Combined Use of Surgery and Radiation in the Treatment of an Intradural Myxoid Liposarcoma in a Dog

Introduction

Liposarcoma is a malignant tumor of soft tissues.¹ Although metastatic spinal liposarcoma has been reported in humans, primary spinal liposarco-ma remains a very rare condition.² Only a few cases of primary liposarcoma of the spine have been reported in humans, and a single case exists in the dog.^2–4 In all published cases, the tumor was in an extradural location.^2–4 The purpose of this report is to describe an unusual case of spinal cord compression from an intradural myxoid liposarcoma in a dog, which has not been reported previously. The clinical and imaging findings and details on the use of surgery and radiation therapy in the dog are all provided.

Case Report

A 9-year-old, spayed female Cavalier King Charles spaniel was referred for evaluation of intermittent lameness in the right forelimb and cervical spinal hyperesthesia of 2 months’ duration. The dog had been treated with prednisone by the referring veterinarian, without significant improvement. The only abnormalities found on physical examination were the presence of an ulcerative stomatitis and resistance to manipulation of both thoracic limbs. Neurological examination revealed normal mental status, a mild ataxia in all four limbs, and weakness predominantly in thoracic limbs. Conscious proprioception was decreased in the right pelvic and thoracic limbs. Spinal reflexes were normal in all limbs. Marked hyperesthesia was elicited with manipulation of the head and neck. On the basis of the neurological examination, a focal spinal cord lesion between the first cervical (C₁) and the fifth cervical (C₅) vertebrae was considered likely. Differential diagnoses included intervertebral disk disease, neoplasia, meningomyelitis, syringomyelia or hydromyelia, and diskospondilitis.

Results of hematology and biochemical analyses were normal. Survey radiographs of the spine, thorax, and abdomen did not reveal any abnormalities. A cerebellomedullary myelogram was performed by injecting iopamidol^a (0.3 mL/kg intravenously [IV]) into the subarachnoid space. Myelography indicated a marked, focal compression of the spinal cord between C₁ and the second cervical (C₂) vertebrae. The contrast medium outlined a large filling defect within the dorsal aspect of the subarachnoid space, causing a “golf tee sign” [Figure 1]. The radiographic findings were consistent with an intradural-extramedullary mass.

Computed tomography^b (CT) of the neck was performed before and after administration of iodinated contrast medium^c (2 mL/kg IV) in order to clarify the size, location, extent of the mass, and degree of spinal cord compression, and to assist with surgical planning. Results of plain CT showed no abnormalities. Images taken after injection of contrast medium revealed a large (6 × 9 mm), contrast-enhanced mass within the vertebral canal at the level of C_1–2. The mass was located dorsolaterally and was more prominent on the right side [Figure 2]. There was no evidence of bony changes, but marked spinal compression was evident.

Treatment with prednisolone^d (0.5 mg/kg per os [PO] q 24 hours) was initiated until an exploratory laminectomy could be performed 1 week later. Clinical signs improved with the treatment, but the dog still had proprioceptive deficits in both the right thoracic and pelvic limbs. The dog was anesthetized, and a dorsal, right-sided laminectomy was performed at the level of the atlas and axis. The laminectomy of the axis extended from the spinous process to the articular process, allowing removal of two-thirds of the length of the vertebra. The spinous process of the axis was not removed completely to avoid as much vertebral instability as possible.⁵ One-half of the dorsal atlas was also removed. The interacuate ligament was partially eliminated to expose the spinal cord, and this resulted in significant hemorrhage that was controlled by gentle compression. A durotomy was performed to expose a firm, friable, and yellowish mass [Figure 3] located principally along the right dorsal aspect of the spinal cord. The mass did not appear to infiltrate the cord parenchyma. Abnormal tissue was removed as completely as possible by gentle dissection and submitted for histological evaluation. The laminectomy was covered with a fat graft and cervical musculature. Subcutaneous tissues and skin were apposed routinely.

Postoperatively, the dog recovered rapidly and was discharged in 4 days. At that time, conscious proprioception was decreased in all four limbs, but the dog was able to walk unassisted and no neck pain was detected. Postoperative medications included prednisolone (0.5 mg/kg PO q 24 hours) for 10 days and amoxicillin/clavulanic acid^e (15 mg/kg PO q 12 hours) for 1 week. Histopathology of the mass revealed abundant and atypical myxoid stroma. Clusters of epithelioid cells with ovoid nuclei and nucleoli of variable sizes were regularly seen. Large, clear spaces were present in the extracellular compartment, and clear vacuoles were common within the tumor cells [Figure 4]. Material in the spaces and vacuoles stained poorly with periodic acid-Schiff stain, indicating the presence of glucosaminoglycans. Multinucleated giants cells were also seen. Histopathology suggested a poorly differentiated sarcoma (e.g., myxoid liposarcoma or myxoid chondrosarcoma) or a chordoma.

