veterinary sciences Case Report Intracranial Granular Cell Tumours in Three Dogs: Atypical Magnetic Resonance Imaging Features and Immunohistochemical Study Clàudia Mayor 1,2 , Judit Verdés 1,2 , Jaume Alomar 3 , Rosa Novellas 1,2 , Martí Pumarola 4 and Sònia Añor 1,2, * 1 Fundació Hospital Clínic Veterinari, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain 2 Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain 3 Servei de Diagnòstic de Patologia Veterinària, Departament de Sanitat i Anatomia d’Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain 4 Unitat de Patologia Murina i Comparada, Departament de Sanitat i Anatomia d’Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain * Correspondence: sonia.anor@uab.cat Simple Summary: Intracranial granular cell tumours are rare tumours of unknown cellular origin. In this case series. we describe three dogs with neurological signs that had magnetic resonance imaging of the brain, and were diagnosed with granular cell tumours through histopathological and histochemical studies. Magnetic resonance imaging characteristics were atypical, showing hypointense lesions on T2-weighted images in all cases. Immunohistochemical studies helped in characterising the tumours and excluded a Schwann cell origin. The findings of this case series indicate that granular cell tumours can be hypointense on T2-weighted magnetic resonance images, and that the cell of origin remains to be determined. Abstract: Intracranial granular cell tumours (GCT) are uncommon neoplasms of uncertain cellular Citation: Mayor, C.; Verdés, J.; origin that are rarely reported in dogs. This case series describes three aged dogs that presented Alomar, J.; Novellas, R.; with neurological signs in which magnetic resonance (MR) imaging revealed plaquelike extra-axial Pumarola, M.; Añor, S. Intracranial lesions that were hypointense on T2-weighted (T2w) images. The surgical biopsy of the lesions Granular Cell Tumours in Three and necropsies were followed by histochemical characterisation with periodic acid–Schiff (PAS) Dogs: Atypical Magnetic Resonance staining and immunohistochemistry with ubiquitin, S-100, and SOX-10 to elucidate the cellular origin. Imaging Features and The immunohistochemical study indicated that these intracranial GCTs were not of Schwann cell Immunohistochemical Study. Vet. Sci. origin. In conclusion, GCTs should be considered a differential diagnosis of intracranial, extra-axial 2023, 10, 134. https://doi.org/ hypointense brain lesions on T2w MR images. 10.3390/vetsci10020134 Academic Editor: Louise van der Keywords: granular cell tumour; magnetic resonance imaging; immunohistochemistry; brain; dog Weyden Received: 17 January 2023 Revised: 6 February 2023 1. Introduction Accepted: 7 February 2023 Published: 9 February 2023 Granular cell tumours (GCTs) are rare neoplasms that can be found in the nervous system of humans and dogs, and extraneurally. Intracranial GCTs were reported in several species, including rats (where they account for the most common intracranial neoplasia), dogs, one cat, a ferret, and most recently a python [1–4]. In dogs, GCTs were described as Copyright: © 2023 by the authors. affecting the spinal cord and peripheral nerves in two cases [5,6]. Licensee MDPI, Basel, Switzerland. The origin of these neoplasms remains uncertain: they are thought to arise from This article is an open access article Schwann cells in people, but in other species, immunohistochemical and ultrastructural distributed under the terms and electron microscopic studies have not been able to elucidate a cell of origin. Several cells conditions of the Creative Commons were proposed, including astrocytes, and meningeal and glial cells [2,7,8]. Attribution (CC BY) license (https:// GCT diagnosis relies mainly upon distinctive cellular and histopathological character- creativecommons.org/licenses/by/ istics. Typical cells are large round-to-polygonal cells with abundant eosinophilic granules 4.0/). Vet. Sci. 2023, 10, 134. https://doi.org/10.3390/vetsci10020134 https://www.mdpi.com/journal/vetsci Vet. Sci. 2023, 10, 134 2 of 11 within the cytoplasm and eccentric nucleus, and immunohistochemical studies revealed commonly periodic acid–Schiff (PAS) positivity [2,7,8]. Given their rarity, only 19 intracranial GCT have been reported in the literature since 1978 [2,8–17], and information regarding their typical features in advanced imaging techniques was only described in scant reports, with a total of 12 cases [8,15–17]. Anwer and Vernau (2013) performed the largest study of a confirmed GCT. In that study, GCTs appeared as extra-axial plaquelike lesions, hyperintense on precontrast T1-weighted (T1w) images and isohyperintense on T2-weighted (T2w) sequences. Peritumoral oedema and mass effect were also typical characteristics [16]. Here, we describe a case series of three confirmed intracranial GCT that presented to the Veterinary Teaching Hospital of the Universitat Autònoma de Barcelona from 2019 to 2022, all of which had in common an atypical magnetic resonance (MR) imaging feature: they were hypointense on T2w images. To the best of the authors’ knowledge, this is the first description of T2w hypointense intracranial GCT in dogs. All cases underwent a complete neurological examination by a neurology and neuro- surgery resident under the direct supervision of a board-certified specialist (SA). All MR images were reviewed by four counterparts: a neurology and neurosurgery resident with the board-certified specialist supervisor (SA), and by a diagnostic imaging resident (JV) with a board-certified radiologist (RN). Histopathological studies were performed by a pathology resident (JA) and board-certified pathologist (MP). 