Diagnosis and Staging of Spine Tumors Rakesh Donthineni, MD, MBAa,b,* KEYWORDS  Spine  Tumor  Diagnosis  Benign  Malignant  Metastasis

percentage develop symptoms.8,9 Apart from the hematopoietic tumors, including myeloma and lymphoma, the primary malignant tumors of the spine include chordoma, chondrosarcoma, osteosarcoma, and others.

PRESENTATION Patients with spinal tumors most often present with axial pain, and some with radicular pain (if the tumor is extends to and compresses the nerves). A lesser percentage present with cauda equina syndrome and most of these are a result of metastatic disease and rapidly growing tumors. The cervical lesions tend to progress slowly in terms of neurologic symptoms, whereas the thoracolumbar lesions are more aggressive and are more clinically affected. About 60% will present with central or nerve root symptoms, and more than a third will present with a motor deficit. Sphincter function alterations in isolation are less frequent (less than 3%).10 Patients with cord compression not only have symptoms of sensory or motor disturbances, but most of them (>90%) have pain. There is often a delay from the time of the presentation of symptoms to the alterations in signs, and therefore, a delay in evaluation by the primary care doctor to the point of full diagnosis and management by a specialist. Plain radiographs may help in diagnosis in a fifth of the patients, whereas an MRI is much more useful in identifying the level of compression.11 As part of the patient evaluation and follow-up, the extent of the neurologic dysfunction should be carefully mapped.12

Financial disclosure: no funding of any sort was obtained to conduct this review. a Spine and Orthopaedic Oncology, 5700 Telegraph Avenue, Suite 100, Oakland, CA 94609, USA b Department of Orthopaedics, University of California Davis, Suite 3800, Y Street, Sacramento, CA 95817, USA * Spine and Orthopaedic Oncology, 5700 Telegraph Avenue, Suite 100, Oakland, CA 94609. E-mail address: [email protected] Orthop Clin N Am 40 (2009) 1–7 doi:10.1016/j.ocl.2008.10.001 0030-5898/08/$ – see front matter ª 2008 Elsevier Inc. All rights reserved.

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As the expected incidence of cancers in the United States approaches 1.5 million cases for 2008, and with more than 0.5 million deaths, it ranks second only to cardiovascular disease in significance. Nearly three quarters of all cancers are diagnosed in persons 55 years and older. The incidence per year of breast and prostate cancers are approximately 180,000 each, and slightly more for lung cancer. With the improvement in diagnosis and treatment methods, there is an increasing trend in long-term survival by about 30%.1 As patients with cancers have longer survival, there is an expected increase in the prevalence of metastatic disease. With a higher incidence and prevalence of cancers of other organs of the body, there are more symptomatic or asymptomatic cases of metastatic disease to the spine than primary tumors.2 Autopsy studies demonstrated between 30% and 90% of spinal metastases in patients with a history of other malignancy. The common primaries were lung, breast, lymphoma, and myeloma. Nearly 17% of patients with other primaries may present with spinal cord compression as a result of metastases.3–5 Metastases to the spine have a predilection toward the thoracic spine, followed by the lumbar and cervical.6 More than 2000 bone and joint cancers and about 10,000 soft tissue cancers are diagnosed per year.1 The incidence of benign tumors of the spine is a little more than 1% of all primary skeletal tumors, and nearly 5% for malignant tumors.7 Within the benign tumors, giant cell tumors, osteoid osteomas, osteoblastomas, and hemangiomas are more likely. Although the incidence of hemangioma of the spine is about 10% in the general population, only a small

