Final Diagnosis -- Neurothekeoma



Neurothekeoma, (Dermal nerve sheath myxoma), is a rare neoplasm of the dermis. It typically arises on the upper extremities and the head and neck region. It is usually seen in the first three decades of life with predilection for females. No association with neurofibromatosis syndrome has been documented. Clinically, the tumor presents as a solitary nodule, skin-coloured measuring <3cm in greatest dimension. The tumor is considered to arise form nerve sheath based on morphology and immunochemical profile.

Histologically, the tumor has a distinctive appearance. It is unencapsulated, yet well defined, mass that is composed of variable size lobules located mainly in the reticular dermis with minimal involvement of the subcutaneous tissue. The papillary dermis is usually spared. The tumor lobules are separated by thin fibrovascular septae. The lobules consist of stellate and delicate spindle cells dispersed in a myxoid stroma, arranged in lamellar and often concentric pattern. The cytoplasm is pale and indistinct. The nuclei are elongated often angulated with inconspicuous nucleoli and uniformly distributed chromatin.

Some tumor lobules may show round larger cells with eosinophilic abundant cytoplasm and plump vesicular nuclei. Hyperchromatic nuclei and multinucleated cells may also be seen. Occasional mitotic figures are common. However, abnormal mitoses are not a feature of this tumor. Lymphocytes, mast cells and plasma cells can be seen scattered around and within the tumor.

The differential diagnosis includes dermal myxoma, which is usually hypocellular and contains abundant stromal mucin, myxoid neurofibroma and superficial angiomyxoma that is characterized by lack of circumscription, epithelial elements and inconspicuous blood vessels.

Immunohistochemical stains shows that tumor cells are reactive for S-100, vimentin, collagen IV and low-affinity nerve growth factor receptor. The cells are variably positive for CD57 and GFAP. EMA positive cells sometimes surround individual lobules of tumor cells.

Treatment of neurothekeoma is a complete excision as recurrence may occur. However, the tumor is considered benign and has no evidence of malignant potential.

Neurothekeoma has three recognized variants including myxoid, intermediate (mixed), and cellular variant, based on the presence and the percentage of the epithelioid component.

The cellular variant of neurothekeoma was first described by Rosati et al as a typical nerve sheath myxoma with abundant cellular lobules of epithelioid cells. Many authors consider the "cellular neurothekeoma", which was described in 1990 by Barnhill, a separate entity as it has different morphological and immunohistochemical features. It is S100 negative, PGP9.5 positive and focally positive for SMA. However, it is still an area of controversy.

Patient Follow up

Patient underwent complete re-excision of the lesion with negative margins and she is doing fine with no recurrence to date.


  1. Mackee PH, Calonji EC, Gartner SR. Pathology of the skin 3rd edition. Elsevier and Mosby 2005. p.1782-5.
  2. Weeden D. Skin Pathology 2nd edition. Curchil Livingston 2002. p.984-6.
  3. Elder D, Elenitsas R, Johnson B, Murphy G. Lever's histopathology of the Skin, Vol. 35. 9th ed. Lippincott Williams & Wilkins, 2004. p. 1126-9.
  4. Gallager RL, Helwig EB. NeurothekeomaFa benign cutaneous tumor of neural origin. Am J Clin Pathol 1980;74:759-64.
  5. Barnhill RL, Mihm MC Jr. Cellular neurothekeoma. A distinctive variant of neurothekeoma mimicking nevomelanocytic tumors. Am J Surg Pathol 1990;14:113-20.
  6. Rosati LA, Fratamico FC, Eusebi V. Cellular neurothekeoma. Appl Pathol 1986;4:186-91.
  7. Argenyi ZB, LeBoit PE, Santa Cruz D, Swanson PE, Kutzner H. Nerve sheath myxoma (neurothekeoma) of the skin: light microscopic and immunohistochemical reappraisal of the cellular variant. J Cutan Pathol 1993;20:294-303.
  8. Laskin WB, Fetsch JF, Miettinen M. The ''neurothekeoma'': immunohistochemical analysis distinguishes the true nerve sheath myxoma from its mimics. Hum Pathol 2000;31:1230-41.
  9. Zelger BG, Steiner H, Kutzner H, Maier H, Zelger B. Cellular ''neurothekeoma'': an epithelioid variant of dermatofibroma? Histopathology 1998;32:414-22.
  10. Papadopoulos EJ, Cohen PR, Hebert AA. Neurothekeoma: report of a case in an infant and review of the literature. J Am Acad Dermatol 2004;50: 129-34.
  11. Livasy CA,Woosley JT. Solitary nasal ala nodule in a young woman. Cellular neurothekeoma. Arch Dermatol 2003;139:531-6.
  12. Benbenisty KM, Andea A, et al. Atypical Cellular Neurothekeoma Treated with Mohs Micrographic Surgery. Dermatol Surg 2006;32:582-587.

Contributed by Amer Heider, MD and Jonhan Ho, MD

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