Neurothekeoma: An Analysis of 178 Tumors With Detailed Immunohistochemical Data and Long-term Patient Follow-up Information

Abstract

This report describes the clinicopathologic findings in 176 patients who presented with 178 tumors currently referred to as neurothekeomas. Our study group included 64 males and 112 females, ranging from 20 months to 85 years old at the time of their first surgical procedure (median age: 17 y). Twenty-four percent of patients were <or=10 years of age and only 20% of patients were >or=30 years of age at initial diagnosis. The patients typically presented with a solitary, superficial, slow-growing, and relatively asymptomatic mass in the 0.3 to 2.0 cm size range. One patient had multiple tumors. More than 75% of the lesions involved the head (n=63), upper extremities (n=44), and shoulder girdle (n=27) regions. The tumors were evident a few weeks to 4 years (median duration: approximately 7 mo) before surgical resection was sought. Histologically, the lesions involved the dermis and/or subcutis, and they formed multinodular masses with varying amounts of myxoid matrix and peripheral fibrosis. On the basis of the amount of myxoid matrix, the tumors were subclassified as cellular (n=63), mixed (n=67), or myxoid (n=48). All cases had spindled and epithelioid mononuclear neoplastic cells with relatively abundant cytoplasm and indistinct cell borders. The majority of cases also had occasional multinucleated tumor cells. The lesional cells had a strong tendency for whorled growth, and oftentimes, focal fascicular growth was also present. Nuclear atypia was minimal in 62 cases, mild in 73 cases, at least focally moderate in 41 cases, and focally marked in 2 cases. Mitotic activity ranged from 0 to 124 mitotic figures/25 wide-field high power fields (WHPFs) (median mitotic count: 4 mitotic figures/25WHPFs). Twenty-five lesions had >10 mitotic figures/25WHPFs. A total of 16 cases (9%) had atypical mitotic figures. Osteoclastlike giant cells were detected in 39% of cases. Immunoreactivity was typically present for vimentin, NKI/C3, CD10, microphthalmia transcription factor, and PGP9.5, and focal reactivity was sometimes noted for smooth muscle actin and CD68. All tumors tested were negative for S100 protein, glial fibrillary acidic protein, and Melan A. The overwhelming majority of cases had involvement of the tissue margins. A complete follow-up record is available for 71 patients (40.3%) with follow-up intervals ranging from 3 years 2 months to 34 years 9 months (median: 17 y 9 mo). Limited or incomplete follow-up information is also available for an additional 14 patients with follow-up intervals ranging from weeks to approximately 10 years (median: 5 mo). Regrowth of tumor after biopsy or local excision was reported in 13 patients, one of whom had 2 recurrences. However, because of the nature of our consultation practice and a tendency for clinicians to specifically send us cases with a complex clinical course, this is believed an overestimation of the true recurrence rate. Neurothekeomas are morphologically and immunohistochemically distinct from true nerve sheath myxomas. An origin from fibroblastic cells with the abili...

Differential gene expression profiles of neurothekeomas and nerve sheath myxomas by microarray analysis

“…[27][28][29] The gene expression profiles of these four histological entities are shown in Figures 5-7. Greater numbers of differentially expressed genes between nerve sheath myxomas and neurothekeomas suggest that they are not related ( Figure 5).…”

“…30,33,34 All slides were re-reviewed by three authors (SS, SB and SD) and appropriately categorized based on histological and immunohistochemical criteria set forth by the Armed Forces Institute of Pathology, World Health Organization and Hornick and Fletcher's reviews of neurothekeomas and cellular fibrohistiocytic tumors (Table 1). 22,[27][28][29]35,36 Exclusion criteria included cases with scant tissue remaining in the block and cases without unanimous agreement on the definitive diagnosis. Analysis was also limited to blocks of tissue with at least 40% tumor cells.…”

“…These cases included patients diagnosed with myxoid, mixed or cellular neurothekeomas (nine cases), dermal nerve sheath myxomas (five cases), cellular fibrous histiocytomas (seven cases) and dermal schwannomas (seven cases; Table 1 Reported clinical, histological and immunological findings of neurothekeomas, cellular fibrous histiocytomas and dermal nerve sheath myxomas. [27][28][29]36 Neurothekeoma Cellular fibrous histiocytoma Nerve sheath myxoma Figures 1-4). Areas of the slide (B5 mm 2 ) with maximal tumor tissue were circled and corresponding areas were macrodissected from the tumor blocks for RNA isolation.…”

“…[14][15][16][17] However, subtle morphologic differences, divergent immunohistochemical staining in human tissue and ultrastructural studies led many authors to question the relationship between neurothekeomas and nerve sheath myxomas. 1,7,9,11,[18][19][20][21][22][23][24][25][26][27][28][29] Recent work by Fetsch et al, 28 using a combination of morphological, immunohistochemical and ultrastructural data, strongly argues that nerve sheath myxomas represent a myxoid variant of schwannoma. Using similar studies, Hornick and Fetsch both underscore previous suggestions that neurothekeomas represent a variant of cutaneous fibrohistiocytic tumors, which are benign fibroblastic and histiocytic tumors with a wide range of histomorphologic appearances.…”

“…Using similar studies, Hornick and Fetsch both underscore previous suggestions that neurothekeomas represent a variant of cutaneous fibrohistiocytic tumors, which are benign fibroblastic and histiocytic tumors with a wide range of histomorphologic appearances. 27,29 To date, there have been no molecular studies examining these entities. Recent biotechnological advances have optimized conditions to improve the quality and quantity of RNA extracted from formalin-fixed paraffin-embedded tissues.…”