Correspondence Clinical Letter
Clinical Letter Desmoplastic cellular neurothekeoma mimicking basal cell carcinoma
DOI: 10.1111/ddg.12523
Dear Editors, Neurothekeomas are benign cutaneous tumors, which were first reported by Pulitzer and Reed in 1985 [1]. Cellular neurothekeomas, which account for approximately 35 % of neurothekeomas, have been proposed to be a distinct and rare entity histogenesis [2]. Furthermore, desmoplastic cellular neurothekeomas account for only 3–4 % of cellular neurothekeomas [2, 3], and can clinically mimic benign or malignant skin tumors [4]. Despite the rarity of desmoplastic cellular neurothekeomas, it is important to keep this entity in mind when encountering a desmoplastic lesion on histopathology.
A 29-year-old woman with an unremarkable medical history presented with nodule on her nose. The lesion had grown over the past two months and had not responded to cryotherapy. Physical examination revealed an asymptomatic firm skin-colored dome-shaped nodule with erosion, which may have been caused by the previous cryotherapy, and telangiectatic surface on her nose (Figure 1a). The clinical differential diagnosis included basal cell carcinoma, epidermoid cyst, follicular neoplasm, adnexal tumor or dermal melanocytic nevus. The tumor was excised. The histopathological findings showed an unremarkable epidermis, but a fascicular and nodular arrangement of spindled and epithelioid cells in the dermis. These cells had a pale cytoplasm with vesicular nuclei and indistinct membranes. There was a sclerotic background with thickened collagen bundles which separated and encompassed the tumor cells, and an increased mitotic count up to 1–2/10 high power fields was noted (Figure 1b-f). Immunohistochemical studies showed negative reactivity for S-100 protein, HMB-45 (melanosome specific antigen), D2–40, cytokeratin AE1/AE3, EMA (epithelial membrane antigen), CD34, GFAP (glial fibrillary acidic
Figure 1 An asymptomatic erythematous to skin-colored nodule with erosion and telangiectases on the nose (a). An unencapsulated dermal tumor (hematoxylin & eosin stain, original magnification x40) (b). Tumor cells extending into subcutaneous fat and smooth muscles (hematoxylin & eosin stain, original magnification x100) (c). Spindled to epithelioid tumor cells arranged in a fascicular or nodular pattern at the periphery of the tumor, which hinted at neurothekeoma, and desmoplastic hyalinized stroma in the tumor background (hematoxylin & eosin stain; original magnification x200) (d). Spindled to epithelioid tumor cells with mild increased mitotic rate (hematoxylin & eosin stain; original magnification x400) (e). Atypical epithelioid cells were separated by abundant keloid-like stroma with thickened collagen bundles (hematoxylin & eosin stain; original magnification x400) (f).
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1303
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Figure 2 Immunohistochemical studies. Negativity for S-100 protein of tumor cells (original magnification x200) (a). Focally positivity for MiTF of tumor cells (original magnification x400) (b). Positivity for NSE of tumor cells (original magnification x400) (c). Diffusely positivity for CD10 of tumor cells (original magnification x200) (d). Positivity for CD68 of tumor cells (original magnification x400) (e). Negativity for GFAP of tumor cells (original magnification x200) (f).
