Cancer, Spinal Cord, Intramedullary

Article Author:
Stanley Hoang
Article Editor:
Fassil Mesfin
Updated:
10/27/2018 12:31:53 PM
PubMed Link:
Cancer, Spinal Cord, Intramedullary

Introduction

Tumors in the spine comprise about 15% of all tumors in the central nervous system. They usually are benign and cause symptoms primarily through compression of the spinal cord and nerves. Spinal tumors can be classified into three groups, based on their locations: extradural, intradural-extramedullary, and intramedullary.  Extradural tumors are most common, as they occupy the vertebrae body or structures outside the dura. They are most commonly metastatic. Intradural extramedullary tumors are the second most common and come from the leptomeninges or nerve roots. These tumors are located inside the dura, but external from the spinal cord, as exemplified by meningiomas or neurofibromas. The least common (2% to 5%) are intramedullary spinal cord tumors (IMSCT); these arise from the spinal cord proper, leading to invasion and destruction of the gray and white matter. Ependymomas and astrocytomas are the most commonly encountered intramedullary spinal cord tumors, followed by hemangioblastomas. Other entities include lipomas, germ cell tumors, gangliogliomas, germinomas, lymphomas, and metastases. 

Etiology

Although IMSCT is mostly sporadic, some of them are associated with clinical syndromes such as neurofibromatosis 1, 2 (NF-1, NF-2) and Von Hippel-Lindau disease (VHL). NF-1 is due to a mutation on chromosome 17, which encodes a tumor suppressor gene. About 19% of patients with NF-1 develop IMSCT. NF-1 is largely associated with neurofibromas (intradural extramedullary), but in relation to IMSCTs, astrocytomas are most frequently encountered. NF-2 is due to a mutation on chromosome 22 and can be seen in about 2% of patients with IMSCTs. They commonly are associated with ependymomas and occasionally meningiomas (extramedullary). In VHL, hemangioblastomas are the most commonly found IMSCT. 

Epidemiology

About 80% of intramedullary tumors are gliomas, which can be subdivided into astrocytomas and ependymomas. Astrocytomas are more common findings in children with IMSCTs, while ependymomas are more often found in adults with IMSCT. Astrocytomas peak in the third to fifth decades, often low-grade, and are found most commonly at the thoracic level. Ependymomas are more commonly found in the lower cord, conus, and filum, with a slight male predominance, and peak in the third to sixth decades. Hemangioblastomas are the third most common IMSCT, making up about 2% to 15%. Metastatic intramedullary tumors are rare and most frequently develop from lung and breast tumors. 

Pathophysiology

Astrocytomas are glossy, infiltrative tumors with a poorly defined surgical resection plane. They can form a cavity in the spinal cord, known as a syrinx, and can degenerate into a malignant subtype. Ependymomas arise from ependymal cells, are soft and encapsulated, grow slowly, and are more centrally located, appearing as a focal enlargement within the spinal cord. A common histologic subtype is a WHO grade II cellular variant, with perivascular pseudorosettes. In the filum terminale, micropapillary ependymoma, a WHO grade I tumor is most commonly found. Ependymomas can span in length across 3 to 4 vertebral bodies, whereas astrocytomas can span 5 to 6 segments on average. Hemangioblastomas are small tumors that are highly vascularized but rarely extend beyond one or two vertebral bodies. Cyst formation is common, and the tumor is more often found in men.   

History and Physical

The most common presenting symptom in patients with IMSCT is a pain, which classically worsens at night when the patient is recumbent and can be diffuse or radicular in nature. If the dermatomal distribution is unusual for a disk herniation, IMSCT should be suspected.  The pain also can be local, causing stiff neck or back, and can be described as burning and bilateral. As IMSCT can impinge on the motor or sensory nerves, sensory changes such as paresthesia can be seen, followed by motor disturbances as the second or third most common complaint.  In children, gait disturbance frequently is seen.  In addition to motor weakness, patients also can have clumsiness and ataxia, atrophy, muscle twitches, fasciculations, and decreased deep tendon reflexes. Loss of bowel and bladder function can occur at a later stage and can lead to retention, incontinence, or impotence. In children, diagnosis is especially difficult, where IMSCT can remain asymptomatic for a long time. Children can have nonspecific complaints, and their symptoms can be misperceived as clumsiness, although scoliosis can be seen in 30% of patients.

Evaluation

Following the identification of symptoms, MRI is the preferred modality to characterize IMSCT for further treatment planning. MRI can show the size, location, length, extent of surrounding edema, the presence of the cord-tumor interface, and associated cysts or syringomyelia. Although each of the three common types of IMSCT has a particular T1-, T2-, and contrast-enhanced T1 weighted imaging pattern, differentiation between them based on imaging alone remains difficult. Both ependymomas and astrocytomas span multiple vertebral segments, enhance with contrast, are hypo- or isointense on T1-weighted, and are hyperintense on T2 weighted images. Ependymomas often are located centrally within the spinal cord leading to symmetric expansion, occupy the whole width of the cord, and enhance diffusely with a well-defined border. Astrocytomas tend to be positioned more eccentrically, can be non-enhancing or have an enhancing nodule or large satellite cysts, and usually, do not have a well-defined border. Intratumoral hemorrhage can be seen in both types, but are more common in ependymomas. Hemangioblastomas have homogeneous contrast enhancement compared to the more heterogenous pattern found in astrocytomas or ependymomas. They also have mural nodules, are associated with syringomyelia, and can have significant surrounding edema. As they are highly vascularized tumors, spinal angiography is helpful to characterize feeding vessels and associated dilated pial veins from vascular shunting and can help in the consideration for pre-operative embolization.

Treatment / Management

Surgical resection should be performed as soon as possible following a diagnosis of IMSCT, as outcomes correlate with preoperative neurologic condition, and observation can lead to further neurologic deficits, some of which are irreversible. The goals of surgical resection are to obtain tissue diagnosis, maximize tumor resection, and improve neurologic functions. Intraoperative somatosensory and motor evoked potentials are used to monitor for changes in neurologic function and help guide resection. The extent of total resection is greatly dependent on the presence of a clear plane between tumor and normal spinal cord tissue.  Astrocytomas are infiltrative nonencapsulated tumors that are challenging to resect. For low-grade astrocytoma, if a plane can be developed between the tumor and spinal cord, gross total resection is an option; however, for high-grade astrocytoma or low-grade astrocytoma with no definable plane of resection, biopsy plus limited resection is recommended, as aggressive resection can lead to significant neurologic deficits. Postoperative radiotherapy can be used for high-grade astrocytomas. Ependymomas are benign with a distinct tumor and normal spinal cord interface, making gross total resection an option for cure. The rate of recurrence is dependent on the extent of tumor resection, and with the presence of a discrete surgical plane, gross total resection is reported in more than 90% of cases of ependymomas. Similarly, hemangioblastomas also can be resected circumferentially, and pre-operative embolization can attenuate their rich vascular supply.  Complete excision is possible in 83% to 92% of patients with clinical improvements noted following resection. Generally, for IMSCT, better long-term outcomes are seen in patients with less preoperative deficits, and recurrence depends on the extent of resection and tumor histology.  Adjuvant therapies, including radiotherapy and chemotherapy, are often reserved for tumor recurrence, high-grade lesions, or when there are contraindications to resection. Further research into novel treatment strategies is needed to improve outcomes, especially for astrocytomas with no clear surgical resection planes.