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Spinal Neoplasms in Small Animals
Spinal Neoplasms i n S m a l l An i m a l s Rodney S. Bagley,
DVM
KEYWORDS Dog Cat Spine Neoplasm Tumor Spinal cord
Spinal cord disease can result from a variety of disease processes.1–3 Neoplastic disease can similarly involve the spinal cord, dura, exiting peripheral nerves, or perispinal tissues (eg, the vertebrae and ligaments) and result in clinical signs of spinal cord dysfunction. Because of the fact that many of these neoplastic processes are locally aggressive, early recognition of such diseases is important. This recognition often requires some type of advanced imaging of the spinal cord unless the abnormality obviously involves the vertebra. Surgical treatments are often employed for definitive diagnosis of the tumor and for decompression of the spinal cord. Other treatments, such as radiation therapy and chemotherapy, are used in some instances. Outcomes of animals affected with spinal tumors are dependent upon the growth characteristics and biologic behavior of the tumor itself and the degree of associated spinal cord damage. CLASSIFICATION
Spinal neoplasms are often categorized initially based upon the anatomic area, in relation to the dura and spinal cord, of spinal involvement.4–17 Tumors are grouped into those primarily arising from an extradural location (extradural), within the dura but outside the spinal cord proper (intradural/extramedullary), or arising within the spinal cord parenchyma proper (intramedullary). Obviously, depending upon growth characteristics and tumor aggressiveness, tumors can expand and extend from one of these strict anatomic areas to involve another. This expansion is most often seen with peripheral nerve sheath tumors that may begin in an extradural location but may traverse the dura into the intradural/extramedullary space, and eventually, into the spinal cord gray matter. Spinal tumors may also be classified into primary tumors (those tumors that arise from cells native to the spinal, dural, and perispinal tissues) or secondary tumors (those tumors that have metastasize from another location within the body).18–27 This system lends information as to whether the disease is localized or systemic and influences treatment and prognosis.
Neurology and Neurosurgery, Department of Clinical Sciences, Iowa State University, College of Veterinary Medicine, 1600 South 16th street, Ames, IA 50011-1250, USA E-mail address: [email protected] Vet Clin Small Anim 40 (2010) 915–927 doi:10.1016/j.cvsm.2010.05.010 vetsmall.theclinics.com 0195-5616/10/$ – see front matter ª 2010 Elsevier Inc. All rights reserved.
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Understanding the initial anatomic location of the cell of origin of the tumor aids in predicting the type of tumor present. Extradural tumors are the most common of all spinal tumors in dogs and cats (Fig. 1). These tumors include primary and secondary bone tumors (osteosarcoma, fibrosarcoma, chondrosarcoma), hemangiosarcoma, multiple myeloma and other plasma cell tumors, liposarcoma, and lymphosarcoma. Carcinomas are often found to metastasize to the extradural spinal location.20 Lymphosarcoma is the most commonly recognized spinal tumor in cats.28–30 Less commonly, benign neoplasms of bone, such as osteomas, fibromas, chondromas, and lipomas, may be present.31,32 Vascular expansile lesions have been seen in cats.33 In some instances, proliferations of bone and connective tissues mimic tumors but are not neoplastic. One example is multiple cartilaginous exostoses.34–37 These abnormalities are proliferations of bone and cartilage that are thought to result from aberrant growth displaced chondrocytes from the metaphyseal growth plates of bone. Subsequently, this disease is most often seen in younger animals (<18 months of age). Dogs, cats, and other species, including humans, have been reported with this disease. The boney and cartilaginous proliferations are often multiple and can affect the long bones, ribs, or vertebrae. The bony protuberances may be palpable. If these proliferations of cartilage affect the vertebrae, varying degrees of spinal pain, paresis, or paralysis may result. Radiographs of the affected bones often show proliferations of bone that are smooth, contoured, irregular, and multilobulated. These bony proliferations, however, may eventually become malignant as the animal ages.38,39 Intradural but extramedullary tumors include meningiomas and nerve sheath tumors.10,15,40–45 Meningiomas are most often found in the cervical area followed by the lumbar area. These tumors are infrequently found in the thoracic area. In the lumbar area, these tumors often proliferate around, entwine, and become adherent to exiting peripheral nerves. Primary neoplasia may involve numerous peripheral nerves within or around the spinal cord (Figs. 2 and 3). Clinical signs are related to dysfunction of the involved
Fig. 1. Transverse, T2-weighted MRI of the cervical spine of a dog with an extradural tumor. There is tumor both extradural (small arrow) and lateral to the vertebrae (larger arrows).
Spinal Neoplasms in Small Animals
Fig. 2. Intraoperative view following laminectomy of a dog with a nerve sheath tumor abutting the dura (arrows).
peripheral nerves. General clinical signs reflect lower motor neuron dysfunction. These signs include hyporeflexia to areflexia, hypotonia to atonia, neurogenic atrophy, and abnormal proprioception. Primary neoplasia involving the peripheral nervous system usually results in clinical dysfunction localized to one body area or nerve segment. Nerve sheath tumors are one of the most common types of primary neoplasia of the peripheral nervous system. These tumor types include schwannomas, neurofibromas, and neurofibrosarcomas. Histologic differentiation is sometimes difficult and the biologic behavior is similar allowing for the use of the generic grouping within the nerve sheath tumor category. These tumor types can arise from the Schwann (myelinated) cell of the peripheral nervous system, from connective tissue elements associated with the peripheral nerve, or from the axon and cell body. Tumors often involve nerves of the thoracic limbs but any peripheral nerve, including cranial nerves, may be involved. Nerve sheath tumor, for example, may involve the sciatic nerve and result in pelvic limb lameness. Importantly, nerve sheath tumors may involve the nerve at any site along its length. Distally located tumors may be focally painful if palpated, and may sometimes result in firm enlargements that may be tubular or spherical in shape. These tumors tend to feel firm upon palpation. Additionally, there is an unusual intradural but extramedullary tumor that has been referred to by various terms, including neuroepithelioma and spinal cord
Fig. 3. Intraoperative view following brachial plexus exploration from a dog with a peripheral nerve sheath tumor. Note the enlarged, discolored nerve (Larger arrows) compared with an adjacent normal nerve (smaller arrows).
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blastoma.4,46–49 This tumor tends to occur in young animals and often occurs in the T11 to L2 area of the spinal cord. German shepherds may be overrepresented with this tumor type.4 In some instances a histologically similar tumor may be present in other locations rather than limited to the T11 to L2 region, and in other breeds of dogs besides German Shepherds. Intramedullary tumors include astrocytomas, oligodendrogliomas, and ependymomas. These tumors arise from cells within the spinal cord parenchyma.4,6,10,15,50 They are often poorly encapsulated and sometimes difficult to differentiate from normal spinal cord tissue (Fig. 4). In some instances, however, the tumors are well encapsulated and firm, making differentiation easier. Metastatic disease can also affect the spinal cord.18–20,25,26,51 Both extradural and intramedullary metastasis is possible. Carcinomas are one of the most common types of tumors associated with extradural metastasis. In some instances, clinical signs of the metastasis may be apparent before clinical signs of the primary tumor. Hemangiosarcoma has resulted in intramedullary spinal cord metastasis.26 CLINICAL FEATURES
Clinical signs of spinal tumor are never pathognomonic because these signs are prototypical of spinal cord dysfunction and pain.3,10,33,36,40,41,52 The location that the spinal cord is involved will determine the presence of associated upper-motor or lowermotor neuron (LMN) signs. If the tumor begins in a peripheral nerve, clinical signs usually involve a nonlocalizable lameness, monoparesis, localized appendicular muscle atrophy, or pain.53 Dogs with nerve sheath tumor may initially present for lameness and may be initially diagnosed as having some orthopedic and musculoskeletal causes for the dysfunction. Complicating the ultimate diagnosis, many animals will concurrently have minor
Fig. 4. Transverse, T2-weighted MRI of the spinal cord of a dog with an intramedullary lesion. There is a hyperintense lesion presence within the spinal parenchyma. Histologic diagnosis was a glioma (arrow).
