Dermatologic Manifestations of Neurilemmoma Clinical Presentation

While neurilemmomas almost always occur as solitary lesions with no associated genetic syndrome, in some instances they are multiple or occur in association with neurofibromatosis, particularly NF2. Rare examples are associated with NF1 (ie, von Recklinghausen disease).

• Patients generally report a slow-growing tumor, which has been present for several years.
• Pain and neurologic symptoms are uncommon unless the tumor is large or, by virtue of a deep-seated location, is impinging on neighboring structures.
• Waxing and waning of the tumor size may be noted and is attributed to fluctuations in the amount of cystic change within the neoplasm.

Neurilemmomas have a predilection for the head, neck, and flexor surfaces of the upper and lower extremities. One rare case report described subungual (under the nailbed) schwannoma.^[3] The feet are usually spared. The spinal roots and the cervical, sympathetic, vagus, peroneal, and ulnar nerves are affected most commonly. Superficial neurilemmomas in the skin may display a prominent plexiform (nodular) growth pattern. Deep-seated tumors are found most commonly in the posterior mediastinum and the retroperitoneum. Intracranial neurilemmomas comprise approximately 8% of all primary tumors of this region.

• Sensory nerves tend to be affected selectively. The auditory nerve is overwhelmingly the most frequently involved. Acoustic neurilemmomas, also known as vestibular schwannoma, acoustic neuroma, or acoustic neurinoma, arise from the vestibular nerve, and they are observed in the setting of NF2. Patients with NF2 and acoustic neurilemmomas may present with bilateral hearing loss. If the tumor becomes large, it may eventually press against nearby brain structures (eg, brain stem, cerebellum), becoming life threatening.
• Neurilemmomatosis or schwannomatosis, a variant of NF2, is an autosomal dominant disorder with full penetrance. Although very few familial cases of neurilemmomatosis have been reported, most (90%) neurilemmomas in this setting have been multiple, encapsulated, and located in the subcutaneous tissue,^[4] while 10% have been plexiform, involving the neck, trunk, and extremities.
• When the tumor involves small nerves (see the image below), it is freely movable. When the tumor involves large nerves (see the image below), it is movable but moves along the long axis of the nerve where the attachment restricts mobility. A small, clinically freely movable neurilemoma found in the subcutaneous tissue. Note the pale-yellow, somewhat-translucent cut surface. The tumor also exhibits a slight nodular growth pattern on the cut surface. Courtesy of the Atlas of Tumor Pathology Armed Forces Institute of Pathology Fascicles, Tumors of the Peripheral Nervous System. Used with permission. A larger neurilemoma (5 cm in diameter) arising from a peripheral nerve showing irregularly lobulated and secondary degenerative changes, ie, partly cystic with calcification (the so-called ancient change). Hemorrhage and opaque creamy-yellow areas of tumor are also seen on this cut surface.
• Most neurilemmomas are asymptomatic, nontender, and not associated with neurologic signs or symptoms.
• A special form of inherited neurilemmoma (ie, psammomatous melanotic variant) occurs in the setting of Carney complex, which is an autosomal dominant disorder characterized by the combination of spotty pigmentation (ie, lentigines), cardiac myxomas, and endocrine overactivity. More than 50% of patients with a psammomatous melanotic neurilemmoma (ie, schwannoma) have Carney complex. In contrast to the conventional neurilemmoma, the melanotic variant is not associated with NF2; thus, conventional neurilemmomas are not observed in association with Carney complex. Another difference between the 2 variants is that approximately 10% of melanotic tumors are malignant, whereas conventional neurilemmomas almost never undergo malignant change.
• A very rare case of a vestibular schwannoma associated with a monoclonal plasma cell neoplasm has been reported.^[5]
• Benign intranodal neurilemmoma is an extremely rare tumor arising from a nerve sheath within a lymph node. A case presented as a parotid gland tumor has been described.^[6]

The etiology of neurilemmomas is uncertain. Most tumors have shown genetic aberrations (ie, ring chromosome 22).^[7]

• The NF2 gene has been localized to band 22q12. Alteration or loss of the NF2 gene product (also designated as Merlin), a presumed tumor suppressor gene, is postulated to be involved in neurilemmoma formation.^[8] Partial or complete monosomy of the chromosome occurs (ie, loss or mutation of both NF2 alleles and mutation of the NF2 gene protein).
• The negative staining of neurilemmoma cells by immunohistochemical stain for NF2 protein suggests that loss of NF2 protein function is a prerequisite for neurilemmoma formation.
• More than 150 cases of radiation-induced intracranial and peripheral neurilemmomas have been reported.^[9] The mean latency period is approximately 20 years, and most of these are solitary tumors.
• Bilateral eighth cranial nerve schwannomas indicate neurofibromatosis of NF2 type. Unusual locations and associations with meningeal proliferation are also seen with NF2.^[10]
• Clonal t (2;13) in occasional intraosseous schwannomas of the mandible have been identified. The significance of this chromosomal abnormality related to diagnosis or prognosis of this neoplasm is not yet clear.^[11]