Cellular variant of neurothekeoma

ARTICLE

A 19-month-old male patient was admitted to our department with an isolated asymptomatic nodular lesion localized on the right parasternal area. Physical examination revealed a 1.5 cm raised, smooth, reddish nodule of rubbery consistency, with regular edges. The lesion was well demarcated, nontender and movable on the underlying tissues (Fig. 1). It had appeared about 1 year before as an erythematous papule which progressively increased in size. Ultrasonography, performed at 6 months after lesion onset, showed a dermo-hypodermic solid nodular mass. The lesion was biopsied and the histology is shown in Figure 2.

The histologic examination was consistent with the diagnosis of cellular neurothekeoma (NT). Immunohistochemistry showed positive staining for neuron specific enolase (NSE), vimentin, type IV collagen (coll IV) and alpha-smooth muscle actin (SMSA), while no reactivity was obtained using anti-CD57 and anti-CD34 monoclonal antibodies. Staining for S-100 protein was limited to rare dendritic cells scattered among the tumor cells which were negative (Table I).

Therefore, the tumor was surgically removed and at one year follow-up the patient presents no evidence of recurrence.

Comments

NT is a rare benign tumor that originates from the peripheral nerve sheath proliferation [1-3]. It mainly arises in the skin and is localized in the central area of the face, in the neck, upper limbs and shoulders [3-5], although mucosal, muco-cutaneous [3, 6] and intraspinal cases [7] have been described. It is more frequent in females (sex ratio 2-4.3/1), with a prevalence between the first and the third decade of life [2-4]. Generally asymptomatic, most lesions present as papules or nodules, flesh-colored to pink-reddish, of variable consistency, a mean diameter of 1 cm but growing with time [2, 3, 6]. The clinical diagnosis is commonly nevus, dermatofibroma or cyst [3, 6].

Histopathologically, NT is almost always localized within the reticular dermis and characterized by distinctive cytologic and architectural findings: either a cellular pattern or a myxomatous pattern [1-3, 6].

The cellular variant of NT appears as a not well-circumscribed tumor with an infiltrating or nodular growth pattern, characterized by the presence of epithelioid cells, with basophilic and relatively enlarged nuclei and abundant cytoplasm. The cells are embedded in a scarce myxoid matrix and configurated in nests or short fascicles arranged in a linear or, less commonly, concentric array. Multinucleated giant cells are occasionally found and mitotic figures are rare [2, 3, 6]. However, very rare cases of cellular NT with atypical or worrisome features have been described; these include large size, deep penetration, marked cytologic pleomorphism, high mitotic rate, diffusely infiltrative borders and vascular invasion [7].

The myxomatous variant of NT appears as a well-circumscribed nodule encapsulated by fibrous tissue, and characterized by the presence of a few dendritic cells, with basophilic stellate or spindle nuclei and eosinophilic large cytoplasm. The cells are embedded in abundant mucinous material rich in acid mucopolysaccharides and are configurated in a multilobular or plexiform array. Multinucleated giant cells are also present. Mitotic figures are rare and focal atypia can be present [1-3, 6].

In both variants, a grenz zone of unaffected dermis separates the epidermis from the tumor. Malignant melanoma, spindle and epithelioid cell (Spitz) nevus, cellular blue nevus, fibrohistiocytic proliferations and dermal smooth muscle tumors have to be histologically differentiated from cellular NT [7, 9]. Immunohistochemically, the myxomatous variant generally exhibits strong positivity for S-100 protein, whereas the cellular variant results negative. This allows the differentiation of cellular NT from melanoma [1, 2, 9, 10]. Our immunohistochemical findings showed positive staining for NSE, vimentin, coll IV and SMSA while no labeling was obtained for CD57, CD34 and S-100 protein. These results are in keeping with those reported in the literature for cellular NT [3, 6, 7, 10-12].

The cellular variant of NT generally appears in younger people and is localized on the head, whereas the myxomatous variant occurs in older patients and locates on the back, elbows and ears [6, 10]. Thus, it was suggested that the myxomatous variant could represent an older or later stage of cellular NT [2, 6]. However, the relatively short interval of development of the myxomatous variant and the different anatomic sites of appearence of the two forms are in favour of the existence of two distinct subtypes [6, 11]. Currently, it is proposed that myxomatous and cellular NT may represent separate entities originating from different cell types. Although most authors agree about a nerve sheath differentiation from Schwann cells or perineural cells for the myxomatous variant of NT, there is no consensus as to the cellular variant, which is predominantly composed of undifferentiated mesenchymal cells suggesting a different origin [2, 3, 6, 10]. It has been also proposed that cellular NT may represent an epithelioid variant of pilar leiomyoma [12]. Finally, mixed and calcific variants of NT have been recently described [3].

References

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10. Chang SE, Lee TJ, Ro JY, Choi JH, Sung KJ, Moon KC, Koh JK. Cellular neurothekeoma with possible neuroendocrine differentiation. J Dermatol 1999 ; 26: 363-7.

11. Strumia R, Lombardi AR, Cavazzini L. Cellular neurothekeoma. Acta Derm Venereol 1999 ; 79: 162-3.

12. Calonje E, Wilson-Jones E, Smith NP, Flectcher CDM. Cellular "neurothekeoma": an epithelioid variant of pilar leiomyoma? Morphological and immunohistochemical analysis of a series. Histopathology 1992 ; 20: 397-404.