An 11-year-old male Labradoodle presented on November 24, 2018, to his primary veterinarian for abnormal behavior over the preceding 24 h and suspected seizure activity. While at the clinic, the patient suffered a generalized tonic clonic seizure that was minimally responsive to diazepam and required administration of propofol. He was initially transferred to an emergency critical care facility and subsequently referred to Veterinary Neurology & Imaging of the Chesapeake for specialized care.

At the referral facility, neurological examination revealed cranial nerve deficits, left-sided vision loss, reduced and delayed postural reactions, left-sided ataxia, and dull mentation. An MRI performed on November 26, 2018, revealed a 4.6 × 2.5 × 2.0 cm mass in the right falx cerebri, compressing the right frontal olfactory bulb (Figure 1). The mass was initially suspected to be intra-axial. The patient was managed with prednisone and phenobarbital between diagnosis and surgery.

A transfrontal craniotomy was performed on December 18, 2018, along the right side of the frontal/olfactory bulb. Ultrasound was used to localize the abnormal tissue and associated cyst. An incision was made in the dura, and the mass along with the affected brain tissue was resected. The incision was closed with Gelfoam, and a fat graft was placed over the craniotomy site in the frontal sinus. The outer frontal bone was closed using polypropylene mesh.

The patient appeared to be recovering postoperatively, but began to decline 24 h later. A CT scan on December 20, 2018, revealed pneumocephalus, prompting a revision surgery to remove the air and reseal the frontal sinus and olfactory bulb. The patient then remained hospitalized for five more days before discharge.

At discharge, the patient’s neurological status was quiet but responsive to stimuli. He exhibited mild tetraparesis, right-sided pacing and circling, mild proprioceptive deficits in the left limbs, and an abnormal menace response in the left eye. He was discharged on prednisone, gabapentin, and phenobarbital as maintenance therapy.

Histopathological evaluation of the resected tissue showed polygonal neoplastic cells arranged predominantly in islands and whorls, with some sheeting. There was moderate mitotic activity, anisocytosis, and anisokaryosis, with large areas of necrosis present. No true invasion of neuroparenchyma was observed. The tumor was diagnosed as a meningothelial meningioma. However, the presence of necrosis, a sheet-like pattern, and moderate mitotic index warranted classification as a Grade II atypical meningioma (9).

Following surgery, the patient received immunotherapy with an autologous tumor cell lysate vaccine combined with toll-like receptor ligands. The vaccine was prepared by the University of Minnesota (10) using tumor tissue collected during surgery. The vaccine protocol, including the use of imiquimod, is described in Anderson et al. (10).

At the postoperative exam on December 31, 2018, the patient’s vision was noted to have improved, although right-sided pacing and circling persisted, and proprioceptive deficits in the left limbs remained. The first vaccine and imiquimod treatment were administered on January 14, 2019. Vaccinations continued at two-week intervals, with progressive neurological improvement. By the fifth vaccine, all neurological symptoms had resolved.

The patient experienced a brief seizure on March 1, 2019, which responded to an increase in prednisone and phenobarbital. Following stabilization, the patient resumed maintenance doses following initial stabilization. No further seizures occurred during vaccine treatment. On March 25, 2019, the patient presented for the sixth and final vaccine, but treatment was delayed due to a cough and diarrhea, which resolved with symptomatic therapy. The final vaccine was administered on April 1, 2019, at which time the neurological examination remained normal.

Attempts to taper prednisone, gabapentin, and phenobarbital followed. Seizure activity returned after dosage reduction, though episodes were brief and followed by rapid recovery. On May 6, 2019, phenobarbital was increased again, while tapering of gabapentin and prednisone continued. The final prednisone dose was administered at the end of May 2019.

A neurological exam on July 5, 2019, revealed recurrence of postural deficits in the left pelvic limb. After discontinuation of the vaccine series, seizures recurred approximately every 6–8 weeks. Based on these findings and the recommendation of Dr. Pluhar from the University of Minnesota, booster doses of the autologous lysate vaccine and imiquimod were administered. The owner noted a persistent cough and intermittent ataxia during this period. The second booster was administered on November 25, 2019. Thoracic radiographs were performed and were within normal limits for the patient’s age and breed. The third booster was given on January 20, 2020, with a normal neurological examination and no seizures reported since November 25, 2019.

