Presentation

As in the case of any suspected spinal neoplasm, it is essential to perform a detailed physical exam and gather the patient′s history to guide the diagnostic process. In the case of CVJ tumors, clinical diagnosis is difficult as it may present similarly to pathologies of degenerative and traumatic origin. Nonetheless, there are several physical signs and reported symptoms that may suggest the presence of a CVJ tumor—the most common symptoms being mechanical and occipital neuralgia. As is the case for lesions in the cervical spine, mechanical pain is present in flexion and extension. However, lesions of the CVJ are distinguished from those in the subaxial spine by eliciting increased pain during rotational motion. It is postulated that the elicited rotational pain is due to stress at the atlantoaxial facet articulations and broad insertion of muscles to C2 and the occiput. Symptoms of occipital neuralgia are thought to originate from compression of the C2 sensory nerve root.1 Nocturnal pain and persistent, progressive pain are symptoms that may help guide tumor diagnosis. The afflicted segment can be approximated during physical exam via percussion or applied pressure to the symptomatic region. Other reported signs and symptoms include vertigo, dysarthria, dysphagia, and paraspinal muscular pain and spasm, the latter possibly resulting from spinal deformity and collapse.11

Signs and symptoms of neurological deficit are less common presentations than mechanical and occipital neuralgia, which may be due to the combination of the generous subarachnoid space at the CVJ (wider canal) and diagnostic advancements such as magnetic resonance imaging (MRI) that allow for the earlier detection of neoplasms during initial noxious presentations. When neurological deficit is present, it is more frequently due to atlantoaxial subluxation than direct tumor compression of the cord and brainstem.1 Nonetheless, patients may present with neurological deficit. Common signs include hyperreflexia, abnormal plantar responses, bowel and bladder dysfunction, spasticity, paraparesis, and occasionally Brown-Sequard syndrome. The most frequently involved cranial nerve is the spinal accessory nerve and, when compromised, patients present with torticollis and/or weakness of the trapezius and sternocleidomastoid muscles. Cerebellar ataxia may be present if the tumor extends across the foramen magnum.11

Laboratory Studies

Blood and serum studies may be useful in the diagnosis of metastatic lesions but have limited utility in the diagnosis of primary tumors. Nonetheless, serum-elevated serum markers such as prostate-specific antigen, carcinoembryonic antigen, and lactate dehydrogenase provide useful information to a diagnosis. In some cases, an elevated erythrocyte sedimentation rate can be found in the setting of a variety of benign and malignant primary tumors; however, this finding is common to any infection. A low hematocrit may suggest a marrow infiltrative process. Lastly, urine and serum electrophoresis should be obtained if a concern for plasmacytoma or multiple myeloma exists.13

Imaging

Numerous imaging modalities are helpful in the diagnosis of lesions at the CVJ, including plain radiography, computed tomography (CT), MRI, fluorodeoxyglucose positron emission tomography (FDG-PET), and nuclear scintigraphy. Plain radiography is usually the first imaging modality employed, and it may help in detecting lytic lesions, abnormal masses, pathological fractures, spinal deformities, and subluxation of the upper cervical spine. However, decisions and diagnoses are seldom made on the basis of plain radiography due to its insensitivity in the detection of spinal neoplastic processes.13

MRI is the gold standard for diagnosing metastatic and primary spine tumors due to its unmatched sensitivity and ability to exceptionally visualize soft tissue structures and bone–soft tissue interfaces of the CVJ. The latter allows for an anatomically accurate and highly detailed representation of paraspinal, neural, and osseous tumor involvement.1,13

CT provides highly detailed representations of the bony anatomy of the spine, providing a sensitive means of assessing lytic bone destruction and spinal alignment. CT is also useful for performing preoperative planning measurements of the bony spine, thereby being an essential tool for planning surgical intervention. CT with myelography can also provide a detailed rendering of the neural elements and thus serves as the imaging of choice for those patients in whom MRI is contraindicated.1,13

Bone scans serve as screening tools for tumor identification because they detect osteoblastic activity. However, a positive finding on a bone scan should be confirmed with MRI or CT because positive findings are nonspecific for tumor type. FDG-PET can help in distinguishing benign from malignant processes.14

Lastly, it should be mentioned that digital subtraction angiography permits elucidation of lesion vascularization and provides the possibility of embolization. Embolization is indicated for highly vascular tumors, and its use can significantly diminish the amount of intraoperative bleeding in highly vascular tumors, such as aneurysmal bone cysts. This decrease in bleeding allows for more aggressive tumor resection. However, it should be noted that embolization to the cervical spine is difficult because the tumor′s blood supply is from the carotid and pharyngeal arteries.11