Spinal Neoplasms in Small Animals
orthopedic or musculoskeletal abnormalities. Progression of signs reflective of an LMN dysfunction ultimately suggests a nervous-system origin of the problem. Pain upon direct palpation may be present, with some dogs requiring sedation or anesthesia for adequate palpation of this area. Some animals, even at seemingly adequate depths of anesthesia, will awaken quickly during palpation indicative of a painful reaction. Occasionally an obvious mass or tissue enlargement is palpated. These masses may be linear, tubular, or spherical as they course along the affected nerve. Nerve sheath tumors may also result in a chronically painful condition. In some animals this manifests only in signs of depression and behavioral change and obvious localized pain may not be found on physical examination. Associated behavior abnormalities include aggression toward owners, unwillingness to play, and a general lethargy. These clinical signs could reflect a variety of clinical diseases and may prompt pursuit of diagnostic evaluations for systemic disease. If the nerve roots involved are not associated with the cervical or lumbar intumescence, the animal may only have spinal pain. The limb may be positioned in a more flexed posture (nerve root signature). Clinical signs usually progress to proprioceptive impairment. Occasionally an animal will present with acute paraplegia or tetraplegia caused by spinal cord compression. This compression may result from the effects of the mass itself or from associated spinal cord pathophysiologic alterations, including edema, ischemia, infarction, or hemorrhage as a consequence of the mass. These latter abnormalities often account for the acuity of onset of clinical signs that often accompany spinal tumors. Importantly, a spinal tumor should not be overlooked as a cause of acute spinal cord dysfunction. Clinical signs of all tumor types depend upon the level of spinal cord involvement. Tumors of the C6 to T2 segments or brachial plexus nerves may be associated with ipsilateral Horner’s syndrome or ipsilateral loss of cutaneous trunci contraction. Generally, extradural and intradural extramedullary tumors result in some form of pain, whereas the intramedullary tumors may be nonpainful. If, however, the tumor causes expansion of the spinal cord resulting in stretching of nerve roots or compression of the dura, hyperesthesia may be present. The progression of clinical signs is often more chronic with the extradural tumors and more acute with the intramedullary tumors. SPINAL TUMORS IN CATS
Cats have some different features with regards to spinal tumors.26–30,37,45,51,52,54 Lymphosarcoma appears to be the most common tumor affecting the spinal cord followed by osteosarcoma.29 Cats with lymphosarcoma were typically younger at initial examination, had a shorter duration of clinical signs, and had lesions in more regions of the central nervous system than did cats with other types of tumors. In 22 of 26 (84.6%) cats with lymphosarcoma, the tumor was also found in extraneural sites. Feline leukemia virus status was inconsistent. Osteosarcoma in the vertebrae of cats may act less aggressively compared with similar tumors in dogs. DIAGNOSIS
Diagnosis of a spinal tumor is often presumptively made using survey spinal radiographs, myelography, or advanced imaging (CT and MRI).10,55,56 Tumors of bone may be evident on survey radiographs as osteolytic/osteoproliferative processes. These bony changes need to be differentiated from diskospondylitis and vertebral bony osteomyelitis. Classically, vertebral tumors do not cross the joint space (intervertebral disk). Rarely, however, vertebral tumors invade adjacent vertebral bodies and
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therefore appear to ‘‘jump’’ the joint. Extradural compression of the spinal cord overlying the vertebral body rather than the intervertebral disk space is suspicious for neoplasia. Soft tissue tumors are usually not apparent on survey radiographs. Nerve sheath tumors, however, may involve exiting peripheral nerves within the intervertebral foramina.10 The foramen where the abnormal nerve is exiting may be enlarged and visible on survey radiographs. Myelography has historically been used to outline the subarachnoid space and determine if spinal cord compression or expansion is present. However, myelography is now increasingly less used with the advent of advanced imaging, such as MRI. MRI is superior to myelography in almost all instances of spinal imaging. The principle location description of tumor categories still remains from the myelography era. In extradural tumors, one or both of the contrast columns may be shifted axial (toward the center of the spinal canal). Clues to the presence of an extradural tumor include compression of the spinal cord primarily overlying a vertebral body rather than the intervertebral disk space and annular compressive lesions of the dura. These same imaging features may also be seen with intervertebral disk disease and other spinal cord compressive diseases and therefore should not be considered pathognomonic for extradural spinal tumor. With intradural but extramedullary tumors, spinal imaging will often result in a characteristic pattern of expansion of the subarachnoid space and outlining of the tumor in negative shadow, referred to as a golf tee (Fig. 5).10,33,57 Nerve sheath tumors may also expand to either side of where the nerve traverses the dura, giving these tumors a dumbbell-shaped appearance. Conversely, expansion of the dural tube in 90 opposed radiographic views is indicative of an intramedullary lesion. Advanced imaging studies, such as CT or MRI, have greatly improved the ability to determine the extent of any spinal tumor.58 The major advantage of both CT and MRI techniques is the ability to noninvasively image structures below to the surface of the body. Advantages of CT imaging include the ability to image in planes giving a spatial orientation to abnormalities seen. Disadvantages include its use of ionizing radiation (radiation exposure) and the poor imaging of the spinal cord. Spatial resolution, especially for small animals like as cats, may not be adequate to determine small (<5 mm) lesions. With CT, a myelogram is often necessary as part of the CT evaluation process to more accurately outline the subarachnoid space. Unfortunately, by having to perform myelography, the inherent risks to the animal from myelography are introduced into the cost/benefit of the procedure. In some instances, a series of scans are performed before and after intravenous injection of an iodinated contrast material. Abnormalities disrupting the blood-spinal cord or blood-nerve barrier may become more apparent
Fig. 5. Lateral, MRI myelographic view of a dog with an intradural but extramedullary lesion showing a golf-tee sign (arrow).
