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Neurothekeoma was originally described in 1969 under the designation "nerve sheath myxoma."6 More than a decade later, Gallager and Helwig published a series of 53 similar neoplasms, proposing the term neurothekeoma. 5 Within this later series, a variant was described which lacked the myxoid stroma seen in conventional neurothekeomas. In addition, the pattern of growth and cytologic features of this variant differed significantly, with the formation of fascicles and nests comprised of more plump epithelioid and spindled cells. The term "cellular neurothekeoma" was introduced by Rosati in 1986 to create a distinction between this lesion and the conventional neurothekeoma.7 Investigators have further elaborated on the distinctions between these neoplasms, many suggesting that they are either distinct variants of the same entity or entirely different entities based on their morphologic, ultrastructural, and immunohistochemical features.2,3,4
Cellular Neurothekeoma is an unusual neoplasm most commonly arising in the head and neck region of adolescents and young adults.1,2,3 The clinical presentation and morphologic features of this neoplasm, may lead to confusion in differentiating it from both epithelioid and spindle cell Spitz's nevi.1 In rare cases, marked nuclear pleomorphism or an infiltrative pattern of growth may be present, causing some to consider malignant melanoma in the differential diagnosis.1,3 Unlike conventional Neurothekeomas which consistently exhibit immunophenotypic and ultrastructural evidence of nerve sheath differentiation, Cellular Neurothekeomas lack S100 immunoreactivity and appear more fibroblastic by electron microscopy.2,3,4,9
Left, Low power view of a wedge-shaped dermal neoplasm (H & E). Right,
Markedly pleomorphic nuclei evident on high-power examination.
Proposed lines of differentiation for cellular neurothekeomas have included nerve sheath (Schwann cell), perineural fibroblast, and smooth muscle.2,4,8,9
Histopathologically, Cellular Neurothekeoma is comprised of fascicles and nests of plump spindled and epithelioid cells displaying a lobulated growth pattern. At scanning magnification, the neoplasms are typically symmetrical and based in the mid dermis, with sparing of the overlying epidermis. Individual cells have abundant amphophilic to eosinophilic cytoplasm and ill-defined cell borders. Nuclei are round to oval with occasional intranuclear pseudo-inclusions (similar to those seen in melanocytic neoplasms) identified in some cases, a feature not emphasized in previous reports. Nuclear pleomorphism varies from inconspicuous to marked with typical mitotic figures presenting infrequently. 3 The present case exhibited marked nuclear atypia prompting close histopathologic discrimination prior to rendering the appropriately benign diagnosis. Although the myxoid component, characteristic of conventional neurothekeoma, is not extensive in cellular variants, it often is present to a limited degree with occasional cells appearing surrounded by a grey-blue mucinlike substance.
Strong reactivity with antibodies directed against NKI-C3.
The histopathologic differential diagnosis includes dermal Spitz's nevus, cellular blue nevus, and metastatic melanoma. By hematoxylin and eosin staining, differentiation may be exceedingly difficult, however, clues do exist. Observers may note that there is no significant maturation of lesional cells into the dermis and their cytoplasm is often more eosinophilic than one might expect in a melanocytic neoplasm. Cellular Neurothekeomas tend to arise in a dense collagenous stroma without desmoplasia. In addition, although the presence of a mucin-like substance does not rule out a melanocytic lesion, it would be rare in this setting whereas it is commonplace in Cellular Neurothekeomas. Once the Cellular Neurothekeoma is included in the differential diagnosis, the distinction can be made with certainty using Immunohistochemistry studies directed against the S100 protein, are uniformly negative in cellular neurothekeoma while lesional cells possess strong reactivity for NKI-C3.
1. Barnhill RL, Mihm MC. Cellular neurothekoma: A distinctive variant of neurothekoma mimicking nevomelanocytic tumors. Am J Surg Pathol 1990;14(2):113-120.
2. Barnhill RL, Dickersin GR, Nickeleit V, Bhan AK, Muhlbauer JE, Phillips ME, Mihm MC. Studies on the cellular origin of neurothekeoma: Clinical, light microscopic, immunohistochemical, and ultrastructural observations. J Am Acad Dermatol 1991;25:80-88.
3. Busam KJ, Mentzel T, Colpaert C, Barnhill RL, Fletcher CDM. Atypical or worrisome features in cellular neurothekeoma: A study of 10 cases. Am J Surg Pathol 1998;22(9):1067-1072.
4. Calonje E, Wilson-Jones E, Smith NP, Fletcher CDM. Cellular neurothekeoma: an epitheloid varient of pilar leiomyoma? Morphological and immunohistochemical analysis of a series. Histopathology 1992;20:397-404.
5. Gallager RL, Helwig EB. Neurothekeoma-A benign cutaneous tumor of neural origin. Am J Clin Pathol 1980;74:759-764.
6. Harkin JC, Reed RJ. Tumors of the peripheral nervous system. In: Atlas of Tumor Pathology. 2nd series. Fasicle 3. Washington, DC: Armed Forces Institute of Pathology 1969;60-64.
7. Rosati LA, Fratamico CM, Eusebi V. Cellular neurothekeoma. Appl Pathology 1986;4:186-191.
8. Wang AR, May D, Bourne P, Scott G. PGP9.5: A marker for cellular neurothekoma. Am J Surg Pathol 1999;23(11):1401-1407.
9. Webb JN. The histogenisis of nerve sheath myxoma: report of a case with electron microscopy. J Pathol 1979;127:35-37.