Optic Chiasm and Bilateral Optic Nerve Oligodendroglioma in A 29‐Month‐Old German Shepherd

ABSTRACT

Objective

To report the first documented case of high‐grade optic chiasm and nerve oligodendroglioma in a young dog and contribute to the comparative study of gliomas in humans and canines.

Animal Studied

A 29‐month‐old male intact German Shepherd.

Procedures

Over 2 months, the patient underwent repeated physical and ophthalmic examinations, systemic health assessments (complete blood count, serum biochemistry, urinalysis, and infectious disease testing), anesthetized MRI, ultrasound‐guided biopsy of the left retrobulbar mass, and necropsy. Histopathologic and immunohistochemical analyses, including OLIG2 and GFAP immunohistochemistry, were performed.

Results

MRI evaluation identified a large, lobulated, asymmetric mass with retrobulbar involvement and compression of the optic chiasm and optic nerves. The mass exhibited hyperintense signals on T2‐weighted and T2‐FLAIR sequences, mixed intensity on T1‐weighted imaging, and heterogeneous contrast enhancement, with areas of necrosis and meningeal enhancement suggestive of an aggressive neoplasm. Gross necropsy findings and histopathologic examination of post‐mortem tissues confirmed the diagnosis of a high‐grade oligodendroglioma, with tumor cells demonstrating marked nuclear atypia, high mitotic activity, and OLIG2 nuclear immunoreactivity.

Conclusions

The tumor's localization and histological characteristics suggested a primary origin within the optic pathway, differing from typical canine oligodendrogliomas. This case emphasizes the rarity of canine optic pathway oligodendrogliomas, a diagnosis that is similarly uncommon in human medicine. Dogs have been proposed as an intermediate animal model for human gliomas, and this case underscores the need for further molecular characterization of canine gliomas to improve diagnostic accuracy, therapeutic strategies, and comparative oncology insights.

1. Introduction

Gliomas in dogs are common primary neoplasms of the central nervous system (CNS), mainly affecting aged patients and brachycephalic breeds [1]. These tumors arise from non‐neuronal tissue of the CNS and are classified according to their cell of origin: astrocytomas, oligodendrogliomas, and undefined tumors [2, 3]. Astrocytomas and oligodendrogliomas are the most reported, each having an overall incidence of about 15% of all primary tumors, and mainly arise from the white or gray matter of the cerebral hemispheres—rarely the optic pathway [1]. Between 1972 and 2025, there have only been a handful of reports of astrocytomas [4, 5] and undefined gliomas [6, 7, 8] arising in the canine optic nerve and/or retina. Outside of these reports, a pathology collection containing 4941 canine ocular neoplasms found the incidence of primary astrocytomas or oligodendrogliomas in the retina, optic nerve head, and/or optic nerve to be just 0.36%. In contrast, the incidence of meningioma, the most common optic nerve neoplasm, was 1.7%. Of the already rare optic pathway gliomas reported in this ocular pathology collection, only one was an oligodendroglioma [9]. This unilateral retinal and distal optic nerve oligodendroglioma—diagnosed in an enucleated globe of a 9‐year‐old female spayed dog—is the sole case of a primary ocular oligodendroglioma reported anywhere in current literature.

The existing classification system for canine gliomas was published in 1999 [2]. To improve existing glioma classification methods—by creating a more complete histologic atlas and yielding greater harmonization of phenotypic characterization between canine and human gliomas—a revised diagnostic classification system was published in 2018 [3]. Following the revised classification system, this case report describes the clinical, gross pathologic, histopathologic, and immunohistochemical features of a rare primary optic chiasm and nerve high‐grade oligodendroglioma in a young German Shepherd.

2. Case History

A 35‐kg, 29‐month‐old, male intact German Shepherd was referred to the ophthalmology service of North Carolina State University College of Veterinary Medicine (NCSU CVM) for evaluation of acute blindness. A week before presentation, the dog began bumping into items due to peripheral vision loss. Four days later, transient left eye chemosis developed and resolved before evaluation by the referring veterinarian. A physical exam revealed bilaterally absent menace responses and palpebral reflexes; the dog was referred to NCSU CVM on the same day for evaluation.

