Are You Confident of the Diagnosis?

Schwannomas are benign tumors of the peripheral nerve sheath. Sporadic schwannomas occur as a single, isolated lesion. Multiple schwannomas are almost always a sign of an underlying genetic syndrome, most commonly neurofibromatosis type 2 (NF2) or schwannomatosis. They do not occur in NF1.

Characteristic findings on physical examination

Psammomatous melanotic shwannomas are a part of Carney complex. Schwannomas present as slow-growing tumors. Because they displace, but do not destroy the nerve, pain is uncommon. The exception is in schwannomatosis, where pain is a major feature. Rarely, the patient may complain of paresthesias or weakness.

Cutaneous schwannomas present as either subcutaneous nodules or dermal plaques. The most common location is the flexural surfaces of the extremities, followed by the head and neck. The subcutaneous nodules are well-circumscribed, firm, and spherical. Pain may be elicited with pressure. Paresthesias may occur with percussion. The nodules are generally mobile in a side to side motion, but not in a vertical direction.

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The subcutaneous nodules occur in both NF2 and schwannomatosis. In schwannomatosis, they may string along the nerve like pearls on a necklace. The plaques present as discrete, well-circumscribed, slightly raised lesions, often with overlying hypertrichosis and faint hyperpigmentation. The plaque-like lesions occur only in NF2. Multiple schwannomas may be localized to one body segment. Melanotic schwannomas in Carney complex commonly involve the spinal nerves and viscera, but rarely present in the skin.

Expected results of diagnostic studies

Biopsy is often required to confirm the diagnosis. Histologically, Schwannomas are encapsulated spindled cell tumors. They are composed of hypercellular Antoni A areas (spindle-shaped Schwann cells arranged in interlacing fascicles and Verocay bodies) and hypocellular Antoni B areas (gelatinous and microcystic tissue with widely separated Schwann cells). Immunoperoxidase staining for S100 protein is strongly and uniformly positive. A cellular variant has also been described, which lacks Antoni B areas and Verocay bodies. Additionally, melanotic schwannomas have heavy melanotic pigmentation and calcification.

If multiple lesions are present, especially in the setting of a positive family history or symptoms (pain, weakness, tinnitus, hearing loss or vertigo), MRI of brain and/or spinal cord looking for evidence of vestibular schwannomas or involvement of other cranial, spinal and peripheral nerves should be done. Genetic testing is available for NF2 and schwannomatosis.

Diagnosis confirmation

The clinical differential diagnosis includes other entities that present as subcutaneous nodules or deep dermal palques. These include neurofibroma; lipoma; angiolipoma; leiomyoma; eccrine spiradenoma; and neuroma. Diagnosis is made by histopathologic examination.

Who is at Risk for Developing this Disease?

Scwannomas are rare tumors that can present at any age. They are most common in adults. Peak onset is in the third to sixth decade. There is no racial or sex predilection. Ninety percent are solitary and are not associated with an underlying genetic disease. Multiple lesions are common in individuals with NF2 or schwannomatosis.

What is the Cause of the Disease?

Schwannomas are tumors of the Schwann cells. As the Schwann cells proliferate, they displace normal nerve fibers to the periphery, while remaining contained within the perineurium. NF2-associated schwannomas and many sporadic schwannomas are caused by loss of function of the NF2 gene, which is located on chromosome 22q12.2.

NF2 encodes a tumor suppressor protein, merlin (schwannomin). Mutations cause decreased or absent production of merlin, which leads to tumor formation. Other genetic or epigenetic events may be necessary for tumor growth, but these events are unknown. At least some schwanommatosis-associated schwannomas are due to germline mutations in INI1/SMARCB1.

Systemic Implications and Complications

Rarely, cutaneous schwannomas may cause neurologic deficits, such as weakness, due to compression of the nerve. Malignant degeneration is unlikely. Multiple schwannomas are highly suspicious for NF2 or schwanommatosis. Scwhannomas of the cranial nerves or spinal roots can cause neurologic deficits, hearling loss, and chronic pain.

NF2 is an autosomal dominant disorder characterized by bilateral vestibular schwannomas, schwannomas of other central or peripheral nerves (including skin), meningiomas and cataracts. Schwannomatosis is associated with the development of multiple schwannomas, but not vestibular tumors. Workup and management of these disorders is detailed in the chapter entitled Neurofibromatosis. Carney complex is a rare disorder that includes lentigines, myxomas, and endocrine neoplasms.

Treatment Options

Surgical treatment is generally reserved for symptomatic cases. Complete surgical excision is usually curative. Because the tumor is contained within the perineurium, care should be taken to avoid damage of the affected nerve.

Optimal Therapeutic Approach for this Disease

After determining whether or not a lesion(s) is isolated or part of a syndrome, consideration can be given as to whether or not to have lesions excised based on associated symptomatology.

Patient Management

In most cases, a biopsy will be necessary to confirm the diagnosis. Patients with solitary schwannomas and no family history or signs or symptoms of NF2 or schwanomatosis should be reassured that this is a benign tumor. Solitary tumors are unlikely to be associated with an underlying disease. Surgical excision can be offered to patients with large or symptomatic tumors. If a patient has more than one schwannoma, they should be evaluated for NF2 and/or schwannomatosis with MRI of the brain and spinal cord, ophthalmologic examination, and hearing evaluation (BAER).

Unusual Clinical Scenarios to Consider in Patient Management

Rarely, malignant schwannomas may appear (malignant peripheral nerve sheath tumors). Any schwannoma that undergoes rapid growth must be evaluated for this possibility by appropriate imaging and pathologic examination.

What is the Evidence?

Scheithauer, BW, Woodruff, JM, Eriandson, RA. “Tumors of the peripheral nervous system”. Atlas of tumor pathology. 1999. pp. 1-415. (Provides a detailed histologic description of schwannomas.)

Hanemann, CO, Evans, DG. “News on the genetics, epidemiology, medical care and translational research of Schwannomas”. J Neurol. vol. 253. 2006. pp. 1533-41. (A well-written and updated review on all aspects of schwannomas.)

Kurtkaya-Yapicier, O, Scheithauer, B, Woodruff, JM. “The pathobiologic spectrum of schwannomas”. Histol Histopathol. vol. 18. 2003. pp. 925-34. (Reviews the spectrum of schwannomas including their essential clinicopathologic features and differential diagnosis.)

Knight, DMA, Birch, R, Pringle, J. “Benign solitary schwannomas”. J Bone Joint Surg. vol. 89B. 2007. pp. 382-7. (A review of 234 surgically treated solitary schwannomas.)