Case and research letter
Squamous cell carcinoma in an immunosuppressed patient on voriconazole
Carcinoma espinocelular en un paciente inmunosuprimido en tratamiento con voriconazol
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B, Biopsy showed an epidermal folliculotropic infiltrate (hematoxylin eosin, original magnification ×4) and lymphocytes permeating the follicle (inset: hematoxylin eosin, original magnification ×40). C and D, Immunohistochemical staining showed abundant B cells (CD20<span class="elsevierStyleSup">+</span> and CD79<span class="elsevierStyleSup">+</span>; original magnification ×4). E and F, The lymphocytic infiltrate was composed almost entirely of CD4<span class="elsevierStyleSup">+</span> lymphocytes that surrounded the hair follicles.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.M. Otero Rivas, P. Sánchez Sambucety, L.M. Valladares Narganes, M.Á. Rodríguez Prieto" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M.M." "apellidos" => "Otero Rivas" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Sánchez Sambucety" ] 2 => array:2 [ "nombre" => "L.M." "apellidos" => "Valladares Narganes" ] 3 => array:2 [ "nombre" => "M.Á." 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Carrascosa, G.E. Solano-López, E. Vargas, J. Fraga" "autores" => array:4 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Carrascosa" "email" => array:1 [ 0 => "rachel170786@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "G.E." "apellidos" => "Solano-López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "E." "apellidos" => "Vargas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "J." "apellidos" => "Fraga" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario La Princesa, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario La Princesa, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Carcinoma espinocelular en un paciente inmunosuprimido en tratamiento con voriconazol" ] ] "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" => 809 "Ancho" => 1000 "Tamanyo" => 162789 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Recurrence of squamous cell carcinoma in the area close to the graft.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Voriconazole is a second-generation triazole antifungal agent that inhibits the enzyme cytochrome P450, which is required for the synthesis of ergosterol, a sterol that maintains the integrity of the fungal cell wall.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> In 2002 voriconazole was approved by the US Food and Drug Administration for the treatment of serious fungal infections including those caused by <span class="elsevierStyleItalic">Fusarium</span> and <span class="elsevierStyleItalic">Aspergillus s</span>pecies.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The main adverse effects of voriconazole are visual disturbances, elevated transaminase levels, gastrointestinal upset, and skin rashes, including photosensitivity, cheilitis, and xerosis.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> Prolonged use has been associated with the development of liver spots, actinic keratoses, squamous cell carcinoma (SCC), and even cutaneous melanoma.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Most of the patients who develop SCC are immunocompromised (bone marrow, stem cell, or lung transplant recipients).<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We describe the case of a 30-year-old man with Fitzpatrick skin phototype II and low sun exposure who had been diagnosed with cystic fibrosis. In 1998, at the age of 17, he underwent a double lung transplant. He was prescribed immunosuppressive therapy with tacrolimus, prednisone, and mycophenolate mofetil. In 2007, the patient underwent a right lower lobectomy for tuberculosis and pulmonary aspergillosis and began antifungal treatment with voriconazole. In 2011, after 3 years of treatment with voriconazole, he developed a fast-growing nodule in the left parietal region and multiple actinic keratoses on the rest of the scalp (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The tumor was excised by Mohs micrographic surgery and closed using a full-thickness skin graft. Histology revealed a moderately differentiated SCC (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) with tumor-free margins. Voriconazole