Continuing Education Activity

The vast majority of tumors of the peripheral nervous system arise from the cells of Schwann, rather than from the nerve cells themselves. Schwann cells, or neurilemma, are cells that are responsible for the production of the myelin sheath around neuronal axons. This activity reviews the presentation, pathogenesis, and management of patients presenting with neurilemmomas. We examine the complications and briefly explore the impact of the disorder on patients and highlight the importance of an interdisciplinary approach to treat these individuals appropriately.

Objectives:

• Describe the most frequent presentation of neurilemmomas.
• Summarize the pathophysiology of neurilemmomas.
• Explain the management of neurilemmomas.
• Explain the role of the interprofessional team in optimizing the management of neurilemmomas.

Introduction

The vast majority of tumors of the peripheral nervous system arise from the cells of Schwann, rather than from the nerve cells themselves.  Schwann cells, or neurilemma, are cells that are responsible for the production of the myelin sheath around neuronal axons. Most of these tumors are benign and designated as "schwannomas" or "neurilemmomas," and may appear spontaneously as solitary lesions, or as part of an underlying clinical condition such as neurofibromatosis. These vast majority of these tumors are slow-growing, encapsulated tumors of these Schwann cells within a collagenous matrix.

Etiology

Neurilemmomas arise from the cells of Schwann and may occur spontaneously, or in conjunction with clinical syndromes such as neurofibromatosis type 2, Schwannomatosis, and Carney complex.[1]

Epidemiology

Vestibular neurilemmomas were found to have an incidence ranging from 0.01% to 0.1% in the general population with a peak age of 20 to 50, without a clear preference for sex.[2] In an autopsy study of elderly patients with neurofibromatosis type 2, the incidence of sporadic central schwannoma was found to be much higher at 4.5%.[1][3][4][5][6] 

Histopathology

Histologic examination of the well-circumscribed neurilemmoma shows degenerative changes and a variable presentation of compact spindles, referred to as "Antoni A" bodies and microcystic areas with a high concentration of macrophages and collagen fibers, designated as "Antoni B" bodies. Additionally, nuclear palisading around cell bodies is described as Verocay bodies and is strongly suggestive of neurilemmomas. Schwannomas classically stain strongly for S100 protein expression on immunohistochemistry and will have pericellular type IV collagen in abundance. Glial fibrillary acid protein (GFAP), podoplanin, calretinin, and SOX10 may be present in varying degrees within different subtypes of neurilemmomas.[7][8][9][10]

History and Physical

Patients with a neurilemmoma typically present with an asymptomatic mass but may experience pain and paresthesias throughout the distribution of the entire nerve as the tumor grows larger and applies pressure to the nerve. Neurilemmomas of the posterior spinal nerve will produce sensory symptomatology, while compression of the anterior spinal nerves may produce motor deficits.

On physical exam, physicians may notice a palpable mass that can be mobilized in the plane orthogonal to the axis of the affected nerve, but not longitudinally aligned with the affected nerve. 

Neurilemmomas most frequently occur in the neck and mediastinum, and when present in the extremities are far more common along the flexor surfaces.[1][11]

Evaluation

On CT scans, neurilemmomas are hypodense compared to muscle and enhance with contrast. On MRI, neurilemmomas are isointense to muscle on T1-weighted imaging and bright on T2-weighted imaging with occasional low signal cysts. While inconsistent, the best way to distinguish a neurilemmoma from a neurofibroma is an eccentric displacement of the nerve and heterogeneous appearance with cystic degeneration, suggestive of a schwannoma.[2][12]

Biopsy of the neoplasm, as discussed above, is the best way to confirm a diagnosis of a schwannoma, with a defined fibrous capsule and Antoni A and Antoni B bodies on histology.[13]

Treatment / Management

Neurilemmomas and neurofibromas can often be managed non-operatively, with observation if asymptomatic or causing minimal symptoms. If there is a concern for malignancy or are symptoms causing distress, surgery is the mainstay of intervention. The goal of any surgical treatment is the removal of the tumor without neurological impairment. Removing neurilemmomas without damaging the nerve is easier than in the removal of a neurofibroma due to the fibrous capsule containing neurilemmomas.[14][15][16]

Electrophysiologic monitoring is important during the removal of neurilemmomas. A longitudinal incision is marked over the tumor site, allowing for exposure of normal nerve proximal and distal to the tumor. Using vessel loops, the healthy nerve is wrapped proximal and distal to the tumor, and the nerve is carefully dissected away from the tumor capsule using Metzenbaum scissors. The tumor is generally removed as a solitary mass when possible.[17]

Differential Diagnosis

Solitary neurofibromas are benign peripheral nerve tumors that also arise from cells of Schwann that more classically involve the skin or subcutaneous tissue. Like neurilemmomas, neurofibromas are very slow-growing tumors but differ in their histology in that they are not encapsulated as neurilemmomas are. Histopathologically compared to neurofibromas, and protein staining is classically limited to peripheral axons in neurilemmomas.[7][18]

Prognosis

In a study by Kim et al., patients that underwent surgical removal of neurilemmomas in the brachial plexus who had full strength pre-operatively maintained their normal strength in 88% of cases. 90% of those who had post-operative weakness had strength that was either improved or unchanged from their preoperative examination.[17] In another series by Young et al., 52% of patients who underwent resection had resolution of their symptoms, with 18% having improved symptoms.[19]

Complications

Neurilemmomas of the extremities are typically asymptomatic and only create a mass. Sometimes, however, the mass effect of the neoplasm can cause dysfunction of the nerve. While most symptoms are pain in the distribution of the nerve and sensory deficits or paresthesias, neurilemmomas of the anterior nerves of the spinal cord may produce symptoms of weakness and motor dysfunction as well. 

If excised surgically, neurilemmomas are typically removed without damage to the nerve, as the tumor is derived from the surrounding cells of Schwann and not directly from the nerve axon themselves. That being said, any surgery carries risk. Injury to the nerve itself is uncommon, but always a possibility through traction injuries or disruption of the axon. As with all surgery, wound complications may occur as well. Recurrence is possible, but rare in benign tumors of the nerve sheath.

Deterrence and Patient Education

Neurilemmomas are benign findings, and while they can produce symptoms due to mass effects on surrounding tissues, they generally are not a cause for concern. If a patient experiences pain or neurologic deficit, disfigurement, bleeding, or if there is suspicion for a developing malignancy, surgery may be indicated. Surgical intervention does yield very favorable outcomes, with some expected risk of associated nerve damage. 

Enhancing Healthcare Team Outcomes

Appropriate management of neurilemmomas requires a cooperative effort of the interdisciplinary healthcare team. Any mass of unknown etiology should be evaluated by an appropriate healthcare professional. First-line providers should have a basic knowledge of benign nerve sheath tumors to order appropriate testing and help patients choose the best course of management. Referral to specialists such as neurologists and surgeons as appropriate will also be critical for the appropriate monitoring of tumors and guiding the patient towards an optimal outcome.

As always, the cooperation of the entire medical team is critical. Nurses and office staff must be comfortable in their working environment to provide the best possible care, and communication is key to enacting the agreed-upon plan of management. Furthermore, if surgical intervention is required, operating room nurses and staff must be familiar with standard surgical procedures and comfortable with executing the operative plan. [Level 5]