Introduction

Spinal choroid plexus tumors (CPTs), gliomas derived from the epithelium of the choroid plexus, account for ∼5% of primary brain tumors in dogs.^1,2 Primary CPTs are usually found in either the lateral, third, or fourth ventricles or the lateral apertures. CPTs can cause drop metastasis; in this scenario, tumor cells are disseminated or “dropped” via cerebrospinal fluid (CSF) flow in the ventricular system to the adjacent tissue in the brain or spinal cord.³ There are only three reports of spinal CPT in dogs.^4–6 All of these dogs were diagnosed at necropsy, and no follow-up or treatment was reported. This case report describes the clinical, histopathological, and imaging findings and long-term clinical outcome in a dog with a spinal CPT.

Case Report

Diagnostic Investigation

Results of complete blood count and serum biochemical analyses were unremarkable. Radiographs of the thoracolumbar spine revealed mild in situ disc calcification at the L1–L2 intervertebral disc space. Thoracic and abdominal radiographs were unremarkable. MRI of the thoracolumbar spine performed using an open system with a magnetic-field strength of 0.4 Tesla^a demonstrated an intradural-extramedullary mass lesion (2.4 × 5.4 × 5.7 mm) in the right dorsolateral aspect of the spinal cord at the level of T12 (Figures 1A–D) and extradural spinal cord compression at the left ventrolateral aspect of L1–L2 (Figures 1E, F). The intradural-extramedullary mass was hyperintense on T2-weighted images (T2WIs) and mildly hyperintense on T1-weighted images (T1WIs) compared with the spinal cord. Enhancement of the mass lesion was observed on T1WIs after IV administration of contrast medium^b (Figure 1D). On T2WIs, hyperintensity within the spinal cord and mild enlargement of the central canal were observed adjacent to the area of the mass lesion (Figure 1A). When compared with adjacent discs, hypointensity and subtle disc space narrowing of the L1–L2 intervertebral disc were observed on T2WIs. The extradural lesion was hypointense on T1WIs and T2WIs. Lumbar CSF collection was attempted, but no fluid could be obtained. MRI of the brain was not performed. The presumptive diagnosis was intradural-extramedullary spinal tumor (such as meningioma, malignant peripheral nerve sheath tumor, lymphoma, or metastatic tumors) and compressive intervertebral disc extrusion. The area of hyperintensity within the spinal cord was presumed to be intraparenchymal edema and inflammation associated with the mass lesion.

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Outcome

Pathologic evaluation of the mass yielded a histological diagnosis of CPT at the level of T12. Microscopically, the tumor consisted of delicate fibrovascular connective tissue fronds that were covered by a single or pseudostratified layer of cuboidal or elongated epithelial tumor cells with basally located monomorphic nuclei (Figure 2A). There was no evidence of mitotic activity (0/10 high-power fields) or necrosis, but foci of calcification were identified (Figure 2B). Immunohistochemical staining of the tissue was not performed. Spinal drop metastasis from a primary intracranial CPT was suspected. The extruded material at L1–L2 was diagnosed as nucleus pulposus.

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The dog regained DPP 1 day postoperatively and was paraplegic with intact DPP in both hind limbs and tail when discharged 7 days postoperatively. The dog was nonambulatory paraparetic 2 wk postoperatively and regained the ability to ambulate with support 2 mo postoperatively.

At 4 mo postoperatively, the dog was able to ambulate independently with normal conscious proprioception. A second MRI using a closed system with a magnetic-field strength of 1.5 Tesla^c was performed to evaluate the entire central nervous system (CNS). The MRI demonstrated a mass lesion (10.0 × 7.9 × 11.0 mm) within the right lateral aperture of the fourth ventricle (Figures 3A–C). The well-circumscribed mass was noted to be isointense on T1WIs, hyperintense on T2WIs, and hyperintense on T1WIs following IV contrast medium administration^b. On the basis of the location of the mass and history of the spinal CPT, the intracranial lesion was suspected to be a primary CPT. The owners declined further treatment, owing to the absence of clinical signs associated with the intracranial lesion.

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At 17 mo postoperatively, decreased postural reactions in both hind limbs and vision loss in the right eye were noted. A third MRI was performed, demonstrating an increase in size (21.2 × 18.5 × 21.9 mm) of the previously noted intracranial mass lesion (Figures 3D–F). The two follow-up extensive MRI studies at 4 and 17 mo postoperatively demonstrated no local recurrence of the spinal lesion at the level of T12 or metastasis in the entire CNS. CSF analysis was not performed in consideration of the risk of brain herniation. In accordance with the owner’s wishes, the dog was observed closely at home without treatment.

At 19 mo postoperatively, a telephone interview with the owner revealed that the dog went blind and gradually became unable to walk. The dog died at home at 25 mo postoperatively. The owners reported that the dog started to have episodes of generalized seizures 1 wk prior to the death. Necropsy was not performed.

Discussion

In human medicine, CPTs are classified according to the World Health Organization histopathological classification system as either grade 1 choroid plexus papillomas (CPPs) or grade 3 choroid plexus carcinomas (CPCs), with a much less common grade 2 atypical CPPs (APPs) added in 2007.⁷ In a meta-analysis of studies involving 98 dogs diagnosed with CPTs, 60% of tumors were classified as CPPs, 16% as CPCs, and 5% as APPs (19% CPTs lacked further differentiation).⁴ Another study involving 56 dogs with CPTs classified 36% as CPPs and 64% as CPCs, with none meeting the criteria for APPs.⁴ In the present case, the histopathological findings of the spinal tumor were similar to those of CPPs, and typical malignant signs of CPCs, such as nuclear pleomorphism, frequent mitoses, high nucleus-to-cytoplasm ratios, increased cellular density, and blurring of the papillary pattern with poorly structured sheets of tumor cells and necrotic areas, were not shown. However, the excised specimen from the spinal cord did not allow for assessment of “brain invasion,” which is one of the frank signs of CPCs described in the World Health Organization classification.^8,9 Because histopathological evaluation of the intracranial lesion was not performed, histopathological classification of the CPT in the present case is uncertain.

