Received: 2 December 2021 Revised: 9 March 2022 Accepted: 21 March 2022 DOI: 10.1002/vrc2.365 CASE REPORT Companion or pet animals Clinical, imaging and histopathological characteristics of a malignant intracranial meningioma with pulmonary metastasis in a dog Sonia Ortiz-Nisa, Cristian de la Fuente Fabiano Sant´Ana Martí Pumarola, Sonia Añor, 1 Departament de Medicina i Cirurgia Animal, Facultat de Veterinària, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain 2 Fundació Hospital Clínic Veterinari, Universitat Autònoma de Barcelona, Barcelona, Spain 3 Veterinary Pathology Department, Brasília University, Brasília, Brazil 4 Unitat de Patologia Murina i Comparada (UPMiC), Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain Correspondence Abstract Sonia Añor, Departament de Medicina i Cirurgia Animal, Facultat de Veterinària, Universitat A 13-year-old Spanish Breton was presented for a hyperacute onset of dull mentation Autònoma de Barcelona, Bellaterra, 08193 followed by a generalised tonic-clonic seizure and recumbency. An intracranial mag- Barcelona, Spain. netic resonance imaging study identified a well-demarcated intraventricular mass, and Email: Sonia.Anor@uab.cat cerebrospinal fluid analysis revealed moderate neutrophilic pleocytosis and proteinor- rachia. A tentative diagnosis of meningioma was made and medical treatment was started. After a short initial improvement, the patient died 3 weeks later. Histopathology confirmed the presence of a malignant meningioma (World Health Organization grade III) and pulmonary metastasis. This is, to our knowledge, the first reported case of a canine intracranial meningioma with pulmonary metastasis showing magnetic resonance imaging and immunohistochemical characterisation of the tumour. BACKGROUND CASE PRESENTATION Meningiomas are common intracranial neoplasms derived A 13-year-old, male, neutered Spanish Breton was presented from meningothelial cells, which have been well described to the veterinary hospital for a hyperacute onset of dull menta- in the veterinary literature. They are usually slow growing, tion followed by a generalised tonic-clonic seizure. The owner benign tumours that account for 45% of all primary intracra- also described a dramatic change in the patient’s mental sta- nial tumours in dogs.1–4 tus the same morning of the presentation. The dog was very Based on the human World Health Organization (WHO) quiet and less responsive than normal early in the morning, classification, most canine meningiomas are histologically and progressed to show incoordination and hypersalivation classified as benign (56%) or grade I.5 Grade II or atypical during the next few hours. At night, the dog’s mentation meningiomas are 43% of all of them, and grade III or anaplas- was severely depressed and a generalised tonic-clonic seizure tic variants are the least common, accounting for 1%.1,3 developed. By then, the owner decided to take dog to the Distant metastasis of intracranial meningiomas is veterinary hospital. Before this event, no abnormalities had extremely rare, with less than 1% reported in humans, been observed. Abnormal findings on physical examination and just one study in dogs describing three cases.6,7 included tachypnoea, tachycardia and hyperthermia (39.7◦ C). This case is of interest because it describes an extremely Neurological examination showed dull mentation, ambula- rare presentation of a commonly diagnosed intracranial tory tetraparesis with generalised proprioceptive ataxia and neoplasia such as meningioma. This is the first description absent proprioceptive positioning in all four limbs. Menace of the immunohistochemical and MRI features of a canine response was inconsistent in the left eye, and nasal mucosa malignant intracranial meningioma with metastasis to the sensation was decreased on the left side. Neuroanatom- lung. ical localisation was right prosencephalon. Differential This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2022 The Authors. Veterinary Record Case Reports Published by John Wiley & Sons Ltd on Behalf of British Veterinary Association. Vet Rec Case Rep. 2022;e365. wileyonlinelibrary.com/journal/vrc2  of  https://doi.org/10.1002/vrc2.365  of  Veterinary Record Case Reports diagnoses included vascular accident, intoxication, neoplasia, inflammatory/infectious or, less likely, metabolic disease. LEARNING POINTS/TAKE-HOME MESSAGES ∙ Malignant meningiomas are very