protein), p16, p53, p63, and desmin. Expressions of CD10, NSE (neuron-specific enolase), actin, and H-caldesmon were diffusely positive, MiTF (microphthalmia transcription factor) focally weakly positive, and CD68 (PGM-1) focally positive (Figure 2a–f). Due to the negative reactivity for EMA and AE1/AE3, an epidermal, adnexal or glandular origin was less-likely. Negativity for S-100 protein and HMB-45 also ruled out the melanocytic tumors. In addition, low-grade sarcoma, such as low-grade fibromyxoid sarcoma and myoepithelioma, and other malignant tumors, such as sclerosing epithelioid fibrosarcoma and melanoma, were ruled out because of the positive reactivity of H-caldesmon and the negative reactivity of D2–40, CD34, p16, p53, p63, EMA, S-100 protein, GFAP, and desmin. Furthermore, it was unlikely to be of neural origin due to the negativity for GFAP and S-100. Therefore, according to the clinical, histopathological, and immunohistochemical findings, desmoplastic cellular neurothekeoma was diagnosed. Cellular neurothekeoma typically presents as a relatively asymptomatic, superficial, slow-growing nodule over the head and neck or upper extremities in children or young adults, with a 2 : 1 female to male predominance. The size of the tumors ranges from 0.3 to 2.0 cm, and the average duration from presentation to surgical excision is a few weeks to four years. In addition, there is a mean mitotic rate of 3 per 10 high power fields, so that the tumor easily be mistaken for malignant [2,
244
3]. The differential diagnosis includes a granulomatous process, desmoplastic melanocytic tumors, desmoplastic squamous cell carcinoma, benign fibrous histiocytoma, low-grade sarcoma, plexiform fibrohistiocytic tumor, benign cutaneous plexiform hybrid tumor of perineurioma and cellular neurothekeoma, and piloleiomyoma [2, 3, 5]. Despite the benign nature of the lesion, cellular neurothekeoma can be mistaken for a malignant tumor because of the presence of mitotic activity and extension into the deeper dermis or skeletal muscles. In particular, desmoplastic melanoma may have an intraepidermal or junctional component. S-100 protein is helpful to differentiate the tumors. Plexiform fibrohistiocytic tumors, benign cutaneous plexiform hybrid tumors of perineurioma and cellular neurothekeoma are the most difficult to differentiate due to the similarity in immunohistochemical findings [6, 7]. A recent study showed that MiTF may be helpful in differentiating the tumors due to prevailing immunoreactivity noted in cellular neurothekeoma [8]. Other features of plexiform fibrohistiocytic tumors include greater subcutaneous involvement than neurothekeomas, distinctive biphasic architecture, and osteoclastic giant cells surrounded by fascicles of fibroblastic spindle cells [5]. Complete excision is curative, and recurrence has rarely been reported after surgical intervention [2, 3]. An interesting finding in our study was the expression of H-caldesmon; however it is somewhat compatible with the proposed myofibrogenesis of cellular neurothekeomas [3]. In
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1303
Correspondence Clinical Letter
our case, it may prove to be a new marker for cellular neurothekeomas. Further large-scale studies are needed to elucidate this hypothesis. In summary, we report a case of a rare desmoplastic cellular neurothekeoma on the nose, which may be mistaken for other malignant tumors clinically or histopathologically. It is important to keep this rare entity in mind when evaluating a desmoplastic skin lesion.
References
Conflicts of interest None.
4
Yu-Ching Weng1, Jui-Lung Shen1, Chii-Shuenn Yang2, Wen-Hao Li1
5
(1) Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan (2) Department of Pathology, Taichung Veterans General Hospital, Taichung, Taiwan
1 2
3
6
7
8
Correspondence to Wen-Hao Li, MD Department of Dermatology Taichung Veterans General Hospital No. 1650, Sec. 4, Taiwan Boulevard
Pulitzer DR, Reed RJ. Nerve-sheath myxoma (perineurial myxoma). Am J Dermatopathol 1985; 7: 409–21. Fetsch JF, Laskin WB, Hallman JR et al. 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. Hornick JL, Fletcher CD. Cellular neurothekeoma: detailed characterization in a series of 133 cases. Am J Surg Pathol 2007; 31: 329–40. D’Antonio A, Cuomo R, Angrisani B et al. Desmoplastic cellular neurothekeoma mimicking a desmoplastic melanocytic tumor. J Am Acad Dermatol 2011; 65: e57–8. Chang WT, Wu YH, Wu NL, Chang KM. Desmoplastic cellular neurothekeoma. Dermatologica Sinica 2014; 32: 193–4. Yamada S, Kitada S, Nabeshima A et al. Benign cutaneous plexiform hybrid tumor of perineurioma and cellular neurothekeoma arising from the nose. Diagn Pathol 2013; 8: 165. Requena L, Sitthinamsuwan P, Fried I et al. A benign cutaneous plexiform hybrid tumor of perineurioma and cellular neurothekeoma. Am J Surg Pathol 2013; 37: 845–52. Fox MD, Billings SD, Gleason BC et al. Expression of MiTF may be helpful in differentiating cellular neurothekeoma from plexiform fibrohistiocytic tumor (histiocytoid predominant) in a partial biopsy specimen. Am J Dermatopathol 2012; 34: 157–60.