2. Case Presentation 2.1. Case 1 A 13-year-old female neutered French bulldog presented an acute onset of cluster generalised tonic–clonic seizures the same day of consultation. On presentation, general physical examination was within normal limits. Neurological examination revealed an obtunded mental status with right pleurothotonus, a tendency to circle to the right side, absent postural reactions on the left limbs and decreased on the right limbs, and absent menace response on the left eye. These abnormalities were consistent with a lesion in the right prosencephalon. A complete blood cell count (CBC), full serum biochemical profile, thoracic radio- graphs, and abdominal ultrasound were all unremarkable. A routine MR imaging study was performed with T1w, T2w, fluid attenuation inver- sion recovery (FLAIR), postcontrast T1 (T1w+c), gradient echo (T2*) transverse sequences (see Figure 1), and T2w, T1w and T1w+c sagittal sequences. Diffuse thickening of the meninges covering the left hemisphere was seen. A plaque- like lesion extending from the left olfactory bulb involving the meninges along the convexity of the whole hemisphere, extending to the falx cerebri and affecting partially the adjacent right cerebral hemisphere, was observed. The mass was markedly hypointense with respect to grey matter on T2w, FLAIR and T2* sequences, isointense on T1w with focal areas of hy- perintensity, and showed marked and uniform enhancement after contrast administration. Adjacent to this lesion, mild diffuse T2w and FLAIR hyperintensity was present affecting the brain parenchyma. The lesion was causing a severe mass effect over the left lateral ventricle and subfalcine brain herniation of the left cerebral hemisphere. The cerebral sulci of the affected side were moderately attenuated, suggesting increased intracranial pressure. The brain MR imaging study included the first cervical spine segments where an additional intramedullary lesion was detected: an ill-defined lesion, hyperintense on T2w images and hypointense on T1w images was present in the C2 spinal cord parenchyma, which occupied over 40% of the spinal cord diameter. No contrast enhancement was observed after gadolinium administration. Differential diagnoses of the main lesion included primary intracranial extra-axial neo- plasia (lymphoma, histiocytic sarcoma, GCT, meningioma), metastasis or an early subacute subdural haemorrhage. The C2 intramedullary lesion was consistent with syringomyelia, which could be attributed to the cerebrospinal fluid (CSF) flow disruption caused by the Vet. Sci. 2023, 10, 134 3 of 11 Vet. Sci. 2023, 10, x FOR PEER REVIEW 3 of 11 intracranial mass. Nonetheless, other causes of syringomyelia (such as breed-related) could not be ruled out. Figure1.1.Magnetic Figure Magneticresonance resonance(MR)(MR)imaging imagingofofthe thebrain brainofofCase Case1,1,transverse transverseimages imagesatatthe thelevel levelofof the thalamus. A plaquelike extra-axial mass is visible covering the left hemisphere with the thalamus. A plaquelike extra-axial mass is visible covering the left hemisphere with (A) a marked (A) a marked hypointense signal on T2-weighted (T2w) sequences and (B) fluid attenuation inversion hypointense signal on T2-weighted (T2w) sequences and (B) fluid attenuation inversion recovery recovery (FLAIR). (C) T1-weighted (T1w) hyperintensity was not visible, but (D) marked enhance- (FLAIR). (C) T1-weighted (T1w) hyperintensity was not visible, but (D) marked enhancement after ment after contrast administration could be detected. Note the severe mass effect and peritumoral contrast oedemaadministration could causing occlusion be left of the detected. lateral Note the severe mass effect and peritumoral oedema ventricle. causing occlusion of the left lateral ventricle. Differential diagnoses of the main lesion included primary intracranial extra-axial A CSF sample was collected from the cerebromedullary cistern after brain MR imag- neoplasia (lymphoma, ing. The analysis histiocytic revealed sarcoma, GCT,dissociation: albuminocytologic meningioma), metastasis normal total or an early sub- nucleated cell count (TNCC) of 2 WBC/µL (reference range < 5 WBC/µL) with increased total syringo- acute subdural haemorrhage. The C2 intramedullary lesion was consistent with protein myelia, whichofcould concentration be attributed 49.5 mg/dL to therange (reference cerebrospinal < 20 mg/dL). fluid (CSF) flow disruption caused by the intracranial A surgical mass. biopsy Nonetheless, procedure through other causes of syringomyelia a rostrotentorial craniotomy(such and as breed-re- durectomy lated) could not be ruled out. was performed, and a sample of the mass from the temporal meninges and a fragment of A CSF temporal sample bone were was collected submitted forfrom the cerebromedullary histopathological study. cistern after brain MR imag- ing. Microscopic The analysisevaluation revealed revealed albuminocytologic dissociation: a diffuse thickening of the normal total nucleated dura mater cell with several count (TNCC) of 2 WBC/µL (reference range < 5 WBC/µL) with increased foci of chondroid metaplasia. Neoplastic cells were large with eccentric nuclei and packed total protein concentration cytoplasmic of 49.5 mg/dL granules. (reference The adjacent range