rare in both dogs INVESTIGATIONS and humans. ∙ Distant metastases of intracranial meningiomas Blood tests, urinalysis and abdominal ultrasound revealed no are even more unusual in both dogs and humans. abnormalities, but thoracic radiographs showed a multiple ∙ Primary and metastatic meningiomas are expected nodular pattern scattered throughout both lungs (Figure 1a,b). to inmunostain positively to S100 protein and MRI of the brain was performed using a 0.4 Tesla permanent vimentin, and they are expected to be negative to magnet unit (Hitachi Aperto Lucent Hitachi Medical Systems, glial fibrillary acidic protein, epithelial membrane Madrid, Spain). Sequences performed included T2-weighted antigen and cytokeratins. images (WI) in transverse, sagittal and dorsal planes; pre- ∙ To the authors’ knowledge, this is the first report and postcontrast T1-WI in transverse and sagittal planes; describing a canine intraventricular malignant T2-weighted fluid attenuated inversion recovery images meningioma with pulmonary metastasis and its (T2-FLAIR), and T2*-WI in transverse plane. Gadolinium magnetic resonance imaging and immunohisto- (Dotarem 0.5 mmol/ml, Dotarem-Guerbet Laboratories, chemical features. Madrid, Spain) was the contrast agent used at a dose of ∙ Although rare, malignant meningiomas should be 0.1 mmol/kg intravenously (IV). considered, and the presence of metastasis should Imaging identified a single, well-defined intraventricular be ruled out in patients with meningiomas. mass located in the midline and dorsal to the thalamus. The mass was round to oval in shape, and measured 2.13 cm cran- iocaudally, 1.40 cm dorsoventrally and 2.40 cm transversely. It was heterogeneously hyperintense on T2-WI and T2-FLAIR, and iso- to hypointense on T1-WI compared to the normal DIFFERENTIAL DIAGNOSIS gray matter. Contrast enhancement was marked and homo- geneous (Figure 2a–f). Mass effect was identified causing col- Choroid plexus tumour, ependymal tumour or meningioma lapse of the lateral ventricles in their central portion, and tha- are the main differential diagnoses for ventricular tumours. lamic compression with caudoventral displacement of cere- Intraventricular neurocytoma and lymphoma have also been bral parenchyma. The cerebellum was flattened in its rostral described. aspect, and it was mildly compressed by the caudal colliculus, which was displaced caudally. Moderate generalised efface- ment of the cerebral sulci was also observed. TREATMENT Cerebrospinal fluid (CSF) was collected from the cere- bellomedullar cistern and analysis revealed a moderate The patient was hospitalised and palliative medical treatment neutrophilic pleocytosis (60 WBC/µl; reference range with anti-inflammatory doses of prednisone (0.5 mg/kg IV ≤5 WBC/µl), and proteinorrachia (864 mg/dl; reference every 24 hours), phenobarbital (3 mg/kg IV every 12 hours) range <30 mg/dl).8 No microorganisms were identified on and diazepam in case of seizures (1 mg/kg IV) was started. cytological examination. Radiation therapy was rejected by the owner. FIGURE  Thoracic radiographs. Right lateral (a) and ventrodorsal view (b). Multifocal nodular pattern affecting several lung lobes in both hemithoraxes (arrows) Veterinary Record Case Reports  of  F I G U R E  Magnetic resonance images (MRI) of the intraventricular meningioma. Transverse T2-weighted images (WI) (a), T1-WI (b) and T1-WI postcontrast (c) images; and sagittal T2-WI (d), T1-WI (e) and T1-WI postcontrast (f) sequences. A well-defined mass, round to oval shaped, is present within the lateral ventricles. It is heterogeneous and hyperintense on T2-WI (a and d), iso- to hypointense on T1-WI images (b and e), and strongly contrast enhancing (c and f). It measures 2.13 × 1.4 × 2.4 cm (craniocaudally × dorsoventrally × transversely) and causes a moderate mass effect displacing and compressing adjacent structures (0.4 T MRI system) OUTCOME AND FOLLOW-UP The dog’s neurologic condition improved progressively, and no further seizures were observed for the rest of the days of hospitalisation. The patient was discharged 4 days after admis- sion with mild generalised proprioceptive ataxia, but the rest of the neurological examination was unremarkable. A week later, the neurological examination was normal on recheck appointment and the owner reported a positive progress. The third week after discharge, there was an acute worsening of clinical signs. The owner