Primary Lumbar Extradural Hemangiosarcoma in a Dog

Introduction

Various types of primary or metastatic neoplasms may affect the vertebral column.^1–5 Tumors may be categorized based on the anatomic location in relationship to the spinal cord and include intramedullary, intradural extramedullary, or extradural locations. Previous retrospective studies report approximate equal distribution between extradural and intradural tumors.^4,5 Of the metastatic neoplasms, carcinomas have been reported to metastasize to the extradural vertebral canal location.⁶ On the other hand, when hemangiosarcoma (HSA) or lymphosarcoma metastasizes to the spinal cord, they are commonly found as an intramedullary lesion.⁷

HSA is a malignant neoplasm of vascular endothelial origin that can arise from any vascular tissue. In dogs, typical primary sites include the spleen, liver, and right atrium. Dermis, subcutaneous tissues, lungs, kidneys, oral cavity, muscles, bones, urinary bladder, eyes, and peritoneum have also been reported.^8,9 Most affected dogs develop metastatic disease within 6 mo of initial diagnosis, with common sites of metastasis being the liver, mesentery, omentum, and lungs.¹⁰ German shepherd dogs, golden retrievers, Labrador retrievers, and standard poodles are over represented, with no sex predilection and a mean age of approximately 10 yr at time of diagnosis.

In general, treatment consists of cytoreductive surgery and chemotherapy. Adjunctive doxorubicin-based chemotherapy, either with or without the addition of cyclophosphamide or vincristine, has provided the longest survival times.^11,12 A more contemporary approach is the daily administration of low doses (metronomic dosing) of chemotherapy agents, thereby shifting the therapeutic target from the cancer cells to the endothelial cells by administering frequent, low doses of chemotherapy.^13–16 By so doing, the common problems of toxicities and drug resistance may be largely avoided.²²

In the case reported herein, primary extradural HSA arising in the epidural space of the lumbar vertebral column was diagnosed based on a lack of evidence of a primary lesion elsewhere. This case report describes the clinical presentation, MRI findings, treatment, and outcome in a dog with primary extradural HSA 15 mo after initial diagnosis.

Case Report

A 9 yr old castrated male golden retriever weighing 36 kg was evaluated at a referral practice for a 2 wk history of progressive left-sided pelvic limb paresis and fecal and urinary incontinence. Other medical history included idiopathic epilepsy, which was well controlled with phenobarbital^a [1.25 mg/kg per os (PO) q 12 hr] and potassium bromide^b (62.5 mg/kg PO q 24 hr). When the referring veterinarian initially examined the dog, radiographs of the lumbar vertebrae were normal. The dog was treated for approximately 5 days with carprofen^c (2.1 mg/kg PO q 12 hr). Despite treatment, the dog became progressively paraparetic and was referred.

At the time of referral, physical examination revealed mild atrophy of the pelvic limb musculature. On neurological examination, lower motor neuron quality paraparesis was evident by a short-strided gait and hypotonia in both pelvic limbs, with bilateral postural reaction deficits that were worse on the left side. When the dog's weight was supported, the postural reactions appeared normal. The patellar and withdrawal (flexor) reflexes were decreased bilaterally. Hypotonia of the anal sphincter, hypalgesia of the perineum, and an easily expressible urinary bladder were observed. The dog was not painful on palpation along the vertebral spinous processes. Based on the neurological exam findings, the neuroanatomical diagnosis was consistent with a lesion affecting the fourth lumbar to third sacral spinal cord segments, their respective nerve roots, spinal nerves, or nerves including the femoral, sciatic, pelvic, and pudendal nerves. Differential diagnoses at that time included intervertebral disc disease, myelitis, endocrine neuropathies, and neoplasia (primary or metastatic).

A complete blood cell count, serum biochemical profile, and three-view thoracic radiographic study were within reference limits. MRI of the lumbar and sacral vertebrae was performed using a 1.0 Tesla MRI system.^d T2-weighted (T2W) and T1-weighted (T1W) images were acquired in the sagittal and transverse planes with 3 mm slice thickness for all sequences. Additionally, T1W images were acquired using chemical shift fat saturation after the IV administration of 0.1 mmol/kg of gadodiamide.^e

A focal, well-demarcated, extradural mass that measured approximately 2.3 cm × 1.1 cm × 0.6 cm was identified within the left dorsolateral aspect of the vertebral canal, markedly compressing and deviating the spinal cord to the right and ventrally. The mass extended from the caudal third of the fourth lumbar vertebra to the cranial third of the fifth lumbar vertebra. Compared with normal spinal cord, the mass was heterogeneously hyperintense on T2W images (Figure 1A) and homogenously isointense to the spinal cord on a T1W (Figure 1B) image. Postadministration of gadodiamide, the lesion displayed strong, homogenous contrast enhancement (Figures 1C, D). On the sagittal images, epidural fat cranial and caudal to the mass appeared widened, suggesting an extradural location of the lesion. Abnormalities of the vertebrae and adjacent tissues were not identified.

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A left-sided hemilaminectomy was performed from the midbody of the fourth lumbar vertebra to the midbody of the fifth lumbar vertebra. A well-circumscribed, brown to black colored, oblong mass was removed from the epidural space and submitted for histopathological evaluation.

On histological evaluation with hematoxylin and eosin, the mass was composed of neoplastic cells lining variably sized blood-filled clefts and channels (Figure 2A). The neoplastic cells were spindle-shaped with abundant eosinophilic cytoplasm and oval nuclei with finely stippled chromatin and prominent nucleoli (Figure 2B). There was moderate nuclear and cellular pleomorphism. Mitoses averaged 3/high-power field. Admixed were occasional lymphocytes, plasma cells, hemosiderophages, and foci of hematopoietic cells. The neoplastic spindle cell population demonstrated positive immunoreactivity for Factor VIII-related antigen, supporting endothelial cell origin (Figure 2C). Cells also demonstrated positive immunoreactivity for vimentin (Figure 2D), establishing their mesenchymal origin. Based on histological evaluation, the mass was consistent with HSA.

