A nerve sheath tumor is an abnormal growth originating in the protective covering of a peripheral nerve (nerves outside the brain and spinal cord). These tumors arise from the cells that form the nerve’s supporting structure, primarily Schwann cells. Because peripheral nerves extend throughout the body, these growths can occur virtually anywhere, including the limbs, trunk, head, and neck. While most nerve sheath tumors are benign, their location and size can cause significant issues by pressing on the nerve or surrounding tissues.
Primary Types of Nerve Sheath Tumors
Schwannomas are the most common type, arising exclusively from the Schwann cells that produce the insulating myelin sheath. These tumors are typically solitary, slow-growing, and nearly always benign. Schwannomas are usually well-encapsulated, forming a distinct mass that pushes the nerve fibers aside rather than intertwining with them. This characteristic often simplifies their surgical removal without damaging the underlying nerve.
Neurofibromas also originate from Schwann cells, but they include a complex mixture of other non-neoplastic cells, such as fibroblasts, perineurial cells, and mast cells, all intermixed with the nerve’s axons. Unlike Schwannomas, neurofibromas are generally non-encapsulated, causing them to blend with the nerve bundle and making surgical separation difficult. They can be solitary or multiple; the plexiform subtype, which grows along the length of a nerve bundle, is a hallmark of Neurofibromatosis Type 1 (NF1).
The rarest and most serious classification is the Malignant Peripheral Nerve Sheath Tumor (MPNST). These aggressive cancers are highly cellular and can arise spontaneously or, more commonly, from a pre-existing plexiform neurofibroma, particularly in individuals with NF1. The malignant transformation is marked by additional genetic changes, such as mutations in tumor suppressor genes like TP53. MPNSTs are characterized by rapid growth and a high risk of spreading to other parts of the body.
Clinical Presentation and Symptoms
Many small nerve sheath tumors do not cause noticeable problems and are often discovered incidentally during imaging for an unrelated condition. When symptoms occur, they are directly related to the tumor’s size, location, and the degree of compression on the affected nerve. A common presentation is the development of a palpable mass or lump under the skin that grows slowly over time.
The pressure on the nerve fibers can lead to localized pain, which may be aching, burning, or sharp. Patients may also experience sensory changes, such as numbness, tingling, or “pins and needles” in the area the affected nerve supplies. If the growth involves a motor nerve, it can result in muscle weakness or difficulty coordinating movement. For tumors affecting specific cranial nerves, like the vestibulocochlear nerve, symptoms can include hearing loss, tinnitus, or balance issues.
Underlying Causes and Genetic Links
Nerve sheath tumors are caused by a genetic mutation that instructs nerve sheath cells to multiply uncontrollably. While many cases occur sporadically, a significant number are strongly linked to inherited genetic conditions known as neurofibromatoses. These conditions are inherited in an autosomal dominant pattern, meaning a child has a 50% chance of inheriting the mutation.
Neurofibromatosis Type 1 (NF1), the most common form, is caused by a mutation in the NF1 gene located on chromosome 17. This gene codes for the protein neurofibromin, which acts as a tumor suppressor. Loss of function in neurofibromin leads to the formation of multiple neurofibromas and an increased risk of developing MPNST.
Neurofibromatosis Type 2 (NF2) is a distinct condition resulting from a mutation in the NF2 gene on chromosome 22, which codes for the tumor suppressor protein merlin. NF2 primarily predisposes individuals to the development of multiple Schwannomas, particularly bilateral vestibular Schwannomas that affect the nerves of hearing and balance.
Schwannomatosis
A third condition, Schwannomatosis, involves mutations in genes like SMARCB1 and LZTR1. It is characterized by the presence of multiple Schwannomas without the bilateral vestibular tumors seen in NF2.
The Diagnostic Process
Diagnosis begins with a comprehensive patient history and physical examination. A healthcare provider will evaluate the patient’s symptoms, check for any palpable masses, and perform a neurological exam to assess nerve function, looking for signs of weakness, numbness, or abnormal reflexes. This assessment helps determine which nerve may be involved and the extent of functional impairment.
Imaging studies are used to visualize the tumor and define its size and location relative to the nerve. Magnetic Resonance Imaging (MRI) is the preferred method, as it provides detailed, three-dimensional images of soft tissues and can often distinguish a nerve sheath tumor from other types of masses. Computed Tomography (CT) scans may also be used, particularly to evaluate the tumor’s effect on surrounding bone structures.
While imaging can strongly suggest the presence of a nerve sheath tumor, a biopsy is often necessary for a definitive diagnosis and classification. This procedure involves removing a small tissue sample from the mass, which is then analyzed by a pathologist. Microscopic analysis confirms the specific tumor type (e.g., Schwannoma or neurofibroma) and, importantly, whether the growth is benign or malignant. Genetic testing may also be performed to screen for the underlying mutations associated with NF1 or NF2.