During physical examination, the dog was bright, alert, responsive, aggressive, and in good body condition. History revealed normal appetite, drinking, urination, defecation, and activity level. The dog was not current on preventatives, was receiving no medications, and had no previous history of ocular issues. Ophthalmic examination was performed by a board‐certified ophthalmologist, including slit lamp biomicroscopy, indirect fundoscopy, and rebound tonometry. Schirmer tear tests and fluorescein staining were not completed due to the patient temperament. Ophthalmic examination revealed dilated and minimally responsive pupils in both eyes (OU), absent menace responses and dazzle reflexes OU, and present palpebral and vestibulo‐ocular reflexes. Intraocular pressures (Icare Tonovet, Icare) were 21 mmHg in the right eye (OD) and 21 mmHg in the left (OS). Indirect fundoscopy revealed a prominent optic nerve head OS. No additional ocular abnormalities were noted. A mixed rod/cone electroretinogram (ERG; RETIport, Roland Consult) performed at 3.0 cd s m⁻² following 10 min of dark adaptation revealed within normal limits b‐wave amplitudes: 215 mV OD and 94 mV OS. NCSU CVM Neurology consultation revealed no significant abnormalities. Based on exam findings, bilateral vision loss was localized to the optic nerves and chiasm.

Complete blood count (CBC), serum biochemistry profile, urinalysis, infectious disease testing, and advanced imaging were recommended. All except imaging were initially performed. The dog was started on oral (PO) medications: prednisone 1.16 mg/kg once daily, clindamycin 13 mg/kg twice daily, and doxycycline 5 mg/kg twice daily. CBC revealed a mild monocytosis (1.188 × 10³ /UL; RI: 0.075–0.850) and eosinophilia (1.307 × 10³ /UL; RI: 0.030–1.264). The serum biochemistry profile was unremarkable. Urinalysis via cystocentesis showed 1+ protein, trace ketones, 2+ bilirubin, and 3+ blood. Enzyme‐linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA) for common infectious agents (Dirofilaria immitis, Ehrlichia canis, Ehrlichia ewingii, Ehrlichia chaffeensis, Anaplasma phagocytophilum, Anaplasma platys, Borrelia burgdorferi, Neospora caninum, and Toxoplasma gondii) were all negative. Subsequent exams approximately every 2 weeks showed no improvement in vision, and clinical signs progressed to include multifocal hypopigmented retinal folds in the non‐tapetal fundus OU, optic nerve head swelling OU with hemorrhage OS, superficial corneal ulcers OU, and exophthalmos OS (Figure 1). Due to the progression of disease over approximately 2 months, advanced imaging was pursued.

FIGURE 1.

Clinical photograph showing significant exophthalmos OS, superficial corneal ulcers OU (fluorescein stain positive) and mydriasis OU.

Premedication included 30 mcg/kg of dexmedetomidine per rectal, followed by intravenous (IV) catheter placement and administration of butorphanol 0.4 mg/kg and maropitant citrate 1.0 mg/kg IV. Anesthesia was induced with propofol 2.6 mg/kg IV. The dog was intubated with a 14 mm endotracheal tube, and anesthesia was maintained via 1.5% isoflurane and oxygen.

A 3 Tesla MRI scanner (MAGNETOM Skyra, Siemens) and 18‐channel knee coil were used for image acquisition; a web‐based DICOM viewer—eUnity (Mach 7 Technologies, Burlington, VT, USA) was used for image interpretation. Images were acquired in transverse, sagittal, dorsal, and dorsal oblique (optimized for the optic nerve) planes. Pre‐contrast sequences included T2‐weighted, T2 FLAIR (Fluid‐Attenuated Inversion Recovery), T1 FLAIR, T2‐SWI (Susceptibility Weighted Imaging), DWI (Diffusion‐Weighted Imaging) and T1 3D MPRAGE (Magnetization‐Prepared Rapid Gradient Echo).