Spinal Neoplasms in Small Animals
with this technique. Loss of integrity of these barriers or increased vascularity may result in an area of increased uptake (whiteness) after intravenous contrast enhancement. Contrast enhancement is most often seen with tumors, vascular abnormalities, and inflammatory foci; however, it may also be seen with intervertebral disk disease. MRI is the imaging modality of choice for a variety of spinal lesions.58 MRI affords superior anatomic evaluation of soft tissue structures. Similar to myelography, MRI is helpful in determining the presence of a spinal cord compressive or expansile lesion. MRI, however, is superior to all other spinal studies in delineating soft tissue components of spinal lesions.36,59 Most epidural tumors invade the surrounding vertebral body before impinging on the spinal cord. Thus, bony destruction of the vertebrae may be a clue to an underlying neoplastic process. In general, on T1-weighted images, vertebral bone marrow signal should be roughly equivalent to disk material. In instances of diffuse marrow involvement, the disk spaces will show greater signal intensity than the vertebral marrow. Tumors are typically vascular and invasive, breaking the normal integrity of the blood brain barrier thus intravenous injection of a contrast agent generally results in some degree of either diffuse or focal enhancement in the area affected by tumor. Contrast enhancement does not precisely define the tumor borders; neoplastic cells are generally found outside the enhanced portion of the mass. Gadolinium administration may not be as helpful in identifying tumors that involve the vertebral bodies, because gadolinium-enhanced osseous lesions may have an appearance similar to that of normal marrow. Particular enhancing characteristics have been inconsistent various tumors. Intradural, extramedullary tumors may result in a similar golf-tee appearance to the subarachnoid space, which is most evident on T2-weighted images. These tumors are occasionally less obvious because they may have little contrast with respect to the adjacent spinal cord. These tumors may also not be as obvious on sagittal images if they are primarily lateral to the spinal cord. Intravenous gadolinium-DTPA (Magnevist, Berlex Laboratories, Cedar Knolls, NJ, USA), enhances these tumors increasing their signal intensity on T1-weighted images. Dorsal and transverse contrast-enhanced images are helpful images to detect this category of tumors. Intramedullary tumors generally cause the spinal cord to be expanded. On T1-weighted images, most intramedullary neoplasms have diminished signal intensity with respect to the cord. On T2-weighted images, they usually have a brighter signal than cord, which often reflects associated spinal cord edema or hemorrhage. Most tumors have a nonhomogenous signal intensity and indistinct margins between tumor and surrounding normal cord. TREATMENT
Treatment options for spinal tumors include surgical removal and possibly radiation therapy.36,40–42,47,60–64 Surgical removal is most often reserved for extradural tumors, however, both intradural/extramedullary and intramedullary tumors have also been successfully resected. The ultimate prognosis depends upon degree of local resection, degree of spinal infiltration, associated spinal damage before and during surgery, surgeon experiences with spinal neoplastic conditions, and tumor type. SURGERY
Extradural tumors are removed by laminectomy, either dorsal or hemilaminectomy. Ventral slotting is inadequate for removal of most cervical tumors. Abnormal tissue is identified and removed via blunt or sharp dissection. Advanced imaging studies
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before surgery help in determining the extent of the tumor and involved vital structures but even with MRI the extent of the neoplastic process may be underappreciated. The surgical keys are obviously adequate lesion exposure and subsequent removal. Most surgical problems and failures result from inadequate surgical exposure. In some instances, increased bone removal necessary for tumor resection will result in a need for surgical stabilization through internal fixation. If the surgeon is not experienced in surgical spinal stabilization (if that becomes necessary) this can result in surgical failure. For spinal tumor removal, especially with intradural or intramedullary lesions, the vertebral structure needs to be removed. Caution is used during drilling with lesions that involve the vertebrae because the consistency and strength of this bone may be compromised, which may lead to unwarranted entry of the spinal canal with the drill. Also, if the tumor involves large vascular structures, such as the vertebral artery or sinus, bleeding during resection can be significant and life threatening. One of the most important aspects of surgical tumor removal is the surgeon’s experience either visually or through touch in determining the border between tumor and normal or normal, but damaged tissue. General surgical oncologic principles are often not applicable for neurosurgical oncology. Wide surgical margins are a main tenet of surgical oncology, however, they are often an unrealistic goal when dealing with neoplasia in the vertebrae or spinal cord because of the obvious vital nature of the surrounding nervous system. With vertebral neoplasia a significant portion, if not all of a vertebral body, lamina, or pedicles, may be involved requiring extensive surgical resection.65 Although total vertebrectomy is possible, tumor margins often extend to the edge and beyond reasonable limits of vertebral resection. If the amount of bone removal is excessive, surgical stabilization of the involved spinal segments is necessary. This stabilization can be accomplished with spinal fractures using a combination of bone screws, Steinmann pins, K-wires, and polymethylmethacrylate or other techniques. If the tumor is located within the proximal brachial plexus or associated peripheral nerve, an approach to this area may be necessary concurrently with an approach that will afford lateral access to the cervical spinal cord.53,66–68 In this situation, the animal is positioned in lateral recumbency with the side of the exploration facing upward. Some prefer, if a hemilaminectomy is also to be performed, to tilt the dorsal aspect of patients in a dorsolateral direction to varying degrees (20 –45 ). A hemilaminectomy can also be performed with the animal in lateral recumbency. Nerve sheath tumors tend to expand intradurally and form bulbous enlargements into the spinal cord. The enlargements tract inward with the nerve rootlets and often hide underneath the spinal cord ventrally. Magnification and microdissectors and scissors are used for tumor removal. Hemorrhage from venous sinuses is controlled by adequate removal of compressive material, absorbable gelatin sponge (Gelfoam) or similar material (autogenous muscle), or some combination of the two. Once the spinal cord is decompressed it should be visible lying flat along the floor of the vertebral canal. Gelatin sponge is placed in the bony defect. The muscles, subcutaneous tissues, and skin are routinely apposed. RADIATION THERAPY
Conventional radiation therapy is being used with increasing frequency in dogs with spinal tumor.60,69 Overall, however, small numbers of animals with spinal tumors have been treated. Radiation therapy is more apt to control tumor progression; however, in some instances it may eradicate the tumor completely. Significant and
Spinal Neoplasms in Small Animals
rapid reduction in spinal lymphoma, for example, may occur following radiation therapy. The main goal of the treatment is to administer to the tumor the highest possible dose while minimizing the dose to the surrounding normal tissue. Radiation protocols vary.69 Fractional dosing schemes have been used to decrease the acute toxicity of the radiation. The majority of dogs treated for spinal tumors receive 38 to 48 Gy total dose administered in smaller (3–4 Gy) fractions each. These doses appeared to be generally well tolerated for the periods studied. Some of the reports indicated neurologic and pathologic change compatible with acute radiation induced necrosis. A fraction size of 3 Gy may reduce the incidence of late-responding tissue response. It is recommended, therefore, that daily fractions of 3 Gy be given with the total normal tissue dose below 50 to 55 Gy. Side effects include radiation damage to normal structures surrounding the abnormality. Both acute, early delayed, and late delayed affects can be seen. The acute affects may be the result of edema caused by tumor kill and may be reversed with antiedema medications. The later effects may not be reversible and may be as detrimental to the animals as the underlying disease. CHEMOTHERAPY
Chemotherapies are infrequently used for primary spinal tumors.70 In some instances, similar chemotherapeutic agents used for appendicular osteosarcoma (cisplatin, carboplatin) are used for vertebral osteosarcoma. Spinal or perispinal lymphoma may be responsive to similar chemotherapeutic agents as for systemic lymphoma. Because of the good cerebrospinal fluid penetration of cytosine arabinoside, this drug is often added to spinal lymphoma treatment regimes. PROGNOSIS OF ANIMALS WITH SPINAL TUMOR
There are too few large series assessing prognoses of animals with spinal tumors to make accurate treatment recommendations for affected animals. Individual animals with tumors in each of the 3 locations (extradural, intradural/extramedullary, and intramedullary) have been successfully treated with combinations of surgery or radiation therapy, but overall efficacy of specific treatments in statistically significant numbers of affected animals is not determined. Advances in microsurgical techniques have afforded the ability to successful operate tumors involving the spinal cord; however, reports of larger numbers of similarly affected animals will be required to make objective outcome conclusions. In one report of 37 dogs with a variety of spinal tumors, median survival of all dogs that survived 20 days following diagnosis was 240 days.9 A total of 40% of these dogs, however, were euthanized or died within the first 20 days following diagnosis. These dogs were not figured into the overall survival statistics. Tumors primary involving the vertebral body may be associated with shorter survival times. Reviews of spinal tumors and peripheral nerve sheath tumors have been reported.9,40,41,71 Median survival in dogs with spinal tumors that had surgery varied depending upon whether the tumor was benign or malignant.40 For nerve sheath tumors, prognosis was influenced by whether the tumor was more peripheral in location versus involving the nerve plexus or root (median survival plexus group 360 days, median survival root group 150 days). Intramedullary tumors have historically been diagnosed at necropsy with infrequent reports of treatment. Surgical removal is occasionally successful and, with refinements in microsurgical experiences, should be used more frequently in the future following advancements in all types of primary spinal cord surgeries.
