History
A 20-month-old 35-kg neutered male German Shepherd Dog was presented to the Cornell University Hospital for Animals Neurology service for evaluation of chronic, progressive ataxia and paraparesis. The clinical signs began approximately 10 months prior and were characterized by intermittent dragging predominantly of the right hind limb. This progressed to consistent dragging and knuckling of both hind limbs and perceived spinal pain. Lumbar spinal radiographs through the referring veterinarian yielded no significant findings. The patient was prescribed deracoxib and gabapentin (unknown dosages) and was instructed to strictly cage rest for 4 to 6 weeks. The patient experienced progression of clinical signs so he was referred for further evaluation. Physical examination findings were not significant with the exception of moderate muscle atrophy of the right hind limb. A neurologic evaluation was performed with results as follows.
Assessment
Anatomic diagnosis
The dog’s abnormal postural reactions in the pelvic limbs, with the right side worse than the left, combined with clinically normal spinal reflexes were suggestive of right-lateralized T3 through L3 myelopathy. Progressive ambulatory paraparesis was consistent with T3 through L3 myelopathy or, less likely, disease bilaterally affecting L4 through S3 spinal cord segments and associated nerve roots, neuromuscular junctions, or muscles. Proprioceptive ataxia of the pelvic limbs with the right side worse than the left suggested T3 through L3 myelopathy or, less likely, disease bilaterally affecting L4 through S3 spinal cord segments and associated nerve roots. Generalized hind limb muscle atrophy affecting the right side more than the left suggested disuse atrophy secondary to T3 through L3 myelopathy or, less likely, neurogenic or secondary to myopathy. Signs of pain elicited on palpation of the cranial aspect of the lumbar portion of the vertebral column were consistent with cranial lumbar region (eg, T3 through L3) myelopathy or, less likely, focal myopathy or referred pain (eg, from other spinal cord segments or the abdomen).
Likely location of the lesion
Paraparesis and abnormal postural reactions with clinically normal reflexes in the pelvic limbs and clinically normal thoracic limbs were consistent with a lesion affecting the T3 through L3 spinal cord segments. The finding of the right hind limb being more affected than the left hind limb supported a right-lateralizing process.
Etiologic diagnosis
Differential diagnoses for a chronic, progressive, painful, right-lateralized, T3-L3 myelopathy in a young dog included neoplasia (with spinal nephroblastoma as the top differential), an immune-mediated inflammatory disorder (meningomyelitis of unknown etiology), or an infectious process causing meningomyelitis (such as diskospondylitis, Neospora spp, or Toxoplasma gondii). A congenital or anomalous process, such as vertebral malformation or a subarachnoid diverticulum, could be suspected given the patient’s young age, though typically these disorders are not painful. Finally, intervertebral disc herniation would follow the finding of pain shown in this case, but would be unlikely given this patient’s age and the slow progression and chronicity of signs. The moderate generalized muscle atrophy of the right hind limb was suspected to be secondary to chronic disuse. To evaluate these differential diagnoses, a routine hemogram (CBC), chemistry panel, urinalysis, lumbar spinal radiographs, thorax and abdominal CT, T3 through sacrum magnetic resonance imaging (MRI; 1.5 Tesla Toshiba Vantage Atlas), and lumbar cerebrospinal fluid (CSF) tap were performed.
Diagnostic test findings
Bloodwork revealed a mild hypercalcemia (11.2 mg/dL; reference range 9.4 to 11.1 mg/dL). Referral lumbar radiographs were negative for bony proliferative or lytic lesions. MRI revealed a large solitary, right-sided, intradural-extramedullary mass at the level of L1 causing severe compression of the spinal cord at this region. The mass was T2 hypointense, T1 isointense, and strongly contrast-enhancing (Figures 1–3). Regionally, the spinal parenchyma surrounding the mass from the level of T8 through L3 demonstrated T2 hyperintensity without contrast enhancement and this was prioritized as edema associated with the mass lesion. CT (Toshiba Aquilion-LB 16 slice) performed following MRI confirmed an intradural-extramedullary spinal cord mass at the level of L1 with no evidence of thoracic or abdominal metastasis, though mild left axillary lymphadenopathy of questionable significance was present. Lumbar CSF analysis demonstrated mild mononuclear pleocytosis (total nucleated cell count, 7 cells/µL; reference range, < 5/L; RBC count, 0 cells/µL; reference range, < 5/µL) with high total protein (90 mg/dL; reference range < 45 mg/dL), and lymphocytes were the dominant cell population (61% of the sample).