The MRI revealed a large extracranial and intracranial extra‐axial mass, significantly affecting the left retrobulbar area (Figure 2A). The intracranial portion of this lobulated and asymmetric mass was centered at the middle and rostral cranial fossa, extending caudally into the pituitary fossa (Figure 2B). It caused a significant mass effect in the right cavernous sinus region (Figure 3E), while extending rostrally and causing significant expansion of the right orbital fissure (Figure 3C). While dorsally displacing the optic chiasm, it also extended rostrally through the optic canals, leading to a large left conical retrobulbar mass effect, with only mild extension to the right retrobulbar region (Figure 3B). The left optic nerve displayed a mild, indistinct enlargement in its mid retrobulbar section, while the right appeared normal (Figure 4). The mass was hyperintense on T2w, T2‐FLAIR, and showed mixed intensity on T1w images, relative to the brain tissue and extraocular muscles. It demonstrated marked heterogeneous contrast uptake mostly in the intracalvarial, canalicular, and retrobulbar areas, with central non‐enhancing regions suggestive of necrosis, particularly in the left retrobulbar area (Figure 3A–E). There was also notable meningeal enhancement, appearing as a circumferential dural tail (Figure 3D). The left extraocular muscles showed significant enhancement and enlargement, though differentiation from the mass was challenging due to border effacement (Figures 3B and 4B). SWI data identified pronounced susceptibility artifacts, including a large amorphous area within the left extracranial portion of the mass corresponding to non‐enhancing regions, suggestive of hemorrhage and/or mineralization. DWI/ADC (Apparent Diffusion Coefficient) maps showed complex diffusion characteristics within the mass, suggesting areas of restricted diffusion (indicating cytotoxic edema or infarction) and hemorrhage (Figure 5). Mild left mandibular and medial retropharyngeal lymphadenopathy was also identified. Overall, findings were consistent with a highly aggressive and invasive mass primarily impacting the right cavernous sinus and extending into orbital and retrobulbar areas, worse on the left. Based on the imaging features, differentials included orbital meningioma, peripheral nerve sheath tumor, round cell neoplasia, or a high‐grade glial cell tumor.

FIGURE 2.

3D volume renderings of T2‐weighted dorsal plane MRI. Insets show the precise imaging plane for each image. (A) Sequence optimized for the optic nerve. Black arrows delineate the approximate margins of the conical mass, showing its left retrobulbar, canalicular and intracranial extent, as well as the resultant significant left exophthalmos. (B) Standard sequence with histogram adjustments highlighting the mass. White arrows indicate the mass margins, including intracranial extension and involvement of the contralateral right orbital fissure.

FIGURE 3.

T1‐weighted post‐contrast reformatted slices (0.7 mm thickness). The top series is a transverse plane sequence through the mass at the following locations: (A) retrobulbar, (B) just cranial to the optic canal, (C) optic chiasm, (D) just cranial to the orbital fissure, and (E) the intracranial component at the pituitary level. The bottom series (F‐J) shows corresponding sagittal reference frames. The mass demonstrates marked heterogenous contrast enhancement overall, with central non‐enhancing regions suggestive of necrosis, particularly a large retrobulbar area. Asterisk in (D) indicates a dural tail sign, consistent with meningeal enhancement.

FIGURE 4.

High‐resolution images focused on the optic nerve with insets showing the exact imaging plane. (A) T2‐weighted dorsal plane image optimized for the optic nerve. Small white arrows outline the retrobulbar portion of the mass encasing the optic nerve, which displays a focal, ill‐defined hypointense thickening mid‐aspect. (B) T1‐weighted post‐contrast dorsal plane image optimized for the optic nerve, acquired at a level just dorsal to (A). Small black arrows trace the enhancing retrobulbar portion of the optic nerve sheath complex extending towards the optic chiasm.

FIGURE 5.

MRI susceptibility and diffusion sequences at the retrobulbar (A–C) and pituitary (D–F) levels. (A) Susceptibility‐weighted image (SWI) reveals an amorphous area of susceptibility artifact (white long arrow), suggestive of hemorrhage and/or mineralization. (B) Diffusion‐weighted image (DWI) and (C) corresponding apparent diffusion coefficient (ADC) map demonstrate complex diffusion characteristics, including areas of significantly restricted diffusion (dotted black lines). (D) SWI shows ill‐defined, tubular to coalescing nodular areas of susceptibility artifact (black long arrow), suggestive of hemorrhage and/or mineralization. (E) DWI and (F) corresponding ADC map indicate complex diffusion characteristics with areas of mildly restricted diffusion (dotted white lines).

