Case and Research Letters
An Amelanotic Dysplastic Melanocytic Nevus Induced by Vemurafenib
Nevus melanocítico atípico amelanótico inducido por vemurafenib
J.R. Estela Cubells
, A.M. Victoria Martínez, V. Oliver Martínez, V. Alegre de Miquel
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Servicio de Dermatología, Consorcio Hospital General Universitario de Valencia, Valencia, España
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Estela Cubells, A.M. Victoria Martínez, V. Oliver Martínez, V. Alegre de Miquel" "autores" => array:4 [ 0 => array:4 [ "nombre" => "J.R." "apellidos" => "Estela Cubells" "email" => array:1 [ 0 => "j.estela@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A.M." "apellidos" => "Victoria Martínez" ] 2 => array:2 [ "nombre" => "V." "apellidos" => "Oliver Martínez" ] 3 => array:2 [ "nombre" => "V." "apellidos" => "Alegre de Miquel" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Consorcio Hospital General Universitario de Valencia, Valencia, España" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Nevus melanocítico atípico amelanótico inducido por vemurafenib" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 737 "Ancho" => 981 "Tamanyo" => 241115 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Nests of melanocytes in the basal layer of the epidermis with sparse single melanocytes in the upper layers (Melan-A, original magnification ×100).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Vemurafenib is a B-raf kinase inhibitor developed to treat metastatic melanoma in patients with the <span class="elsevierStyleItalic">BRAF</span> V600E mutation, which is found in 40% to 60% of patients with advanced melanoma. It acts by inhibiting the BRAF/MEK/ERK mitogen-activated protein kinase (MAPK) pathway at the BRAF/MEK step. Recent studies have reported that vemurafenib is associated with a 63% reduction in risk of death.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Adverse effects include joint pain, photosensitivity, alopecia, fatigue, hyperkeratosis, xerosis, nonspecific rash, keratoacanthoma, and squamous cell carcinoma.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–5</span></a> We report the case of a patient with stage IV melanoma who developed a clinically amelanotic dysplastic melanocytic nevus 2 months after starting treatment with vemurafenib.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 42-year old white man who had been diagnosed with a stage IV melanoma on the right arm 6 years earlier. Sentinel node biopsy results were positive and the patient underwent right axillary lymph node dissection followed by interferon therapy. Follow-up screening 6 years after surgery led to the detection of 2 pulmonary nodules and metastatic lesions in the C5 and T11 vertebrae, both iliac wings, and the sacrum. After confirmation of the presence of the <span class="elsevierStyleItalic">BRAF</span> V600E mutation, treatment was started with 960 mg of vemurafenib every 12 hours. Two months into treatment, we examined a 10 × 8-mm<span class="elsevierStyleSup">2</span> papular lesion on the left thigh that had been absent at the preceding visit, 1 month earlier, and had grown to this size gradually. The lesion was dome-shaped, skin-colored, and asymptomatic (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). With a suspected diagnosis of hypertrophic actinic keratosis, complete excisional biopsy of the lesion was performed. Histologic findings included a proliferation of melanocytes in the epidermis and papillary dermis, with mild architectural disorder (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Melanocytes were arranged in nests in the epidermis and papillary dermis, and nuclear pleomorphism was mild. Immunohistochemical staining with Melan-A and HMB-45 showed a proliferation of melanocytes in the basal layer of the epidermis and scattered single melanocytes in the upper layers (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). All these findings were consistent with a dysplastic nevus.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In cells with wild-type <span class="elsevierStyleItalic">BRAF</span>, vemurafenib increases phosphorylation of ERK (extracellular signal–regulated kinase) and thus paradoxically induces hyperactivation of the MAPK signaling pathway, promoting cell proliferation and survival. Hyperactivation is responsible for adverse effects such as keratoacanthoma, squamous cell carcinoma, and actinic keratosis. This paradoxical activation effect can also trigger progression of benign melanocytic lesions to melanoma.