Meningioma

Meningiomas are the most common benign intradural tumors of the CVJ ( Fig. 38.1 ). One study of 133 intradural extramedullary foramen magnum tumors reported 75% meningiomas and 13% neurofibromas.15 Meningiomas are slow-growing tumors that originate from arachnoid cap cells and commonly attach to the dural covering of the brain and spinal cord.16 The World Health Organization (WHO) classifies meningiomas as grade 1 (benign), grade 2 (atypical), and grade 3 (anaplastic), which account for 80%, 5% to 20%, and 1% to 2% of all meningiomas, respectively.17,18 In large clinical series, there is a strong association between outcome and grade.19 On MRI, meningiomas classically present as an intradural, extramedullary mass that is iso- or hypointense on T1-weighted images, hyperintense on T2-weighted imaging, and uniformly contrast enhancing with gadolinium. Other characteristic findings are an enhancing dural tail and hyperostosis of adjacent bone. Meningiomas often express hormonal receptors, which may explain the increased prevalence of meningiomas in women, where the overall ratio is 2:1 in the brain and up to 10:1 in the spine.20 The best established of these receptors is the progesterone receptor, which is found in more than two thirds of these tumors. Additionally, > 30% of meningiomas also express estrogen receptors, and ∼40% express androgen receptors. Moreover, patients with meningiomas have been found to have a higher incidence of breast cancer, and breast cancer patients have a higher incidence of meningiomas.21 The most frequent genetic alteration seen in meningiomas is the loss of the neurofibromatosis type 2 (NF2) gene on chromosome 22q, which encodes a tumor suppressor called merlin (also known as schwannomin). Merlin is related to molecules of the protein 4.1 superfamily that are involved with cell growth and regulation.18,20

Gross total resection is the gold standard treatment for these tumors. Surgical resection generally leads to good outcomes and low recurrence rates in the spine,22 and gross total resection of spinal meningiomas is achieved in 82 to 97% of cases.23,24 Interestingly, it has been reported that atypical and anaplastic meningiomas are found less frequently at the cranial base and spine,25 and the recurrence rate of spinal meningiomas is lower when compared with their intracranial counterparts.26 Chemo-therapy has not been shown to be effective in the treatment of meningiomas.27 Targeted therapies against the hormonal receptors have been disappointing,28 but other adjuvant therapies such as hydroxyurea and other targeted therapies are currently under evaluation.29 Radiation is reserved for poor surgical candidates, subtotal resection, unresectable tumors, or high-grade and recurrent tumors. When radiation was required in the past, spinal meningiomas were treated with traditional fractionated external beam radiotherapy, as frame-based stereotactic radiosurgery devices could not treat lesions below the foramen magnum. New advances with frameless radiosurgical techniques have overcome these shortcomings, and preliminary data report good control of spinal meningiomas after CyberKnife (Accuray, Sunnyvale, California) radiosurgical ablation.30

Neurofibroma

These tumors are the second most common intradural extramedullary tumors arising in the CVJ and account for 15% of all nerve sheath tumors.31 They are described as elongated, lobulated masses that are well circumscribed though not encapsulated.32 Macroscopically, they exhibit intraneural growth (vs. extraneural growth of schwannomas) with functioning fascicles traversing the tumor. Neurofibromas may arise sporadically in some patients, but up to 60% are found in patients with neurofibromatosis type 1 (NF1).32 Mutations on chromosome 17q12 are seen in patients with NF1, and this mutation is also implicated in sporadic cases.33 Unlike in meningiomas, men and women are affected equally. The cell of origin is under debate; some believe that the tumor is mesenchymal in origin, whereas others believe that the Schwann cell is the cell of origin.32,33 The MRI signal characteristics of neurofibromas are similar to those of meningiomas except that they do not exhibit a dural tail. Larger tumors and tumors from patients with NF1 have about a 5 to 10% chance of malignant transformation, which usually presents as a rapid increase in the size of the tumor and pain.33 Pain, neurological deficit, cosmesis, rapid growth, and concern for malignant transformation are indications for treatment. If treatment is necessary, gross total resection with the assistance of electrophysiological monitoring is the treatment of choice. However, complete resection can be difficult without sacrificing the involved nerve root, which may result in neurological deficits. Preoperative counseling is critical in managing expectations of the patients with regards to complete versus subtotal resection and postoperative neurological deficits. Fortunately, pain relief is seen in > 85% of patients after surgery, even if only subtotal resection is achieved, and the recurrence rate after resection is ∼12%.31,34