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Donthineni The cause of the axial pain in patients with spinal tumors is because of the destructive effect of the tumor, the cortical breakdown, and also from extension into the canal with compression of the cord. Weakening of the vertebrae will likely lead to fractures, micro or macro, causing pain. The posterior longitudinal ligament is the weakest barrier for tumor growth, and the tumor often extends at points of perforating vessels. Spread to adjacent vertebrae is likely at the edge of the level involved beneath the longitudinal ligament, and via paravertebral muscles.13,14 The extension of metastatic tumors to the axial spine is mainly through the vascular mechanism, either by seeding via the arterial system or a closer spread via the valveless extradural venous system (Batson’s venous plexus). A more direct extension is seen in the pulmonary apical tumors. Although the mechanical spread of the tumors seems logical, the tendency of the tumors to settle in some environments more than others, as related to the molecular and surface protein behavior, should not be ignored.15–18 In patients with a history of a previous adenocarcinoma or other malignancies, a new focus of tumor in the skeletal system often correlates with the historical primary, but needs to be corroborated. Without such a history, an unidentified focus should prompt the search for the primary. A thorough history, examination, the basic laboratory studies, plain radiographs, and other appropriate imaging of the affected site, whole body technetium-99m-phospate bone scan, and CT scan of the chest, abdomen, and pelvis often identifies most of the primary sites. Biopsy of the lesion adds significant information, but if done alone has a lesser yield than the combine effort. There may still be a small percentage where the primary may not be identifiable.4,19–22 Once identified, whether a primary or secondary tumor, the next step should be the appropriate planning for management. Although imaging studies, such as MRI and CT, have greatly assisted in diagnosing based on radiographs, only a few tumors can be diagnosed without a histologic evaluation. Osteoid osteoma is one such tumor that can be diagnosed on the plain radiographs and CT, and one can proceed with the treatment, whether it be a surgical excision or a percutaneous ablation (radiofrequency ablation). With regard to metastatic disease, the indications for surgical intervention are intractable pain, worsening neurologic deficit, a pathologic fracture, and instability.

LABORATORY AND IMAGING STUDIES Apart from the basic workup of a patient with the spine tumor, most of the blood and serum studies

do not contribute much to the diagnosis in primary tumors of the musculoskeletal system. Elevated erythrocyte sedimentation rate can be found in round cell tumors, benign or malignant, and also in infections. Serum and urinary protein electrophoresis are helpful in identifying myeloma. Low hematocrit may suggest a marrow infiltrative process, although it could also signify an advanced stage malignancy. As part of the workup, imaging studies follow suit. Plain radiographs should be included, as they are easily accessible and allow approximate localization of the disease process (if visible on the radiographs), but also assist in evaluating the curvature of the spine and any changes in its structural appearance secondary to changes in the biomechanics. Lytic tumors are not easily identified on plain radiographs until close to 50% of bone destruction occurs. Increasing destruction (cross-sectional area) and a poor bone mineral density in combination contribute to a higher likelihood for compressive fractures. In the thoracic vertebrae, although a larger defect may portend to a compression fracture, the intact costovertebral joints play a significant support to the overall structure, and as such, any involvement of these joints rapidly leads to a vertebral collapse.23–26 Once the involved level is identified, CT and MRI are the studies of choice to give much more data on the distribution of the tumor within the vertebrae, its extension, and effects on the local anatomy. MRI with intravenous contrast (Gadolinium) will assist in identifying the areas of most activity, and may direct the placement of the biopsy needle to achieve a high yield. Whole-body technetium99m bone scan will help identify other sites of involvement, and hence help stage the disease, or even identify another location that may be an easier site for obtaining a piece of tissue for diagnostic purposes (Fig. 1). Angiography may be used, but more as a treatment in benign highly vascular tumors (eg, ABC, GCT) or in preparation for the surgical treatment of a vascular tumor (eg, renal and thyroid metastases, and multiple myeloma) and thereby decreasing the blood loss intraoperatively.27–30

BIOPSY A biopsy is mandatory if the isolated spinal lesion is unknown, even in the face of a distant history of a primary malignancy, as occasionally a new primary may be encountered. If the patient has a known history of metastatic disease with multiple lesions, the new troublesome spinal lesion may be

Diagnosis and Staging of Spine Tumors

Fig. 1. Whole body bone scan demonstrating the extensive metastatic disease.

treated without the need for further histologic proof before dealing with the offending lesion. Before planning the biopsy, the imaging studies need to be evaluated to ascertain the exact location of the tumor within the spinal column, and also to identify the most viable area on the MRI (with intravenous contrast), henceforth yielding the best tissue for diagnosis. The process of obtaining the tissue may be with a fine needle, core, incisional, or excisional. Needle and core biopsies are conducted percutaneously, with the difference being in the diameter of the bore. Incisional biopsy is conducted when an open approach to the tumor is conducted and a small piece of the tumor is obtained for analysis, leaving the rest in situ. In excisional biopsy, the whole tumor is removed with an intralesional, marginal, or wide margin. Percutaneous biopsies, with fine needle aspiration or core biopsy, for musculoskeletal lesions have a favorable outcome in about 75% of the cases.31 Fine needle aspiration may be adequate in metastatic tumors or in recurrences, whereas in cases of primary tumors, adequacy of tissue helps in the accuracy of diagnosis. Also, sufficient tissue is needed for not only for the standard stains in histology, but also possibly for immunostains and other studies, including cytogenetics. Increasing the diameter of the needle will obtain more