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SUMMARY
Diagnosis and treatment of spinal neoplastic disease is increasingly occurring in the modern veterinary era. Most of the recent advancements in this field have resulted from (1) increased use of imaging modalities, such as MRI, which provide important anatomic information, such as tumor extent and involvement, and (2) increased surgical experiences with tumor removal in or surrounding the spinal cord. Surgery of the spine is more successful in the modern era as veterinarians better understand the limitations of the spinal cord to surgical manipulation during tumor removal. Increasing use of additional treatment modalities, such as radiation therapy, chemotherapies, and the like, will hopefully result in increased survival and quality of life for animals with spinal neoplastic disease. REFERENCES
1. Bagley RS. Fundamentals of veterinary clinical neurology. Ames (IA): Wiley Blackwell; 1996. 2. de Lahunta A. Veterinary neuroanatomy and clinical neurology. 2nd edition. Philadelphia: WB Saunders; 1983. 3. Gilmore DR. Neoplasia of the cervical spinal cord and vertebrae in the dog. J Am Anim Hosp Assoc 1983;19:1009–14. 4. Gilmore DR. Intraspinal tumors in the dog. Comp Cont Educ Pract 1983;5:55–64. 5. Gruber A, Kneissl S, Vidoni B, et al. Cervical spinal chordoma with chondromatous component in a dog. Vet Pathol 2008;45(5):650–3. 6. Huisinga M, Henrich M, Frese K, et al. Extraventricular neurocytoma of the spinal cord in a dog. Vet Pathol 2008;45(1):63–6. 7. Levy MS, Kapatkin AS, Patnaik AK, et al. Spinal tumors in 37 dogs: clinical outcome and long-term survival (1987–1994). J Am Anim Hosp Assoc 1997;33:307–12. 8. Luttgen PJ, Braund KG, Brawner WR Jr, et al. A retrospective study of twenty-nine spinal tumours in the dogs and cat. J Soc Adm Pharm 1980;21:213–26. 9. Petersen SA, Sturges BK, Dickinson PJ, et al. Canine intraspinal meningiomas: imaging features, histopathologic classification, and long-term outcome in 34 dogs. J Vet Intern Med 2008;22(4):946–53. 10. Rizzo SA, Newman SJ, Hecht S, et al. Malignant mediastinal extra-adrenal paraganglioma with spinal cord invasion in a dog. J Vet Diagn Invest 2008;20(3):372–5. denas S, Pumarola M, An˜or S. Imaging diagnosis–cervical spine chondroma in 11. Ro a dog. Vet Radiol Ultrasound 2008;49(5):464–6. 12. Summers BA, Cummings JF, de Lahunta A. Veterinary neuropathology. St. Louis (MO): Mosby; 1995. 13. Wright JA. The pathological features associated with spinal tumours in 29 dogs. J Comp Pathol 1985;95:549–57. 14. Wells MY, Weisbrode SE. Vascular malformations in the thoracic vertebrae of three cats. Vet Pathol 1987;24:360–1. 15. Zaki FA, Prata RG, Hurvitz AI, et al. Primary tumors of the spinal cord and meninges in six dogs. J Am Vet Med Assoc 1975;166:511–7. 16. Bentley JF, Simpson ST, Hathcock JT, et al. Metastatic thyroid solid-follicular carcinoma of the cervical portion of the spine of a dog. J Am Vet Med Assoc 1990;197:1498–500. 17. Byrne TN. Spinal cord compression from epidural metastasis. N Engl J Med 1992;327:614. 18. Cooley DM, Waters DJ. Skeletal metastasis as the initial clinical manifestation of metastatic carcinoma in 19 dogs. J Vet Intern Med 1998;12:288–93.
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19. Jeffery ND, Phillips SM. Surgical treatment of intramedullary spinal cord neoplasia in two dogs. J Soc Adm Pharm 1995;36:553–7. 20. Macpherson GC, Chadwick BJ, Robbins PD. Intramedullary spinal cord metastasis of a primary lung tumour in a dog. J Soc Adm Pharm 1993;34:242–6. 21. Platt SR, Sheppard BJ, Graham J, et al. Pheochromocytoma in the vertebral canal of two dogs. J Am Anim Hosp Assoc 1998;34:365–71. 22. Uchida K, Morozumi M, Yamaguchi R, et al. Diffuse leptomeningeal malignant histiocytosis in the brain and spinal cord of a Tibetan Terrier. Vet Pathol 2001; 38:219–22. 23. Van Ham L, van Bree H, Maenhout T, et al. Metastatic pilomatrixoma presenting as paraplegia in a dog. J Soc Adm Pharm 1991;32:27–30. 24. Waters DJ, Hayden DW. Intramedullary spinal cord metastasis in the dog. J Vet Intern Med 1990;4:207–15. 25. Woo GH, Bak EJ, Lee YW, et al. Cervical chondroid chordoma in a Shetland sheep dog. J Comp Pathol 2008;138(4):218–23. 26. Lane SB, Kornegay JN. Spinal lymphosarcoma. In: August JR, editor. Consultations in feline internal medicine. Philadelphia: WB Saunders; 1991. p. 487. 27. Marioni-Henry K, Van Winkle TJ, Smith SH, et al. Tumors affecting the spinal cord of cats: 85 cases (1980–2005). J Am Vet Med Assoc 2008;232(2):237. 28. Suess RP Jr, Martin RA, Shell LG, et al. Vertebral lymphosarcoma in a cat. J Am Vet Med Assoc 1990;197:101. 29. Aloisio F, Levine JM, Edwards JF. Immunohistochemical features of a feline spinal cord gemistocytic astrocytoma. J Vet Diagn Invest 2008;20(6):836–8. 30. Appel SL, Moens NM, Abrams-Ogg AC, et al. Multiple myeloma with central nervous system involvement in a cat. J Am Vet Med Assoc 2008;233(5):743–7. 31. Marks SL, Bellah JR, Wells M. Resolution of quadriparesis caused by cervical tumoral calcinosis in a dog. J Am Anim Hosp Assoc 1991;27:72–6. 32. Reif U, Lowrie CT, Fitzgerald SD. Extradural spinal angiolipoma associated with bone lysis in a dog. J Am Anim Hosp Assoc 1998;34:373–6. 33. Wright JA, Bell DA, Clayton-Jones DG. The clinical and radiological features associated with spinal tumours in thirty dogs. J Soc Adm Pharm 1979;20:461–72. 34. Banks WC, Bridges CH. Multiple cartilaginous exostoses in a dog. J Am Vet Med Assoc 1956;110:156. 35. Chester DK. Multiple cartilaginous exostoses in two generations of dogs. J Am Vet Med Assoc 1971;159:895. 36. Gavin PG, Bagley RS. Practical small animal MRI. Ames (IA): Wiley Blackwell; 2009. 37. Pool RR, Carrig CB. Multiple cartilaginous exostoses in a cat. Vet Pathol 1972;9: 350–9. 38. Doige CE, Pharr JW, Withrow SJ. Chondrosarcoma arising in multiple cartilaginous exostoses in a dog. J Am Anim Hosp Assoc 1978;14:605–11. 39. Owen LN, Bostock DE. Multiple cartilaginous exostoses with development of a metastasizing osteosarcoma in a Shetland sheepdog. J Soc Adm Pharm 1971;12:507–12. 40. Brehm DM, Vite CH, Steinberg HS, et al. A retrospective evaluation of 51 cases of peripheral nerve sheath tumors in the dog. J Am Anim Hosp Assoc 1995;31:349–59. 41. Bradley RL, Withrow SJ, Snyder SP. Nerve sheath tumors in the dog. J Am Anim Hosp Assoc 1982;18:915–21. 42. Fingeroth JM, Prata RG, Patnaik AK. Spinal meningiomas in dogs: 13 cases (1972–1987). J Am Vet Med Assoc 1987;191:720. 43. Raskin RE. An atypical spinal meningioma in a dog. Vet Pathol 1984;27:538–40.