The patient, still maintained on isoflurane, was transferred for biopsy. Two ultrasound‐guided left retrobulbar mass biopsies were collected using a 16 g Tru‐cut biopsy needle and were fixed in 10% neutral buffered formalin. Histologic evaluation revealed an atypical spindle cell proliferation. Immunohistochemistry was not pursued at the time of biopsy. Due to the advanced disease noted on MRI and inconclusive biopsies, the owner elected euthanasia followed by necropsy. Gross postmortem examination revealed a 3 cm in diameter mass extending from the left optic chiasm to the retrobulbar tissue (Figure 6A). On cut surface, the mass was firm, white to tan, with scattered dark red to brown foci and occasional mineralization (Figure 6B). The globe was shrunken and irregular, with corneal ulceration and complete optic nerve effacement by the tumor, but no invasion into the globe itself. Top differentials based on the mass's gross appearance and location included peripheral nerve sheath tumor, retrobulbar meningioma, rhabdomyosarcoma, and other neoplasms. Histologic evaluation of postmortem tissue revealed dense sheets of round cells with round nuclei and a clear, non‐staining perinuclear halo. The cells markedly expanded the retrobulbar skeletal muscle, effaced the optic nerve, and obscured the optic chiasm (Figure 6C), more severely on the left than the right. Small numbers of cells infiltrated into the overlying hypothalamus. Round cells were often supported by branching capillaries and a mucinous stroma (Figure 6D). The mitotic count was 3 in 2.37 mm². Extensive areas of necrosis, microvascular proliferation, and occasional reactive fibroplasia were present. Neoplastic cells exhibited robust nuclear immunoreactivity to oligodendrocyte transcription factor 2 (OLIG2) in approximately 40%–50% of the cells (Figure 6D inset), with no cytoplasmic immunoreactivity to glial fibrillary acidic protein (GFAP). OLIG2 and GFAP immunohistochemistry were retrospectively applied to the biopsy sample after postmortem examination, and scattered atypical cells revealed weak nuclear reactivity to OLIG2 but no cytoplasmic immunoreactivity with GFAP.

FIGURE 6.

(A) Dorsal brain with left globe and periorbital tissue attached. The retrobulbar soft tissue extending ventrally to the optic chiasm is markedly expanded by a firm neoplasm (asterisk). (B) Formalin‐fixed, cut surface of the left whole globe and the associated retrobulbar mass. The mass (asterisk) is firm, white to tan, with scattered dark red to brown foci and occasional mineralization. The globe was shrunken and irregular, with corneal ulceration and complete effacement of the optic nerve by the neoplasm, but no invasion into the globe itself. (C) Optic chiasm and nerve. The optic chiasm and nerve are markedly infiltrated by abundant sheets of the neoplastic cells (asterisk) with extension and marked expansion of the adjacent meninges (arrowhead). Hematoxylin and eosin (HE) stain. (D) Optic nerve oligodendroglioma. The neoplasm is composed of dense sheets of round cells with round nuclei and a clear, non‐staining perinuclear halo. Round cells are often associated with microvascular proliferation and a mucinous stroma. HE stain. Inset: Optic nerve oligodendroglioma. Neoplastic cells demonstrate robust intranuclear immunoreactivity to OLIG2. OLIG2 immunohistochemistry.

Together, histologic cellular morphology and immunohistochemistry results were most consistent with an oligodendroglioma. Due to the microvascular proliferation, large areas of necrosis, and mitotic count, this tumor was classified as a high‐grade oligodendroglioma. Other histologic findings included secondary superficial keratitis, corneal erosion, and a diaphanous‐type hepatocellular vacuolation presumably due to oral glucocorticoid administration. No evidence of metastasis was observed.

3. Discussion

We report a rare case of a young dog with a high‐grade oligodendroglioma mainly affecting the optic chiasm and left optic nerve, causing a significant left‐sided retrobulbar mass effect. Neoplastic cells were observed invading into the retrobulbar skeletal muscle and hypothalamus; however, cellular invasion into the retina and other brain parenchyma was not noted. This is unusual, as canine oligodendrogliomas typically originate within the cerebrum and rarely metastasize or spread beyond local tissue invasion [10]. Though primary CNS oligodendroglioma spread to the meninges or ventricles has been reported in dogs [10], there is only one case of a canine intracranial oligodendroglioma infiltrating the optic nerve and rare reports of primary optic nerve oligodendrogliomas extending into the cranial vault to the level of the optic chiasm [7, 11]. The lack of significant intra‐axial involvement, in conjunction with the clinical presentation of acute bilateral blindness without other apparent neurological signs in our patient, suggests that this tumor originated within the optic pathway, consistent with a primary optic chiasm and nerve oligodendroglioma. Leptomeningeal gliomatosis has been reported in canines [12] and was considered as a differential for this case as significant meningeal spread was noted on MRI, suggesting the oligodendroglioma could have originated from the leptomeninges. However, histology did not support this differential, as neither restricted nor disseminated subarachnoid infiltration by sheets of neoplastic glial cells was observed. Given this negative finding, the neoplasm in this case is considered to have originated from the optic chiasm and nerve.

