Are You Confident of the Diagnosis?

Nerve sheath myxomas (NSMs) are rare tumors of peripheral nerves. NSMs were once considered to be myxoid variants of neurothekeoma (NTKs), but recent data suggest they are distinct entities.

Characteristic findings on physical examination

NSMs typically present as slow-growing, solitary, superficial, multinodular masses from 0.5 to 2.0 cm with a strong predilection for the extremities, particularly fingers / hands, knees, and ankles / feet. Peak incidence is in the 4th decade.

Expected results of diagnostic studies

Routine hemotoxylin and eosin (H&E) stains demonstrate a multinodular dermal and / or subcutaneous tumor composed of spindled and epithelioid cells within an abundant myxoid stroma. The cells are often epithelioid and arranged in cords or nests; stellate or spindled cells are also usually present.

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Diagnosis confirmation

Clinically, NSM may resemble a ganglion cyst, epidermal inclusion cyst, giant cell tumor of the tendon sheath(soft dermal nodule attached to the tendon), traumatic neuroma (tender dermal nodule at location of trauma, often an amputation stump), or schwannoma (tender or nontender dermal nodule). Histopathologically, NSMs may closely simulate myxoid variants of NTK; other simulators are myxomas, myxofibrosarcomas, myxoid schwannomas, and myxoid neurofibromas

NSMs favor the distal extremities, are surrounded by a rim of compressed collagen, and the neoplastic cells express S100 protein, vimentin, glial fibrilllary acidic protein (GFAP), neuron specific enolase (NSE), and CD57; EMA (epithelial membrane antigen) often labels a small population of of perineurial cells adjacent to the myxoid lobules; CD34 highlights a sparse population of intraneural fibroblasts; collagen IV is expressed by the rim of compressed connective tissue. In contrast, NTKs favor the trunk or proximal extremities, have an infiltrative architecture rather than a distinct collagenous border, and do not express S100, CD34, or EMA.

Neither myxofibrosarcomas nor myxomas express S100 protein. Myxoid variants of schwannomas usually have a well-developed capsule more distinct than those of NSMs; neurofibromas have a more diffuse growth pattern.

Who is at Risk for Developing this Disease?

A small number of patients relate a history of trauma at the site of the tumor but no convincing association between NSMs and risk factors has been established.

What is the Cause of the Disease?

There are rare reports of antecedent trauma, but the etiology is uknown; NSMs appear to be closely related to schwannomas.

Systemic Implications and Complications

No systemic implications are known.

Treatment Options

The treatment of choice is conservative complete excision; marginal or ’simple’ excision has a relatively high recurrence rate (up to 47%), but data correlating larger margins with risk of recurrence do not yet exist. Up to 50% of cases recur if incompletely excised.

Optimal Therapeutic Approach for this Disease

The treatment of choice is conservative but complete excision in order to avoid local recurrence.

Patient Management

Nerve sheath myxomas are benign and complete excision is curative; recurrence is common with incomplete excision.

Unusual Clinical Scenarios to Consider in Patient Management

Recurrence is common if incompletely excised. Recurrence is also theoretically possible if satellite lesions are undetected at time of complete excision, but tumor satellites are not commonly reported and they appear to be infrequent.

There are rare reports of nerve sheath myxoma occurring in the oral cavity.

What is the Evidence?

Fetsch, JF, Laskin, WB, Miettinen, M. “Nerve sheath myxoma: a clinicopathologic and immunohistochemical analysis of 57 morphologically distinctive S100 protein and GFAP positive myxoid peripheral nerve sheath tumors with a predilection for the extremities and a high local recurrence rate”. Am J Surg Pathol. vol. 29. 2005. pp. 1615-24. (This article describes a large series of nerve sheath myxomas and highlights their predilection for the extremities (86%), their distinct pathologic features, and their tendency for local recurrence if treated by local excision only.)

Sheth, S, Li, X, Binder, S, Dry, SM. “Differential gene expression profiles of neurothekeomas and nerve sheath myxomas by microarray analysis”. Modern Pathol. vol. 24. 2011. pp. 343-54. (These authors provide molecular data supporting the idea that nerve sheath myxomas are very closely related to schwannomas, rather than neurothekeomas.)

Fetsch, JF, Laskin, WB, Hallman, JR, Lupton, GP, Miettinen, M. “Neurothekeoma: an analysis of 178 tumors with detailed Immunohistochemical data and long-term patient follow-up information”. Am J Surg Pathol. vol. 31. 2007. pp. 1103-14. (This article describes the findings of the largest reported case series of neurothekeoma with an emphasis on the features that differentiate it from nerve sheath myxoma.)