Peripheral nerve tumor

Peripheral nerve tumors, also called tumors of peripheral nerves or tumors of the peripheral nervous system, are a diverse category with a range of morphological characteristics and biological potential.^[1] They are categorized as either benign or malignant peripheral nerve sheath tumors.^[2][3]

Peripheral nerve tumor
MRI (coronal plane) showing the site of MPNST in the left tibia.
Specialty	Neurosurgery

Description

They vary from benign (soft tissue perineurioma and schwannoma) that can be completely removed to benign (plexiform neurofibroma) that may be locally aggressive to extremely malignant (malignant peripheral nerve sheath tumors [MPNST]).^[1] New and more precisely defined entities include malignant melanotic nerve sheath tumor (formerly known as melanotic schwannoma) and hybrid nerve sheath tumors.^[4][5] The majority of peripheral nerve tumors are benign tumors of the nerve sheath (usually schwannomas); on rare occasions, they are metastatic tumors or originate from the nerve cells.^[6][7]

Most peripheral nerve tumors occur for unknown reasons. Some, including schwannomatosis and neurofibromatosis (types 1 and 2), are associated with recognized hereditary disorders. Others may be caused by gene mutations. In the case of schwannomatosis and neurofibromatosis, tumors can grow on or close to nerves anywhere in the body. Frequently, there are several tumors.^[8]

The typical symptoms involve a combination of pain, loss of nerve function, and/or a palpable (or radiographically apparent) mass affecting a peripheral nerve. The etiology and importance of the last two symptoms should be apparent. For example, the presence of a severe nerve palsy is highly suggestive of malignancy as it is most likely the result of the tumor invading and destroying nerves.^[7]

Methods used to identify tumors of the peripheral nervous system include a family history of any predisposition syndrome, including neurofibromatosis types 1 and 2, a targeted and comprehensive physical examination, and radiological investigations, the primary one being magnetic resonance imaging.^[9][10] Other radiological investigations may include plain radiographs, ultrasound examination, computed tomography, and positron emission tomography.^[11] Definitive diagnosis is made by tumor biopsy.^[12] Surgery is the most common method of treating peripheral nerve sheath tumors.^[11] In malignant tumors, complete resection is the only known curative treatment (with a sufficiently wide margin or even amputation to improve prognosis).^[12] For larger lesions or those with a more aggressive histology, adjuvant radiation is recommended. Novel or combination therapies that are the focus of ongoing clinical trials are highly desirable.^[13][14]

Epidemiological and clinical features

Formally, the majority of these tumors lack a CNS WHO grade; instead, neoplasms should be graded within each category of tumor.^[5]

Peripheral nerve tumors^[5][2]

Tumor type	Malignancy	Estimated incidence	Location
Schwannoma	Benign	1.09 per 100,000/year	Skin and subcutaneous tissues of the head and neck, or along the flexor surfaces of the extremities Spinal intradural extramedullary site with growth into foraminal space Eight cranial nerve (bilateral involvement in NF2)
Neurofibroma (Localized, diffuse, plexiform subtype)	Benign	5.3% of all benign soft tissue tumors	Skin, with predominant dermal involvement, less frequently medium-sized nerves, a nerve plexus, a major nerve trunk, or spinal nerve roots Bilateral and/or multiple spinal root involvement in NF1 Spinal cord compression Cranial nerve involvement is ultrarare
Perineurioma (Intraneural and soft tissue subtypes)	Benign	1% of nerve sheath and soft tissue neoplasms, respectively (>50 cases of intraneural perineuriomas and >300 cases of soft tissue perineuriomas have been described)	Common presentation: focal, unilateral lesion affecting major peripheral nerves (sciatic, median, radial, brachial plexus) and their branches. Uncommon locations: cranial nerves, lateral ventricle, oral cavity, skin, and mandible. Bilateral or unilateral multifocal lesions are rare
Hybrid nerve sheath tumor	Benign	Very rare	The most common site is the fingers Rare cases of cranial nerves involvement
Malignant peripheral nerve sheath tumour (MPNST) (epithelioid and perineural subtypes)	Malignant	2–10% of soft tissue sarcomas. Epithelioid MPNST is particularly rare (~5% of all MPNST)	Extremities, trunk, head, and neck area
Malignant melanotic nerve sheath tumour (MMNST)	Malignant	Very rare	Common sites are spinal or autonomic nerves near the midline Uncommon sites: gastrointestinal tract, bone, soft tissues, heart, bronchus, liver, and skin
Neuroendocrine tumour (previously paraganglioma)	Malignant	Very rare	Cauda equina region