Dermatologic Manifestations of Neurilemmoma 

A neurilemmoma is a benign, usually encapsulated neoplasm derived from Schwann cells and, along with neurofibroma, constitutes one of the 2 most common benign peripheral nerve sheath tumors. The peripheral nervous system can be defined as nervous tissue outside the brain and spinal cord. It extends from the glial-schwannian junction in the cranial nerves and spinal roots to the termination of the nerve fibers in their end organ receptors and includes the posterior root ganglia and those of the autonomic nervous system. Neurilemmomas may affect any location in the course of the peripheral nervous system (ie, cranial and spinal nerve roots, cranial and peripheral nerves, end organ receptors, small nerve twigs). They are common in paravertebral locations and the flexor regions of the extremities (especially near the elbow, wrist, and knee) and occasionally involve the skin. The presence of a noninvasive tumor next to a peripheral nerve suggests the diagnosis of neurilemmoma.

Four major forms of neurilemmoma are recognized. These include conventional (common, solitary), cellular, plexiform, and ancient forms.^{[1, 2]} Specific variants, such as plexiform and giant sacral neurilemmoma, have been associated with an increased risk of local recurrence following incomplete excision. Other variants are associated with genetic syndromes such as Carney complex (ie, psammomatous melanotic schwannoma), neurofibromatosis type 2 (NF2, ie, cranial or spinal root neurilemmoma), and neurilemmomatosis (schwannomatosis), which is a variant of NF2 characterized by multiple neurilemmomas.

Of note, the benign nerve sheath tumors are classified as World Health Organization grade I on the basis of their benign cytologic features, in contrast to the malignant counterparts, which are World Health Organization grade III or IV.

The synonym schwannoma is often used interchangeably with neurilemmoma. Other synonyms include neurolemmoma and peripheral fibroblastoma.

An understanding of the relationship of the Schwann cell to other neuronal elements in the peripheral nervous system is helpful in conceptualizing the pathophysiology of a neurilemmoma.

The peripheral nervous system differs from the central nervous system in the nature of its supporting cell; the Schwann cell supports the former and the neuroglial cells support the latter. It is generally accepted that in embryogenesis, the Schwann cells are derived from the neural crest and are of neuroectodermal origin. As the peripheral nerves form, the Schwann cells migrate peripherally from the spinal ganglia, parallel to the axons, and encase them with their cytoplasm. In myelinated fibers, only one axon segment is encased by one Schwann cell.

The myelin sheath is created by a synthesis and wrapping of Schwann cell plasma membrane around the axon. Schwann cells sheath the axons from the point at which the latter penetrate the pia mater to their terminations. Upon penetrating the pia, the neuroglia is lost; the individual nerve fibers pass through a sievelike structure composed of reticulin (young collagen fibers), and, thereafter, each is contained within its ensheathing tube of reticulin and Schwann cell elements.

At this site, perineurial cells (perineural epithelium) also make their appearance. In nonmyelinated nerves, several axon segments are ensheathed by a common Schwann cell. In a fully developed nerve, a layer of connective tissue, or epineurium, surrounds the entire nerve trunk. Several nerve fascicles lie within the confines of the epineurium, and each is surrounded by a well-defined perineurium. The smallest connective tissue unit of the nerve is the endoneurium, which is a network of fibroblasts, blood vessels, and collagen encircling individual nerve fibers).

Neurilemmomas arise within a nerve consisting of a single fascicle. The tumors are composed entirely of the supporting Schwann cells and peripherally displaced nerve fibers, resulting in a globoid eccentric tumor mass. In the early intrafascicular growth phase, small neurilemmomas displace nerve fibers without forming a capsule. The larger tumors increase the size of the parent nerve and become separated from surrounding fascicles by a capsule derived from perineurium and epineurium, as demonstrated in the image.

Most neurilemmomas are of the conventional (common) type, arise as solitary tumors smaller than 10 cm, and are not associated with a genetic syndrome. They display the classic gross and microscopic features described in Histologic Findings. The cellular variant is rare in the skin, developing more commonly as a tumor of the mediastinum, retroperitoneum, and deep soft tissue. It is composed of a hypercellular mass of spindle-shaped cells forming intertwining fascicles and cords. Mild-to-moderate cytologic atypia and a low mitotic rate (5 mitoses per 20 high-powered fields) are characteristic.

The plexiform variant demonstrates a multinodular growth pattern of predominantly Antoni type A tissue (see Histologic Findings) in the dermis and subcutis. In contrast to plexiform neurofibroma, plexiform neurilemmoma is not pathognomonic of neurofibromatosis and malignant transformation is exceedingly rare. Ancient neurilemmomas are characterized by degenerative changes and cytologic atypia typical of Antoni type B tissue, of which they are almost entirely composed. Despite sometimes striking cytologic atypia, mitotic figures are rare.

Frequency

United States

The exact prevalence of neurilemmomas (benign schwannomas) of all anatomic sites is unknown. In 1971, Ingles and colleagues reviewed 3364 cases of neurogenic neoplasms of the intercostal nerves and posterior mediastinum reported in the literature and found that 141 cases (4.2%) were neurilemmomas. This rate placed third, after neurofibromas and ganglioneuromas. In 1935, a review by Stout showed a rate of neurilemmomas associated with NF2 of approximately 18%. Numerous subsequent reports have confirmed that this association is more than coincidental.

Mortality/Morbidity

Neurilemmomas behave in a benign fashion. Incompletely excised examples are capable of slow recurrence. Higher recurrent rates are noted with intraspinal, sacral, and intracranial neurilemmomas and with the plexiform variety. Locally aggressive behavior is observed in tumors with increased cellularity, higher mitotic rates (mean, 4 per 10 high-power fields), and underlying bone extension (observed in occasional cases of orbital neurilemmoma). One newborn with an orbital tumor died of a locally invasive tumor within a year.

Large tumors (eg, giant sacral schwannomas) are prone to local recurrence. A recent clinicopathologic study has found that patients with asymptomatic neurilemmomas occurring in association with NF2 not only have more severe neurologic deficits but also have little postoperative improvement and a higher rate of tumor recurrence. Malignant schwannomas (neurofibrosarcoma) arise de novo or in neurofibromas in the setting of neurofibromatosis. They are not regarded to be malignant counterparts of neurilemmomas.

Race

No racial predilection is noted for this neoplasm.

Sex

The tumor affects the sexes in roughly equal numbers. However, intracranial neurilemmomas are encountered more commonly in female patients; the rate for female patients with neurilemmoma is reported as 76%.

Age

Neurilemmomas occur in persons of any age but are most common in patients aged 20-50 years. The cellular form of neurilemmoma has a peak incidence in the fourth decade of life, and approximately 5% of neurilemmomas occur in childhood and adolescence. Three congenital cases have been reported. In the nearly 50 reported cases of plexiform neurilemmoma, the age ranged from 50 days to 80 years, with a mean of 34 years. In melanotic neurilemmoma, the age range was reported at 10-84 years, with a mean age of 37 years. Overall, approximately 75% of neurilemmomas occur in the first 4 decades of life.