described a sudden onset of dull mentation, constant panting and recumbency, and sudden death 1 hour later on his way to the hospital. A postmortem examination, authorised by the owner, was performed. On gross examination of the brain, a well- circumscribed and firm intraventricular mass was identified (Figure 3). Several firm nodules were also identified in the lungs, spreading over all lobules (Figure 4). Microscopic examination of the brain mass evidenced a F I G U R E  Macroscopic view of the fixed brain. Transverse section of non-encapsulated but well-defined neoplastic cell prolifera- the mass at the level of the lateral ventricles and caudate nucleus. A tion of fusiform cells with a solid growth pattern (Figure 5a). well-circumscribed and firm mass is exposed, and it is occupying both lateral ventricles Abundant and wide necrotic areas, with a large number of active macrophages and neutrophils and several blood vessels, were present (Figure 5b). The cells were medium to large, with brain parenchyma showed microspongiosis, diffuse and reac- a big round or irregular nucleus, lax chromatin and sometimes tive gliosis and perivascular cuffs of inflammatory and neo- apparent nucleoli (Figure 5c). The cytoplasm was scarce, but plastic cells. eosinophilic when evident. Anisocytosis, anisokaryosis and The pulmonary nodules consisted of neoplastic prolif- numerous mitoses were found. The neoplastic population fol- erations of similar fusiform cells, with more pleocytosis lowed a perivascular and papillary pattern. The perilesional than those in the brain. The nodules were non-encapsulated  of  Veterinary Record Case Reports but well delimited, and compressed the lung parenchyma (Figure 5e). Marked anisokaryosis with large and ovoid or lobed nucleus and elongated eosinophilic cytoplasm were present (Figure 5f,g). Mitoses were frequent. The growth pat- tern included solid areas of neoplastic cells organised in dense bundles, mixed with areas in which neoplastic cells were sur- rounding an eosinophilic material made of necrotic cellular debris, with the presence of a purulent inflammatory infiltrate. A Masson’s trichrome stain of the brain sections evidenced the presence of scarce collagen fibres mainly located in the perivascular spaces. In the lung mass, large amounts of colla- gen fibres were found between the neoplastic cell population. Immunohistochemistry was also used to characterise the neoplastic cell population. On brain sections S100 protein immune-stained positively up to 60% of cells (Figure 5d), and up to 80% of cells stained positively in the pulmonary mass (Figure 5h). Small numbers of neoplastic cells were positive to vimentin (VIM) in the encephalic mass, but 40%–60% of neo- plastic cells were positive to the same marker in the pulmonary mass. No positivity was observed (brain or lung) to glial fib- rillary acidic protein (GFAP), epithelial membrane antigen (EMA) or cytokeratins (CK). The findings were consistent with a malignant brain menin- gioma (WHO grade III) with pulmonary metastasis. DISCUSSION F I G U R E  Macroscopic view of the fresh lungs. Several firm nodules, This report describes the clinical, imaging and histopatho- from 2 to 4 cm diameter (arrows), are seen throughout the parenchyma, logical characteristics of a malignant meningioma with pul- spreading among all lobules monary metastasis in a dog. F I G U R E  Four microscopic images of the brain mass (a–d) and four microscopic images of the pulmonary mass (e–h) at different magnifications. (a) Meningioma stained with haematoxylin eosin (HE) compressing the adjacent brain parenchyma (arrows). Bar = 1 mm. (b) Meningioma stained with HE with perivascular and papillary pattern (round markers). Abundant and wide necrotic areas (square marker), with large number of active macrophages and neutrophils (arrows). Bar = 200 µm. (c) At high magnification, medium to large size, fusiform or irregular, neoplastic cells with a big round or irregular nucleus. Bar = 100 µm. (d) Immunohistochemical staining for S100 protein. High numbers of perivascular brown-stained immunopositive cells within the brain mass are mixed with an inflammatory cell population. Bar = 100 µm. (e) A well-delimited pulmonary metastatic meningioma compressing the lung parenchyma is shown. Bar = 2.5 mm. (f) Metastatic meningioma composed of fusiform or irregular neoplastic cells, with large and ovoid or lobed nucleus (marked