treatment was discontinued once the diagnosis was confirmed. Three months later, the patient developed a recurrence in the left parietal region, near the skin graft (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). As tumor adhesion to the cortex was observed during resection of the lesion, the periosteum was excised and an osteotomy of the outer table performed. Weeks later, the patient developed left and right cervical lymph node metastases, for which he underwent bilateral lymph node dissection (4/29 positive nodes on the right side and 1/32 on the left) and subsequently received adjuvant radiotherapy at a dose of 50<span class="elsevierStyleHsp" style=""></span>Gy (60<span class="elsevierStyleHsp" style=""></span>Gy for level-II lymph node metastases). After 6 months free of disease, the patient developed a right cervical node recurrence with microscopic spread to surrounding soft tissues. The lesion was completely removed and the patient is currently awaiting adjuvant treatment.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Skin tumors in patients with chronic immunosuppression are more common and usually more aggressive than in the general immunocompetent population. Furthermore, despite the small number of cases described in the literature, there is increasing evidence linking prolonged voriconazole treatment in immunocompromised patients with the development of multiple cutaneous SCCs that are more aggressive and more likely to recur locally than those observed in the general population.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> While the prolonged immunosuppression of the patient in the present case was likely an important factor influencing both the development and the aggressive course of the SCC, it is likely that prolonged treatment with voriconazole was the determining factor. To date, at least 18 cases of voriconazole-associated SCC have been described (2 children and 16 adults),<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> all involving tumors in sun-exposed areas such as the face, neck, and dorsum of the hands. The scalp was affected in only in 6 these cases.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The mechanism that underlies the development of these tumors is unclear. A repeated, extensive, and intense phototoxic stimulus affecting sun-exposed areas may explain the appearance of preneoplastic lesions such as actinic keratoses, which subsequently progress to SCCs. Photocarcinogenesis is usually caused by cellular DNA damage, which in the present case was likely mediated by voriconazole and/or its metabolites, either directly or by oxidative stress.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Particular care should be taken when prescribing voriconazole to immunosuppressed patients, especially if it is anticipated that the treatment will be long term or if the patient has a low phototype (I-II).<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,8</span></a> It is recommended that these patents are closely monitored and take sun protection measures, which include avoiding sun exposure, wearing appropriate clothing, and using suncream.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a> In some cases it may be necessary to discontinue voriconazole treatment. The possibility of substituting voriconazole with another antifungal agent with a suitable spectrum (especially posaconazole or itraconazole) should also be considered.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></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: Carrascosa R, Solano-López GE, Vargas E, Fraga J. Carcinoma espinocelular en un paciente inmunosuprimido en tratamiento con voriconazol. Actas Dermosifiliogr. 2014;105:424–426.</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" => 862 "Ancho" => 1001 "Tamanyo" => 247184 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Fast-growing tuberous lesion in the left parietal region.</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" => 613 "Ancho" => 1001 "Tamanyo" => 291519 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Moderately differentiated squamous cell carcinoma (hematoxylin eosin, original magnification ×10). The composition of the tumor, which consists of nests and strings of epithelial cells with extensive foci of keratotic differentiation, is shown in greater detail in the inset (hematoxylin eosin, original magnification ×400).</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" => 809 "Ancho" => 1000 "Tamanyo" => 162789 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Recurrence of squamous cell carcinoma in the area close to the graft.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanoma associated with long-term voriconazole therapy: A new manifestation of chronic photosensitivity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D.D. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 7 | 12 | 19 |
