Cellular neurothekeoma

(Greek theke, sheath)

Definition

A dermal/subcutaneous tumour of uncertain histogenesis. At one time considered the cellular equivalent of dermal nerve sheath myxoma, these two entities are not longer considered to be related. The mixed-type variant of neurothekeoma has a myxoid component but should be classified with other neurothekeomas.

Epidemiology

This tumour may occur at any age, including in children, with most cases occurring before the age of 40 years. There is a female predominance.

Clinical features

Presentation is usually with a painless mass. Tumours most commonly occur on the upper extremity (particularly shoulder), followed by the head (particularly face) and neck, lower limbs and trunk.

Macroscopic appearance

The mean tumour size is 1 cm and most are smaller than 2 cm.

Histopathology

All tumours have a dermal component and about half extend into the subcutis. The margins are ill-defined and may infiltrate fat or skeletal muscle. A Grenz zone separates the tumour from the epidermis. The tumour is lobulated or micronodular. A few cases are plexiform. It is composed of nests of cells which vary from epithelioid to spindled with pale cytoplasm. The cells may be surrounded by dense collagen. Some cases have a myxoid stroma, of variable extent. Nuclear pleomorphism is usually mild but a minority of cases include markedly atypical cells. Mitotic figures average 3 per 10 HPF. A minority of cases have Touton or osteoclast-like giant cells.

Immunohistochemistry

	NKI-C3	133/1331, 9/113
	NSE	110/1231, 0/124
	SMA	73/1271, 1/124
	Desmin	1/1151, 0/124
	S-100	0/1331, 0/113 , 3/124
	S100A6	7/72
	PGP9.5	3/72, 12/12(with antigen retrieval)3
	Microphthalmia transcription factor	9/113
	GFAP	negative1
	MART-1	negative1
	Leu-7	0/124
	Synaptophysin	0/124
	EMA	1/124
	Vimentin	12/124

Ultrastructure

Specific features are lacking, the cells appearing to be myofibroblastic.

Differential diagnosis

Dermal nerve sheath myxoma (DNSM): usually occurs in middle-aged adults, on the distal extremities, rarely on the face. The myxoid stroma is extensive. The tumour lobules are sharply demarcated. There is consistent positivity for S-100 and GFAP. The differential is clinically important because DNSM has a high recurrence rate.
Spitz naevus: like, cellular neurothekeoma, occurs on the head and neck in the first two decades of life. Spitz naevus has a junctional component. It shares positivity for NKI-C3 and NSE but is also positive for S-100 and MART-1.
Pilar leiomyoma: has more elongated nuclei and more eosinophilic cytoplasm. There is positivity for desmin.
Plexiform fibrohistiocytic tumour also occurs in the skin and subcutis of children and young adults. The cell population is biphasic, comprising mononuclear histiocytoid cells and osteoclast-like giant cells. May be positive for NKI-C3 and NSE.

Prognosis

Cellular neurothekeomas are benign tumours that do not recur, even when incompletely excised. Cytological atypia does not seem to be of prognostic significance.

References

1 Hornick JL,Fletcher CD. Cellular neurothekeoma: detailed characterization in a series of 133 cases. Am J Surg Pathol 2007; 31:329-40

2 Fullen DR, Lowe L,Su LD. Antibody to S100a6 protein is a sensitive immunohistochemical marker for neurothekeoma. J Cutan Pathol 2003; 30:118-22 FULL TEXT

3 Page RN, King R, Mihm MC, Jr., et al. Microphthalmia transcription factor and NKI/C3 expression in cellular neurothekeoma. Mod Pathol 2004; 17:230-4 FULL TEXT

4 Wang AR, May D, Bourne P, et al. PGP9.5: a marker for cellular neurothekeoma. Am J Surg Pathol 1999; 23:1401-7

This page last revised 9.6.2007.