Intraspinal nerve sheath tumors, also known as intradural Chewang cell tumors, account for approximately 25% of intradural spinal tumors and can occur in all segments of the spinal canal, mostly solitary, with a peak incidence between the ages of 40 and 60 years and no significant difference between the sexes. Intraspinal nerve sheath tumors originate from the dorsal spinal nerve roots and may produce submural infiltration when they grow centripetally, which is more common in cases of rhombic neurofibroma. Nerve sheath tumors of the brachial or lumbar plexus can grow along multiple nerve roots into the dura mater. In contrast, paravertebral Schwann cell tumors that extend into the spinal canal are usually located outside the dura. Approximately 2.5% of intradural nerve sheath tumors are malignant, and at least half of these occur in patients with polyneurofibromatosis.
Intradural nerve sheath tumors – pathogenesis
I. Pathogenesis
It is widely believed that tumor development and growth are primarily the result of molecular alterations at the genetic level. Many cancers are thought to form due to loss of normal tumor suppressor genes and activation of oncogenes. Two types of neurofibromatosis have been extensively studied. Genetic studies have suggested that the NF1 and NF2 genes are located on the long arms of chromosomes 17 and 22, respectively. Both types of neurofibromatosis are inherited in an autosomal dominant fashion with a high rate of epistasis. the incidence of NF1 is approximately 1 in 4000 births, half of which are sporadic cases, caused by newer mutations. In addition to spinal neurofibromas, clinical manifestations of NF1 include café-au-lait pigmentation, skin nodules, skeletal abnormalities, subcutaneous neurofibromas, peripheral plexiform neuromas, complicated by certain common childhood tumors, such as optic nerve and hypothalamic gliomas, and ventricular meningiomas. Intralesional neurofibromas are far less common than those occurring outside the spinal canal. the NF1 gene encodes a neuronal fiber belonging to the GTPase-activating protein family of molecules (220-KD). the GTP protein is activated by its ligand and is involved in the downregulation of the ras oncogene. It is currently hypothesized that mutations in the NF1 gene lead to the formation of a mutated gene product, which is thus unable to efficiently elicit the deoxygenation response of GTP and therefore promotes the upregulation of the ras gene, which enhances the signaling of the growth factor pathway and ultimately leads to the appearance of the characteristic products of NF1 tumors and the formation of NF1 tumors.
II. Pathogenesis
Nerve sheath tumors can be classified as Schwann cell tumors or neurofibromas. Although tissue culture, electron microscopic analysis and immunohistochemistry support that both neurofibromas and Schwann cell tumors have a common origin from Schwann cells, however, the heterogeneity of neurofibroma morphology suggests the involvement of other cells, such as perineuronal cells and fibroblasts. Because of the differences in morphologic, histologic, and biological features, neurofibromas and Schwann cell tumors are considered to be two relatively independent groups. Neurofibromas are characterized histologically by the presence of fibrous tissue and scattered nerve fibers within the tumor. In general, the tumor causes the affected nerve to produce a spindle-shaped expansion, making it almost impossible to identify the boundary between the tumor and the nerve tissue, and multiple neurofibromas are often diagnosed as multiple neurofibromatosis. Schwann cell tumors are generally spherical in shape and do not produce enlargement of the affected nerve, but the differential diagnosis is more difficult when they grow eccentrically and have obvious attachment sites.
Intraspinal nerve sheath tumors – Symptoms and signs
The duration of the disease is mostly long, with the shortest history in the thoracic segment and longer in the cervical and lumbar segments, sometimes lasting more than 5 years. The tumor has an acute course with cystic changes or bleeding.