Sagittal-cut T2-weighted MRI image demonstrating a focal mass at the level of L1. The mass is hypointense in this sequence.
Citation: Journal of the American Veterinary Medical Association 261, 4; 10.2460/javma.22.07.0309
Sagittal-cut T1-weighted with contrast MRI image demonstrating a focal mass at the level of L1. The mass is demonstrating strong contrast enhancement.
Citation: Journal of the American Veterinary Medical Association 261, 4; 10.2460/javma.22.07.0309
Transverse-cut T1-weighted with contrast MRI image demonstrating a focal mass at the level of the caudal endplate of L1. The mass is demonstrating strong contrast enhancement.
Citation: Journal of the American Veterinary Medical Association 261, 4; 10.2460/javma.22.07.0309
Based on history, physical exam, neurological exam, and diagnostics, the patient had a focal intradural-extramedullary mass at the level of L1 that caused a chronic, progressive, painful, right-lateralizing T3-L3 myelopathy for which our top differential diagnosis was a spinal nephroblastoma. The CSF tap revealed lymphocytic pleocytosis and hyperproteinemia, indicating neurovascular inflammation that could be consistent with tumor compression or less likely could be due to another inflammatory process. The CT revealed mild left axillary lymphadenopathy that was believed to be an incidental finding. Bloodwork revealed mild hypercalcemia that could be supportive of a neoplastic process due to hypercalcemia of malignancy or could be due to another cause, such as a spurious result or a normal variant for this patient.
Definitive diagnosis and treatment of spinal nephroblastoma rely on surgical cytoreduction of the tumor and submission for histopathology. A dorsal laminectomy of L1 and L2 was performed to excise the tumor. Once durotomy was performed and the tumor was visualized, it became evident that the tumor was fatty-textured, lobulated, and friable with a dark red color. The tumor looked to have invaginated into the spinal cord parenchyma, thus appearing to have an invasive intramedullary component. This differed from what was expected from the MRI, where the tumor looked largely extramedullary, but is a documented occurrence with this tumor type.1 Tumor histopathology confirmed the diagnosis of ectopic nephroblastoma.
Comments
Spinal nephroblastoma is a rare congenital neoplasm of dogs arising from ectopic embryonal kidney cells.1,2 During development these cells are theorized to aberrantly migrate to the meninges, where they undergo neoplastic transformation to become nephroblastomas. These tumors typically occur in young dogs between 6 months and 2 years old and studies have shown an overrepresentation of this tumor type in German Shepherd Dogs and Golden Retrievers, though other breeds are reported.2 There are less than 60 cases reported in the veterinary literature, and as such, treatment standards, prognosis, and outcomes are highly variable.2
Diagnosis relies on adequate history, physical exam, neurologic exam, and advanced imaging modalities.1 On diagnostic imaging, these tumors are typically found between thoracic vertebra 10 (T10) and lumbar vertebra 3 (L3) and predominantly have an intradural-extramedullary localization, although they can be infiltrative into the spinal cord parenchyma.1,2 MRI is the preferred diagnostic tool to characterize these tumors due to its greater sensitivity in evaluating the neuroparenchyma compared to other imaging modalities.3 A CSF analysis is usually unrewarding and characterized by non-specific evidence of inflammation (mild pleocytosis and mildly elevated total protein), consistent with the CSF findings of the case presented here.2 Histopathologic staining can be helpful in differentiating spinal nephroblastomas from other intradural spinal tumors. Staining for Wilms’ Tumor (WT)-1 antigen, a protein derivative of the WT-1 gene, is currently used to positively diagnose spinal nephroblastomas in humans (also called Wilms’ tumor), and some studies have productively used it to diagnose dogs.2 This tumor type is rarely locally invasive or metastatic, although there have been reports of metastasis to the caudal vena cava, multifocally within the spinal cord, and mediastinal lymph nodes, among other locations.2,4
