.