Biopsy

Biopsies can be categorized as excisional biopsies, open incisional biopsies, and needle biopsies and can determine tumor pathology, which is essential for planning appropriate intervention. For example, a biopsy can provide a diagnosis of round cell tumors, such as lymphomas or Ewing sarcoma, where the most primary intervention is chemotherapy. However, the most common percutaneous needle biopsies are difficult to perform for CVJ lesions due to the complex anatomy of this region. Furthermore, these biopsies risk providing a false-negative <25% of the time. Open incisional and excisional biopsies are alternatives and indicated for establishing the diagnosis, although they are technically challenging in this region. It should be mentioned that transoral biopsies are contraindicated in this region to avoid seeding of the mouth with tumors.1,15

Metastatic Tumors

Although the bony spine is the third most frequent localizing site of distant metastases, metastatic disease to the CVJ accounts for only 0.5% of spine metastases. The mean age at presentation for affected patients is 60 years old, and the majority of tumors derive from carcinomas of the breast, prostate, and lung. Patient history is crucial because any patient with a history of cancer presenting with a constellation of findings suggestive of a neoplasm in the spine should automatically be thought to have a metastatic lesion. Mechanical (flexion, extension, and rotational) pain is most common. Neurological deficit is less common, occurring in only 0 to 22% of cases. MRI is the ideal modality as it provides an excellent visualization of bone and soft tissue interfaces, thereby elucidating tumor extension and involvement of adjacent structures. T2-weighted series are preferential to T1-weighted (without contrast) as they allow for assessing the presence or absence of spinal cord compression. T1-weighted imaging with contrast is an acceptable alternative to T2-weighted imaging. CT imaging can demonstrate lytic bone destruction or sclerotic tumor bone involvement and provides information on spine alignment crucial for preoperative planning.1 Tumors can be effectively managed through radiation and/or surgery, typically yielding decreased pain and improved function. Survival is variable and dependent on the pathology (i.e., origin) of the metastatic lesion.6

Malignant Primary Tumors

Multiple myeloma and plasmacytomas are the most common primary malignant tumors of the bony spine and the second most common to affect the CVJ. Plasmacytomas are considered benign lesions of lymphoid lineage that may differentiate into more aggressive neoplasms collectively known as multiple myeloma. These lesions are characterized by pathognomonic malignant cells in the bone marrow. Patients frequently present with diffuse osteoporosis and osteolytic bone destruction, resulting in local bony pain. Neurological deficits may also be present but are less common. A diagnostic workup of suspected cases consists of laboratory and imaging utilities. The imaging workup should include plain and CT radiographic imaging to reveal the lytic and cystic characteristic appearance of the lesions. A whole body bone scan is also useful in localizing additional lesions in the axial and appendicular skeleton. MRI may be useful in evaluating lesion extension into the spinal canal. A laboratory workup should include a complete blood cell count, electrolyte balance, and serum/urine electrophoresis. Patients afflicted with multiple myeloma are commonly severely anemic and hypercalcemic due to extensive neoplastic infiltration of the bone and marrow. Immune electrophoresis demonstrates monoclonal hypergammaglobulinemia in serum or Bence Jones proteins in urine, both of which are strong indicators of multiple myeloma. It should be noted that to diagnose multiple myeloma (versus a plasmacytoma), characteristic lesions must be in multiple locations. Plasmacytomas themselves have a benign course with a median survival of ~10 years. However, plasmacytomas are capable of transforming into a malignant myeloma, leaving patients with a median survival of 28 months. Optimal treatment of plasmacytomas involves a combination of pharmacotherapy and radiotherapy. The pharmacotherapy includes chemotherapeutic agents such as cyclophosphamide, melphalan, carmustine, and lomustine. It also includes adjuvant bisphosphonates to counteract osteoclastic tumor activity. Low-dose radiation (20 Gy in 10 fractions) is often sufficient to treat cases with absent cord compression. Surgical intervention is indicated in circumstances of bony cord compression not relieved by radiotherapy and in cases of severe spinal instability due to the multiple lesion pattern characteristic of multiple myeloma. Postoperative radiation therapy is also considered beneficial.11,15–17

Chordomas are the most common primary malignant tumors that affect the CVJ. They originate from remnants of the primitive notochord. Despite appearing histologically low grade, they are considered malignant due to their high recurrence rate and difficulty to completely resect. Although chordomas can be found throughout the bony spine, they are most commonly found at the two ends of the primitive notochord (35% of them affecting the clivus and CVJ). When occurring at the CVJ, they mostly involve the clivus and extend caudally to C1 and rarely C2. They are more common in males near the fifth to sixth decade than in other populations. When localized to the cervical spine, chordomas primarily present with mechanical neck pain. Occasionally, patients may present with an oropharyngeal mass, airway obstruction, and/or dysphagia due to the extensive soft tissue components of the tumor. On CT, chordomas appear as lytic bone lesions with abnormally large soft tissue components and, in 30% of cases, growth-associated calcification. Chordomas are best visualized on T2-weighted or T1-gadolinium enhanced MRI. On T2-weighted images, chordomas demonstrate a hyperintense signal in comparison to muscular tissue. In diagnostic biopsies, chordomas are known to seed along needle tracts; thus, transoral percutaneous biopsies are generally contraindicated in the suspicion of chordomas. Chordomas are best treated through a wide surgical excision (en bloc resection). In cervical lesions, surgical interventions are multidisciplinary, often requiring the participation of plastic surgeons and otolaryngologists to assist in approach and closure. Transglossal and transmandibular approaches are used because they provide the necessary working room and visualization to achieve complete resection. Lastly, it should be noted that proton beam therapy has recently emerged as an adjunct to surgery for treatment of lesions in difficult locations.18,19