The most common first symptom is nerve root pain, followed by sensory abnormalities and motor disorders. The pain of upper cervical tumor is mainly in the neck and neckline, occasionally radiating to the shoulder and upper arm; the pain of cervicothoracic tumor is mostly located in the back of the neck or upper back, and radiates to one or both shoulders, upper limbs and chest; the pain of upper thoracic tumor often manifests as back pain, radiating to the shoulder or chest; the pain of thoracic tumor is mostly located in the thoracolumbar region, radiating to the abdomen, groin and lower limbs. The pain of tumor of thoracolumbar segment is located in the lumbar region and may radiate to the groin, arm, thigh and calf. The pain of lumbosacral segment tumor is located in the lumbosacral region, buttocks, perineum and lower limbs.
Abnormal sensation as the first symptom accounts for 20%, which can be divided into two categories: hypersensitivity and hyperalgesia. The former manifests as ankylosing sensation, numbness, coldness, soreness, swelling and burning; the latter is mostly a combination of pain, temperature and tactile hyperalgesia.
Dyskinesia is the third most common first symptom. Depending on the location of the tumor, it may produce neurogenic or fascicular damage resulting in motor deficits.
The main clinical signs and symptoms of spinal nerve sheath tumors are pain, sensory abnormalities, motor deficits and sphincter dysfunction. The incidence of sensory abnormalities is about 85% and the incidence of pain is nearly 80%.
Sensory disorders generally begin distally and progress gradually upward. Patients have early subjective sensory abnormalities with no specific findings on examination, followed by hypoesthesia and finally loss of all sensation along with motor function. There is no spinal cord parenchyma in the cauda equina of the cone, so the sensory abnormalities are distributed in a peripheral nerve pattern, typically the skin of the anus and perineum shows numbness in the saddle area.
Most patients come to the hospital with varying degrees of mobility difficulties, and half of them already have limb paralysis. The time of detection of dyskinesia varies depending on the site of the tumor, with cone or cauda equina tumors showing significant dyskinesia at an advanced stage and thoracic segment tumors showing symptoms earlier.
Sphincter dysfunction is often a late symptom, indicating partial or complete compression of the spinal cord.
There is obvious neurogenic pain, motor and sensory disorders develop from the bottom up, there is a skin hypersensitivity zone at the level of tumor segment, especially when there is spinal cord hemisection syndrome, which is manifested as ipsilateral upper motor neuronal motor paralysis and hyperalgesia of touch and deep sensation below the lesioned segment, loss of pain and temperature sensation on the contralateral side, as well as cerebrospinal fluid dynamics changes often cause increased pain, all suggest the possibility of extramedullary spinal cord nerve sheath tumor. The diagnosis of extramedullary spinal cord nerve sheath tumor should be confirmed by necessary supporting tests.
The following complications may occur when spinal cord nerve sheath tumors are treated surgically.
1. epidural hematoma
Incomplete hemostasis of the paravertebral muscles, vertebrae, and dural venous plexus can lead to postoperative hematoma, resulting in increased limb paralysis, which occurs mostly within 72 h after surgery, even when a drainage tube is placed. If this phenomenon occurs, it should be actively explored to remove the hematoma and completely stop the bleeding.
2. Spinal cord edema is often caused by surgical operations that damage the spinal cord, with clinical manifestations similar to those of hematoma. Treatment is based on dehydration and hormones, and in severe cases, reoperation may be performed to open the dura.
3, cerebrospinal fluid leakage is mostly caused by poor suturing of the dura mater and muscle layer, if there is drainage, the drainage tube should be removed in advance. If there is little leakage, change the medicine and observe. If the leakage cannot be stopped or there is much leakage, the fistula should be sutured in the operating room.
4. Incisional infection and fissure
Those with poor general condition, poor healing ability of the incision or cerebrospinal fluid leakage are prone to occur. Intraoperative attention should be paid to aseptic operation. In addition to antibiotic treatment after surgery, the systemic condition should be actively improved, with special attention to protein and multivitamin supplementation.
Intraspinal nerve sheath tumor – related tests Because spinal nerve sheath tumors mostly occur in the subarachnoid space, tumor growth is more likely to cause subarachnoid space blockage, so lumbar puncture
The lumbar puncture test is usually performed to detect different degrees of subarachnoid obstruction. As a result of subarachnoid obstruction, the cerebrospinal fluid circulation below the tumor site is impaired, and the tumor cells are shed, resulting in increased cerebrospinal fluid protein content.