Taichung 40705 Taiwan E-mail: [email protected]
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1303
245
Clinical Letter Desmoplastic cellular neurothekeoma mimicking basal cell carcinoma
DOI: 10.1111/ddg.12523
Dear Editors, Neurothekeomas are benign cutaneous tumors, which were first reported by Pulitzer and Reed in 1985 [1]. Cellular neurothekeomas, which account for approximately 35 % of neurothekeomas, have been proposed to be a distinct and rare entity histogenesis [2]. Furthermore, desmoplastic cellular neurothekeomas account for only 3–4 % of cellular neurothekeomas [2, 3], and can clinically mimic benign or malignant skin tumors [4]. Despite the rarity of desmoplastic cellular neurothekeomas, it is important to keep this entity in mind when encountering a desmoplastic lesion on histopathology.
A 29-year-old woman with an unremarkable medical history presented with nodule on her nose. The lesion had grown over the past two months and had not responded to cryotherapy. Physical examination revealed an asymptomatic firm skin-colored dome-shaped nodule with erosion, which may have been caused by the previous cryotherapy, and telangiectatic surface on her nose (Figure 1a). The clinical differential diagnosis included basal cell carcinoma, epidermoid cyst, follicular neoplasm, adnexal tumor or dermal melanocytic nevus. The tumor was excised. The histopathological findings showed an unremarkable epidermis, but a fascicular and nodular arrangement of spindled and epithelioid cells in the dermis. These cells had a pale cytoplasm with vesicular nuclei and indistinct membranes. There was a sclerotic background with thickened collagen bundles which separated and encompassed the tumor cells, and an increased mitotic count up to 1–2/10 high power fields was noted (Figure 1b-f). Immunohistochemical studies showed negative reactivity for S-100 protein, HMB-45 (melanosome specific antigen), D2–40, cytokeratin AE1/AE3, EMA (epithelial membrane antigen), CD34, GFAP (glial fibrillary acidic
Figure 1 An asymptomatic erythematous to skin-colored nodule with erosion and telangiectases on the nose (a). An unencapsulated dermal tumor (hematoxylin & eosin stain, original magnification x40) (b). Tumor cells extending into subcutaneous fat and smooth muscles (hematoxylin & eosin stain, original magnification x100) (c). Spindled to epithelioid tumor cells arranged in a fascicular or nodular pattern at the periphery of the tumor, which hinted at neurothekeoma, and desmoplastic hyalinized stroma in the tumor background (hematoxylin & eosin stain; original magnification x200) (d). Spindled to epithelioid tumor cells with mild increased mitotic rate (hematoxylin & eosin stain; original magnification x400) (e). Atypical epithelioid cells were separated by abundant keloid-like stroma with thickened collagen bundles (hematoxylin & eosin stain; original magnification x400) (f).
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1303
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Correspondence Clinical Letter
Figure 2 Immunohistochemical studies. Negativity for S-100 protein of tumor cells (original magnification x200) (a). Focally positivity for MiTF of tumor cells (original magnification x400) (b). Positivity for NSE of tumor cells (original magnification x400) (c). Diffusely positivity for CD10 of tumor cells (original magnification x200) (d). Positivity for CD68 of tumor cells (original magnification x400) (e). Negativity for GFAP of tumor cells (original magnification x200) (f).
