879783 research-article2019 JOR0010.1177/2055116919879783Journal of Feline Medicine and Surgery Open ReportsÁlvarez et al Case Report Journal of Feline Medicine and Surgery Open Cerebral gliosarcoma with Reports 1­–6 © The Author(s) 2019 perivascular involvement in a cat Article reuse guidelines: sagepub.com/journals-permissions https://doi.org/10.1177/2055116919879783 DOI: 10.1177/2055116919879783 journals.sagepub.com/home/jfmsopenreports This paper was handled and processed by the European Editorial Office (ISFM) Patricia Álvarez1, Annette Wessmann1, Mireia Pascual2, for publication in JFMS Open Reports Oriol Comas2, Dolors Pi3 and Martí Pumarola3 Abstract Case summary A 5-year-old neutered male domestic shorthair cat presented with an 18-month history of facial tics, and progressive general ataxia, weakness, lethargy and anorexia of 2 weeks’ duration. MRI of the brain showed a well-defined heterogeneous hyperintense mass on T1-weighted and T2-weighted images, with central hypointensity in the rostral commissure and septum pellucidum, and perilesional hyperintensity in fluid-attenuated inversion recovery, suggestive of perilesional oedema. Gross examination in a transverse section of the brain at the level of the septum pellucidum revealed a 0.2 cm brown soft mass. Histopathological examination identified a biphasic neoplastic proliferation of mesenchymal and neuroepithelial cell populations. Fusiform cells were predominately distributed in bundles showing a high degree of anisocytosis and marked immune-positive reaction to vimentin immunochemistry, confirming a sarcomatous origin. Additionally, high numbers of astrocytic cells were identified by an intense immunopositive reaction to glial fibrillary acidic protein and negative reaction to oligodendrocyte transcription factor 2 immunochemistry. Vascular invasion of the neoplasia into the wall of a medium branch of the rostral cerebral artery was present (secondary Scherer structures). Based on these characteristics, the tumour was defined as a gliosarcoma. Gliosarcoma is a recognised astrocytoma grade IV anaplastic glial cell tumour with sarcomatous differentiation. Relevance and novel information To our knowledge, this is the first report describing a cerebral gliosarcoma in a cat including clinical, MRI, macroscopic and histopathological features and immunolabelling characteristics. Keywords: Brain; neoplasia; glioma; histopathology; immunohistochemistry; Scherer structures; MRI Accepted: 9 September 2019 Introduction This case report describes a cerebral gliosarcoma in a The reported incidence of feline intracranial neoplasia is cat presenting with MRI, macroscopic and histopatho- 3.5 in 100,000 cats, or as high as 2.2%.1 Glial cell tumours logical features, and immunolabelling characteristics. are reported infrequently, with an incidence of 7.5% of all intracranial tumours, being the fourth most common central nervous system (CNS) neoplasia in cats.2 1Neurology and Neurosurgery Service, Pride Veterinary Centre, Astrocytomas are considered the most frequent type of Derby, UK 2BalmesVet ClínicaVeterinaria, Barcelona, Spain feline glial cell tumour.3 3Unit of Murine and Comparative Pathology, Department of Gliosarcoma is classified by the World Health Animal Medicine and Surgery, Veterinary Faculty, Autonomous Organization as a subtype of glioblastoma grade IV astro- University of Barcelona, Spain cytoma.4 Gliosarcoma is an infrequently reported primary CNS neoplasm in people and has only been described in Corresponding author: Annette Wessmann DrMedVet, DipECVN, PGCertAcPrac, FHEA, one dog in the veterinary literature.5 It has a bimorphic MRCVS, Pride Veterinary Centre, Riverside Road, Pride Park, population characterised by diffuse anaplastic astrocytic Derby DE24 8HX, UK neoplastic cells with sarcomatous differentiation. Email: annette.wessmann@scarsdalevets.com Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). 