Schwannoma

As the name implies, schwannomas are of Schwann cell origin and are the most common peripheral nerve sheath tumors. They occasionally occur in the CVJ ( Fig. 38.2 ), are usually sporadic, but can sometimes be associated with NF2. The NF2 gene on chromosome 22q12 is thought to be a tumor suppressor and is also altered in > 50% of sporadic schwannomas.17 Schwannomatosis35 and Carney complex36 are two other conditions that predispose patients to schwannomas. Similar to neurofibromas, schwannomas occur equally in men and women. MRI characteristics of these tumors are similar to meningiomas except that they lack a dural tail and more frequently exhibit cystic changes and increased peripheral enhancement. Small to medium-size schwannomas can usually be resected en bloc by circumferential dissection of the passerby fascicles. In larger tumors, intratumoral debulking is often necessary prior to complete resection.32 The single nerve fascicle that gives rise to the tumor can often be isolated; electrophysiological monitoring can be used to confirm nonconducting. Complete resection can be achieved without any postoperative neurological deficit. If a functional fascicle cannot be dissected free, a small residual should be left to avoid postoperative neurological deficit.32,33 Even after subtotal resection, recurrence usually does not occur until many years later.37 At some centers, these tumors are treated with stereotactic radiosurgery if surgery is thought to be too risky or there is recurrence after prior resection. It has been found that patients with NF2 have a higher chance of recurrence with a 39% recurrence rate at 5 years when compared with an 11% recurrence rate at 5 years in patients with sporadic schwannomas.38

Malignant Peripheral Nerve Sheath Tumor

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare type of soft tissue sarcoma arising from Schwann cells or pluripotent neural crest cells of peripheral nerves and account for 5 to 10% of the 6000 soft tissue sarcomas diagnosed in the United States each year.39 They are associated with NF1, and ∼4 to 10% of patients with NF1 will develop these tumors.40 The CVJ as the primary site is exceedingly rare but may be involved by secondary extension. There appears to be no racial or sex propensity, and these tumors can occur at any age, but mostly commonly occur in the seventh decade in sporadic cases and in the third or fourth decade in patients with NF1.41,42 There have been case reports of MPNST occurring many years after radiation exposure. Work-up includes careful neurological exam and imaging with MRI. These tumors are often positive on positron emission tomography (PET); however, fluorodeoxyglucose (FDG)-PET is unhelpful in determining histological grade.43 Any biopsy should be planned carefully, with the biopsy track amenable to resection at the time of definitive surgery. Unfortunately, the prognosis is poor in most patients. The mainstay of treatment is wide surgical resection followed by adjuvant radiotherapy. The goal of surgery is gross total resection with clear margins of ≥ 2 cm. Surgical resection is achievable in ∼20% of paraspinal tumors and 95% of extremity tumors.40,44–48 Adjuvant radiotherapy improves local control in high-grade sarcomas and is recommended by the Oncology Group Consensus on MPNST.49 Chemotherapy has a modest activity in high-grade sarcomas, with a meta-analysis of high-grade sarcomas showing a nonsignificant 4% overall survival benefit. Local recurrence rates can be as high as 50%, and aggressive initial therapy affords the best chance for survival.50,51 Distant metastases develop in the lung, liver, brain, lymph nodes, skin, or soft tissue.44 Five-year survival rates for sporadic cases can be as high as 50% or as low as 10% for those with NF1.