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44. Targett MP, Dyce J, Houlton JEF. Tumours involving the nerve sheaths of the forelimb in dogs. J Small Anim Pract 1993;34:221. 45. Yoshioka MM. Meningioma of the spinal cord in a cat. Comp Cont Educ Pract 1987;9:34–8. 46. Blass CE, Kirby BM, Kreeger JM, et al. Teratomatous medulloepithelioma in the spinal cord of a dog. J Am Anim Hosp Assoc 1988;24:51–4. 47. Ferretti A, Scanziani E, Colombo S. Surgical treatment of a spinal cord tumor resembling nephroblastoma in a young dog. Prog Vet Neurol 1993;4:84–7. 48. Moissonnier P, Abbott DP. Canine neuroepithelioma: case report and literature review. J Am Anim Hosp Assoc 1993;29:397–401. 49. Summers BA, deLahunta A, McEntee M, et al. A novel intradural extramedullary spinal cord tumor in young dogs. Acta Neuropathol 1988;75:402–10. 50. De Vries-Chalmers Hoynk van Paperdrecht HR, Vos JH, van Nes JJ. Spinal cord ependymoma in two young dogs. Vet Q 1988;10:205–10. 51. Morita T, Kondo H, Okamoto M, et al. Periventricular spread of primary central nervous system T-cell lymphoma in a cat. J Comp Pathol 2009;140(1):54–8. 52. Shell L, Dallman M, Sponenburg P. Chondrosarcoma in a cat presenting with forelimb monoparalysis. Comp Cont Educ Pract 1987;9:391–7. 53. Steinberg HS. Brachial plexus injuries and dysfunction. Vet Clin North Am 1988; 18:565–80. 54. Flatland B, Fry MM, Newman SJ, et al. Large anaplastic spinal B-cell lymphoma in a cat. Vet Clin Pathol 2008;37(4):389–96, 3. 55. McCarthy RJ, Feeney DA, Lipowitz AJ. Preoperative diagnosis of tumors of the brachial plexus by use of computed tomography in three dogs. J Am Vet Med Assoc 1993;202:291–4. 56. Morgan JP, Ackerman N, Bailey CS, et al. Vertebral tumors in the dog: a clinical radiologic and pathologic study of 61 primary and secondary lesions. Vet Radiol Ultrasound 1980;21:197–212. 57. Bagley RS, Tucker RL. Specialty Board Review, neuroradiology. Prog Vet Neurol 1996;7:62. 58. Gambardella PC, Osborne CA, Stevens JB, et al. Multiple cartilaginous exostoses in the dog. J Am Vet Med Assoc 1975;166:761. 59. Kippenes H, Gavin PR, Bagley RS, et al. Magnetic resonance imaging features of tumors of the spine and spinal cord. Vet Radiol Ultrasound 1999;40:627–33. 60. Bailey CS. Long-term survival after surgical excision of a schwannoma of the sixth cervical spinal nerve in a dog. J Am Vet Med Assoc 1990;196:754. 61. Bell FW, Fenney DA, O’Brien TJ, et al. External beam radiation therapy for recurrent intraspinal meningioma in a dog. J Am Anim Hosp Assoc 1992;28:318–22. 62. Dernell WS, Van Vechten BJ, Straw RC, et al. Outcome following treatment of vertebral tumors in 20 dogs (1986–1995). J Am Anim Hosp Assoc 2000;36: 245–51. 63. Jeffery ND. Treatment of epidural haemangiosarcoma in a dog. J Small Animal Practice 1991;32:359–62. 64. Parker AJ, Park RD. Successful removal of a spinal cord tumor. Canine Pract 1974;1:35–7. 65. Yturraspe DJ, Lumb WV, Young S, et al. Neurologic and pathological effects of second lumbar spondylectomy and spinal column shortening in the dog. J Neurosurg 1975;42:47–58. 66. Lipsitz D, Bailey CS. Lateral approach for cervical spinal cord decompression. Prog Vet Neurol 1992;3:39–44.
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67. Piermattei DL, Greely RG. An atlas of surgical approaches to the bones of the dog and cat. 4th edition. Philadelphia: WB Saunders; 2004. 68. Sharp NJH. Craniolateral approach to the canine brachial plexus. Vet Surg 1988; 17:18–21. 69. Powers BE, Beck ER, Gillette EL, et al. Pathology of radiation injury to the canine spinal cord. Int J Radiat Oncol Biol Phys 1992;23:539–49. 70. Clemmons RM, Gorman NT, Calderwood Mays MB. Lumbar epidural chondrosarcoma in a dog treated by excision and chemotherapy. J Am Vet Med Assoc 1983; 183:1006–7. 71. Seppa¨la¨ MT, Haltia MJJ, Sankila RJ, et al. Long-term outcome after removal of spinal schwannoma: a clinicopathological study of 187 cases. J Neurosurg 1995;83:621.
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KEYWORDS Dog Cat Spine Neoplasm Tumor Spinal cord
Spinal cord disease can result from a variety of disease processes.1–3 Neoplastic disease can similarly involve the spinal cord, dura, exiting peripheral nerves, or perispinal tissues (eg, the vertebrae and ligaments) and result in clinical signs of spinal cord dysfunction. Because of the fact that many of these neoplastic processes are locally aggressive, early recognition of such diseases is important. This recognition often requires some type of advanced imaging of the spinal cord unless the abnormality obviously involves the vertebra. Surgical treatments are often employed for definitive diagnosis of the tumor and for decompression of the spinal cord. Other treatments, such as radiation therapy and chemotherapy, are used in some instances. Outcomes of animals affected with spinal tumors are dependent upon the growth characteristics and biologic behavior of the tumor itself and the degree of associated spinal cord damage. CLASSIFICATION
Spinal neoplasms are often categorized initially based upon the anatomic area, in relation to the dura and spinal cord, of spinal involvement.4–17 Tumors are grouped into those primarily arising from an extradural location (extradural), within the dura but outside the spinal cord proper (intradural/extramedullary), or arising within the spinal cord parenchyma proper (intramedullary). Obviously, depending upon growth characteristics and tumor aggressiveness, tumors can expand and extend from one of these strict anatomic areas to involve another. This expansion is most often seen with peripheral nerve sheath tumors that may begin in an extradural location but may traverse the dura into the intradural/extramedullary space, and eventually, into the spinal cord gray matter. Spinal tumors may also be classified into primary tumors (those tumors that arise from cells native to the spinal, dural, and perispinal tissues) or secondary tumors (those tumors that have metastasize from another location within the body).18–27 This system lends information as to whether the disease is localized or systemic and influences treatment and prognosis.
Neurology and Neurosurgery, Department of Clinical Sciences, Iowa State University, College of Veterinary Medicine, 1600 South 16th street, Ames, IA 50011-1250, USA E-mail address: [email protected] Vet Clin Small Anim 40 (2010) 915–927 doi:10.1016/j.cvsm.2010.05.010 vetsmall.theclinics.com 0195-5616/10/$ – see front matter ª 2010 Elsevier Inc. All rights reserved.