The tumor cells are shed, resulting in an increase in the protein content of the cerebrospinal fluid. In addition, because the tumor is in the spinal canal, it is usually free, so the symptoms can be aggravated after lumbar puncture and release of cerebrospinal fluid. This is due to the altered dynamics in the spinal canal and the increased compression of the spinal cord by the tumor.
Spinal plain film: the direct sign is nerve sheath tumor
Indirect signs are the corresponding changes caused by tumor compression of the spinal canal and its adjacent bony structures, including destruction of the vertebral arch, widening of the distance between the vertebral roots, or even loss of destruction of the vertebral roots, depression of the vertebral body or enlargement of the intervertebral foramen.
Myelography: The rate of complete obstruction of the subarachnoid space is about 95% or more, with a typical cup-shaped filling defect.
CT and MRI: CT scan is difficult to make a definite diagnosis. Tumor on MRI
T1-weighted images show extramedullary low-signal tumor foci, and T2-weighted images show high-signal tumor foci. After enhancement, solid tumors show homogeneous enhancement, cystic tumors show circumferential enhancement, and a few tumors show inhomogeneous enhancement. Depending on the anatomical level of the tumor, there is a corresponding spinal cord displacement.
Intradural Nerve Sheath Tumor – Differentiation
The primary differential diagnosis for intradural tumors is spinal meningioma. Spinal meningiomas are often found in the thoracic spine. However, the incidence is significantly higher in women than in men. Tumors rarely grow into the neural foramen and present as paravertebral masses. For lesions with a tumor centered in the neural foramen or paravertebral soft tissue, the differential diagnosis should consider lesions such as ganglioneuroblastoma, neuroblastoma, paraganglioma, or carcinoma and sarcoma of local origin with centripetal extensions originating from the sympathetic chain or dorsal root ganglion.
Intraspinal nerve sheath tumor – Disease treatment
1.Treatment
Treatment of benign nerve sheath tumors is primarily surgical resection. In the vast majority of cases, the tumor can be cured by a standard posterior laminectomy and total resection of the tumor. Recurrence is generally rare if the tumor is surgically removed in its entirety. The vast majority of nerve sheath tumors are located on the dorsal or dorsal aspect of the spinal cord and are easily seen after the dura mater is opened. Tumors located ventrally may require severance of the odontoid ligament to obtain adequate visualization. Lumbar tumors may be recessed by the cauda equina or spinal cone, and in these cases, the nerve roots are separated to provide adequate exposure, and usually the tumor presses the cauda equina or cone to one side. When adequate exposure is obtained, the interface between the tumor and the nerve or spinal cord is easily identifiable. There is usually an arachnoid layer immediately adjacent to the tumor, and this layer is a porous structure that independently wraps around the dorsal and ventral nerve roots. Intraoperatively, a sharp dissection is performed to disconnect and separate the tumor, and the surface of the capsule wall is electrocoagulated to reduce the tumor volume. The nerve roots proximal and distal to the tumor should be severed so that the tumor can be completely removed. If the tumor is large, intracapsular resection and intracapsular decompression can be performed first, and the nerve roots from which the tumor originates must be cut. Occasionally, some small branches of the nerve roots can be preserved, especially in smaller tumors. Dissection of these nerve roots, even at the level of cervical and lumbar spine expansion, rarely causes severe neurological deficits, and the function of these nerve roots is usually compensated by the adjacent nerve roots. In these cases, the interface between the tumor and the spinal cord is often difficult to separate, and total resection of the tumor can be obtained by removing some of the segmental soft tissue.
