A rubbery dermal nodule

The lesion most likely represents?

• Myxoid neurofibroma

• Superficial acral fibromyxoma

• Nerve sheath myxoma (NSM)

• Cellular neurothekeoma

• Perineurioma.

Nerve sheath myxomas are benign peripheral nerve sheath tumors of Schwann cell origin[1] that affect men and women equally. NSM can be seen in a wide age distribution, but is most commonly found in the third and fourth decades of life.[2] It frequently involves the extremities, particularly the hands/fingers, knees/pretibial region, and trunk, [Figure 1][1] but has been described in the head, neck and oral cavity.[1,3] The preoperative differential diagnosis can be broad, including ganglion cyst, epidermal inclusion cyst, fatty tumor, neurofibroma, schwannoma, xanthoma, and papilloma.[1,4]

Figure 1.

A rubbery dermal nodule

Clinically, NSMs present as solitary, superficial masses that are slow growing and typically painless.[4] The lesions typically range from 0.5 to 2.5 cm in diameter, but can present as large as 4.5 cm in diameter.[1] The affected tissue has a rubbery, firm consistency that upon cut section shows small, well-demarcated mucoid nodules.[1] NSM primarily involves the dermis and subcutis[1] and only rarely involves deep soft tissue.[5]

Histopathological examination reveals multinodular/multilobular tissue bordered by a band of dense fibrous connective tissue [Figures 2 and 3].[6] The tumor consists of scattered clusters of spindle and stellate Schwann cells embedded within a highly myxoid matrix.[3] Epithelioid Schwann cells may be present, arranged in cords or tightly packed syncytial aggregates.[7] Individual lobules are separated by thin fibrous septae. Occasional vacuolated Schwann cells may be present.[1] Intratumor nerve fibers are rarely found with neurofilament staining.[1] NSMs demonstrate the pleomorphism of nuclei, but little atypia and only rare mitoses.[7]

Figure 2.

Scanning magnification reveals myxoid islands containing stellate nuclei (×4)

Figure 3.

Higher power magnification reveals that lack of atypia in the stellate population. The tumor stained strongly for S-100 protein (×40)

Nerve sheath myxoma is immunoreactive for S-100 protein, glial fibrillary acidic protein (GFAP), neuron-specific enolase, and CD57.[1,8] There is very limited reactivity to CD34, and epithelial membrane antigen (EMA) decorates the perineurial cells in the bordering fibrous connective tissue.[3] The immunoreactivity of these tumors, along with its morphological features, indicates their close relationship with schwannomas.[3]

The term NSM was used by Harkin and Reed in the Atlas of Tumor Pathology series of the Armed Forces Institute of Pathology in 1969[9] In 1980,[10] Gallager and Helwig introduced the term neurothekeoma to describe spindled fascicular lesions involving the superficial dermis. Since then, the term myxoid neurothekeoma has been used as a synonym for NSM.[11] In contrast, cellular neurothekeoma is negative for S-100 protein and demonstrates greater overlap with plexiform fibrohistiocytic tumor.[11] Both of the latter are strongly positive for NKIC3 and CD10, but MiTF staining is restricted to cellular neurothekeoma, suggesting that the two are distinct.[12] The differential diagnosis is important because, while both may recur locally after excision, only plexiform fibrohistiocytic tumor has the potential for metastasis.[13]

Differential diagnosis primarily includes other benign peripheral nerve sheath tumors and highly myxoid tumors.[6] Myxoid neurofibroma is a tumor that also originates from Schwann cells. The tumor has a uniform myxoid stroma with moderate cellularity and sinusoidal spindled nuclei. The presence of intratumor axons is an important distinguishing feature from NSM and can be demonstrated with silver stains or with immunohistochemical staining for neurofilament protein. Perineuriomas are distinguished from NSM by their strong immunoreactivity for EMA and nonreactivity for S-100, GFAP, and CD34.[1] Perineuriomas typically form distinctive whorled, basket weave-like growth patterns.[1] Superficial acral fibromyxomas commonly occur on a digit or extremity, and appear as fibromyxoid tumors within the dermis and subcutis.[7] They demonstrate uniform fibromyxoid nodules and lack a fibrous connective tissue border. Immunohistochemical staining typically demonstrates the reactivity to both CD34 and CD99 and no staining for S-100 protein.[7]

Treatment involves simple surgical resection to prevent local recurrence.[1] While the rate of recurrence may be as high as 50%, neither the primary nor recurrent tumors demonstrate any potential for metastasis.[1]