protein), p16, p53, p63, and desmin. Expressions of CD10, NSE (neuron-specific enolase), actin, and H-caldesmon were diffusely positive, MiTF (microphthalmia transcription factor) focally weakly positive, and CD68 (PGM-1) focally positive (Figure 2a–f). Due to the negative reactivity for EMA and AE1/AE3, an epidermal, adnexal or glandular origin was less-likely. Negativity for S-100 protein and HMB-45 also ruled out the melanocytic tumors. In addition, low-grade sarcoma, such as low-grade fibromyxoid sarcoma and myoepithelioma, and other malignant tumors, such as sclerosing epithelioid fibrosarcoma and melanoma, were ruled out because of the positive reactivity of H-caldesmon and the negative reactivity of D2–40, CD34, p16, p53, p63, EMA, S-100 protein, GFAP, and desmin. Furthermore, it was unlikely to be of neural origin due to the negativity for GFAP and S-100. Therefore, according to the clinical, histopathological, and immunohistochemical findings, desmoplastic cellular neurothekeoma was diagnosed. Cellular neurothekeoma typically presents as a relatively asymptomatic, superficial, slow-growing nodule over the head and neck or upper extremities in children or young adults, with a 2 : 1 female to male predominance. The size of the tumors ranges from 0.3 to 2.0 cm, and the average duration from presentation to surgical excision is a few weeks to four years. In addition, there is a mean mitotic rate of 3 per 10 high power fields, so that the tumor easily be mistaken for malignant [2,
244
3]. The differential diagnosis includes a granulomatous process, desmoplastic melanocytic tumors, desmoplastic squamous cell carcinoma, benign fibrous histiocytoma, low-grade sarcoma, plexiform fibrohistiocytic tumor, benign cutaneous plexiform hybrid tumor of perineurioma and cellular neurothekeoma, and piloleiomyoma [2, 3, 5]. Despite the benign nature of the lesion, cellular neurothekeoma can be mistaken for a malignant tumor because of the presence of mitotic activity and extension into the deeper dermis or skeletal muscles. In particular, desmoplastic melanoma may have an intraepidermal or junctional component. S-100 protein is helpful to differentiate the tumors. Plexiform fibrohistiocytic tumors, benign cutaneous plexiform hybrid tumors of perineurioma and cellular neurothekeoma are the most difficult to differentiate due to the similarity in immunohistochemical findings [6, 7]. A recent study showed that MiTF may be helpful in differentiating the tumors due to prevailing immunoreactivity noted in cellular neurothekeoma [8]. Other features of plexiform fibrohistiocytic tumors include greater subcutaneous involvement than neurothekeomas, distinctive biphasic architecture, and osteoclastic giant cells surrounded by fascicles of fibroblastic spindle cells [5]. Complete excision is curative, and recurrence has rarely been reported after surgical intervention [2, 3]. An interesting finding in our study was the expression of H-caldesmon; however it is somewhat compatible with the proposed myofibrogenesis of cellular neurothekeomas [3]. In
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1303
Correspondence Clinical Letter
our case, it may prove to be a new marker for cellular neurothekeomas. Further large-scale studies are needed to elucidate this hypothesis. In summary, we report a case of a rare desmoplastic cellular neurothekeoma on the nose, which may be mistaken for other malignant tumors clinically or histopathologically. It is important to keep this rare entity in mind when evaluating a desmoplastic skin lesion.
References
Conflicts of interest None.
4
Yu-Ching Weng1, Jui-Lung Shen1, Chii-Shuenn Yang2, Wen-Hao Li1
5
(1) Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan (2) Department of Pathology, Taichung Veterans General Hospital, Taichung, Taiwan
1 2
3
6
7
8
Correspondence to Wen-Hao Li, MD Department of Dermatology Taichung Veterans General Hospital No. 1650, Sec. 4, Taiwan Boulevard
Pulitzer DR, Reed RJ. Nerve-sheath myxoma (perineurial myxoma). Am J Dermatopathol 1985; 7: 409–21. Fetsch JF, Laskin WB, Hallman JR et al. 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. Hornick JL, Fletcher CD. Cellular neurothekeoma: detailed characterization in a series of 133 cases. Am J Surg Pathol 2007; 31: 329–40. D’Antonio A, Cuomo R, Angrisani B et al. Desmoplastic cellular neurothekeoma mimicking a desmoplastic melanocytic tumor. J Am Acad Dermatol 2011; 65: e57–8. Chang WT, Wu YH, Wu NL, Chang KM. Desmoplastic cellular neurothekeoma. Dermatologica Sinica 2014; 32: 193–4. Yamada S, Kitada S, Nabeshima A et al. Benign cutaneous plexiform hybrid tumor of perineurioma and cellular neurothekeoma arising from the nose. Diagn Pathol 2013; 8: 165. Requena L, Sitthinamsuwan P, Fried I et al. A benign cutaneous plexiform hybrid tumor of perineurioma and cellular neurothekeoma. Am J Surg Pathol 2013; 37: 845–52. Fox MD, Billings SD, Gleason BC et al. Expression of MiTF may be helpful in differentiating cellular neurothekeoma from plexiform fibrohistiocytic tumor (histiocytoid predominant) in a partial biopsy specimen. Am J Dermatopathol 2012; 34: 157–60.
Taichung 40705 Taiwan E-mail: [email protected]
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1303
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