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Understanding the initial anatomic location of the cell of origin of the tumor aids in predicting the type of tumor present. Extradural tumors are the most common of all spinal tumors in dogs and cats (Fig. 1). These tumors include primary and secondary bone tumors (osteosarcoma, fibrosarcoma, chondrosarcoma), hemangiosarcoma, multiple myeloma and other plasma cell tumors, liposarcoma, and lymphosarcoma. Carcinomas are often found to metastasize to the extradural spinal location.20 Lymphosarcoma is the most commonly recognized spinal tumor in cats.28–30 Less commonly, benign neoplasms of bone, such as osteomas, fibromas, chondromas, and lipomas, may be present.31,32 Vascular expansile lesions have been seen in cats.33 In some instances, proliferations of bone and connective tissues mimic tumors but are not neoplastic. One example is multiple cartilaginous exostoses.34–37 These abnormalities are proliferations of bone and cartilage that are thought to result from aberrant growth displaced chondrocytes from the metaphyseal growth plates of bone. Subsequently, this disease is most often seen in younger animals (<18 months of age). Dogs, cats, and other species, including humans, have been reported with this disease. The boney and cartilaginous proliferations are often multiple and can affect the long bones, ribs, or vertebrae. The bony protuberances may be palpable. If these proliferations of cartilage affect the vertebrae, varying degrees of spinal pain, paresis, or paralysis may result. Radiographs of the affected bones often show proliferations of bone that are smooth, contoured, irregular, and multilobulated. These bony proliferations, however, may eventually become malignant as the animal ages.38,39 Intradural but extramedullary tumors include meningiomas and nerve sheath tumors.10,15,40–45 Meningiomas are most often found in the cervical area followed by the lumbar area. These tumors are infrequently found in the thoracic area. In the lumbar area, these tumors often proliferate around, entwine, and become adherent to exiting peripheral nerves. Primary neoplasia may involve numerous peripheral nerves within or around the spinal cord (Figs. 2 and 3). Clinical signs are related to dysfunction of the involved
Fig. 1. Transverse, T2-weighted MRI of the cervical spine of a dog with an extradural tumor. There is tumor both extradural (small arrow) and lateral to the vertebrae (larger arrows).
Spinal Neoplasms in Small Animals
Fig. 2. Intraoperative view following laminectomy of a dog with a nerve sheath tumor abutting the dura (arrows).
peripheral nerves. General clinical signs reflect lower motor neuron dysfunction. These signs include hyporeflexia to areflexia, hypotonia to atonia, neurogenic atrophy, and abnormal proprioception. Primary neoplasia involving the peripheral nervous system usually results in clinical dysfunction localized to one body area or nerve segment. Nerve sheath tumors are one of the most common types of primary neoplasia of the peripheral nervous system. These tumor types include schwannomas, neurofibromas, and neurofibrosarcomas. Histologic differentiation is sometimes difficult and the biologic behavior is similar allowing for the use of the generic grouping within the nerve sheath tumor category. These tumor types can arise from the Schwann (myelinated) cell of the peripheral nervous system, from connective tissue elements associated with the peripheral nerve, or from the axon and cell body. Tumors often involve nerves of the thoracic limbs but any peripheral nerve, including cranial nerves, may be involved. Nerve sheath tumor, for example, may involve the sciatic nerve and result in pelvic limb lameness. Importantly, nerve sheath tumors may involve the nerve at any site along its length. Distally located tumors may be focally painful if palpated, and may sometimes result in firm enlargements that may be tubular or spherical in shape. These tumors tend to feel firm upon palpation. Additionally, there is an unusual intradural but extramedullary tumor that has been referred to by various terms, including neuroepithelioma and spinal cord
Fig. 3. Intraoperative view following brachial plexus exploration from a dog with a peripheral nerve sheath tumor. Note the enlarged, discolored nerve (Larger arrows) compared with an adjacent normal nerve (smaller arrows).
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blastoma.4,46–49 This tumor tends to occur in young animals and often occurs in the T11 to L2 area of the spinal cord. German shepherds may be overrepresented with this tumor type.4 In some instances a histologically similar tumor may be present in other locations rather than limited to the T11 to L2 region, and in other breeds of dogs besides German Shepherds. Intramedullary tumors include astrocytomas, oligodendrogliomas, and ependymomas. These tumors arise from cells within the spinal cord parenchyma.4,6,10,15,50 They are often poorly encapsulated and sometimes difficult to differentiate from normal spinal cord tissue (Fig. 4). In some instances, however, the tumors are well encapsulated and firm, making differentiation easier. Metastatic disease can also affect the spinal cord.18–20,25,26,51 Both extradural and intramedullary metastasis is possible. Carcinomas are one of the most common types of tumors associated with extradural metastasis. In some instances, clinical signs of the metastasis may be apparent before clinical signs of the primary tumor. Hemangiosarcoma has resulted in intramedullary spinal cord metastasis.26 CLINICAL FEATURES
Clinical signs of spinal tumor are never pathognomonic because these signs are prototypical of spinal cord dysfunction and pain.3,10,33,36,40,41,52 The location that the spinal cord is involved will determine the presence of associated upper-motor or lowermotor neuron (LMN) signs. If the tumor begins in a peripheral nerve, clinical signs usually involve a nonlocalizable lameness, monoparesis, localized appendicular muscle atrophy, or pain.53 Dogs with nerve sheath tumor may initially present for lameness and may be initially diagnosed as having some orthopedic and musculoskeletal causes for the dysfunction. Complicating the ultimate diagnosis, many animals will concurrently have minor
Fig. 4. Transverse, T2-weighted MRI of the spinal cord of a dog with an intramedullary lesion. There is a hyperintense lesion presence within the spinal parenchyma. Histologic diagnosis was a glioma (arrow).
Spinal Neoplasms in Small Animals
orthopedic or musculoskeletal abnormalities. Progression of signs reflective of an LMN dysfunction ultimately suggests a nervous-system origin of the problem. Pain upon direct palpation may be present, with some dogs requiring sedation or anesthesia for adequate palpation of this area. Some animals, even at seemingly adequate depths of anesthesia, will awaken quickly during palpation indicative of a painful reaction. Occasionally an obvious mass or tissue enlargement is palpated. These masses may be linear, tubular, or spherical as they course along the affected nerve. Nerve sheath tumors may also result in a chronically painful condition. In some animals this manifests only in signs of depression and behavioral change and obvious localized pain may not be found on physical examination. Associated behavior abnormalities include aggression toward owners, unwillingness to play, and a general lethargy. These clinical signs could reflect a variety of clinical diseases and may prompt pursuit of diagnostic evaluations for systemic disease. If the nerve roots involved are not associated with the cervical or lumbar intumescence, the animal may only have spinal pain. The limb may be positioned in a more flexed posture (nerve root signature). Clinical signs usually progress to proprioceptive impairment. Occasionally an animal will present with acute paraplegia or tetraplegia caused by spinal cord compression. This compression may result from the effects of the mass itself or from associated spinal cord pathophysiologic alterations, including edema, ischemia, infarction, or hemorrhage as a consequence of the mass. These latter abnormalities often account for the acuity of onset of clinical signs that often accompany spinal tumors. Importantly, a spinal tumor should not be overlooked as a cause of acute spinal cord dysfunction. Clinical signs of all tumor types depend upon the level of spinal cord involvement. Tumors of the C6 to T2 segments or brachial plexus nerves may be associated with ipsilateral Horner’s syndrome or ipsilateral loss of cutaneous trunci contraction. Generally, extradural and intradural extramedullary tumors result in some form of pain, whereas the intramedullary tumors may be nonpainful. If, however, the tumor causes expansion of the spinal cord resulting in stretching of nerve roots or compression of the dura, hyperesthesia may be present. The progression of clinical signs is often more chronic with the extradural tumors and more acute with the intramedullary tumors. SPINAL TUMORS IN CATS