2 Journal of Feline Medicine and Surgery Open Reports  Figure 1 MRI of the brain. Mid-line well-defined heterogeneous mass at the level of the rostral commissure and septum pellucidum. The mass is hypointense in (a,b) T2-weighted imaging and (c) T1-weighted imaging (T1WI), with (d) marginal contrast enhancement after gadolinium administration. The mass showed perilesional hyperintensity in (e) fluid-attenuated inversion recovery and (f) marginal T1WI ring signal void in T2* gradient echo images Case description infection (toxoplasmosis) alongside a gastric protector A 5-year-old neutered male domestic shorthair cat pre- used preventively (omeprazole 1 mg/kg IV q24h). sented with an 18-month history of facial twitches, gen- The following day, the cat’s mental and hydration sta- eralised ataxia and abnormal behaviour characterised by tus had normalised and the cervical ventroflexion reduced interaction with the family members. The cat resolved, yet the marked hindlimb ataxia, ambulatory deteriorated acutely 2 weeks prior to presentation, show- paraparesis and head tremor persisted. A repeat blood ing progressive generalised weakness, which was worse analysis was within normal limits. The cat was anaesthe- in the pelvic limbs, lethargy and weight loss. Water tised and underwent MRI of the brain using a 0.25 T unit intake was restricted 5 days prior to presentation, as the (Imagovet). MRI showed a fairly well-defined 0.5 cm cat would only drink from the tap but was unable to heterogeneous hyperintense mass on T1-weighted imag- reach it. ing (T1WI) and T2-weighted imaging (T2WI) in the ros- Clinical examination revealed 5% dehydration, mild tral commissure and septum pellucidum with central obtundation, generalised weakness, cervical ventroflex- hypointensity in T1WI, T2WI, fluid-attenuated inversion ion, intermittent head tremors and ambulatory tetra­ recovery and signal void in T2* gradient echo images. paresis with reduced postural reactions in all limbs, Marginal ring enhancement surrounding the mass lesion indicative primarily of forebrain dysfunction. A meta- was observed following intravenous gadolinium bolic disorder was considered. A complete blood count (0.01 mmol/kg) administration. The imaging features and serum biochemistry showed mild erythrocytosis were suggestive of neoplasia or a congenital vascular (50%; reference interval [RI] 24–45%), mild neutrophilic malformation (Figure 1). leukocytosis (13.1 K/μl; RI 2.5–12.5 K/μl), uraemia Methylprednisolone (2 mg/kg IV followed by PO (114.9 mg/dl; RI 18–60 mg/dl), raised alkaline phos- treatment q24h) was added as palliative treatment for phatase (205 U/l; RI 0–80 U/l) and severe hypernatrae- perilesional oedema resulting in partial improvement mia (>189 mmol/l; RI 150–160 mmol/l). A feline characterised by increased appetite and a brighter men- leukaemia virus and feline immunodeficiency virus tal status. A couple of weeks later, further deterioration SNAP test was negative. Abdominal ultrasound and uri- occurred, characterised by obtundation, generalised nalysis were within normal limits and urine culture was weakness and inappetence. Considering the poor prog- negative. Intravenous fluid therapy was used to correct nosis, the owner requested euthanasia. Permission for the dehydration. Empirical therapy with clindamycin macroscopic post-mortem examination and histological (12.5 mg/kg IV q12h) was added to treat a potential viral examination of the brain was given. Álvarez et al 3 Gross findings of the brain showed a 0.2 cm diameter the possible haemorrhage suggested by findings on the brownish mass with a soft-to-gelatinous consistency MRI gradient echo sequence. located at the level of the septum pellucidum. No macro- The bimorphic neoplastic population consisted of scopic abnormalities were found on examination of the two cell types. One population was characterised by thoracic and abdominal cavities. Histological study of the fusiform cells predominately distributed in bundles brain confirmed the mass as a bimorphic neoplastic cel- showing a high degree of anisocytosis and anisokaryosis lular proliferation located in the rostral cerebral hemi- with a low mitotic index. The identification of mitotic spheres at the level of the septum pellucidum (Figure 2). figures was facilitated by Ki-67 immunohistochemistry Areas of haemorrhage were not identified, contrary to (IHC). This population showed a high immunopositive reaction to vimentin IHC and a weak reaction to smooth muscle actin (SMA) IHC alongside collagen fibres stained with Masson’s trichrome stain. These histo- pathological features are specific for a mesenchymal sarcomatous cell origin (Figure 3). The second neoplastic population was defined as astrocytic in origin as it involved high numbers of astrocytic-like cells. This glial cell type was character- ised by large round-to-polygonal cells with eosino- philic cytoplasm showing a moderate degree of anisocytosis and anisokaryosis with a moderate mitotic index. They showed a high immunopositive reaction to glial fibrillary acidic protein (GFAP) IHC not only in Figure 2 Neoplastic cellular proliferation, indicated by the