tissue and is helpful in sclerotic lesions, but the associated rates of complications increase.32 Albeit the varying results, image-guided transpedicular biopsy of the vertebral lesion is still the favored technique, the choice of imaging either fluoroscopy or CT (Figs. 2 and 3).33 Percutaneous CT guided (via the pedicle or otherwise) is often the standard approach by the interventional radiologists, as they have access to the appropriate imaging machines, and the overall accuracy has been reported to be about 89%, with lytic lesions having a better yield (93%) versus the sclerotic/ blastic lesions (76%). The sclerotic lesion accuracy is less than that for lytic or mixed lytic-sclerotic lesions or compression fractures, and also the false negative biopsies are higher in the sclerotic lesions. The accuracy is also lower if the lesion is visible on the MRI but not clear on CT imaging at the time of the biopsy.34 MRI-guided biopsies are available and can helpful in locating the biopsy needle in the viable part of the tumor to give a higher diagnostic yield.35 Open incisional or excisional biopsies must be properly planned and approached with an incision small enough to allow a future resection, in cases of recurrence or when dealing with a primary malignancy. Contamination of neighboring structures should be limited as much as possible, and the path of approach should be away from any vital neurovascular structures, as any contamination would require resection of these structures to prevent or decrease recurrences. Meticulous hemostasis is a must, as the seeping blood may

Fig. 2. Fluoroscopy-guided transpedicular approach for a vertebral body biopsy.

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Fig. 3. CT scan demonstrating the lytic tumor, and the biopsy track through the pedicle.

act as a low-barrier pathway for tumor invasion. Any cortical windows created to obtain tumor specimen need to be covered with either bone wax or cement (PMMA) to contain hemorrhage and tumor spillage. During the surgical preparation and draping, if a frozen section pathologic analysis is being considered, before the final treatment at the same surgical setting, a new set of instruments and drapes are mandatory to prevent accidental tumor seeding. This also applies when harvesting bone autograft from another site.36 Excisional biopsy may be performed for osteoid osteoma. In tumors such as osteoblastoma, aneurysmal bone cyst, and unknown metastatic adenocarcinoma, an intraoperative frozen section analysis is necessary before the definitive treatment of excision or cord decompression.

and occasionally chondroblastomas, benign skeletal tumors do not metastasize. Primary malignant tumors of the skeletal system often metastasize to lungs, and also to bones. A chest CT and a whole body bone scan will help identify these other locations. The Musculoskeletal Tumor Society’s staging system (adapted from Enneking and colleagues)39 is used extensively for tumors of the pelvis and extremities. The staging is based on either benign (1 5 latent, inactive; 2 5 active, but slow growing; 3 5 active and aggressive growth) or malignant tumors (I, II, and III). Low-grade primary malignant tumors are graded ‘‘I’’ and high are graded ‘‘II.’’ The tumor’s location within the compartment is denoted as ‘‘A’’ or extracompartmental as ‘‘B.’’ Those with spread beyond the local site (skip metastases or distant metastases) are denoted ‘‘III.’’ Although there was a notable difference between the outcomes of stages I, II, and III, the location of the tumor within a compartment or its extension outside does not affect the long-term outcome significantly.40 Systematic evaluation of spine tumors was developed by Tomita and colleagues41 and also by Weinstein-Boriani-Biagini.42,43 The WBB (Weinstein-Boriani-Biagini) staging system is based on viewing the affected vertebra in an axial view and dividing it into 12 equal radial segments (‘‘clock-face’’). The five outer to inner concentric layers are labeled A to E, with ‘‘A’’ as the extraosseous layer, and sequentially layering in to ‘‘E’’ as the dural involvement (Fig. 4). In the cervical vertebrae, ‘‘F’’ indicates involvement of the vertebral foramen (Fig. 5).