Chondrosarcomas are malignant cartilaginous tumors. Although they most frequently affect the thoracic spine (60%), chondrosarcomas also occur in the cervical spine (20%). They typically present during the fifth or sixth decade and affect men twice as often as women. Symptoms develop gradually due to the neoplasm′s indolent growth rate. Experienced pain is usually described as focal and dull with a nocturnal exacerbation. A physical exam may yield a palpable mass in the neck as the tumor most frequently involves the posterior elements. Neurological deficit manifests in ~50% of patients at presentation but may be less common in tumors localizing to the CVJ. Chondrosarcoma lesions can be clearly visualized through CT, demonstrating characteristic evidence of lytic and destructive lesions, thickening of the vertebral cortex, bony focal expansion, and exophytic extension into soft tissue. On CT, conventional chondrosarcomas demonstrate a ring-and-arc pattern. Undifferentiated and mesenchymal chondrosarcomas demonstrate bone destruction. Clear cell chondrosarcomas show calcified lytic bone lesions and encompassing sclerosis. MRI may demonstrate soft tissue impingement and invasion by the neoplasm. Prognosis is related to the grade of the lesion. Chondrosarcomas are predominantly resistant to radiotherapy and chemotherapy and are best treated with surgical intervention. En bloc excision is ideal because intralesional (extracapsular) excision has been associated with a high rate of local recurrence. However, high-dose photon radiotherapy and hypofractionated stereotactic radiosurgery are being investigated as alternative therapies, particularly to treat lesions in areas, such as the CVJ, where total tumor removal is difficult. Lastly, angiography and embolization should be considered in the treatment of these highly vascular tumors.11,20

Osteosarcomas are among the most frequent malignant conditions that affect bony tissues. However, the majority of osteosarcomas occur in the appendicular skeleton with only 5% occurring in the axial skeleton. Osteosarcomas do not demonstrate a preference for location in the axial skeleton. Tumors most frequently arise during the second and third decade. Studies have found positive associations in patients with a history of Paget disease and hereditary retinoblastoma and in patients previously exposed to ionizing radiation. The majority of patients present with focal pain. When localized to the CVJ, patients less frequently present with neurological symptoms. When radiographically imaged (CT or plain), the lesions show a combination of both lytic and sclerotic growth patterns. The utility of MRI depends on the extent of tumor mineralization. Nonmineralized tumors display high intensity on T2-weighted series and hypointensity in T1-weighted images. In contrast, mineralized tumors are hypointense in both T1- and T2-weighted series. PET may yield the best diagnostic information in the case of osteosarcomas because the imaging utility is particular in detecting the increased bone turnover characteristic of osteosarcomas. Overall, survival prognosis for osteosarcomas is dismal with a median survival time of 2 years. En bloc surgical excision is ideal, and care must be taken to reduce breaching of tumor margins to diminish the incidence of recurrence. Chemotherapy regimens can be coupled to surgical intervention to reduce the incidence of recurrence. Conventional radiotherapy as a primary means of treatment is not recommended because many tumors have been found to be radioresistant. Nonetheless, radiotherapy has been found to be beneficial to treat microscopic postoperative residual tumor.11,12,15

Ewing sarcoma is one of the least frequent adult primary osseous malignant neoplasms occurring at the CVJ, although it is one of the most frequently occurring in children and adolescents. The neoplasm is of unknown origin and consists of a small round cell neoplasia. The most commonly presenting symptoms are pain and swelling. Additionally, the condition frequently presents with systemic symptoms, such as fever, and is commonly misdiagnosed as infection. Neurological symptoms may occur but are less common. Conventional radiography yields a mottled, moth-eaten appearance indicative of poorly defined margins and irregular bone destruction. A whole body bone scan is useful to detect additional lesions, which are a common finding in patients afflicted with this neoplasm. Additional diagnostic utilities include a serum lactate dehydrogenase test that suggests the potential presence of this illness. The current treatment of choice is a four-drug chemotherapeutic regimen consisting of dactinomycin, vincristine, cyclophosphamide, and doxorubicin. Recent studies have suggested the addition of etoposide and ifosfamide to the four-drug regimen, reporting increases in survival up to 24%. Conventional radiotherapy (of ~40–65 Gy) can be jointly administered with chemotherapy. The role of surgical intervention in the management of this disease has not yet been established.11,15,21