In humans, gliomas are the most common tumor of the optic nerve and primarily affect children [13], with one study reporting a mean age of 10.9 years old [14]. However, these pediatric cases are overwhelmingly benign astrocytomas [13], and very few cases of optic nerve oligodendrogliomas have been reported. Only five cases (three of which are pediatric) have been described in the current literature [15, 16, 17, 18, 19], demonstrating that optic pathway oligodendrogliomas are rare in both human and veterinary medicine; of these human case reports, only two involve the optic chiasm [15, 17]. The young age of the dog in this case report draws further parallels to the pediatric cases in human literature.

As suggested by Naranjo et al. [9] and this case study, the metastatic potential of canine ocular gliomas appears low. This is similarly reported in human cases, where malignant optic gliomas are rare occurrences seen almost exclusively with either high‐grade astrocytoma or glioblastoma [20]. Evidence regarding the metastasis of optic pathway oligodendrogliomas, specifically, is limited to the outcomes of the five human case studies previously referenced. In these reports, only one case, a pediatric patient, demonstrated metastasis via cerebrospinal fluid dissemination [15]. However, the limited number of cases makes it difficult to assess the metastatic and prognostic indicators of optic pathway oligodendrogliomas specifically. For oligodendrogliomas as a whole, extra‐CNS or leptomeningeal metastasis is rare in humans, and both are associated with later stages of disease [21].

In human medicine, the vast majority of oligodendrogliomas are diffusely infiltrative within brain tissue, though they may have sharp borders with the surrounding neuroparenchyma. Treatment recommendations have changed in recent years and depend on tumor grade and location, but in all cases, surgical resection (to the extent possible given tumor location) is considered standard of care; more recent studies have shown that following surgical resection, adding chemotherapy such as temozolomide or a combination of procarbazine, lomustine, and vincristine to radiation therapy benefits overall survival [21]. Total surgical resection is associated with significantly improved survival times compared to partial or no surgical resection, but the extent of treatment is limited by tumor location [22]. In the case of human optic pathway gliomas, treatment in the form of chemotherapy and/or radiotherapy is common to combat progressive damage and visual deficits [23]. Regardless of treatment, patients with gliomas limited to the optic nerve or chiasm have significantly longer overall survival than those with intra‐axial gliomas. Chiasmal gliomas with involvement of adjacent brain structures, however, are associated with higher mortality compared to those limited to the optic pathway [14].

There is no literature describing treatment of optic pathway gliomas in canine patients as all cases with reported outcomes proceeded with palliative care or humane euthanasia [9]. When reviewing cases of both high‐ and low‐grade canine intracranial oligodendrogliomas, chemotherapy, surgery, or a combination of both were the most common modalities used when treatment was pursued. Definitive treatment resulted in significantly longer median survival time (MST) than palliative treatment (MST of 84 versus 26 days) [24].

Oligodendrogliomas of the optic pathway are rare neoplasms for humans and canines alike, and our patient represents only the second such canine case reported and the first in a dog of such young age. It is unclear to what extent these rare optic pathway oligodendrogliomas share molecular, etiologic, or prognostic traits with their intracranial counterparts. In 2016, the WHO updated their guidelines for the diagnosis of human CNS tumors, resulting in a classification system now based primarily on molecular characteristics as opposed to histology and morphology [25]. In human medicine, classification of gliomas is based on the presence of specific gene mutations and deletions: 1p/19q codeletion and mutation of isocitrate dehydrogenase 1 or 2, in the case of oligodendrogliomas. This specificity allows for better informed treatment outcomes and prognoses. While similar large scale genetic analysis of canine gliomas has yet to be performed, authors of the newly revised canine classification system believe such research into molecular biomarkers is an important next step to facilitate better characterization of canine gliomas and improved use of dogs as translational preclinical models for humans [3]. Analysis of molecular genotyping data, as has been done in humans, may allow for improved diagnosis, prognosis, and treatment plans for our veterinary patients.

Disclosure

The authors declare no conflicts of interest regarding this article.

Ethics Statement

This study complies with the Guidelines for Ethical Research in Veterinary Ophthalmology (GERVO) and is exempt from approval by an ethics committee.

Consent

Animal owners or owners' representatives provided written consent for the treatment provided and for the publication of data and images.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.