Cats have some different features with regards to spinal tumors.26–30,37,45,51,52,54 Lymphosarcoma appears to be the most common tumor affecting the spinal cord followed by osteosarcoma.29 Cats with lymphosarcoma were typically younger at initial examination, had a shorter duration of clinical signs, and had lesions in more regions of the central nervous system than did cats with other types of tumors. In 22 of 26 (84.6%) cats with lymphosarcoma, the tumor was also found in extraneural sites. Feline leukemia virus status was inconsistent. Osteosarcoma in the vertebrae of cats may act less aggressively compared with similar tumors in dogs. DIAGNOSIS
Diagnosis of a spinal tumor is often presumptively made using survey spinal radiographs, myelography, or advanced imaging (CT and MRI).10,55,56 Tumors of bone may be evident on survey radiographs as osteolytic/osteoproliferative processes. These bony changes need to be differentiated from diskospondylitis and vertebral bony osteomyelitis. Classically, vertebral tumors do not cross the joint space (intervertebral disk). Rarely, however, vertebral tumors invade adjacent vertebral bodies and
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therefore appear to ‘‘jump’’ the joint. Extradural compression of the spinal cord overlying the vertebral body rather than the intervertebral disk space is suspicious for neoplasia. Soft tissue tumors are usually not apparent on survey radiographs. Nerve sheath tumors, however, may involve exiting peripheral nerves within the intervertebral foramina.10 The foramen where the abnormal nerve is exiting may be enlarged and visible on survey radiographs. Myelography has historically been used to outline the subarachnoid space and determine if spinal cord compression or expansion is present. However, myelography is now increasingly less used with the advent of advanced imaging, such as MRI. MRI is superior to myelography in almost all instances of spinal imaging. The principle location description of tumor categories still remains from the myelography era. In extradural tumors, one or both of the contrast columns may be shifted axial (toward the center of the spinal canal). Clues to the presence of an extradural tumor include compression of the spinal cord primarily overlying a vertebral body rather than the intervertebral disk space and annular compressive lesions of the dura. These same imaging features may also be seen with intervertebral disk disease and other spinal cord compressive diseases and therefore should not be considered pathognomonic for extradural spinal tumor. With intradural but extramedullary tumors, spinal imaging will often result in a characteristic pattern of expansion of the subarachnoid space and outlining of the tumor in negative shadow, referred to as a golf tee (Fig. 5).10,33,57 Nerve sheath tumors may also expand to either side of where the nerve traverses the dura, giving these tumors a dumbbell-shaped appearance. Conversely, expansion of the dural tube in 90 opposed radiographic views is indicative of an intramedullary lesion. Advanced imaging studies, such as CT or MRI, have greatly improved the ability to determine the extent of any spinal tumor.58 The major advantage of both CT and MRI techniques is the ability to noninvasively image structures below to the surface of the body. Advantages of CT imaging include the ability to image in planes giving a spatial orientation to abnormalities seen. Disadvantages include its use of ionizing radiation (radiation exposure) and the poor imaging of the spinal cord. Spatial resolution, especially for small animals like as cats, may not be adequate to determine small (<5 mm) lesions. With CT, a myelogram is often necessary as part of the CT evaluation process to more accurately outline the subarachnoid space. Unfortunately, by having to perform myelography, the inherent risks to the animal from myelography are introduced into the cost/benefit of the procedure. In some instances, a series of scans are performed before and after intravenous injection of an iodinated contrast material. Abnormalities disrupting the blood-spinal cord or blood-nerve barrier may become more apparent
Fig. 5. Lateral, MRI myelographic view of a dog with an intradural but extramedullary lesion showing a golf-tee sign (arrow).
Spinal Neoplasms in Small Animals
with this technique. Loss of integrity of these barriers or increased vascularity may result in an area of increased uptake (whiteness) after intravenous contrast enhancement. Contrast enhancement is most often seen with tumors, vascular abnormalities, and inflammatory foci; however, it may also be seen with intervertebral disk disease. MRI is the imaging modality of choice for a variety of spinal lesions.58 MRI affords superior anatomic evaluation of soft tissue structures. Similar to myelography, MRI is helpful in determining the presence of a spinal cord compressive or expansile lesion. MRI, however, is superior to all other spinal studies in delineating soft tissue components of spinal lesions.36,59 Most epidural tumors invade the surrounding vertebral body before impinging on the spinal cord. Thus, bony destruction of the vertebrae may be a clue to an underlying neoplastic process. In general, on T1-weighted images, vertebral bone marrow signal should be roughly equivalent to disk material. In instances of diffuse marrow involvement, the disk spaces will show greater signal intensity than the vertebral marrow. Tumors are typically vascular and invasive, breaking the normal integrity of the blood brain barrier thus intravenous injection of a contrast agent generally results in some degree of either diffuse or focal enhancement in the area affected by tumor. Contrast enhancement does not precisely define the tumor borders; neoplastic cells are generally found outside the enhanced portion of the mass. Gadolinium administration may not be as helpful in identifying tumors that involve the vertebral bodies, because gadolinium-enhanced osseous lesions may have an appearance similar to that of normal marrow. Particular enhancing characteristics have been inconsistent various tumors. Intradural, extramedullary tumors may result in a similar golf-tee appearance to the subarachnoid space, which is most evident on T2-weighted images. These tumors are occasionally less obvious because they may have little contrast with respect to the adjacent spinal cord. These tumors may also not be as obvious on sagittal images if they are primarily lateral to the spinal cord. Intravenous gadolinium-DTPA (Magnevist, Berlex Laboratories, Cedar Knolls, NJ, USA), enhances these tumors increasing their signal intensity on T1-weighted images. Dorsal and transverse contrast-enhanced images are helpful images to detect this category of tumors. Intramedullary tumors generally cause the spinal cord to be expanded. On T1-weighted images, most intramedullary neoplasms have diminished signal intensity with respect to the cord. On T2-weighted images, they usually have a brighter signal than cord, which often reflects associated spinal cord edema or hemorrhage. Most tumors have a nonhomogenous signal intensity and indistinct margins between tumor and surrounding normal cord. TREATMENT
Treatment options for spinal tumors include surgical removal and possibly radiation therapy.36,40–42,47,60–64 Surgical removal is most often reserved for extradural tumors, however, both intradural/extramedullary and intramedullary tumors have also been successfully resected. The ultimate prognosis depends upon degree of local resection, degree of spinal infiltration, associated spinal damage before and during surgery, surgeon experiences with spinal neoplastic conditions, and tumor type. SURGERY
Extradural tumors are removed by laminectomy, either dorsal or hemilaminectomy. Ventral slotting is inadequate for removal of most cervical tumors. Abnormal tissue is identified and removed via blunt or sharp dissection. Advanced imaging studies
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before surgery help in determining the extent of the tumor and involved vital structures but even with MRI the extent of the neoplastic process may be underappreciated. The surgical keys are obviously adequate lesion exposure and subsequent removal. Most surgical problems and failures result from inadequate surgical exposure. In some instances, increased bone removal necessary for tumor resection will result in a need for surgical stabilization through internal fixation. If the surgeon is not experienced in surgical spinal stabilization (if that becomes necessary) this can result in surgical failure. For spinal tumor removal, especially with intradural or intramedullary lesions, the vertebral structure needs to be removed. Caution is used during drilling with lesions that involve the vertebrae because the consistency and strength of this bone may be compromised, which may lead to unwarranted entry of the spinal canal with the drill. Also, if the tumor involves large vascular structures, such as the vertebral artery or sinus, bleeding during resection can be significant and life threatening. One of the most important aspects of surgical tumor removal is the surgeon’s experience either visually or through touch in determining the border between tumor and normal or normal, but damaged tissue. General surgical oncologic principles are often not applicable for neurosurgical oncology. Wide surgical margins are a main tenet of surgical oncology, however, they