Amelanotic primary dermal melanoma with V600E BRAF mutation lable at ScienceDirect DERMATOLOGICA SINICA xxx (2016) 1e2 Contents lists avai Dermatologica Sinica journal homepage http / /www derm sin ic[.]
DERMATOLOGICA SINICA xxx (2016) 1e2 Contents lists available at ScienceDirect Dermatologica Sinica journal homepage: http://www.derm-sinica.com CORRESPONDENCE Amelanotic primary dermal melanoma with V600E BRAF mutation Dear Editor, We herein report the case of a Japanese patient who presented with amelanotic primary dermal melanoma (PDM) with V600E BRAF mutation The lesion developed at the site of previous laser treatment A 52-year-old Japanese female noticed a red papule on her right cheek sometime in 1997 The lesion was allegedly treated with laser ablation by a local doctor without histological diagnosis Sixteen years later, she visited us with complaints of a tumor, which appeared at the same region about half a year ago Physical examination revealed an erythematous induration (Figure 1A) Laboratory investigations were all within normal limits Histopathologically, the cutaneous biopsy specimen revealed aggregates of nests composed of round to ovoid cells with swollen nucleus, prominent nucleolus, and rather abundant eosinophilic cytoplasm Mitotic figures were sparse, but an atypical one was recognized No melanization was seen within the tumor cells (Figure 1B) Atypical melanocytes were not found in the epidermis with multiple tissue sections Immunohistochemical analysis were positive for tyrosinase (Figure 1C) and S-100 protein but negative for Melan-A, HMB-45, MITF, AE1/AE3, CK20, and CD68 BRAF p.V600E mutation was detected by immunohistochemical analysis in dermal tumor cells (Figure 1D) The Ki-67 index was 18.8% The EWSR1eATF1 fusion was undetected in blood plasma and tumor using fluorescence in situ hybridization method Imaging examinations, including computed tomography, magnetic resonance imaging, and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography scan, revealed no primary or metastatic lesion We performed wide excision with a margin of cm from the induration and sentinel lymph node biopsy on the right neck Histopathologically, variously sized nests were scattered from the superficial dermis down to the subcutaneous tissue (Figure 1E) No component of benign intradermal nevus was detected in any of the sections Metastasis was not detected in the four lymph nodes excised The patient has been followed up for 30 months without recurrence or metastasis Differential diagnoses included epithelial tumors, perivascular epithelioid cell tumor, nodular melanoma, atypical Spitz nevus, cutaneous clear cell sarcoma, and metastatic carcinomas Histopathologically, tumor nests composed of round to ovoid cells Conflicts of interest: The authors declare that they have no financial or nonfinancial conflicts of interest related to the subject matter or materials discussed in this article were localized from the dermis to subcutaneous tissue and no atypical cell was found in the epidermis Immunohistochemical analysis was positive for tyrosinase and S-100 protein but repeatedly negative for epithelial markers Nodular melanoma usually grows quite quickly and has poor prognosis The Ki-67 index was reported to be 7.02e12.98% in atypical Spitz nevus and 23.99e49.67% in malignant melanoma.1 In our case, 18.8% index is higher than atypical Spitz nevus but lower than conventional malignant melanoma Cutaneous clear cell sarcoma was excluded based on the histological features and the absence of the EWSR1eATF1 fusion gene.2 No primary melanoma has been found at any other sites with extensive investigations Therefore, we are able to diagnose our case as amelanotic PDM PDM is considered a rare subtype of solitary melanoma confined to the dermis and/or subcutaneous tissue with no known separate primary melanoma and negative metastatic findings on work-up.3 PDM shows a much better prognosis compared with similarly staged cutaneous melanoma, and 5-year survival rate is as high as 80e100% An associated benign intradermal nevus is histopathologically detected in 29% (14/49) of PDM cases,3 which was not found in our case Our case is probably the first amelanotic type of PDM reported in English literature No melanization was found with negative immunohistochemical results for Melan-A, HMB-45, and MITF; however, additional staining for tyrosinase eventually led to the diagnosis of melanoma While tyrosinase antibody is rarely used in Japan, it is used in the form of a pan-melanoma antibody cocktail including Melan-A and HMB-45.4 In our case, the tumor was not likely to be a recurrence of malignant melanoma, because the laser ablation was done 16 years ago The possibility of melanoma development subsequent to laser treatment of histologically diagnosed benign lesions was reported.5 It was also reported that sublethal laser damage could increase p16 expression, and BRAF mutation is detected in most benign melanocytic nevi as well, not just in melanoma.6,7 