STAGING As the imaging modalities and reconstruction options improved, the confidence to resect complicated large tumors also followed suit.37,38 Whether it be primary (benign or malignant) or metastatic tumors, if the goal is to eradicate the tumor, then detailed imaging studies are necessary. Also, as part of understanding the extent of the tumors (primary malignant or metastatic), staging the disease helps prepare how to approach the local spinal tumor. After obtaining the history and physical examination and appropriate imaging studies of the local disease and a biopsy-proven diagnosis, the next step of the staging is to evaluate other sites of involvement. Apart from giant cell tumors

Fig. 4. WBB diagram of the thoracolumbar vertebra. (Courtesy of S. Boriani, MD, New York, NY.)

Diagnosis and Staging of Spine Tumors the patient’s general condition, the primary malignancy, systemic and the extent of local involvement, and other variables. Newer systems are being developed to improve management.6,44–46 As part of systemic staging, following tumor removal, the margin of the resection should be evaluated. There has been much confusion with the terminology for the type of surgery and the final margin. A more standardized approach should be recognized, both for universal use and understanding, but also for the comparison of multi-institutional data for long-term outcome studies.

Fig. 5. WBB diagram of the cervical vertebra. (Courtesy of S. Boriani, MD, New York, NY.)

Tomita’s scoring system describes the location of the tumor within the body (Type 1–3), extension outside the vertebra (Type 4–6), and involvement of other vertebrae (Type 7) (Fig. 6). Within the types 1 to 3, the extent of the tumor is either located within the body, extending to the pedicle, or to the lamina respectively. In Types 4 to 6, there is extension into the spinal canal alone, canal and lateral extraosseous extension, and to adjacent levels respectively. The categories help assist in planning the type of resection, either vertebrectomy (partial or total) and palliative surgery because of extensive involvement and spread. The use of these systems mandates adequate imaging studies (MRI and CT), allows adequate planning of the surgery, and assists in interinstitutional comparison of data for long-term outcomes. With regard to metastatic disease, various algorithms have been developed to help in planning the management. These systems help in evaluating

TERMINOLOGY Intralesional Excision Intralesion excision is defined as piecemeal removal of the tumor. This is further subcategorized based on the capsule. The ‘‘capsule’’ is the reactive zone at the periphery of the tumor. 1. Intracapsular, if tumor removal is incomplete, as gross or histologic remnants inside the tumor capsule can be expected. 2. Extracapsular, if tumor removal includes all of the tumor mass and a surrounding layer of healthy tissue, but microscopic tumor may be left behind as a result of intralesional excision.

En Bloc Resection En bloc resection is defined as in toto removal of the tumor mass, including a cuff of healthy tissue encasing the tumor (margin). The pathologist’s evaluation of the margin allows further subclassification of en bloc resections: 1. Intralesional, if the tumor is violated intentionally (trying to save some of the vital structures

Fig. 6. Tomita’s classification of vertebral tumor involvement. (Courtesy of Katsuro Tomita, MD, Norio Kawahara, MD, and Hideki Murakami, MD, Kanazawa, Japan.)

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Donthineni adhered or encased by the tumor) or unintentionally. 2. Marginal, if the dissection is through the reactive outer area of the tumor (pseudocapsule), potentially leaving microscopic tumor behind. 3. Wide, if a layer of peripheral healthy tissue, a dense fibrous cover (eg, fascia), or an anatomic barrier not yet infiltrated (eg, pleura), fully cover the tumor and the pathologist reading shows a negative margin. Radical resection, as described by Enneking and colleagues,39 suggests en bloc removal of the tumor including the whole compartment and is very rarely if at all used in the spine. An attempt at the radical resection of an affected vertebra would require the removal of the whole vertebra, and ergo, transection of the spinal cord or nerves. Also, if the tumor extends into the spinal canal, a radical resection would require the removal of the whole spinal canal and associated structures, a theoretic but ethically unreasonable concept. As such, the use of ‘‘radical resection’’ has to be carefully used to avoid unnecessary confusion.

SUMMARY The incidences of cancers are increasing, and as patients live longer, the risk of systemic and spinal metastases increases. Proper evaluation of the patient with history, examination, and imaging studies should help identify the cause of the symptoms, and after a histologic diagnosis, the next step is to strategize the management options. Detailed planning and staging will help not only in the surgical resection and reconstruction, but also achieve better outcomes for these patients.

ACKNOWLEDGMENTS Figs. 4 and 5 were used with the kind permission of Dr. Stefano Boriani and Fig. 6 from Drs. Katsuro Tomita, Norio Kawahara, and Hideki Murakami.

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