Radiation therapy as adjuvant therapy for spinal nephroblastoma

History: An 8-month-old male intact Rottweiler presented to his rDVM for evaluation of acute onset of right hind limb (RHL) lameness following a traumatic blow while playing with another dog. Radiographs of the affected limb were normal. The problem was managed conservatively with controlled activity and carprofen, 75mg PO BID for 2 weeks. The lameness progressed to metacarpal knuckling and dragging of the leg. The patient was referred to a neurologist for further evaluation. A neurologic exam localized a lesion to the T3-L3 region with lateralization to the right side. The remainder of the exam was unremarkable. Initial staging tests were done: CBC and chemistry were within normal limits. A lumbar CSF tap was done and results showed a normocellular sample with a mildly elevated protein level (71mg/dL). No other cytological abnormalities were detected.  A myelogram was done next and revealed a contrast filing defect at L1-L2 with a classic “golf-tee” sign consistent with an intradural-extramedullary mass localized to the right (image 1 and 2). A right-sided hemilaminectomy (L1-L2) was done and the intradural mass was removed piecemeal. Histopathology revealed a primitive complex neoplasm comprised of both epithelial and mesenchymal components organized into tubular and glomeruloid structures. There were 5 mitoses/HPF within the mesenchymal component. The mass was noted to be invading the nerve root and white matter and margins were incomplete (images 3-4). Immunohistochemistry was done with a panel of markers and was negative for chromogranin, neurofilament, neuron-specific enolase and glial fibrillary acidic protein. However, the samples were positive for cytokeratin and Wilm’s gene product (WT1) confirming the diagnosis of an incompletely excised nephroblastoma.

Two weeks after neurosurgery, the patient was referred to the oncology service to discuss prognosis and treatment options. The patient presented ambulatory x 4 but exhibiting marked difficulty in rising and a frequent “bunny hopping” gait. There was also significant muscle atrophy in the hind end (R>L). Neurology exam revealed mild bilateral hindlimb ataxia and paraparesis (R>L) with moderate scuffing of the nails of the RHL.  Conscious proprioception was absent on the RHL and delayed on the LHL. But strong withdrawls remained intact. No ataxia or paresis was noted in the thoracic limbs and conscious proprioception in thoracic limbs was also normal. Panniculus and perineal reflexes were intact and spinal palpation was unremarkable. Further staging diagnostics included thoracic radiographs and abdominal ultrasound which were both within normal limits, as well as lateral thoracolumbar radiographs and CT and MRI scans for treatment planning (images 5 and 6).

The MRI showed mild soft tissue swelling with the presence of an autogenous fat graft as well as cord compression and invasion by a hyperintense lesion.

Treatment options were discussed as being limited to radiation therapy and a guarded prognosis was given. The owners elected to proceed with definitive radiation therapy.  A CT scan was obtained for treatment planning (image 7).  The plan was to administer 16×3 Gy fractions to a total of 48Gy via parallel, opposed treatment portals . Prednisone was started at 20mg PO SID. Treatment proceeded uneventfully with relatively stable clinical signs. By 6 weeks post treatment, the patient presented for a recheck and was reportedly showing markedly improved strength in his hind end. He was still showing difficulty in rising with a mild bunny hopping gait but the muscle atrophy was resolved and the CPs were decreased but intact on the RHL and normal on the LHL He was weaned off of the prednisone at this time. At a 3 month recheck, the patient continued to show improved strength. He was rising  with more ease, no longer exhibiting nail scuffing and was able to jump up on his hindlegs with completely normal hindlimb CPs. The patient continued to do very well up to a year post radiation therapy when he was lost to follow-up.

Spinal nephroblastoma in dogs is a very rare disease. Most reports in the veterinary literature are of patients euthanized after imaging or shortly after surgical exploration. Surgery alone is reported to result in survival times of 71 days 1. One report of cytoreductive surgery and radiation reported survival times up to 560 days 2.  In people, Wilm’s tumor is the most common primary malignant renal tumor of childhood. They are histologically diverse with blastalemal, epithelial and stromal components (not all present in each case). Prognosis is dependent on stage and histologic differentiation (anaplastic being worse). In dogs, nephroblastomas can affect spinal or renal tissues. The spinal tumors have a debatable histogenesis in dogs (neural rests vs ectopic renal blastema), however, histology, immunohistochemistry and a virtually uniform spinal involvement at T10-L2 argue more strongly for a renal origin of these tumors. Metastasis is reported to occur in the spine, bone marrow, lung and liver 3.

Submitted by:

David M. Lurie, BVSc, DACVIM (oncology), DACVR (radiation oncology)

References

1: Spinal cord nephroblastoma in dogs: 11 cases (1985-2007). Brewer DM. et al. J Am Vet Med Assoc. 2011 Mar 1;238(5):618-24.

http://avmajournals.avma.org/doi/abs/10.2460/javma.238.5.618

2: Canine spinal nephroblastoma: long-term outcomes associated with treatment of 10 cases (1996-2009). Liebel FX. Vet Surg. 2011 Feb;40(2):244-52.

http://onlinelibrary.wiley.com/doi/10.1111/j.1532-950X.2010.00789.x/full

3: Possible Intraspinal Metastasis of a Canine Spinal Cord Nephroblastoma. Terrel SP. et al. Veterinary Pathology January 2000 vol. 37 no. 1 94-97.

http://vet.sagepub.com/content/37/1/94.short

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Image 1: “golf tee” filling defect

 

 

 

 

 

 

 

 

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Image 2: “golf tee” filling defect

 

 

 

 

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Image 3: Tubular structures

 

 

 

 

 

 

 

 

 

 

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Image 4: Glomeruloid structure

 

 

 

 

 

 

 

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Image 5: CT image post laminectomy, pre-RT.

 

 

 

 

 

 

 

 

 

 

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Image 6: Post laminectomy MRI; white line denotes position of fat graft and region of cord invasion.

 

 

 

 

 

 

 

 

 

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Image 7: RT planning (bilateral opposed fields)

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