are often an unrealistic goal when dealing with neoplasia in the vertebrae or spinal cord because of the obvious vital nature of the surrounding nervous system. With vertebral neoplasia a significant portion, if not all of a vertebral body, lamina, or pedicles, may be involved requiring extensive surgical resection.65 Although total vertebrectomy is possible, tumor margins often extend to the edge and beyond reasonable limits of vertebral resection. If the amount of bone removal is excessive, surgical stabilization of the involved spinal segments is necessary. This stabilization can be accomplished with spinal fractures using a combination of bone screws, Steinmann pins, K-wires, and polymethylmethacrylate or other techniques. If the tumor is located within the proximal brachial plexus or associated peripheral nerve, an approach to this area may be necessary concurrently with an approach that will afford lateral access to the cervical spinal cord.53,66–68 In this situation, the animal is positioned in lateral recumbency with the side of the exploration facing upward. Some prefer, if a hemilaminectomy is also to be performed, to tilt the dorsal aspect of patients in a dorsolateral direction to varying degrees (20 –45 ). A hemilaminectomy can also be performed with the animal in lateral recumbency. Nerve sheath tumors tend to expand intradurally and form bulbous enlargements into the spinal cord. The enlargements tract inward with the nerve rootlets and often hide underneath the spinal cord ventrally. Magnification and microdissectors and scissors are used for tumor removal. Hemorrhage from venous sinuses is controlled by adequate removal of compressive material, absorbable gelatin sponge (Gelfoam) or similar material (autogenous muscle), or some combination of the two. Once the spinal cord is decompressed it should be visible lying flat along the floor of the vertebral canal. Gelatin sponge is placed in the bony defect. The muscles, subcutaneous tissues, and skin are routinely apposed. RADIATION THERAPY
Conventional radiation therapy is being used with increasing frequency in dogs with spinal tumor.60,69 Overall, however, small numbers of animals with spinal tumors have been treated. Radiation therapy is more apt to control tumor progression; however, in some instances it may eradicate the tumor completely. Significant and
Spinal Neoplasms in Small Animals
rapid reduction in spinal lymphoma, for example, may occur following radiation therapy. The main goal of the treatment is to administer to the tumor the highest possible dose while minimizing the dose to the surrounding normal tissue. Radiation protocols vary.69 Fractional dosing schemes have been used to decrease the acute toxicity of the radiation. The majority of dogs treated for spinal tumors receive 38 to 48 Gy total dose administered in smaller (3–4 Gy) fractions each. These doses appeared to be generally well tolerated for the periods studied. Some of the reports indicated neurologic and pathologic change compatible with acute radiation induced necrosis. A fraction size of 3 Gy may reduce the incidence of late-responding tissue response. It is recommended, therefore, that daily fractions of 3 Gy be given with the total normal tissue dose below 50 to 55 Gy. Side effects include radiation damage to normal structures surrounding the abnormality. Both acute, early delayed, and late delayed affects can be seen. The acute affects may be the result of edema caused by tumor kill and may be reversed with antiedema medications. The later effects may not be reversible and may be as detrimental to the animals as the underlying disease. CHEMOTHERAPY
Chemotherapies are infrequently used for primary spinal tumors.70 In some instances, similar chemotherapeutic agents used for appendicular osteosarcoma (cisplatin, carboplatin) are used for vertebral osteosarcoma. Spinal or perispinal lymphoma may be responsive to similar chemotherapeutic agents as for systemic lymphoma. Because of the good cerebrospinal fluid penetration of cytosine arabinoside, this drug is often added to spinal lymphoma treatment regimes. PROGNOSIS OF ANIMALS WITH SPINAL TUMOR
There are too few large series assessing prognoses of animals with spinal tumors to make accurate treatment recommendations for affected animals. Individual animals with tumors in each of the 3 locations (extradural, intradural/extramedullary, and intramedullary) have been successfully treated with combinations of surgery or radiation therapy, but overall efficacy of specific treatments in statistically significant numbers of affected animals is not determined. Advances in microsurgical techniques have afforded the ability to successful operate tumors involving the spinal cord; however, reports of larger numbers of similarly affected animals will be required to make objective outcome conclusions. In one report of 37 dogs with a variety of spinal tumors, median survival of all dogs that survived 20 days following diagnosis was 240 days.9 A total of 40% of these dogs, however, were euthanized or died within the first 20 days following diagnosis. These dogs were not figured into the overall survival statistics. Tumors primary involving the vertebral body may be associated with shorter survival times. Reviews of spinal tumors and peripheral nerve sheath tumors have been reported.9,40,41,71 Median survival in dogs with spinal tumors that had surgery varied depending upon whether the tumor was benign or malignant.40 For nerve sheath tumors, prognosis was influenced by whether the tumor was more peripheral in location versus involving the nerve plexus or root (median survival plexus group 360 days, median survival root group 150 days). Intramedullary tumors have historically been diagnosed at necropsy with infrequent reports of treatment. Surgical removal is occasionally successful and, with refinements in microsurgical experiences, should be used more frequently in the future following advancements in all types of primary spinal cord surgeries.
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SUMMARY
Diagnosis and treatment of spinal neoplastic disease is increasingly occurring in the modern veterinary era. Most of the recent advancements in this field have resulted from (1) increased use of imaging modalities, such as MRI, which provide important anatomic information, such as tumor extent and involvement, and (2) increased surgical experiences with tumor removal in or surrounding the spinal cord. Surgery of the spine is more successful in the modern era as veterinarians better understand the limitations of the spinal cord to surgical manipulation during tumor removal. Increasing use of additional treatment modalities, such as radiation therapy, chemotherapies, and the like, will hopefully result in increased survival and quality of life for animals with spinal neoplastic disease. REFERENCES
1. Bagley RS. Fundamentals of veterinary clinical neurology. Ames (IA): Wiley Blackwell; 1996. 2. de Lahunta A. Veterinary neuroanatomy and clinical neurology. 2nd edition. Philadelphia: WB Saunders; 1983. 3. Gilmore DR. Neoplasia of the cervical spinal cord and vertebrae in the dog. J Am Anim Hosp Assoc 1983;19:1009–14. 4. Gilmore DR. Intraspinal tumors in the dog. Comp Cont Educ Pract 1983;5:55–64. 5. Gruber A, Kneissl S, Vidoni B, et al. Cervical spinal chordoma with chondromatous component in a dog. Vet Pathol 2008;45(5):650–3. 6. Huisinga M, Henrich M, Frese K, et al. Extraventricular neurocytoma of the spinal cord in a dog. Vet Pathol 2008;45(1):63–6. 7. Levy MS, Kapatkin AS, Patnaik AK, et al. Spinal tumors in 37 dogs: clinical outcome and long-term survival (1987–1994). J Am Anim Hosp Assoc 1997;33:307–12. 8. Luttgen PJ, Braund KG, Brawner WR Jr, et al. A retrospective study of twenty-nine spinal tumours in the dogs and cat. J Soc Adm Pharm 1980;21:213–26. 9. Petersen SA, Sturges BK, Dickinson PJ, et al. Canine intraspinal meningiomas: imaging features, histopathologic classification, and long-term outcome in 34 dogs. J Vet Intern Med 2008;22(4):946–53. 10. Rizzo SA, Newman SJ, Hecht S, et al. Malignant mediastinal extra-adrenal paraganglioma with spinal cord invasion in a dog. J Vet Diagn Invest 2008;20(3):372–5. denas S, Pumarola M, An˜or S. Imaging diagnosis–cervical spine chondroma in 11. Ro a dog. Vet Radiol Ultrasound 2008;49(5):464–6. 12. Summers BA, Cummings JF, de Lahunta A. Veterinary neuropathology. St. Louis (MO): Mosby; 1995. 13. Wright JA. The pathological features associated with spinal tumours in 29 dogs. J Comp Pathol 1985;95:549–57. 14. Wells MY, Weisbrode SE. Vascular malformations in the thoracic vertebrae of three cats. Vet Pathol 1987;24:360–1. 15. Zaki FA, Prata RG, Hurvitz AI, et al. Primary tumors of the spinal cord and meninges in six dogs. J Am Vet Med Assoc 1975;166:511–7. 16. Bentley JF, Simpson ST, Hathcock JT, et al. Metastatic thyroid solid-follicular carcinoma of the cervical portion of the spine of a dog. J Am Vet Med Assoc 1990;197:1498–500. 17. Byrne TN. Spinal cord compression from epidural metastasis. N Engl J Med 1992;327:614. 18. Cooley DM, Waters DJ. Skeletal metastasis as the initial clinical manifestation of metastatic carcinoma in 19 dogs. J Vet Intern Med 1998;12:288–93.
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