Three weeks after surgery, radiation therapy of the site was performed because of the extensive nature of the mass, the poor cellular differentiation seen on histopathology, and the inability to achieve clear, wide margins at surgery. Radiation therapy was done with a linear accelerator^f using bilaterally opposed portals and 4 × 4-cm lateral fields centered on the C_1–2 area. Treatment consisted of 33 gray (Gy) delivered in 11 fractions of 3 Gy each, administered on a Monday-Wednesday-Friday schedule.

At a recheck examination 3 months following surgery, the dog was normal. A CT scan performed 6 months after surgery did not reveal any recurrence of the mass. Eighteen months after the surgery, the dog became reluctant to move its neck. A neurological examination at that time revealed only cervical spinal hyperesthesia. Recurrence of the tumor was suspected, and a third CT scan was performed. It revealed a 6 × 10-mm, contrast-enhanced mass located dorsolaterally in the vertebral canal in the area of C_1–2. The mass was most prominent on the left side and was compressing the spinal cord [Figure 5].

Following CT scan, a dorsal left-sided laminectomy was performed at the level of C_1–2, and a new mass was observed through the dura mater. After durotomy, a yellowish, well-circumscribed mass was exposed. The abnormal tissue was well demarcated cranially, caudally, and mediodorsally, but it seemed to infiltrate the spinal cord parenchyma laterally. The mass had the same appearance as the initial tumor. Complete excision of the mass was not performed to avoid excessive damage of the spinal cord. The dog was discharged 2 days following surgery, still exhibiting signs of mild neck hyperesthesia.

Histopathological evaluation of the second mass revealed a myxomatous stroma. Rows and clusters of cells with abundant or eosinophilic, vacuolated cytoplasm were detected [Figure 6]. The tumor appeared similar to but more differentiated than the initial mass. Histopathological findings were consistent with a diagnosis of myxoid liposarcoma.

A fourth CT scan was performed 1 month after the second surgery. A contrast-enhanced lesion measuring 2 × 7 mm was detected along the right side of the lateral vertebral canal. Additionally, another contrast-enhanced lesion measuring 3 × 9 mm was visualized in the dorsal vertebral canal. Spinal cord compression was not observed. These findings were thought to represent postoperative scarring and/or residual tumor. A second course of radiotherapy was performed. The dog was treated with 21 Gy delivered in 3 Gy fractions. A fifth CT scan performed 3 months after the radiotherapy did not show any abnormalities, and the dog was clinically normal at that time.

Eleven months after the second surgery and 29 months after the initial presentation, the dog became depressed and reluctant to move its neck. On recheck examination, the dog was mildly tetraparetic and had marked cervical hyperesthesia. A sixth CT scan was performed and revealed two contrast-enhanced lesions located dorsally and laterally along the right side of the vertebral canal [Figures 7A-7C], suggesting recurrence of the original tumor.

The dog was given prednisolone^d (1 mg/kg PO q 24 hours), and another course of radiotherapy was instituted. This third treatment consisted of 15 Gy delivered in five fractions of 3 Gy each. After radiotherapy, no improvement was noted, so a third surgery was offered to evaluate the degree of spinal cord infiltration and the possibility of removing more tumor as a palliative measure. At surgery, a mass was found dorsally and laterally along the right side that was infiltrating the spinal cord almost completely. Only a small amount of tumor could be removed. Because of the poor prognosis, the owners elected euthanasia of the animal. Necropsy was not permitted. Histopathological evaluation of tissue removed at the third surgery was similar to the prior biopsies.

Discussion

Primary spinal cord tumors are relatively uncommon in dogs.^6,7 Based on anatomical location, spinal cord tumors can be classified as extradural, intradural-extramedullary, or intramedullary.^6,8,9 The intradural-extramedullary tumors are located in the subarachnoid space, within the dura mater but outside the spinal cord. Some studies have estimated that intradural-extramedullary tumors comprise approximately 35% of all spinal cord tumors of the dog, while extradural and intramedullary tumors in the dog represent 50% and 15%, respectively.^5,6 However, several other studies have reported approximately an equal distribution between extradural and intradural tumors.^8,10–12 The most common intradural-extramedullary neoplasms of dogs are the meningioma and peripheral nerve sheath tumor.^6,9 Other tumors with an intradural-extramedullary location that have been reported in dogs include nephroblastoma, lipoma, myxoma/myxosarcoma, glioma, mixed germ cell tumor, lymphoma, and metastatic tumors.^7,13–17