Treatment options include surgical cytoreduction, radiation therapy, and palliative medical management. Surgical cytoreduction accomplishes decompression of the spinal cord and tumor excision for histopathological submission, although some of the tumor may be left behind on a microscopic level.1 Surgery has a mean survival time that is highly variable in the literature, ranging from a few months to 3 years (MST 374 days, sample size 9 dogs [1]; MST 70.5 days, sample size 11 dogs [2]). Radiation therapy used specifically for spinal nephroblastomas is not well characterized in the literature, but some articles suggest it is most beneficial when paired with cytoreductive surgery; one case study5 in particular documents a patient that survived over 5 years post-surgery and radiation therapy, and was ultimately euthanized due to radiation site complications. Anecdotally, survival time with surgery and radiation therapy may be better than what is currently reported in the literature, and further studies with greater case numbers are needed to determine the best treatment modality and expected outcome for these cases. The use of and outcome for chemotherapy in these patients has not been well-described. Palliative care involving medical management with steroids or NSAIDs results in a survival time of days to weeks (MST 55 days, sample size 2 dogs1). Large-scale, case-control studies are warranted in this area to better characterize the pathophysiology, treatment, and prognosis of spinal nephroblastomas in dogs.
The patient highlighted in this report recovered well post-operatively and was discharged from the hospital 5 days later at its pre-operative neurologic status, characterized by ambulatory paraparesis. However, the patient experienced multiple complications following surgery and discharge, including surgical site dehiscence with suspected incisional infection in addition to right coxofemoral luxation. The dehiscence required surgical revision, while the hip luxation was treated simultaneously with closed reduction and an Ehmer sling. The patient had consulted with an oncology service to pursue radiation therapy but was unable to begin treatment due to the complications. The patient was eventually presented through a separate emergency service for euthanasia following acute worsening with inability to walk and concern for quality of life. Re-luxation of the hip was strongly suspected but could not be confirmed prior to euthanasia. Given the patient’s complications, it is unknown if further neurologic improvement would have been achieved with time and radiation therapy, or what survival time may have been without these complications. The patient lived 45 days from time of diagnosis to euthanasia.
References
- 1.↑
Liebel FX, Rossmeisl JH Jr, Lanz OI, Robertson JL. Canine spinal nephroblastoma: long-term outcomes associated with treatment of 10 cases (1996–2009). Vet Surg. 2011;40(2):244–252. doi:10.1111/j.1532-950X.2010.00789.x
- 2.↑
Brewer DM, Cerda-Gonzalez S, Dewey CW, Diep AN, Van Horne K, McDonough SP. Spinal cord nephroblastoma in dogs: 11 cases (1985–2007). J Am Vet Med Assoc. 2011;238(5):618–624. doi:10.2460/javma.238.5.618
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Besalti O, Caliskan M, Can P, Vural SA, Algin O, Ahlat O. Imaging and surgical outcomes of spinal tumors in 18 dogs and one cat. J Vet Sci. 2016;17(2):225–234. doi:10.4142/jvs.2016.17.2.225
- 4.↑
Henker LC, Bianchi RM, Vargas TP, de Oliveira EC, Driemeier D, Pavarini SP. Multifocal spinal cord nephroblastoma in a dog. J Comp Pathol. 2018;158:12–16. doi:10.1016/j.jcpa.2017.10.176
- 5.↑
Tagawa M, Shimbo G, Tomihari M, et al. Intramedullary spinal nephroblastoma in a mixed breed dog. J Vet Med Sci. 2020;82(7):917–921. doi:10.1292/jvms.20-0068