the periphery, but also widely inside the neoplastic dashed circle, affecting the rostral cerebral hemispheres at population (see Figure 3). Oligodendrocyte transcrip- the level of the septum pellucidum. Haematoxylin and eosin tion factor 2 was negative for the neoplastic population. Figure 3 Gliosarcoma. Mixed neoplastic population of two different and intermingled cell types. (a) A distinct neoplastic cell population characterised by astrocytic-like cells (haematoxylin and eosin). (b) Astrocytic cells reacting positively to glial fibrillary acidic protein immunohistochemistry (IHC). (c) The second population was characterised by fusiform cells distributed in bundles (haematoxylin and eosin). (d) Mesenchymal origin is defined by positive immune reaction to vimentin IHC 4 Journal of Feline Medicine and Surgery Open Reports  (ie, intracranial) is the most common presentation; however, it has been sporadically reported as a second- ary neoplasia occurring after radiation of a previous glioblastoma.13 The pathogenesis of gliosarcoma is much debated. Originally, it was believed that the sarcomatous compo- nent was the result of a neoplastic transformation of the endothelial cells in the vessels traversing the glial tumour. However, this theory was discarded as no endothelial markers could be found.14,15 Other groups have suggested the possibility of a malignant transfor- mation of intratumoural proliferating vessels or of glial cells surrounding a pre-existing sarcoma or simply an unfortunate coexistence given the originally low num- ber of cases with this rare entity.16,17 The most recent theory describes a common monoclonal cell origin of glial and sarcomatous cells supported by the finding of identical genetic alterations in both tumour elements as two distinct malignant cell populations (glial and sarcomatous).13,18–20 Gliosarcoma not only shares genetic similarities with glioblastoma, but also clinical, therapeutic and prognos- tic features, making them almost indistinguishable from Figure 4 (a) Perivascular neoplastic infiltration of a medium- each other. Imaging features reveal variable appear- sized branch of the rostral cerebral artery (haematoxylin and ances, including a homogeneous, well-circumscribed, eosin). (b) Sarcomatous origin of the neoplastic population strongly enhancing mass often abutting the dura, simu- is defined by the immune-positive reaction to vimentin lating the appearance of meningiomas, as well as a immunohistochemistry heterogeneous, ill-defined mass with either patchy or peripheral ring enhancement, as seen in this feline Gemistocytes were commonly seen mixed within the patient.21 Considering the different imaging descrip- astrocytic component. tions, MRI cannot be used to reliably differentiate glio- Neoplastic proliferation was further observed in sarcoma from other glial tumours or non-neoplastic continuity from the mass invading the adventitia and CNS pathology, and histopathological examination is middle tunica of a medium branch of the cerebral rostral essential for its definitive diagnosis. artery. Immunolabelling characteristics showed a posi- Vascular malformation such as a hamartoma was also tive reaction to vimentin (Figure 4), and was negative to considered in this cat given the long clinical history and GFAP and SMA IHC. the signal void on gradient echo sequences. Diffusion- Based on these characteristic histopathological weighted imaging was not performed and the histo- features, the neoplasm was characterised as cerebral pathological examination failed to confirm the presence gliosarcoma with perivascular involvement. of haemorrhage or hemosiderin within the neoplasm. The signal void seen may have been an acquisition arte- Discussion fact in this low-field MRI study. Additional acquisition Astrocytomas are reported infrequently in the feline planes and, ideally, a high-field MRI study would have literature.2,6–12 Four different subtypes – pilocytic, proto- been helpful for further identification but were not plasmic, gemistocytic and fibrillary astrocytomas – are performed. described in feline intracranial astrocytoma.12 This case In people, the biological behaviour of gliosarcoma is report identified gliosarcoma as an additional, previ- slightly different to glioblastoma, which may be seen as ously unreported subtype of intracranial astrocytoma in a different clinicopathological entity. Gliosarcomas have a feline patient. a predisposition for supratentorial cerebral lobes (espe- Gliosarcoma is a rare primary neoplasm of the CNS, cially