The association of the incidence of BRAF V600E mutation and clinical subtypes was not statistically significant, which showed that BRAF mutation was detected in 37.7% of superficial spreading melanoma, 30.2% of nodular melanoma, 17.0% of lentigo maligna, and 15.1% of acral or mucosal melanomas.8 Although histological examination was not done before the laser treatment and we could not find dermal component of benign nevus in the resected tumor, laser treatment in our case might still possibly induce malignant transformation of dermal nevus cells harboring BRAF mutation http://dx.doi.org/10.1016/j.dsi.2016.10.001 1027-8117/Copyright © 2016, Taiwanese Dermatological Association Published by Elsevier Taiwan LLC This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/) Please cite this article in press as: Kabuto M, et al Amelanotic primary dermal melanoma with V600E BRAF mutation, Dermatologica Sinica (2016), http://dx.doi.org/10.1016/j.dsi.2016.10.001 Correspondence / Dermatologica Sinica xxx (2016) 1e2 Figure (A) Initial clinical presentation An induration, which measures about 20 mm in diameter with a red nodule about mm at the center, was observed on the patient’s right cheek (B) Histopathological findings in a cutaneous biopsy specimen from indurated lesion revealed nests of round to ovoid cells with swollen nucleus, eosinophilic cytoplasm, and no melanization in the dermis [hematoxylin and eosin (HE); original magnification, 200] (C) Immunohistochemical staining for tyrosinase showed nests of round to ovoid cells with strong positive expression in the dermis (original magnification, 200) (D) Immunohistochemical staining for BRAF p.V600E (clone VE1, Spring Bioscience, Pleasanton, CA, USA) showed positive expression of tumor cells in the dermis (original magnification, 200) (E) Histopathological findings of the resected specimen demonstrated large or small nests from the superficial dermis to the subcutaneous layer (HE; original magnification, 1) Acknowledgments References The authors thank Dr Masanobu Kumakiri for his help with histopathological diagnosis and Ms Yuko Tsukamoto for her help with immunohistochemical analysis Kapur P, Selim MA, Roy LC, et al Spitz nevi and atypical Spitz nevi/tumors: a histologic and immunohistochemical analysis Mod Pathol 2005;18:197e204 Yang L, Chen Y, Cui T, et al Identification of biomarkers to distinguish clear cell sarcoma from malignant melanoma Hum Pathol 2012;43:1463e70 Sidiropoulos M, Obregon R, Cooper C, et al Primary dermal melanoma: a unique subtype of melanoma to be distinguished from cutaneous metastatic melanoma: a clinical, histologic, and gene expression-profiling study J Am Acad Dermatol 2014;71:1083e92 Orchard G Evaluation of melanocytic neoplasms: application of a panmelanoma antibody cocktail Br J Biomed Sci 2002;59:196e202 Zipser MC, Mangana J, Oberholzer PA, et al Melanoma after laser therapy of pigmented lesionsdcircumstances and outcome Eur J Dermatol 2010;20:334e8 Chan HH, Xiang L, Leung JC, et al In vitro study examining the effect of sub-lethal QS 755 nm lasers on the expression of p16INK4a on melanoma cell lines Lasers Surg Med 2003;32:88e93 Kumar R, Angelini S, Snellman E, et al BRAF mutations are common somatic events in melanocytic nevi J Invest Dermatol 2004;122:342e8 Inumaru JS, Gordo KI, Fraga Junior AC, et al Analysis of the BRAF V600E mutation in primary cutaneous melanoma Genet Mol Res 2014;13:2840e8 Miho Kabuto, Noriki Fujimoto*, Kazuya Teramura, Takeshi Nakanishi Department of Dermatology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu-shi, Shiga, Japan Taku Fujimura Department of Dermatology, Tohoku University Graduate School of Medicine, Seiryo-machi 1-1, Aoba-ku, Sendai, Miyagi, Japan Toshiaki Manabe Shiga Medical Center Research for Adults, Research Institute, Moriyama 5-4-30, Moriyama, Shiga, Japan Toshihiro Tanaka Department of Dermatology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu-shi, Shiga, Japan * Corresponding author Department of Dermatology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu-shi, Shiga 520-2192, Japan E-mail address: noriki@belle.shiga-med.ac.jp (N Fujimoto) Received: May 20, 2016 Revised: Sep 19, 2016 Accepted: Oct 19, 2016 Please cite this article in press as: Kabuto M, et al Amelanotic primary dermal melanoma with V600E BRAF mutation, Dermatologica Sinica (2016), http://dx.doi.org/10.1016/j.dsi.2016.10.001 ... Accepted: Oct 19, 2016 Please cite this article in press as: Kabuto M, et al Amelanotic primary dermal melanoma with V600E BRAF mutation, Dermatologica Sinica (2016), http://dx.doi.org/10.1016/j.dsi.2016.10.001... malignant melanoma Hum Pathol 2012;43:1463e70 Sidiropoulos M, Obregon R, Cooper C, et al Primary dermal melanoma: a unique subtype of melanoma to be distinguished from cutaneous metastatic melanoma: ... 2004;122:342e8 Inumaru JS, Gordo KI, Fraga Junior AC, et al Analysis of the BRAF V600E mutation in primary cutaneous melanoma Genet Mol Res 2014;13:2840e8 Miho Kabuto, Noriki Fujimoto*, Kazuya