anisokaryosis) and eosinophilic cytoplasm. Bar = 100 µm. (g) High magnification of the previous image of the pulmonary metastatic meningioma with HE. Bar = 100 µm. (h) Immunopositive S100 protein staining of the pulmonary metastatic meningioma. Bar = 100 µm Veterinary Record Case Reports  of  Malignant meningiomas are uncommon in dogs. Of 112 MULTIPLE CHOICE QUESTION dogs with intracranial meningiomas in a study published by Sturges et al., just one of them was classified as malignant.1 What is the likely diagnosis? A similar scenario is reported in human beings, with a recent review indicating that malignant meningiomas repre- sent 1%–3% of all meningiomas.4 Intracranial meningiomas POSSIBLE ANSWERS TO MULTIPLE CHOICE with metastatic spreading to extra-CNS organs are even less QUESTION common. In dogs, just a prior study reported the clinicopatho- logical features of intracranial meningiomas with pulmonary a) Fungal granulomas metastasis in three dogs and the CT images in two of them, b) Parasitic granuloma but no MRI study or immunohistochemical characterisation c) Pulmonary abscesses was performed in any of them.7 d) Primary pulmonary neoplasia (adenocarcinoma, carci- The MRI characteristics of the mass described herein were noma, squamous cell carcinoma or anaplastic carcinoma) identical to those reported for intracranial meningiomas.1,9,10 e) Metastatic pulmonary neoplasia (meningioma) The mass was large and occupied more than 25% of the cra- nial volume. However, the MRI features of meningiomas can- not predict the pathological grade or the potential growth of CORRECT ANSWER the neoplasm.1 In human medicine, a large tumour volume is the most reliable predictor for high-grade meningioma.11,12 In e) Metastatic pulmonary neoplasia (meningioma). fact, Magill et al. found that tumour sizes greater than 3.2 cm A primary malignant intracranial meningioma with pul- increased the likelihood of being WHO grade II instead of monary metastases was diagnosed in this dog. It has been WHO grade I meningiomas.12 In our case, the tumour diame- described (in a very few cases) as 0.5–4 cm diameter, firm, ter was 2.40 cm, which was a significant size for a dog’s brain. round-shaped nodules scattered throughout both lungs. Neutrophilic pleocytosis in the CSF analysis has been fre- It is an unusual presentation, but pulmonary metastasis quently associated with intracranial meningiomas.13 However, should be ruled out in patients with meningiomas. Dickinson et al. published a retrospective study of 56 dogs with intracranial meningioma and identified neutrophilic CONFLICT OF INTEREST pleocytosis in only 19% of them.14 In addition, it was less likely The authors declare no conflict of interest. in animals with meningiomas located within the mid or ros- tral portions of the cranial fossa. In the case described here, E T H I C S S TAT E M E N T the meningioma was located within the lateral ventricles, and The authors confirm that the ethical policies of the journal, a moderate neutrophilic pleocytosis was identified in the CSF as noted on the journal’s author guidelines page, have been analysis. adhered to. No ethical approval was required as this is a case Clinical signs associated with meningiomas are related report article with no original research data. The owner gave to localisation, size and the presence of secondary changes informed written consent for all the investigations. (oedema, necrosis and inflammation). In the clinical case described here, the response to corticosteroids was most likely F U N D I N G I N F O R M AT I O N due to a reduction of secondary vasogenic oedema. And the The authors received no specific funding for this work. main goal of phenobarbital was to reduce the frequency and the severity of tumour-associated seizures. ORCID Histopathology confirmed that the tumour was a malignant Sonia Añor https://orcid.org/0000-0002-1099-7698 meningioma with pulmonary metastasis, and that the neo- plastic cells in the lungs had even more malignant character- REFERENCES istics than those in the brain. These findings were similar to 1. Sturges BK, Dickinson PJ, Bollen AW, Koblik PD, Kass PH, Kortz those reported in one of the three cases described by Schul- GD, et al. Magnetic resonance imaging and histological classification man et al.7 The immunohistochemical reaction to S100 pro- of intracranial meningiomas in 112 dogs. 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