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 Table of Contents  
Year : 2020  |  Volume : 7  |  Issue : 2  |  Page : 81-83

Subungual myxoid neurothekeoma of the toe: A rare entity

Department of Pathology, Indira Gandhi Medical College and Research Institute, Puducherry, India

Date of Submission09-Feb-2020
Date of Decision17-Apr-2020
Date of Acceptance26-May-2020
Date of Web Publication22-Dec-2020

Correspondence Address:
Dr. Banushree C Srinivasamurthy
Department of Pathology, Indira Gandhi Medical College and Research Institute, Puducherry - 605 013
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijdpdd.ijdpdd_17_20

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Myxoid neurothekeomas are rare benign soft-tissue tumors that are considered to be of the nerve sheath origin. They usually occur in young most commonly on the upper extremities, head, and neck, with a predilection for the female population. Based on histomorphological appearance and immunohistochemical findings, there are three variants of neurothekeoma myxoid, cellular, and mixed type. The myxoid type is characterized by a greater degree of myxomatous changes, less cellularity with well-circumscribed spindle cells in the myxoid matrix, and stain positively for S-100. This has to be differentiated from several myxoid soft-tissue tumors. We present a rare case of myxoid neurothekeoma occurring in elderly females in the toe of the lower extremity.

Keywords: Myxoid, Neurothekeoma, S-100 protein

How to cite this article:
Srinivasamurthy BC, Bhat RV. Subungual myxoid neurothekeoma of the toe: A rare entity. Indian J Dermatopathol Diagn Dermatol 2020;7:81-3

How to cite this URL:
Srinivasamurthy BC, Bhat RV. Subungual myxoid neurothekeoma of the toe: A rare entity. Indian J Dermatopathol Diagn Dermatol [serial online] 2020 [cited 2021 Jun 19];7:81-3. Available from: https://www.ijdpdd.com/text.asp?2020/7/2/81/304333

  Introduction Top

Neurothekeoma is a rare benign tumor of neural origin arising from Schwann cells.[1] Initially, described by Hakin and Reed, in 1969, as nerve sheath myxoma. Later, in the 1980s, Gallager and Helwig described the term neurothekeoma after considering both the histologic nested appearance and the purported nerve sheath differentiation.[2] Clinically, the lesions appear as painless masses of slow-growth, well-defined solitary papule/nodule.[3] Neurothekeomas may be mistaken clinically for the epidermal inclusion cysts, intradermal nevi, lipomas, pilomatrixomas, or dermatofibromas. Based on the amount of myxoid matrix, neurothekeoma is histologically divided into myxoid, intermediate, and cellular types. Immunohistochemical and ultrastructural studies suggest a myxoid variant of neurothekeoma is of neural origin and the cellular variant, of fibrohistiocytic differentiation. In literature, patient age ranges from 20 months to 85 years, with a mean age of 21 years and more commonly seen in females.[4] The majority of neurothekeomas are commonly dermal, other locations such as mucosal, intracranial and intraspinal, and dorsal paravertebral space have also been reported. The diagnosis is challenging in an uncommon presentation and locations.[5]

  Case Report Top

A 55-year-old female presented with painless, slowly-growing swelling in the left little toe of five-year duration. On examination, 20 mm × 15 mm × 10 mm mass with a small pedicle was noted on the subungual region of the little toe of the left lower extremity. Clinical diagnosis of papilloma of the left little toe was made. Complete excision was done and sent for histopathological examination. Grossly, the skin covered pedunculated mass measuring 20 mm × 15 mm with 2 mm pedicle. Cut section showed well-circumscribed lesion in dermis composed of multiple large spaces filled with gelatinous material surrounded by thick fibrous septa [Figure 1]. On histopathological examination, well-circumscribed multinodular dermal tumor composed of a proliferation of spindled cells in a nested pattern embedded within a myxoid stroma and separated by prominent fibrous septae [Figure 2]a, [Figure 2]b, [Figure 2]c. On immunohistochemistry, S-100 protein showed strong and diffuse positivity [Figure 3]a and [Figure 3]b whereas epithelial membrane antigen (EMA) and CD68 were negative. The final diagnosis of myxoid neurothekeoma of the left little toe was made.
Figure 1: Gross specimen showing pedunculated well-circumscribed dermal mass composed of multiple spaces filled with myxoid material

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Figure 2: (a) Photomicrograph (H and E, Scanner view) showing stratified squamous epithelium and subepithelial tumor with multinodularity. (b) Photomicrograph (H and E, ×10) showing varying sized nodules composed of uniform spindled cells in a nested pattern in myxoid matrix separated by prominent fibrous septae. (c) Photomicrograph (H and E, ×40) showing small spindle cells floating in myxoid matrix

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Figure 3: (a and b) Photomicrograph (S100, ×10 and ×40) showing diffuse and strong positivity for S-100 protein (arrow in b)

