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Trang 1Amelanotic 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
examina-tion revealed an erythematous induraexamina-tion (Figure 1A) Laboratory
in-vestigations 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 Mitoticfigures 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
Immuno-histochemical 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
immuno-histochemical analysis in dermal tumor cells (Figure 1D) The Ki-67
index was 18.8% The EWSR1eATF1 fusion was undetected in blood
plasma and tumor usingfluorescence in situ hybridization method
Imaging examinations, including computed tomography, magnetic
resonance imaging, and fluorine-18-fluorodeoxyglucose positron
emission tomography/computed tomography scan, revealed no
pri-mary or metastatic lesion We performed wide excision with a
margin of 1 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
tis-sue (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
Histo-pathologically, tumor nests composed of round to ovoid cells
were localized from the dermis to subcutaneous tissue and no atyp-ical cell was found in the epidermis Immunohistochematyp-ical analysis was positive for tyrosinase and S-100 protein but repeatedly nega-tive 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 malig-nant melanoma.1In 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 histologi-cal features and the absence of the EWSR1eATF1 fusion gene.2No primary melanoma has been found at any other sites with exten-sive 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 metastaticfindings 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 histopath-ologically detected in 29% (14/49) of PDM cases,3which was not found in our case
Our case is probably thefirst 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 malig-nant 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 melano-cytic nevi as well, not just in melanoma.6,7The 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.8Although 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
Conflicts of interest: The authors declare that they have no financial or
non-financial conflicts of interest related to the subject matter or materials discussed
in this article.
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DERMATOLOGICA SINICA xxx (2016) 1e2
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
Trang 2The authors thank Dr Masanobu Kumakiri for his help with
histo-pathological diagnosis and Ms Yuko Tsukamoto for her help with
immunohistochemical analysis
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).
References
1 Kapur P, Selim MA, Roy LC, et al Spitz nevi and atypical Spitz nevi/tumors: a his-tologic and immunohistochemical analysis Mod Pathol 2005;18:197e204
2 Yang L, Chen Y, Cui T, et al Identification of biomarkers to distinguish clear cell sarcoma from malignant melanoma Hum Pathol 2012;43:1463e70
3 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
4 Orchard G Evaluation of melanocytic neoplasms: application of a pan-melanoma antibody cocktail Br J Biomed Sci 2002;59:196e202
5 Zipser MC, Mangana J, Oberholzer PA, et al Melanoma after laser therapy of pig-mented lesionsdcircumstances and outcome Eur J Dermatol 2010;20:334e8
6 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
7 Kumar R, Angelini S, Snellman E, et al BRAF mutations are common somatic events in melanocytic nevi J Invest Dermatol 2004;122:342e8
8 Inumaru JS, Gordo KI, Fraga Junior AC, et al Analysis of the BRAF V600E muta-tion in primary cutaneous melanoma Genet Mol Res 2014;13:2840e8
Received: May 20, 2016 Revised: Sep 19, 2016 Accepted: Oct 19, 2016
Figure 1 (A) Initial clinical presentation An induration, which measures about 20 mm in diameter with a red nodule about 5 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).
Correspondence / Dermatologica Sinica xxx (2016) 1e2 2
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