temporal lobe) and a tendency for extraneural classified as a subtype of glioblastoma defined as a grade metastasis.21 Metastatic disease secondary to a gliosar- IV astrocytoma.4 This tumour type is extremely rare, coma is reported in 11% of the cases via haematogenous reported once in dogs and unreported in cats.5 In people, spread to bone, lymphatic system, lungs, kidney, liver gliosarcoma constitutes 1–8% of all glioblastomas and and, less frequently, spinal cord, and thus extended <0.5% of all intracranial tumours. Primary gliosarcoma imaging is commonly recommended.22 While we cannot Álvarez et al 5 completely exclude metastatic disease in our cat, given population over the glial neoplastic population. As in that the MRI and histopathological examination was people, this feature may have been associated with a limited to the brain, clinical examination and investiga- longer survival time in this cat. Moreover, the tumour tions did not suggest the involvement of other organs. location (septum pellucidum) may have allowed better Histopathological features of gliosarcomas involve a accommodation by adjacent cerebral tissue. mixture of two morphologically distinct neoplastic components, a glial and a sarcomatous component.23 Conclusions The glial element is more frequently astrocytic in Gliosarcoma is a previously unreported subtype of astro- nature, although neoplastic oligodendrocytes have also cytoma in cats and should be considered in the differen- been described.12,24 The second component is sarcoma- tial diagnosis of intracranial tumours. IHC is required to tous and must resemble a spindle cell sarcoma, yet it confirm the mixed glial and sarcomatous neoplastic pop- can also be a fibrosarcoma, an angiosarcoma, a soft tis- ulations. Although the longer-term prognosis is poor, the sue sarcoma or a rhabdomyosarcoma.25 Both compo- clinical course may be long and >1 year. Further studies nents were present in this cat’s diagnosis as the mass are essential to gain a better understanding of this rare was a gliosarcoma with a subjectively stronger sarco- tumour. matous component. Cartilaginous, bony or mesenchy- mal components can also be seen in a gliosarcoma, but Acknowledgements We gratefully acknowledge Ester these were not present in this case. Blasco and Tamara Rivero for their technical assistance. IHC identified these two distinct neoplastic patterns in the cat. The sarcomatous component was naturally Conflict of interest The authors declared no potential arranged in bundles and immunostained for vimentin, conflicts of interest with respect to the research, authorship, which is specific for mesenchymal tumours. The second and/or publication of this article. neoplastic component consisted of astrocytic-like cells, which immunostained for GFAP, the principal marker Funding The authors received no financial support for the research, authorship, and/or publication of this article. for astrocytes. Another significant characteristic of glial cell neoplasia present in this cat was the presence of Ethical approval This work involved the use of non- perivascular infiltration of sarcomatous cell component experimental animals only (owned or unowned), and followed in continuity with the neoplastic mass, which is a histo- established internationally recognized high standards (‘best pathological feature included in the structures of Scherer. practice’) of individual veterinary clinical patient care. Ethical The Scherer structures originally reflect the highly malig- approval from a committee was not necessarily required. nant behaviour of glial cell tumours denoted by its upgraded migratory and invasive capability. Scherer Informed consent Informed consent (either verbal or writ- described four distinct microanatomical features of ten) was obtained from the owner or legal custodian of all malignant cell gliomas – perivascular involvement, peri- animal(s) described in this work for the procedure(s) under- neuronal and perivascular satellitosis, and subpial space taken. No animals or humans are identifiable within this spread of the neoplastic cells – all of which were seen in publication, and therefore additional informed consent for our cat.26 This perivascular pattern could indicate a pos- publication was not required. sible vascular origin of this tumour. References The survival time associated with gliosarcoma is 1 Vandevelde M. Brain tumours in domestic animals: an over­ unknown in animals and poor in people. The mean view. 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