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  Discussion Top

Neurothekeomas are rarely seen in the lower limb. In literature, very few cases have been reported in the lower limb, foot, hallux, and subungual location in the toe.[6] To the best of our knowledge, the present case is only a second case presenting in the toe of the lower limb. The classic or myxoid type with >50% myxoid matrix was first described as a “myxoma of the nerve sheath,” occurring primarily in adults, with a predilection for the head-and-neck region in women. A more cellular variant, with ≤10% mucin content was first described in 1986 by Rosati et al. as cellular neurothekeomas and they are commonly observed in the head-and-neck region of young persons. Unlike the myxoid type, the tumor cells of the cellular variant are not generally stained with markers for the nerve cell origins, such as S100 protein, glial fibrillary acidic protein, nerve growth factor receptor, and CD57, but are positively stained with NKI/C3, Ki-M1p, EMA, and CD68 suggesting possible histo-fibrocystic origin. Mixed-type neurothekeomas show overlapping features of both variants with >10% but ≤50% myxoid matrix. Immunohistochemical analyses of these cases often show confusing features with an irregular or absent reactivity to S100 protein and smooth muscle actin.[4],[7]

Our present case occurred in little toe of the lower extremity in an elderly female and showed multinodularity, predominantly myxoid matrix, and diffuse strong positivity for S-100 protein, negativity for EMA. The cell of origin of neurothekeoma is controversial with theories proposing a proliferation of Schwann cells or other perineural cells. Dual immunoreactivity for NSE and S-100 protein in a myxoid background supports Schwann cell origin, whereas the absence of S-100 protein and positive EMA in the cellular type suggests perineural cell lineage. Gene expression array data righteously supports that nerve sheath myxomas are of peripheral nerve sheath origin and are distinct neoplasms from neurothekeomas.[8]

Histologically, myxoid neurothekeoma should be differentiated from myxoid neurofibroma, plexiform neurofibroma, myxoid schwannoma, extraneural perineuriomas, cutaneous myxoma, intramuscular and juxta-articular myxomas, cutaneous mucinosis, and hamartomas as these lesions show myxoid material along with benign spindled to stellate cells. Myxoid neurofibroma lack multinodularity and show patchy S-100 positivity. Plexiform neurofibroma show multinodularity and S-100 positivity but arise from large nerve trunk rather than cutaneous nerves and will be associated with neurofibromatosis. Myxoid schwannomas express S-100 but lack multinodularity instead show occasional foci of cellular areas with verocay bodies.

Extraneural perineuriomas show multinodularity with nodules composed of spindle cells in storiform, whorled, and fascicular pattern in a myxoid stroma and are EMA positive, S100 negative. Myxomas will be negative for S-100.[9] A very few large follow-up studies shown approximately 3% recurrence rate of neurothekeomas. Risk factors for recurrence are as follows: myxoid type, being female, facial location, younger age at diagnosis, positive margins, and the absence of fat tissue in the sample. The presence of cellular atypia and the number of mitoses were not associated with an increased recurrence rate.[4],[10] Hence, irrespective of site of presentation, typical histomorphological findings of neurothekeoma should be further confirmed on immunohistochemistry and complete excision should be done to prevent recurrence.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Sheth S, Li X, Binder S, Dry SM. Differential gene expression profiles of neurothekeomas and nerve sheath myxomas by microarray analysis. Mod Pathol 2011;24:343-54.  Back to cited text no. 1
Gallager RL, Helwig EB. Neurothekeoma – A benign cutaneous tumor of neural origin. Am J Clin Pathol 1980;74:759-64.  Back to cited text no. 2
Makino T, Utsunomiya T, Kamino Y, Kobayashi R, Fukumoto M, Yamamoto H, et al. Nerve sheath myxoma of the tongue in a child. Int J Oral Maxillofac Surg 2002;31:451-4.  Back to cited text no. 3
Fetsch JF, Laskin WB, Hallman JR, Lupton GP, Miettinen M. Neurothekeoma: An analysis of 178 tumors with detailed immunohistochemical data and long-term patient follow-up information. Am J Surg Pathol 2007;31:1103-14.  Back to cited text no. 4
Malkoc M, Ormeci T, Keskinbora M, Yılmaz A, Korkmaz O, Tanik CB. Nerve sheath myxoma of the dorsal paravertebral space. Int J Surg Case Rep 2014;5:858-60.  Back to cited text no. 5
Avninder S, Ramesh V, Vermani S. Benign nerve sheath myxoma (myxoid neurothekeoma) in the leg. Dermatol Online J 2007;13:14.  Back to cited text no. 6
Yun SJ, Park HS, Lee JB, Kim SJ, Lee SC, Won YH. Myxoid cellular neurothekeoma: A new entity of s100-negative, cd68-positive myxoid neurothekeoma. Ann Dermatol 2014;26:510-3.  Back to cited text no. 7
Akhtar K, Zaheer S, Ray PS, Sherwani RK. Myxoid neurothekeoma: A rare soft tissue tumor of hand in a male toddler. Niger J Surg 2013;19:32-4.  Back to cited text no. 8
[PUBMED]  [Full text]  
Bhat A, Narasimha A, C V, Vk S. Nerve sheath myxoma: Report of a rare case. J Clin Diagn Res 2015;9:ED07-9.  Back to cited text no. 9
Navarrete-Dechent C, Curi-Tuma M, Marín C, González S, Sandoval-Osses M. Cellular neurothekeoma: Case report and its (un) relation with nerve sheath myxoma. An Bras Dermatol 2015;90:156-9.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]


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