Liposarcoma is an uncommon neoplasm in dogs.^18,19 The spinal cord is a rare site for a liposarcoma.² While metastatic spinal liposarcomas have been reported in people, primary spinal liposarcomas have been poorly documented.² All liposarcomas in humans have had an extradural location.^2,3 A myxoid liposarcoma located extradurally at the level of the first two lumbar vertebrae has been reported in an 8-year-old, female Doberman pinscher.⁴ On the basis of histological findings, the three main features of a myxoid liposarcoma are a well-developed vascular pattern, the presence of mononuclear cells, and a copious myxoid matrix containing abundant, nonsulfated glucosaminoglycans.²¹ Myxoid liposarcomas usually contain cells with an abundant, eosinophilic, or vacuolated cytoplasm; a large nucleus; and a small nucleolus.^18,22 In the case reported here, the tumor was classified as a myxoid liposarcoma based primarily on histological findings of myxoid areas associated with cells having prominent cytoplasmic vacuolization, and a vascular pattern typical of liposarcoma.

The goals of the surgery for spinal cord tumors in dogs are to improve spinal cord function by decompression, to remove as much tumor as possible, and to collect tissue for histopathological evaluation.^23,24 In the case reported here, the extensive involvement of the tumor did not allow wide, clear margins to be achieved; therefore, radiation therapy was also recommended. The primary purpose of radiotherapy for spinal cord tumors is to decrease the potential for recurrence following incomplete excision of the mass.^6,23 Although the efficacy of postoperative irradiation of spinal cord tumors in dogs is not well documented, previous reports have suggested it may be beneficial.^25–27

Postoperative radiotherapy for the treatment of spinal sarcomas is limited by the presence of the spinal cord.²⁸ Data in humans suggest that the threshold for radiation injury of the spinal cord is between 45 and 50 Gy using conventional fractionation.^4,29,30 Radiation doses that are considered effective for eradication of microscopic residual tumors are in the range of 60 to 70 Gy.^4,28 Despite suboptimal doses, however, postoperative radiation seems to delay local recurrence and is routinely recommended in humans after resection of high-grade tumors.³ In dogs, liposarcoma has been classified as a tumor with poor responsiveness to radiation therapy.²⁰ In contrast, combined surgery and radiotherapy has achieved local control of liposarcomas in most affected humans and is the therapeutic preference for this tumor.³¹ The long-term prognosis for either humans or animals with primary spinal myxoid liposarcoma has not been well established.²⁸ In the previously mentioned report of spinal liposarcoma in a dog, surgical resection alone provided 7 months of clinical remission before recurrence of the tumor.⁴ In the dog reported here, surgical therapy was considered inadequate, because clean margins could not be achieved. Another stimulus for considering radiation therapy was the poor differentiation noted on histopathological examination of the tumor after the first surgery.³²

The recommended dosage for the treatment of spinal cord tumors in people is a total dose of 45 to 50 Gy given in 1.8 to 2.0 Gy daily fractions.³⁰ Data regarding radiation dosages for spinal cord tumors in dogs are limited. In one study, the thoracic spinal cords of 42 dogs were irradiated.³³ The doses delivered were 0, 44, 52, 60, or 68 Gy in 4 Gy fractions, and dogs were evaluated 1 and 2 years after radiation.³³ Dosages of 60 Gy given in 4 Gy fractions were associated with clinical signs. In dogs with spinal cord tumors, it is desirable to administer as large a total dose as possible without inducing radiation myelopathy.²⁵ In the case reported here, a total dose of 69 Gy was delivered in 3 Gy daily fractions. The doses were delivered over a 30-month period, and the three treatments were separated by 18 and 11 months. No clinical signs attributable to radiation myelopathy were observed during the 30 months of follow-up. Unfortunately, necropsy was not permitted in this dog, so the presence of secondary radiation injury could not be assessed.

This is the second report of spinal liposarcoma in a dog and the first report of an intradural location. It is possible the tumor originated from epidural fat. Another explanation for the location is that the inner layer of the dura mater and the arachnoidea are of mesodermal origin, and this may give rise to neoplastic adipose tissue.¹⁴ Although a necropsy was not performed, it was possible that the spinal tumor was a metastatic lesion but was considered primary, since no other lesions were discovered during the long treatment period.

Conclusion

An intradural-extramedullary myxoid liposarcoma was diagnosed in the region of the C_1–2 vertebrae of a 9-year-old dog. Treatment included three dorsal laminectomies and three courses of radiation therapy, and the dog survived for 30 months. Further investigations are indicated to evaluate the efficacy of postoperative radiation therapy for dogs with spinal cord tumors that cannot be completely removed at surgery.

Acknowledgments

The authors thank Dr. Mercedes Estrada and the histopathology laboratory (Laboratoire d′histo-cytopathologie vétérinaire, 95 rue raspail, Maisons Alfort, France) for their assistance with the photomicrographs and the preparation of this manuscript.