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Additional staging for the dog entailed an echocardiogram and abdominal ultrasound examination, which were normal. An IV doxorubicin^f (30 mg/m²)-based chemotherapy protocol q 2 wk for five cycles (with alternating weekly complete blood cell counts), with the addition of daily oral cyclophosphamide^g (0.5 mg/kg) was used.^12,13 Restaging was performed after completion of the chemotherapy protocol, which included thoracic radiographs, abdominal ultrasound, and echocardiogram. Subsequent follow-up examinations and restaging were performed q 4 mo. At all examinations, the dog remained free of neurological dysfunction with no evidence of primary tumor recurrence or metastatic disease for 15 mo after initial treatment.

Discussion

Information regarding the prognosis and treatment of HSA-associated myelopathy in dogs is limited. Reports of extradural HSA without skeletal involvement in the veterinary literature are even sparser. Two case reports of cervical extradural HSA have been reported.^16,17 One report in a dog describes an extradural HSA in the cervical vertebral column causing pain and paresis.¹⁶ The dog was treated with surgical removal of the mass and doxorubicin. Approximately 11 mo after initial treatment, HSA was found in the spleen. Another report in a horse describes a cervical myelopathy secondary to an extradural HSA in which the horse displayed a cervical myelopathy.¹⁷ At necropsy, neoplastic disease was not found elsewhere.

Other case reports have described a myelopathy secondary to an extradural compressive lesion from primary HSA affecting the bone, which accounts for approximately 2–3% of primary bone tumors of the vertebral column in dogs.^16–20 When HSA involves bone, lysis predominates, and malignant cells can invade surrounding tissue with subsequent extradural spinal compression causing myelopathic signs.³ The prognosis for dogs with primary HSA of bone is poor because <10% survive 1 yr even if the tumor can be excised.¹⁸

One report by Waters et al. (1990) describes a dog with intramedullary spinal cord metastasis. Initially paraplegic, the dog became ambulatory for 17 wk with corticosteroid treatment. The dog was ultimately euthanized due to disseminated HSA.⁸ More aggressive treatment options for intramedullary spinal cord metastasis in humans include spinal irradiation, chemotherapy, and microsurgical resection; however, prognosis is regarded as poor.⁸ Factors contributing to a poor prognosis in dogs include difficulty in achieving an early diagnosis and the frequent presence of widely disseminated disease.

MRI is the modality of choice for evaluation of the vertebral column in humans. Variable MR signal characteristics of primary and metastatic vertebral tumors in humans have been described.²¹ A prior study described MRI features of the most common tumors of the vertebral column in dogs.¹ Extradural tumors consisting of fibrosarcoma, ganglioblastoma, lymphosarcoma, osteosarcoma, and plasmacytoma were found to be predominantly hypointense on T1W images, while on T2W images, the same tumors were found to be hyperintense or isointense with variation in the degree of contrast enhancement.²¹ Intradural, extramedullary tumors were meningiomas and peripheral nerve sheath tumors. Those tumors showed mild to marked contrast enhancement, with the peripheral nerve sheath tumors displaying stronger enhancement. The intramedullary tumor was a HSA. That tumor was isointense on T1W images, hyperintense on T2W images and showed enhancement after contrast administration, similar to the lesion described in the dog presented herein.

In the dog described in this report, neurological examination findings were consistent with a lumbosacral myelopathy. The MRI disclosed a focal, well-demarcated, extradural mass compressing the spinal cord and the adjacent nerve roots at the level of fourth and fifth lumbar intervertebral disc. The imaging characteristics were consistent with previous reports of HSA in other regions of the body.^1,7,22,23 A major limitation of this study was the lack of running a gradient-echo T2*W sequence.²⁴ On gradient-echo T2*W images, magnetically susceptible substances will manifest as a signal void, which can be found with hemorrhage or a hematoma. As a result of its increased sensitivity to susceptibility effects, that type of weighting has been used to detect intracranial hemorrhage.²⁴ That sequence would have allowed identification of the hemorrhagic component in the dog's mass and may have been useful.²⁴

While speculative, it is possible that the mass arose from the endothelium of the vasculature of the epidural fat or possibly from penetrating branches from the radicular artery or vein. Another possible etiology was described by Lamerato-Kozicki et al. (2006) where bone marrow-derived circulating endothelial precursor cells may migrate to peripheral vessels and are responsible for transformation into pathologic angiogenesis.²⁵ The underlying etiology in this dog was unable to be determined from the imaging, gross surgical evaluation, or histopathological studies.

Histopathological and immunohistochemical staining confirmed the diagnosis of HSA. Subsequent staging confirmed the lack of additional neoplastic foci. The patient recovered from the hemilaminectomy surgery and began receiving chemotherapy as described. Based on follow-up examinations, 15 mo after initial treatment, the dog's clinical signs associated with the myelopathy had resolved.

Conclusion

This case report describes a rare, extradural HSA suspected to be of primary neoplastic origin. At the time of this report's acceptance (March 15, 2013), to the authors' knowledge, this was the first report of a primary extradural HSA within the lumbar vertebral canal of a dog with no associated skeletal involvement. Since that time, the clinicopathologic description of a dog with epidural hemangiosarcoma has been reported.²⁶ The authors also describe the successful treatment of such a lesion with surgery and chemotherapy. Although rare, primary HSA should be considered in cases of myelopathies secondary to an extradural compressive mass within the vertebral canal.