Are You Confident of the Diagnosis?

Background and clarification of terms

Neurothekeoma is a designation that has been applied to two different tumors: (1) “Myxoid neurothekeomas”; and (2) “Cellular neurothekeomas.” Recent evidence suggests the two are distinct rather than variants of a single entity. So-called “myxoid neurothekeomas” have characteristics of peripheral nerve sheath tumors, and nerve sheath myxoma is now the preferred nomenclature. Cellular neurothekeomas” appear more closely related to dermatofibromas (fibrous histiocytomas) or fibroblastic tumors; there is little evidence to support a relationship to peripheral nerve sheath. Until additional study suggests a suitable replacement, neurothekeoma remains the preferred term for the non-myxoid types.

General features

Neurothekeomas (NTKs) are rare tumors of uncertain origin. The true incidence is difficult to determine due to the confusing terminology that has been used. Most are benign, but local recurrence has been documented. Despite the name, there is no evidence of an origin from peripheral nerve sheath

They affect both genders and almost any age, but are most common in 2nd decade (median age 17 years) and have a predilection for females. Favored sites are the head (particularly nose, cheeks, orbital region), upper extremities, and shoulder girdle. A firm, solitary, slow-growing dome-shaped nodule in skin and / or superficial subcutis is the common presentation.

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Expected results of diagnostic studies

Biopsy demonstrates a dermal and / or subcutaneous tumor composed of nodules of spindled cells arranged in whorls or fasicles (Figure 1). Tumors range from densely cellular with a collagenous stroma to sparsely cellular with abundant myxoid stroma (leading to confusion with other tumors and the creation of subtypes designated cellular, mixed, and myxoid). Scattered multinucleated giant cells are a common feature. Mitotic activity and cytologic atypia may be marked in a subset of cases. Tumor cells typically express vimentin, NKI/C3, CD10, smooth muscle actin, factor 13a, PGP 9.5, and micropthalmia transcription factor (MITF); they are negative for S100, Melan-A, and GFAP.

Figure 1.

Neurothekeoma. The tumors are usually centered within the dermis, or subcutis and have poorly demarcated borders.

Diagnosis confirmation

Clinical differential diagnosis typically includes cysts, melanocytic nevus, Spitz nevus, dermatofibroma, pilomatricoma, or basal cell carcinoma. Histopathologic differential diagnosis may include nerve sheath myxomas (NSM), plexiform fibrohistiocytic tumor (PFT), perivascular epithelioid cell tumors (PEComas) and melanocytic tumors. In contrast to nerve sheath myxomas and melanocytic lesions, NTKs are negative for S100. Plexiform fibrohistiocytic tumor (PFTs) may closely simulate NTK in both appearance and immunoprofile but usually occurs in deeper soft tissue and has a predilection for extremities; nevertheless, PFTs and NTKs appear to be closely related; PEComas may also be related.

Who is at Risk for Developing this Disease?

Peak incidence in females in the second decade (but almost any age may be affected and the tumor is not uncommon in males).

What is the Cause of the Disease?

The etiology of neurothekeoma is unknown.

Systemic Implications and Complications

No clear association with systemic or genetic conditions has been documented.

Treatment Options

Complete excision is the preferred treatment; wider excision (1 cm) may be prudent in cases with atypical features (higher mitotic rate and cellular atypia), since the biological behavior of NTKs with atypia has not been fully characterized and since “neurothekeoma” may represent a spectrum of neoplasms with varying biological behavior.

Optimal Therapeutic Approach for this Disease

The optimal therapy is complete excision.

Patient Management

Periodic follow-up for possible recurrence is the recommended management; 6 months for initial follow-up is suggested; longer intervals are probably sufficient if there is no evidence of recurrence after 1 year.

Unusual Clinical Scenarios to Consider in Patient Management

In a proportion of cases, mitotic activity and cytologic atypia may be pronounced (leading some pathologists to classify atypical neurothekeomas as malignant fibrous histiocytomas (MFH) or “undifferentiated sarcoma”; however, the superficial and localized nature of true neurothekeomas are not features of an MFH or sarcoma. The significance of atypical features is unknown since these tumors are so rare and since diagnosis may be difficult; metastasis has not been documented, but tumors on the face appear to have a tendency to recur

What is the Evidence?

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 series of neurothekeomas, including a relatively low local recurrence rate; however, it also points out that the significance of atypical features remains unknown.)

Hornick, JL, Fletcher, CD. “Cellular neurothekeoma: detailed characterization in a series of 133 cases”. Am J Surg Pathol. vol. 31. Mar 2007. pp. 329-40. (This large case series demonstrated the predominance of the lesions for the head and neck and proximal extremities and the low tendency for recurrence (except for lesions on the face). The authors suggest that there was no convincing evidence that atypical features suggested a more aggressive course.)