Phenobarbital tapering was initiated on January 9, 2020, due to owner-observed side effect of lethargy. The patient’s disposition returned to the baseline prior to the onset of symptoms associated with the illness. However, two seizures occurred in March 2020, prompting the addition of levetiracetam on March 30, 2020. Neurological examination remained normal, although intermittent coughing persisted.

On July 8, 2020, the patient had one seizure between visits. Thoracic radiographs were repeated due to chronic coughing and revealed soft tissue masses throughout the lungs. The owner declined further diagnostics. Neurological findings were unchanged.

At a follow-up on September 25, 2020, neurological examination remained normal, although the cough persisted and labored breathing was noted. On December 17, 2020, the owner reported hindlimb weakness. Seizure activity remained minimal and appeared linked to missed anticonvulsant doses. Thoracic radiographs at that time showed progression of pulmonary masses. The patient relocated to Arizona in January 2021 and was euthanized on February 2, 2021, due to rapid neurological decline reported by the owner over the previous two weeks. A timeline of the patient’s history is shown in Figure 2.

Necropsy was performed at Midwestern University Diagnostic Pathology Laboratory. The patient was in poor body condition. A focal area of missing frontal bone rostral to the sagittal crest was noted. Upon opening the skull, a flexible gray mesh was found beneath dense connective tissue and overlying a yellow-tan fibrous plate at the level of the frontal sinuses. Beneath this plate was a friable, white-tan mass extending from the olfactory bulbs into both nasal canals and turbinates (Figure 3A).

Six smooth, white-tan nodules were found in the left lung lobes; the right lung lobes were unaffected (Figure 3B). The abdominal cavity contained approximately 50 mL of serosanguinous fluid. Numerous firm white-tan nodules were present throughout the omentum. The liver was infiltrated with hundreds of multifocal, slightly raised white-tan masses. A large, multilobulated white-tan mass was found in the right limb of the pancreas (Supplementary Figure 2A), while the left limb appeared nodular. Similar nodules were found in the spleen, adrenal glands, kidneys, stomach, and omentum.

Impression smears of a lung mass showed high cellularity with mild to moderate blood contamination on a pale eosinophilic background. Spindle-shaped cells, found singly, in streaming aggregates, and occasional whorl-like formations, measured 7–9 μm in width and 50–80 μm in length (Supplementary Figure 1). Cells had moderate N: C ratios, mild to moderate anisocytosis and anisokaryosis, moderate pale basophilic cytoplasm (sometimes containing coarse magenta granules), and centralized oval nuclei with smooth to finely stippled chromatin, and 1–2 distinct nucleoli. Occasional binucleated and rare multinucleated cells were present, with rare mitotic figures. Focal lymphoplasmacytic and macrophagic infiltrates were noted, as well as rare columnar epithelial cell clusters. Findings supported a malignant neoplasm, with differential diagnoses of metastatic meningioma or sarcoma.

Histopathology of the recurrent intracranial and nasal mass showed streams, whorls, and pseudorosettes of spindlyloid to polygonal cells with low mitotic activity, moderate to marked anisocytosis, and mild anisokaryosis, invading the olfactory bulbs (Figure 4A). Pulmonary masses exhibited similar morphology (Figure 4B). Compared to the original tumor, the recurrent intracranial mass had a lower mitotic index, more spindly cells, and clear evidence of tissue invasion.

Histopathology of the pancreatic mass revealed polygonal neoplastic cells in sheets, acini, and islands, with marked anisocytosis, moderate anisokaryosis, a high mitotic rate, and large areas of coagulative necrosis. Similar lesions were observed in the heart, liver, kidneys, spleen, adrenal glands, stomach, and small intestines (Supplementary Figure 2B).

Immunohistochemistry (IHC) was used to differentiate between metastatic meningioma and pancreatic adenocarcinoma in the lungs. Vimentin showed strong positive staining in 60–80% of neoplastic cells in the lungs (Figure 4C) and intracranial mass. Cytokeratin showed mild to moderate reactivity in 60–70% of pancreatic tumor cells (Supplementary Figure 2B), 10–15% of liver cells, and none of the pulmonary neoplastic cells (Figure 4D). S100 was negative with nonspecific background staining in all tissues.

Based on histopathological and IHC findings, the patient was diagnosed with a recurrent and metastatic intracranial meningioma with pulmonary involvement, as well as a separate pancreatic carcinoma with widespread metastases.