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Atypical melanocytic proliferation and the development of new melanomas have been described in patients undergoing treatment with vemurafenib, and vemurafenib-induced changes in preexisting nevi have been observed by dermoscopy.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This case in which a patient on vemurafenib developed an amelanotic dysplastic melanocytic nevus highlights the need to monitor this kind of lesion closely and perform a biopsy if there is any doubt, to ensure early detection of incipient malignancies.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Estela Cubells JR, Victoria Martínez AM, Oliver Martínez V, Alegre de Miquel V. Nevus melanocítico atípico amelanótico inducido por vemurafenib. Actas Dermosifiliogr. 2014;105:726–727.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 737 "Ancho" => 982 "Tamanyo" => 154020 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Papular skin-colored lesion on the left thigh.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 736 "Ancho" => 982 "Tamanyo" => 268553 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Proliferation of melanocytes in the epidermis and papillary dermis, with mild architectural disorder (hematoxylin-eosin, original magnification ×40).</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 737 "Ancho" => 981 "Tamanyo" => 241115 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Nests of melanocytes in the basal layer of the epidermis with sparse single melanocytes in the upper layers (Melan-A, original magnification ×100).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Improved survival with vemurafenib in melanoma with BRAF V600E mutation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.B. 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| 2022 Marzo | 82 | 50 | 132 |
| 2022 Febrero | 84 | 29 | 113 |
| 2022 Enero | 134 | 22 | 156 |
| 2021 Diciembre | 122 | 26 | 148 |
| 2021 Noviembre | 102 | 35 | 137 |
| 2021 Octubre | 73 | 32 | 105 |
| 2021 Septiembre | 78 | 36 | 114 |
| 2021 Agosto | 77 | 22 | 99 |
| 2021 Julio | 69 | 17 | 86 |
| 2021 Junio | 44 | 20 | 64 |
| 2021 Mayo | 51 | 21 | 72 |
| 2021 Abril | 162 | 116 | 278 |
| 2021 Marzo | 79 | 18 | 97 |
| 2021 Febrero | 72 | 25 | 97 |
| 2021 Enero | 39 | 14 | 53 |
| 2020 Diciembre | 47 | 6 | 53 |
| 2020 Noviembre | 21 | 9 | 30 |
| 2020 Octubre | 19 | 8 | 27 |
| 2020 Septiembre | 37 | 13 | 50 |
| 2020 Agosto | 17 | 9 | 26 |
| 2020 Julio | 34 | 12 | 46 |
| 2020 Junio | 27 | 17 | 44 |
| 2020 Mayo | 25 | 9 | 34 |
| 2020 Abril | 34 | 11 | 45 |
| 2020 Marzo | 20 | 13 | 33 |
| 2020 Febrero | 3 | 0 | 3 |
| 2020 Enero | 6 | 3 | 9 |
| 2019 Diciembre | 8 | 1 | 9 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Septiembre | 4 | 0 | 4 |
| 2019 Agosto | 4 | 0 | 4 |
| 2019 Julio | 4 | 2 | 6 |
| 2019 Junio | 4 | 0 | 4 |
| 2019 Mayo | 6 | 11 | 17 |
| 2019 Abril | 2 | 0 | 2 |
| 2019 Marzo | 4 | 7 | 11 |
| 2019 Febrero | 2 | 0 | 2 |
| 2019 Enero | 3 | 0 | 3 |
| 2018 Diciembre | 2 | 0 | 2 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 4 | 0 | 4 |
| 2018 Septiembre | 2 | 0 | 2 |
| 2018 Abril | 0 | 1 | 1 |
| 2018 Marzo | 1 | 7 | 8 |
| 2018 Febrero | 48 | 5 | 53 |
| 2018 Enero | 33 | 6 | 39 |
| 2017 Diciembre | 60 | 7 | 67 |
| 2017 Noviembre | 25 | 6 | 31 |
| 2017 Octubre | 28 | 0 | 28 |
| 2017 Septiembre | 34 | 6 | 40 |
| 2017 Agosto | 38 | 4 | 42 |
| 2017 Julio | 32 | 14 | 46 |
| 2017 Junio | 43 | 9 | 52 |
| 2017 Mayo | 45 | 4 | 49 |
| 2017 Abril | 28 | 6 | 34 |
| 2017 Marzo | 17 | 17 | 34 |
| 2017 Febrero | 21 | 10 | 31 |
| 2017 Enero | 20 | 6 | 26 |
| 2016 Diciembre | 21 | 11 | 32 |
| 2016 Noviembre | 34 | 11 | 45 |
| 2016 Octubre | 44 | 15 | 59 |
| 2016 Septiembre | 39 | 3 | 42 |
| 2016 Agosto | 0 | 2 | 2 |
| 2016 Julio | 4 | 0 | 4 |
| 2016 Junio | 6 | 2 | 8 |
| 2016 Mayo | 4 | 4 | 8 |
| 2016 Abril | 10 | 3 | 13 |
| 2016 Marzo | 9 | 0 | 9 |
| 2016 Febrero | 14 | 6 | 20 |
| 2016 Enero | 6 | 0 | 6 |
| 2015 Diciembre | 11 | 1 | 12 |
| 2015 Noviembre | 12 | 0 | 12 |
| 2015 Octubre | 11 | 0 | 11 |
| 2015 Septiembre | 8 | 3 | 11 |
| 2015 Agosto | 13 | 1 | 14 |
| 2015 Julio | 87 | 5 | 92 |
| 2015 Junio | 57 | 3 | 60 |
| 2015 Mayo | 53 | 2 | 55 |
| 2015 Abril | 26 | 4 | 30 |
| 2015 Marzo | 36 | 4 | 40 |
| 2015 Febrero | 24 | 3 | 27 |
| 2015 Enero | 20 | 2 | 22 |
| 2014 Diciembre | 17 | 4 | 21 |
| 2014 Noviembre | 25 | 5 | 30 |
| 2014 Octubre | 23 | 3 | 26 |
| 2014 Septiembre | 20 | 4 | 24 |
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