Hemangioblastoma

These tumors represent 3 to 11% of intramedullary spinal cord tumors, one third of which are associated with von Hippel-Lindau disease. They consist of thin-walled blood vessels intermixed with large, pale stromal cells and occur slightly more frequently in men.52 Hemangioblastomas strongly enhance after administration of gadolinium and are often associated with noncontrast-enhancing cysts that are frequently larger than the solid portion of the tumor ( Fig. 38.3 ). The cysts can be hyperintense on T2-weighted imaging because of its proteinaceous contents. Patients with von Hippel-Lindau disease often have multiple lesions, especially in the posterior fossa. These tumors are generally located subpially on the dorsal surface and are well demarcated from normal spinal cord tissue. Therefore, gross total resection is often attainable after the tumor’s arterial supply is interrupted at the time of surgery.52 Subtotal resection often leads to recurrence. Significant hemorrhage can be encountered if the tumor is entered prior to coagulation of the blood supply, and some experts even recommend preoperative embolization,53 although this may be limited if there are many feeding vessels. Stereotactic radiosurgical ablation of recurrent, subtotally resected, or unresectable hemangioblastomas has been described.54,55

Lipoma

These tumors rarely present in the spinal cord and are extremely rare in the CVJ ( Fig. 38.4 ). When present, most are located near the cauda equina associated with a tethered cord. Their signal characteristics on MRI are similar to that of fat: noncontrast enhancing, hyperintense on T1-weighted imaging, and hypointense on T2-weighted images. These tumors are well demarcated from normal spinal cord but are adherent to its surrounding tissue; therefore, complete excision often leads to neurological deficit.56 Subtotal resection leaving residual at the interface with the spinal cord is recommended and often leads to pain relief.52 The intraoperative laser is an effective tool used for resection of these tumors.57 Adjuvant therapy is not recommended.

Astrocytoma

These infiltrating tumors, which arise from transformed astrocytes, are the most common intramedullary tumors in the pediatric population and second only to ependymoma in the adult population. Unlike their intracranial counterparts, spinal astrocytomas are generally low grade. The cervical region is the most common location ( Fig. 38.5 ), and there is a slight male predominance. On MRI, spinal astrocytomas are iso- to slightly hypointense on T1-weighted images and hyperintense on T2-weighted images. Despite being low grade, these tumors often contrast enhance after gadolinium administration, though less so than ependymomas. Spinal astrocytomas are infiltrative and therefore are not well defined from surrounding normal tissue. Tumor-associated cysts are common.

In children, pilocytic astrocytomas displace rather than infiltrate the surrounding tissue, allowing gross total resection in many cases. Fibrillary astrocytomas, unfortunately, are infiltrative and are difficult to distinguish from normal tissue intraoperatively. Gross total resection is often not possible without severe neurological deficit. Deficits may occur even when resection is performed exclusively within the tumor because viable axons can traverse the tumor. How aggressively one should resect a low-grade astrocytoma is controversial, as some researchers report excellent prognosis after radical resection, whereas others feel that gross total resection is impossible without damaging normal tissue and that the degree of resection does not alter the prognosis. Surgeons should be careful to spend extra time determining if the tumor is infiltrative or has a clear plane. Patients with ependymomas are often subtotally resected after an intraoperative frozen section reveals low-grade glioma and the tumor is deemed infiltrative. Some authors recommend radiation for all low-grade spinal astrocytomas despite the extent of resection, whereas others recommend adjuvant radiation for subtotal resections only. There are reports of reduced relapse rate after partial resection followed by radiation, whereas other reports did not find any consistent benefit of postoperative radiotherapy. Cooper et al. recommend MRI follow-up for subtotally resected low-grade spinal astrocytomas with radiation.52 Chemotherapy has not been shown to be effective for low-grade spinal astrocytomas. Despite being “low grade,” the 5-year survival of one series where 17 of 21 tumors were grade 1 or 2 was 57%.

In high-grade spinal astrocytomas, the prognosis is uniformly poor and is not altered by surgery. Therefore, aggressive resection at the cost of postoperative neurological deficits is not warranted. Radiation also has not shown a clear benefit, although aggressive radiotherapy to doses that cause cordotomy has been reported to increase survival. This is an option for patients with high-grade spinal astrocytomas who already have poor neurological function. Chemotherapy is being used for this group of patients, but large studies still need to be performed to better define the role of adjuvant chemotherapy.