An increase in protein secretion into the CSF is commonly seen with CPTs in dogs, and CSF protein concentration is usually higher with CPTs compared with other canine brain tumors.^2,4 Westworth and others reported that the protein concentration in CPCs was significantly higher than in CPPs, and only CPCs had a protein concentration higher than 80 mg/dL.⁴ Although immunohistochemical criteria are insufficient to differentiate CPPs from CPCs, immunostaining with markers such as cytokeratin, vimentin, glial fibrillary acidic protein, S-100, Ber-EP4, Ki67/MIB-1, E-cadherin, and beta-catenin, Kir7.1, etc. have been shown to support a diagnosis of human and canine CPTs.^5,8–13 In particular, Kir7.1 is a reliable antibody for diagnostic confirmation of CPTs and highly specific for choroid plexus epithelium in dogs, and it allows for differentiation of CPTs from other primary or metastatic brain tumors, including metastatic carcinomas.^12,13 In veterinary and human medicine, prospective studies are needed to validate the use of immunohistochemistry as a prognostic indicator for patients with CPTs, as such information could be useful for diagnosis and as a basis for future immunotherapy trials. Routine cryopreservation of neoplastic tissue is desirable for future use.

The primary cause of the acute paraplegia in the dog was not determined, and it was unclear whether the spinal CPT resulted in the paraplegia. There was evidence of spinal cord edema and inflammation associated with the spinal CPT on MRI. However, the compression associated with the intervertebral disc extrusion was severe. Neurological deficits were symmetrical, and the cutaneous trunci reflex is not accurate enough to localize a lesion to a specific site in this dog.

In this case report, it was reasonable to assume that the spinal CPT metastasized from the mass lesion located at the right lateral aperture of the fourth ventricle. CPTs are found most frequently in the fourth ventricle; this site accounts for 46% of CPTs in dogs.⁴ There is only a single case report of a primary spinal CPP in human medicine.¹⁴ However, this is an unusual location for a primary CPT. Drop metastasis has been reported to be present at diagnosis in 21% of CPCs, 17% of APPs, and 5% of CPPs in human patients.⁹ In dogs, drop metastasis is seen in ∼50% of CPCs, and the phenomenon is rare in CPPs.^4,10,15 Spinal drop metastasis of CPTs has been described in human medicine.^16–18 A case series reported that 7 of 36 (19%) dogs with CPCs had evidence (gross, microscopic, or both) of spinal cord metastasis at necropsy.⁴ There are two case reports of spinal CPTs in dogs.^5,6 One report described a dog with MRI findings and histopathological diagnosis of lumbosacral spinal CPP.⁵ MRI and histopathological investigation of the brain were not performed in the dog. The other report described a dog with MRI findings (brain and thoracolumbar spine) and histopathological diagnosis of intracranial CPC with metastases to the cervical, thoracic, lumbar, and sacral spinal cord segments.⁶ Both cases were diagnosed at necropsy after euthanasia, and there was no follow-up or treatment. The long-term clinical outcome of spinal CPTs in dogs has not previously been reported.

The additional MRI of the entire CNS, performed on the basis of the histopathological diagnosis of the spinal CPT, detected the mass lesion in the brain that was presumed to be the primary CPT. The additional imaging findings helped us to predict the subsequent clinical signs associated with the brain tumor in the dog. Neuroimaging of the brain should be performed in dogs that are diagnosed with a spinal CPT because a primary CPT involving the spinal cord is quite rare. Assessment of the entire CNS is advocated for dogs and humans with CPT and should be performed in all patients diagnosed with a CPT with or without associated clinical signs.^6,16–18 Moreover, periodical follow-up examinations are advisable in order to detect local recurrence and drop metastasis.¹⁸

Decompressive surgery of the thoracolumbar spine via dorsolateral hemilaminectomy is commonly performed in dogs with intervertebral disc extrusion and spinal tumors.^19,20 Prophylactic fenestration was performed to prevent the future extrusion of disc material in the dog.¹⁹ In addition to providing a histopathological diagnosis of spinal neoplasia, cytoreductive surgery may result in an acute clinical benefit owing to spinal cord decompression.²⁰ Although most gliomas are not amenable to total resection and are prone to local recurrence, the absence of local recurrence on follow-up MRIs in the present case suggests that the spinal CPT was completely resected. In human medicine, spinal metastasectomy is often performed to improve quality of life in patients with CPP, and these patients are frequently treated successfully with resection alone.^16–18 Regardless of histopathological grading, gross total re-section is the most important prognostic factor in CPTs.¹⁸ In contrast, there are no reports of the long-term clinical outcome after canine spinal metastasectomy. Dogs with multiple neoplastic lesions in the CNS are frequently euthanized without histopathological diagnosis or assessment of treatment response. In the dog reported here, surgical resection of a presumptive CPT spinal drop metastasis resulted in 17 mo of relapse-free survival without local recurrence or the development of another metastatic lesion.

Conclusion

This is the first case report of surgical intervention and antemortem histopathological diagnosis of a spinal CPT in a dog with long-term follow-up provided. The case report suggests that surgical intervention could be beneficial in dogs with a CPT spinal drop meta-stasis.