In these cases, it is often difficult to separate the tumor from the spinal cord. The adjacent extension of the subdural tumor should be carefully analyzed before surgery to facilitate the accuracy of the surgical approach. Magnetic resonance examination can usually provide a careful understanding of the adjacent structures of the tumor. However, for dumbbell-shaped tumors, CT tomography after myelography will be more sensitive to facilitate the observation of the spinal canal and paravertebral structures.
Tumors in the paravertebral region of the neck are often difficult to reach via an anterior cervical approach due to the abundance of anterior cervical vascular-neural structures such as the brachial plexus nerve, the posterior group of cerebral nerves and their vertebral arteries, and the mandible and its skull base musculoskeletal appendages further limit the exposure of the upper cervical spine. Fortunately, the vast majority of dumbbell-shaped tumors can be obtained by expanding posterior cranial exposure and obtaining tumor resection. A midline incision with a standard laminectomy allows safe resection of tumors both inside and outside the dura of the spinal canal. Total resection of one articular surface, up to 3 cm (from the dural edge to the paravertebral area), increases paravertebral exposure, and the vertebral artery, which is usually displaced anteromedially, can be well protected by subperiosteal separation of the vertebral artery and its tumor. Although the stability implications of resection of the articular facets of one cervical spine are difficult to determine, laminectomy of one side alone can significantly reduce the damage to spinal stability.
Thoracic tumors expanding paravertebrally can often form large masses that invade the thoracic cavity. The standard posterior approach is difficult to provide adequate visualization of the anterior paravertebral lesion. An anterior transthoracic or extrapleural opening provides good exposure of the anterior vertebral structures. If subdural exposure is necessary, postoperative thoracic leakage of cerebrospinal fluid may occur. This is mainly because negative thoracic pressure and its postoperative closed chest drainage may exacerbate cerebrospinal fluid outflow. A combined anterior and posterior approach increases exposure and can be performed in stages. The lateral extrathoracic approach is extremely valuable in cases requiring both increased intradural and paravertebral exposure, usually with a field hockey stick-like incision to ensure retraction of the paravertebral muscles. The superficial thoracic scapular muscles are stripped at the midline and then rotated laterally along the flap to expose the paravertebral muscles longitudinally. These muscles should be stripped of the posterior spinal accessory structures with the ribs. Rib excision and thoracic decompression can increase extrapleural paravertebral exposure.
Intraspinal exposure can be obtained by medial standard laminectomy of the paravertebral muscles. Cerebrospinal fluid leakage is rare because of the lack of access to the thoracic cavity. Lumbar dumbbell tumors can also be obtained through a lateral approach, at which level the thoracodorsal fascia can be dissected along the skin incision and drawn to the lateral side. The paravertebral muscles of the lumbar spine are very deep and the tumor is often encapsulated within the psoas major muscle. It is difficult to remove the tumor completely through the retroperitoneal approach alone because it is difficult to distinguish the fibers of the psoas major muscle from the connective tissue at the tumor margin. The lumbar plexus nerve roots and their branches, including the femoral nerve, are difficult to identify through the surface of the psoas major muscle and can be easily damaged during retroperitoneal separation. The lateral extraperitoneal approach ensures that the tumor and the psoas major muscle are pursued through the intervertebral foramen, and all separations are performed on the surface of the tumor, allowing identification of the nerve from the proximal end, thus further reducing nerve damage. Intradural subdural tumors can easily be resected through laminectomy. Sacral dumbbell tumors usually require anterior and posterior exposure, maintaining the lateral position, and can be staged or performed simultaneously in one stage.
2.Prognosis
The prognosis for malignant nerve sheath tumors is extremely poor, with survival rarely exceeding 1 year. These tumors must be distinguished from some of the few Schwann cell tumors that exhibit aggressive histologic features, and those with a predisposition to malignancy have a relatively good prognosis.
Some nerve sheath tumors may cause acute spinal cord neurological dysfunction, such as sudden onset of limb pain, limb paralysis, urinary and fecal disorders, due to cystic degeneration or hemorrhage, and should be seen immediately and treated surgically as soon as possible.