| 2024 Octubre | 66 | 59 | 125 |
| 2024 Septiembre | 68 | 32 | 100 |
| 2024 Agosto | 106 | 73 | 179 |
| 2024 Julio | 75 | 52 | 127 |
| 2024 Junio | 89 | 46 | 135 |
| 2024 Mayo | 63 | 43 | 106 |
| 2024 Abril | 62 | 18 | 80 |
| 2024 Marzo | 65 | 30 | 95 |
| 2024 Febrero | 45 | 33 | 78 |
| 2024 Enero | 36 | 29 | 65 |
| 2023 Diciembre | 50 | 24 | 74 |
| 2023 Noviembre | 50 | 24 | 74 |
| 2023 Octubre | 50 | 20 | 70 |
| 2023 Septiembre | 61 | 29 | 90 |
| 2023 Agosto | 53 | 20 | 73 |
| 2023 Julio | 40 | 30 | 70 |
| 2023 Junio | 54 | 17 | 71 |
| 2023 Mayo | 53 | 22 | 75 |
| 2023 Abril | 57 | 24 | 81 |
| 2023 Marzo | 53 | 31 | 84 |
| 2023 Febrero | 46 | 23 | 69 |
| 2023 Enero | 37 | 30 | 67 |
| 2022 Diciembre | 54 | 39 | 93 |
| 2022 Noviembre | 32 | 25 | 57 |
| 2022 Octubre | 23 | 19 | 42 |
| 2022 Septiembre | 34 | 48 | 82 |
| 2022 Agosto | 24 | 33 | 57 |
| 2022 Julio | 37 | 37 | 74 |
| 2022 Junio | 38 | 23 | 61 |
| 2022 Mayo | 49 | 41 | 90 |
| 2022 Abril | 45 | 33 | 78 |
| 2022 Marzo | 49 | 55 | 104 |
| 2022 Febrero | 38 | 26 | 64 |
| 2022 Enero | 29 | 34 | 63 |
| 2021 Diciembre | 28 | 41 | 69 |
| 2021 Noviembre | 48 | 49 | 97 |
| 2021 Octubre | 43 | 52 | 95 |
| 2021 Septiembre | 32 | 23 | 55 |
| 2021 Agosto | 26 | 38 | 64 |
| 2021 Julio | 24 | 30 | 54 |
| 2021 Junio | 26 | 32 | 58 |
| 2021 Mayo | 29 | 24 | 53 |
| 2021 Abril | 51 | 47 | 98 |
| 2021 Marzo | 75 | 16 | 91 |
| 2021 Febrero | 45 | 25 | 70 |
| 2021 Enero | 23 | 16 | 39 |
| 2020 Diciembre | 29 | 10 | 39 |
| 2020 Noviembre | 18 | 10 | 28 |
| 2020 Octubre | 14 | 7 | 21 |
| 2020 Septiembre | 24 | 11 | 35 |
| 2020 Agosto | 20 | 20 | 40 |
| 2020 Julio | 22 | 10 | 32 |
| 2020 Junio | 25 | 19 | 44 |
| 2020 Mayo | 18 | 15 | 33 |
| 2020 Abril | 22 | 12 | 34 |
| 2020 Marzo | 27 | 19 | 46 |
| 2020 Febrero | 1 | 5 | 6 |
| 2020 Enero | 4 | 0 | 4 |
| 2019 Diciembre | 4 | 2 | 6 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Octubre | 0 | 2 | 2 |
| 2019 Septiembre | 4 | 2 | 6 |
| 2019 Agosto | 4 | 6 | 10 |
| 2019 Julio | 2 | 2 | 4 |
| 2019 Junio | 4 | 16 | 20 |
| 2019 Mayo | 1 | 30 | 31 |
| 2019 Abril | 0 | 5 | 5 |
| 2019 Marzo | 0 | 8 | 8 |
| 2019 Febrero | 0 | 1 | 1 |
| 2018 Diciembre | 3 | 4 | 7 |
| 2018 Noviembre | 1 | 0 | 1 |
| 2018 Septiembre | 6 | 0 | 6 |
| 2018 Junio | 1 | 1 | 2 |
| 2018 Mayo | 0 | 1 | 1 |
| 2018 Marzo | 1 | 2 | 3 |
| 2018 Febrero | 36 | 3 | 39 |
| 2018 Enero | 39 | 6 | 45 |
| 2017 Diciembre | 33 | 4 | 37 |
| 2017 Noviembre | 28 | 4 | 32 |
| 2017 Octubre | 23 | 4 | 27 |
| 2017 Septiembre | 40 | 8 | 48 |
| 2017 Agosto | 54 | 4 | 58 |
| 2017 Julio | 50 | 8 | 58 |
| 2017 Junio | 68 | 22 | 90 |
| 2017 Mayo | 62 | 7 | 69 |
| 2017 Abril | 49 | 7 | 56 |
| 2017 Marzo | 38 | 33 | 71 |
| 2017 Febrero | 40 | 7 | 47 |
| 2017 Enero | 13 | 5 | 18 |
| 2016 Diciembre | 26 | 8 | 34 |
| 2016 Noviembre | 49 | 4 | 53 |
| 2016 Octubre | 37 | 5 | 42 |
| 2016 Septiembre | 31 | 9 | 40 |
| 2016 Agosto | 42 | 8 | 50 |
| 2016 Julio | 16 | 8 | 24 |
| 2016 Junio | 13 | 0 | 13 |
| 2016 Mayo | 8 | 3 | 11 |
| 2016 Abril | 2 | 8 | 10 |
| 2016 Marzo | 3 | 2 | 5 |
| 2016 Febrero | 9 | 2 | 11 |
| 2016 Enero | 11 | 1 | 12 |
| 2015 Diciembre | 8 | 0 | 8 |
| 2015 Noviembre | 6 | 4 | 10 |
| 2015 Octubre | 16 | 0 | 16 |
| 2015 Septiembre | 11 | 1 | 12 |
| 2015 Agosto | 10 | 6 | 16 |
| 2015 Julio | 37 | 7 | 44 |
| 2015 Junio | 33 | 1 | 34 |
| 2015 Mayo | 45 | 4 | 49 |
| 2015 Abril | 32 | 1 | 33 |
| 2015 Marzo | 21 | 3 | 24 |
| 2015 Febrero | 21 | 1 | 22 |
| 2015 Enero | 22 | 2 | 24 |
| 2014 Diciembre | 18 | 4 | 22 |
| 2014 Noviembre | 19 | 7 | 26 |
| 2014 Octubre | 21 | 8 | 29 |
| 2014 Septiembre | 9 | 7 | 16 |
| 2014 Agosto | 13 | 2 | 15 |
| 2014 Julio | 32 | 3 | 35 |
| 2014 Junio | 40 | 7 | 47 |
| 2014 Mayo | 24 | 7 | 31 |
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